Reviewer's report
Title:The study of visceral hypersensitivity and psychological stress in
gastroesophageal reflux disease
Version: 1Date:8 December 2010
Reviewer: Zhuo Wang
Reviewer's report:
Major compulsory revisions
1. Only 4 out of 34 patients reported heartburn during acid infusion. It brings up
the question whether 5-minute infusion of 0.1 N HCl is a sufficient stimulus.
Considering that the aim here is to study neural correlates of visceral
hypersensitivity in GERD, using subthreshold stimuli doesn’t seem optimal. The
authors need to elucidate their rationale for not using a stronger stimuli (i.e.,
longer duration) and limitations that may be associated with the current protocol.
There seems to be a fair range (up to 20 minutes of infusion) before inducing
discomfort in healthy controls (page 14, cited work by Ho et al.)
2. The rationale for excluding some NERD-SI- patients based on their responses
to PPI treatment is not clear. Furthermore, since subjects in other groups didn’t
go through this 7-day omeprazole treatment, the authors need to discuss this as
a possible confounding factor when interpreting the data.
3. A major weakness in the analysis of fMRI data is inadequate secondary
analysis to statistically assess between-group differences. The group differences
in the time course of brain activation as presented in Table 4 are important. But
equally important are group differences in the intensity and extend of regional
activation. The authors may want to consider additional analysis addressing
these questions.
Minor essential revisions.
1. Acronyms should be spelt out in the Abstract as well as main body on their first
appearance. E.g., PFC in the Abstract.
2. There are some corrupted characters in the PDF file. E.g., page 2, Abstract, (P
= 0.003 ?0.000).
3. NERD-SI- is misspelled as “NERD-SI” in several places. E.g., page 2, line 3.
4. Redundant sentences “The RE subgroup had the shortest …”, page 2, line
10-14.
5. Should cite work by Dr. Emeran A. Mayer and colleagues using functional
brain imaging to study brain substrates of visceral nociception in healthy subjects
and IBS patients. (Introduction, page 3, last paragraph.)
6. Should cite and discuss Yaguez et al. 2005 Gastroenterology 128(7): 1819.
7. The use of the term “psychological stress” seems ambiguous. “At the
beginning of the psychological stimulation, the participant was informed by an
earphone that some fluid which might cause heartburn would be infused …”. This
appears to this reviewer as a paradigm to investigate pain anticipation, a subject
of much brain imaging research by Dr. Mayer and many others.
8. Unit of measurement should be given. E.g., page 11, unit for plasma SP and
CRH. Table 4, unit for time.
9. Figure 1: Need to label X- (Time) and Y-axis (V %). The three horizontal
arrows and the three vertical line marks for different time point are redundant.
Consider removing the arrows. What are the yellow lines for? What are the
numbers under the figure, “X: 39” etc.? Should use the same font in all figures.
10. Figure 3: Add graph for the control group response to acid. A – E labeling is
not necessary. Use NERD-SI+ and NERD-SI- rather than SI+ and SI- for
consistency. Remove minor tick marks in the X-axis. Fix the major tick mark
labels for the X-axis. Label X-axis as Time (s). Remove markers from the data
lines for clarity (like in Figure 1).
Discretionary revisions
1. The title doesn’t summarize the contents very well. The running title looks
better. A better title should make it clear that this is a functional brain imaging
study of brain responses to actual and anticipated visceral stimuli in GERD
patients.
2. Consider changing “P = 0.000” to “P < 0.001” in text.
3. Consider listing number of female subjects as well. E.g., page 5, “9 RE (7
males, …)” to 9 RE (7 males / 2 females …).
4. Page 13, Discussion: why limit epidemiological data to China? What about for
the world population in general?
5. Figure 2: Consider simply using A and B to label upper and lower panel, and
labeling individual activation map with group name, e.g. Control, RE, etc.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:The study of visceral hypersensitivity and psychological stress in
gastroesophageal reflux disease
Version: 1Date:8 December 2010
Reviewer: Zhuo Wang
Reviewer's report:
Major compulsory revisions
1. Only 4 out of 34 patients reported heartburn during acid infusion. It brings up
the question whether 5-minute infusion of 0.1 N HCl is a sufficient stimulus.
Considering that the aim here is to study neural correlates of visceral
hypersensitivity in GERD, using subthreshold stimuli doesn’t seem optimal. The
authors need to elucidate their rationale for not using a stronger stimuli (i.e.,
longer duration) and limitations that may be associated with the current protocol.
There seems to be a fair range (up to 20 minutes of infusion) before inducing
discomfort in healthy controls (page 14, cited work by Ho et al.)
2. The rationale for excluding some NERD-SI- patients based on their responses
to PPI treatment is not clear. Furthermore, since subjects in other groups didn’t
go through this 7-day omeprazole treatment, the authors need to discuss this as
a possible confounding factor when interpreting the data.
3. A major weakness in the analysis of fMRI data is inadequate secondary
analysis to statistically assess between-group differences. The group differences
in the time course of brain activation as presented in Table 4 are important. But
equally important are group differences in the intensity and extend of regional
activation. The authors may want to consider additional analysis addressing
these questions.
Minor essential revisions.
1. Acronyms should be spelt out in the Abstract as well as main body on their first
appearance. E.g., PFC in the Abstract.
2. There are some corrupted characters in the PDF file. E.g., page 2, Abstract, (P
= 0.003 ?0.000).
3. NERD-SI- is misspelled as “NERD-SI” in several places. E.g., page 2, line 3.
4. Redundant sentences “The RE subgroup had the shortest …”, page 2, line
10-14.
5. Should cite work by Dr. Emeran A. Mayer and colleagues using functional
brain imaging to study brain substrates of visceral nociception in healthy subjects
and IBS patients. (Introduction, page 3, last paragraph.)
6. Should cite and discuss Yaguez et al. 2005 Gastroenterology 128(7): 1819.
7. The use of the term “psychological stress” seems ambiguous. “At the
beginning of the psychological stimulation, the participant was informed by an
earphone that some fluid which might cause heartburn would be infused …”. This
appears to this reviewer as a paradigm to investigate pain anticipation, a subject
of much brain imaging research by Dr. Mayer and many others.
8. Unit of measurement should be given. E.g., page 11, unit for plasma SP and
CRH. Table 4, unit for time.
9. Figure 1: Need to label X- (Time) and Y-axis (V %). The three horizontal
arrows and the three vertical line marks for different time point are redundant.
Consider removing the arrows. What are the yellow lines for? What are the
numbers under the figure, “X: 39” etc.? Should use the same font in all figures.
10. Figure 3: Add graph for the control group response to acid. A – E labeling is
not necessary. Use NERD-SI+ and NERD-SI- rather than SI+ and SI- for
consistency. Remove minor tick marks in the X-axis. Fix the major tick mark
labels for the X-axis. Label X-axis as Time (s). Remove markers from the data
lines for clarity (like in Figure 1).
Discretionary revisions
1. The title doesn’t summarize the contents very well. The running title looks
better. A better title should make it clear that this is a functional brain imaging
study of brain responses to actual and anticipated visceral stimuli in GERD
patients.
2. Consider changing “P = 0.000” to “P < 0.001” in text.
3. Consider listing number of female subjects as well. E.g., page 5, “9 RE (7
males, …)” to 9 RE (7 males / 2 females …).
4. Page 13, Discussion: why limit epidemiological data to China? What about for
the world population in general?
5. Figure 2: Consider simply using A and B to label upper and lower panel, and
labeling individual activation map with group name, e.g. Control, RE, etc.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:The study of visceral hypersensitivity and psychological stress in
gastroesophageal reflux disease
Version: 1Date:8 December 2010
Reviewer: Zhuo Wang
Reviewer's report:
Major compulsory revisions
1. Only 4 out of 34 patients reported heartburn during acid infusion. It brings up
the question whether 5-minute infusion of 0.1 N HCl is a sufficient stimulus.
Considering that the aim here is to study neural correlates of visceral
hypersensitivity in GERD, using subthreshold stimuli doesn’t seem optimal. The
authors need to elucidate their rationale for not using a stronger stimuli (i.e.,
longer duration) and limitations that may be associated with the current protocol.
There seems to be a fair range (up to 20 minutes of infusion) before inducing
discomfort in healthy controls (page 14, cited work by Ho et al.)
2. The rationale for excluding some NERD-SI- patients based on their responses
to PPI treatment is not clear. Furthermore, since subjects in other groups didn’t
go through this 7-day omeprazole treatment, the authors need to discuss this as
a possible confounding factor when interpreting the data.
3. A major weakness in the analysis of fMRI data is inadequate secondary
analysis to statistically assess between-group differences. The group differences
in the time course of brain activation as presented in Table 4 are important. But
equally important are group differences in the intensity and extend of regional
activation. The authors may want to consider additional analysis addressing
these questions.
Minor essential revisions.
1. Acronyms should be spelt out in the Abstract as well as main body on their first
appearance. E.g., PFC in the Abstract.
2. There are some corrupted characters in the PDF file. E.g., page 2, Abstract, (P
= 0.003 ?0.000).
3. NERD-SI- is misspelled as “NERD-SI” in several places. E.g., page 2, line 3.
4. Redundant sentences “The RE subgroup had the shortest …”, page 2, line
10-14.
5. Should cite work by Dr. Emeran A. Mayer and colleagues using functional
brain imaging to study brain substrates of visceral nociception in healthy subjects
and IBS patients. (Introduction, page 3, last paragraph.)
6. Should cite and discuss Yaguez et al. 2005 Gastroenterology 128(7): 1819.
7. The use of the term “psychological stress” seems ambiguous. “At the
beginning of the psychological stimulation, the participant was informed by an
earphone that some fluid which might cause heartburn would be infused …”. This
appears to this reviewer as a paradigm to investigate pain anticipation, a subject
of much brain imaging research by Dr. Mayer and many others.
8. Unit of measurement should be given. E.g., page 11, unit for plasma SP and
CRH. Table 4, unit for time.
9. Figure 1: Need to label X- (Time) and Y-axis (V %). The three horizontal
arrows and the three vertical line marks for different time point are redundant.
Consider removing the arrows. What are the yellow lines for? What are the
numbers under the figure, “X: 39” etc.? Should use the same font in all figures.
10. Figure 3: Add graph for the control group response to acid. A – E labeling is
not necessary. Use NERD-SI+ and NERD-SI- rather than SI+ and SI- for
consistency. Remove minor tick marks in the X-axis. Fix the major tick mark
labels for the X-axis. Label X-axis as Time (s). Remove markers from the data
lines for clarity (like in Figure 1).
Discretionary revisions
1. The title doesn’t summarize the contents very well. The running title looks
better. A better title should make it clear that this is a functional brain imaging
study of brain responses to actual and anticipated visceral stimuli in GERD
patients.
2. Consider changing “P = 0.000” to “P < 0.001” in text.
3. Consider listing number of female subjects as well. E.g., page 5, “9 RE (7
males, …)” to 9 RE (7 males / 2 females …).
4. Page 13, Discussion: why limit epidemiological data to China? What about for
the world population in general?
5. Figure 2: Consider simply using A and B to label upper and lower panel, and
labeling individual activation map with group name, e.g. Control, RE, etc.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
assistant