Reviewer ’s report  
 
Title: A cross -sectional study of nausea in functional abdominal pain: Relation to mucosal mast  
cells and psychological functioning  
 
Version: 0 Date: 28 Jul 2019  
 
Reviewer: Michael Jones  
 
Reviewer's report:  
 
The manuscript by Friesen and colleagues addresses a potentially clinically important question in 
paediatric gastrointestinal disease. In many respects the study is well -conducted and reported. I 
do however have several points for the authors to consider.  
 
1. The Introduction contains some very useful background material but also some that I think is 
either irrelevant or potentially misleading. In the second paragraph on page  4, and onwards, the 
authors quite appropriately attempt to relate previous data to their research question. They 
discuss previous finding in IBS which is a disease for which nausea is not particularly a feature 
and mast cells in relation to abdominal pain  but do not indicate how data on pain might be 
relevant to prevalence of nausea. I would urge the authors to either remove irrelevant material or 
justify its relevance more clearly. The relevance of the previous data on FD is much clearer.  
 
2. On page 9 na usea prevalence for IBS and FD is reported but I am curious about the overlap. 
Since these two conditions are highly comorbid are the overlap patients driving the IBS nausea 
prevalence or is the value similar in pure IBS patients?  
 
3. In both Table 1 and t he Results text prevalence values are reported without any indication of 
uncertainty, confidence intervals or standard error reporting is best practice to avoid over -
interpretation of apparent estimate accuracy.  
 
4. In Tables 2 and 4 was normality of distribution checked prior to use of the t -test? This is an 
assumption that is unlikely to be met by many of the histopathological and psychological 
measures reported.  
 
5. A major potential limitation to the interpreta tion of these data is the potential for confounding. 
The authors conclude that nausea is associated with duodenal mast cell density but are there 
other clinical features that might explain that difference, such as abdominal pain? In a non -
randomised, cross -sectional study such as this, alternate explanations should receive some 
consideration.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which c ontrols are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you reco mmend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicat e the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years rece ived 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 s alary 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 a nswer 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.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understa nd that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors,  which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: A cross -sectional study of nausea in functional abdominal pain: Relation to mucosal mast  
cells and psychological functioning  
 
Version: 0 Date: 28 Jul 2019  
 
Reviewer: Michael Jones  
 
Reviewer's report:  
 
The manuscript by Friesen and colleagues addresses a potentially clinically important question in 
paediatric gastrointestinal disease. In many respects the study is well -conducted and reported. I 
do however have several points for the authors to consider.  
 
1. The Introduction contains some very useful background material but also some that I think is 
either irrelevant or potentially misleading. In the second paragraph on page  4, and onwards, the 
authors quite appropriately attempt to relate previous data to their research question. They 
discuss previous finding in IBS which is a disease for which nausea is not particularly a feature 
and mast cells in relation to abdominal pain  but do not indicate how data on pain might be 
relevant to prevalence of nausea. I would urge the authors to either remove irrelevant material or 
justify its relevance more clearly. The relevance of the previous data on FD is much clearer.  
 
2. On page 9 na usea prevalence for IBS and FD is reported but I am curious about the overlap. 
Since these two conditions are highly comorbid are the overlap patients driving the IBS nausea 
prevalence or is the value similar in pure IBS patients?  
 
3. In both Table 1 and t he Results text prevalence values are reported without any indication of 
uncertainty, confidence intervals or standard error reporting is best practice to avoid over -
interpretation of apparent estimate accuracy.  
 
4. In Tables 2 and 4 was normality of distribution checked prior to use of the t -test? This is an 
assumption that is unlikely to be met by many of the histopathological and psychological 
measures reported.  
 
5. A major potential limitation to the interpreta tion of these data is the potential for confounding. 
The authors conclude that nausea is associated with duodenal mast cell density but are there 
other clinical features that might explain that difference, such as abdominal pain? In a non -
randomised, cross -sectional study such as this, alternate explanations should receive some 
consideration.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which c ontrols are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you reco mmend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicat e the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years rece ived 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 s alary 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 a nswer 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.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understa nd that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors,  which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: A cross -sectional study of nausea in functional abdominal pain: Relation to mucosal mast  
cells and psychological functioning  
 
Version: 0 Date: 28 Jul 2019  
 
Reviewer: Michael Jones  
 
Reviewer's report:  
 
The manuscript by Friesen and colleagues addresses a potentially clinically important question in 
paediatric gastrointestinal disease. In many respects the study is well -conducted and reported. I 
do however have several points for the authors to consider.  
 
1. The Introduction contains some very useful background material but also some that I think is 
either irrelevant or potentially misleading. In the second paragraph on page  4, and onwards, the 
authors quite appropriately attempt to relate previous data to their research question. They 
discuss previous finding in IBS which is a disease for which nausea is not particularly a feature 
and mast cells in relation to abdominal pain  but do not indicate how data on pain might be 
relevant to prevalence of nausea. I would urge the authors to either remove irrelevant material or 
justify its relevance more clearly. The relevance of the previous data on FD is much clearer.  
 
2. On page 9 na usea prevalence for IBS and FD is reported but I am curious about the overlap. 
Since these two conditions are highly comorbid are the overlap patients driving the IBS nausea 
prevalence or is the value similar in pure IBS patients?  
 
3. In both Table 1 and t he Results text prevalence values are reported without any indication of 
uncertainty, confidence intervals or standard error reporting is best practice to avoid over -
interpretation of apparent estimate accuracy.  
 
4. In Tables 2 and 4 was normality of distribution checked prior to use of the t -test? This is an 
assumption that is unlikely to be met by many of the histopathological and psychological 
measures reported.  
 
5. A major potential limitation to the interpreta tion of these data is the potential for confounding. 
The authors conclude that nausea is associated with duodenal mast cell density but are there 
other clinical features that might explain that difference, such as abdominal pain? In a non -
randomised, cross -sectional study such as this, alternate explanations should receive some 
consideration.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which c ontrols are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you reco mmend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicat e the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years rece ived 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 s alary 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 a nswer 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.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understa nd that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors,  which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant