Reviewer ’s report  
 
Title: Prevalence of overlap syndromes and symptoms in pediatric functional dyspepsia  
 
 
Version: 0 Date: 16 May 2016 
 
 
Reviewer: Efstratios  Saliakellis  
 
 
Reviewer's report:  
 
In the present manuscript the authors present a very interesting study that explores the prevalence 
of overlap syndromes and symptoms in pediatric functional dyspepsia (FD).  
FD remains an enigmatic clinical entity, not fully understood in terms of pathophysiology, which 
in turn reflects on the diagnostic and therapeutic limitations encountered in this condition.  
 
A few issues need to be addressed prior to considering this articl e for publication:  
 
1. Style of references: please adopt the one proposed by the journal e.g. use brackets instead of 
parentheses and place the references before full stop.  
 
2. Abstract:  
i. Please include the first sentence of the 'methods' paragraph in the 'results' paragraph as this 
actually presents results of the study (e.g. number of patients enrolled and age range). In this 
sentence you may also consider adding the number of male or female participants.  
 
3. Methods:  
 
Study cohort and exclusion criteria:  
i. Please comment on the two -week acid reduction treatment (e.g. PPIs, Histamine -2 receptor 
antagonists, dosing scheme).  
ii. Except for the upper gastrointestinal (GI) endoscopy did th e authors perform any pH -
impedance studies to assess for non -acid reflux after acid reduction treatment failures? was a pH -
impedance study considered to evaluate patients with symptoms such as excessive 
belching/burping?  
iii. Please comment on the values used by the pathologist to exclude  eosinophilic GI disease; I 
do note that the authors comment on the values used for the esophagus but there is no additional 
data for the stomach and the duodenum.  
iv. Apart from the enumeration of eosinophils, were the b iopsy samples assessed for mast cells?  
 
GI and systemic symptoms:  
i. Please change narration from present to past tense;  
ii. L33 add 'to' ('...sample was selected to complete...');  
iii. Omit questions 1 and 2 from the text;  
iv. Regarding the evaluation  for systemic symptoms: many of them may be present as 
extraintestinal manifestations in children with gastrointestinal food allergy; were the patients 
assessed for food allergies? was any of the v. patients on a food elimination diet?  
vi. Patients presen ting with red flag symptoms e.g. weight loss, were they further investigated for 
organic disease?  
vii. Were patients who presented with symptoms such as vomiting, nausea, early satiety and 
bloating, further investigated with a gastric emptying study?  
viii. Were patients who presented with abdominal pain that increased with eating, further 
investigated with an upper GI contrast study?  
tables do not appear in the manuscript with their numerical order i.e. tables 3, 4 appear in page 6 
whereas tables 1,2 in pag e 7. 
ix. Please merge tables 1 and 2; please do not include in the manuscript tables 3 and 4.  
 
 
 
Statistical analysis:  
i. Please clearly define 'age groups';  
ii. L57 -59: please rephrase as the meaning is not clear and also add a relevant reference.  
 
4. Resu lts: 
i. Please present your results in tables (e.g. one for demographics and another for overlap 
syndromes/symptoms).  
ii. Could the authors provide additional epidemiological data for their cohort (e.g. gestational age 
of the study participants; early life events related to functional GI disorders)?.  
iii. Page 7 L57 -59: was age used as a continuous (t -test) or categorical  variable (chi -square test)? 
if it was used as a categorical variable then please specify the age groups.  
iv. Page 9 ('discussion' section) L4 -9: the authors use the term 'interaction' while interpreting 
their results; could you please specify whether you have analysed your data by performing a 
regression analysis with an interaction variable (gender*age in this case)? if this is true then you 
need to mention it in the 'statistical analysis' section and present the results accordingly.  
 
5. Discussion:  
i. Wo uld the authors consider adding a paragraph outlining the importance of identifying FD 
subtypes and overlap with other syndromes in the overall management of such pediatric patients?  
ii.Please consider adding a paragraph with the strengths and limitations of the present study.  
 
