Title: Prevalence of vomiting and nausea and associated factors after chronic and acute gluten
exposure in celiac disease
Version: 1 Date: 25 Jun 2023
Reviewer's report:
Dear Editor and dear authors,
Ahonen et al wrote a well-written paper including both retrospective and prospective data
and a review of the literature regarding vomiting and nausea in relation to chronic and acute
(re)exposure to gluten in patients with celiac disease. This study/substudies is/are well designed,
although I have some comments and suggestions. Although this manuscript need some revisions
in my opinion, it is defenitely of added value to the current literature. Please see my comments
and suggestions below:
Introduction:
No comments
Material and Methods:
1. The authors stated "To study acute re-exposure to gluten, asymptomatic CeD patients who
had been following a strict GFD >1 year were recruited via advertisements in Celiac Society
newsletters". How strict was strict? It could be interesting to see if there is a difference between
patients with a different amount/numbers of coincidental gluten intake and the presence of
nausea and vomiting after the short gluten challenge. This can be used to strengthen the
hypothesis stated in the discussion section based on the difference found in the consumption of
oats (difference seen in Table 2). I can imaginge that it's not possible to get these data and that
the reliability of that data could be questionable.
2. Small comment: consider to change "refractory sprue" into "refractory celiac disease"
3. Please explain why you chose for consuming 10 grams gluten per day either in wheat, barley,
rye or a combination of all three grains and why you not have chosen for just one of these. I
think that one of your statements in the discussion refers to this point, but please write more
about this in the Material and Methods section: could the patient chose what they used for the
re-exposure to gluten and why have you chosen for this method instead of chosing 1 type?
4. The authors stated "Transglutaminase 2 antibody values (TGA) are not reported here since
they have been measured with several commercial assays with varying reference values." I
understand this argument. However; since the non-biopsy approach is more and more introduced
in adults as well, it is interesting to see if you will find differences in patients with TGA >10x
upper limit of normal (and not using the absolute values based on the cutoff values of the
commercial assays).  I don't expect a difference, but I would suggest to include that in Table 1.
Results:
5. Data regarding nausea as symptom are missing in the retrospective cohort (chronic gluten
exposure). Since this manuscript is about nausea and vomiting I wonder if data regarding nausea
is available? If available, please insert and if not available, please state in the text that it's not
available (the authors already included this statement of non-availability in Table 3).
6. Small comment: I assume that  one of the percentages in the sentence under Literature Review:
"Study design was retrospective in 67% and prospective in 33% of the studies (Table 3).", is a
typo? Please check and change if needed.
Discussion:
The authors performed very nice work. I would  especially like to give them compliments in
how exensively they explained the possibilities of bias, especially the role for recall bias.
Title: Prevalence of vomiting and nausea and associated factors after chronic and acute gluten
exposure in celiac disease
Version: 1 Date: 25 Jun 2023
Reviewer's report:
Dear Editor and dear authors,
Ahonen et al wrote a well-written paper including both retrospective and prospective data
and a review of the literature regarding vomiting and nausea in relation to chronic and acute
(re)exposure to gluten in patients with celiac disease. This study/substudies is/are well designed,
although I have some comments and suggestions. Although this manuscript need some revisions
in my opinion, it is defenitely of added value to the current literature. Please see my comments
and suggestions below:
Introduction:
No comments
Material and Methods:
1. The authors stated "To study acute re-exposure to gluten, asymptomatic CeD patients who
had been following a strict GFD >1 year were recruited via advertisements in Celiac Society
newsletters". How strict was strict? It could be interesting to see if there is a difference between
patients with a different amount/numbers of coincidental gluten intake and the presence of
nausea and vomiting after the short gluten challenge. This can be used to strengthen the
hypothesis stated in the discussion section based on the difference found in the consumption of
oats (difference seen in Table 2). I can imaginge that it's not possible to get these data and that
the reliability of that data could be questionable.
2. Small comment: consider to change "refractory sprue" into "refractory celiac disease"
3. Please explain why you chose for consuming 10 grams gluten per day either in wheat, barley,
rye or a combination of all three grains and why you not have chosen for just one of these. I
think that one of your statements in the discussion refers to this point, but please write more
about this in the Material and Methods section: could the patient chose what they used for the
re-exposure to gluten and why have you chosen for this method instead of chosing 1 type?
4. The authors stated "Transglutaminase 2 antibody values (TGA) are not reported here since
they have been measured with several commercial assays with varying reference values." I
understand this argument. However; since the non-biopsy approach is more and more introduced
in adults as well, it is interesting to see if you will find differences in patients with TGA >10x
upper limit of normal (and not using the absolute values based on the cutoff values of the
commercial assays).  I don't expect a difference, but I would suggest to include that in Table 1.
Results:
5. Data regarding nausea as symptom are missing in the retrospective cohort (chronic gluten
exposure). Since this manuscript is about nausea and vomiting I wonder if data regarding nausea
is available? If available, please insert and if not available, please state in the text that it's not
available (the authors already included this statement of non-availability in Table 3).
6. Small comment: I assume that  one of the percentages in the sentence under Literature Review:
"Study design was retrospective in 67% and prospective in 33% of the studies (Table 3).", is a
typo? Please check and change if needed.
Discussion:
The authors performed very nice work. I would  especially like to give them compliments in
how exensively they explained the possibilities of bias, especially the role for recall bias.
Please review this paper.
user
Title: Prevalence of vomiting and nausea and associated factors after chronic and acute gluten
exposure in celiac disease
Version: 1 Date: 25 Jun 2023
Reviewer's report:
Dear Editor and dear authors,
Ahonen et al wrote a well-written paper including both retrospective and prospective data
and a review of the literature regarding vomiting and nausea in relation to chronic and acute
(re)exposure to gluten in patients with celiac disease. This study/substudies is/are well designed,
although I have some comments and suggestions. Although this manuscript need some revisions
in my opinion, it is defenitely of added value to the current literature. Please see my comments
and suggestions below:
Introduction:
No comments
Material and Methods:
1. The authors stated "To study acute re-exposure to gluten, asymptomatic CeD patients who
had been following a strict GFD >1 year were recruited via advertisements in Celiac Society
newsletters". How strict was strict? It could be interesting to see if there is a difference between
patients with a different amount/numbers of coincidental gluten intake and the presence of
nausea and vomiting after the short gluten challenge. This can be used to strengthen the
hypothesis stated in the discussion section based on the difference found in the consumption of
oats (difference seen in Table 2). I can imaginge that it's not possible to get these data and that
the reliability of that data could be questionable.
2. Small comment: consider to change "refractory sprue" into "refractory celiac disease"
3. Please explain why you chose for consuming 10 grams gluten per day either in wheat, barley,
rye or a combination of all three grains and why you not have chosen for just one of these. I
think that one of your statements in the discussion refers to this point, but please write more
about this in the Material and Methods section: could the patient chose what they used for the
re-exposure to gluten and why have you chosen for this method instead of chosing 1 type?
4. The authors stated "Transglutaminase 2 antibody values (TGA) are not reported here since
they have been measured with several commercial assays with varying reference values." I
understand this argument. However; since the non-biopsy approach is more and more introduced
in adults as well, it is interesting to see if you will find differences in patients with TGA >10x
upper limit of normal (and not using the absolute values based on the cutoff values of the
commercial assays).  I don't expect a difference, but I would suggest to include that in Table 1.
Results:
5. Data regarding nausea as symptom are missing in the retrospective cohort (chronic gluten
exposure). Since this manuscript is about nausea and vomiting I wonder if data regarding nausea
is available? If available, please insert and if not available, please state in the text that it's not
available (the authors already included this statement of non-availability in Table 3).
6. Small comment: I assume that  one of the percentages in the sentence under Literature Review:
"Study design was retrospective in 67% and prospective in 33% of the studies (Table 3).", is a
typo? Please check and change if needed.
Discussion:
The authors performed very nice work. I would  especially like to give them compliments in
how exensively they explained the possibilities of bias, especially the role for recall bias.
assistant