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 controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in t he manuscript or would you recommend 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 indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received 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 futu re? 
 
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 salary 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 answer 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 I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand 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 C reative 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: Prevalence of overlap syndromes and symptoms in pediatric functional dyspepsia  
 
 
Version: 0 Date: 16 May 2016 
 
 
Reviewer: Efstratios  Saliakellis  
 
 
Reviewer's report:  
 
In the present manuscript the authors present a very interesting study that explores the prevalence 
of overlap syndromes and symptoms in pediatric functional dyspepsia (FD).  
FD remains an enigmatic clinical entity, not fully understood in terms of pathophysiology, which 
in turn reflects on the diagnostic and therapeutic limitations encountered in this condition.  
 
A few issues need to be addressed prior to considering this articl e for publication:  
 
1. Style of references: please adopt the one proposed by the journal e.g. use brackets instead of 
parentheses and place the references before full stop.  
 
2. Abstract:  
i. Please include the first sentence of the 'methods' paragraph in the 'results' paragraph as this 
actually presents results of the study (e.g. number of patients enrolled and age range). In this 
sentence you may also consider adding the number of male or female participants.  
 
3. Methods:  
 
Study cohort and exclusion criteria:  
i. Please comment on the two -week acid reduction treatment (e.g. PPIs, Histamine -2 receptor 
antagonists, dosing scheme).  
ii. Except for the upper gastrointestinal (GI) endoscopy did th e authors perform any pH -
impedance studies to assess for non -acid reflux after acid reduction treatment failures? was a pH -
impedance study considered to evaluate patients with symptoms such as excessive 
belching/burping?  
iii. Please comment on the values used by the pathologist to exclude  eosinophilic GI disease; I 
do note that the authors comment on the values used for the esophagus but there is no additional 
data for the stomach and the duodenum.  
iv. Apart from the enumeration of eosinophils, were the b iopsy samples assessed for mast cells?  
 
GI and systemic symptoms:  
i. Please change narration from present to past tense;  
ii. L33 add 'to' ('...sample was selected to complete...');  
iii. Omit questions 1 and 2 from the text;  
iv. Regarding the evaluation  for systemic symptoms: many of them may be present as 
extraintestinal manifestations in children with gastrointestinal food allergy; were the patients 
assessed for food allergies? was any of the v. patients on a food elimination diet?  
vi. Patients presen ting with red flag symptoms e.g. weight loss, were they further investigated for 
organic disease?  
vii. Were patients who presented with symptoms such as vomiting, nausea, early satiety and 
bloating, further investigated with a gastric emptying study?  
viii. Were patients who presented with abdominal pain that increased with eating, further 
investigated with an upper GI contrast study?  
tables do not appear in the manuscript with their numerical order i.e. tables 3, 4 appear in page 6 
whereas tables 1,2 in pag e 7. 
ix. Please merge tables 1 and 2; please do not include in the manuscript tables 3 and 4.  
 
 
 
Statistical analysis:  
i. Please clearly define 'age groups';  
ii. L57 -59: please rephrase as the meaning is not clear and also add a relevant reference.  
 
4. Resu lts: 
i. Please present your results in tables (e.g. one for demographics and another for overlap 
syndromes/symptoms).  
ii. Could the authors provide additional epidemiological data for their cohort (e.g. gestational age 
of the study participants; early life events related to functional GI disorders)?.  
iii. Page 7 L57 -59: was age used as a continuous (t -test) or categorical  variable (chi -square test)? 
if it was used as a categorical variable then please specify the age groups.  
iv. Page 9 ('discussion' section) L4 -9: the authors use the term 'interaction' while interpreting 
their results; could you please specify whether you have analysed your data by performing a 
regression analysis with an interaction variable (gender*age in this case)? if this is true then you 
need to mention it in the 'statistical analysis' section and present the results accordingly.  
 
5. Discussion:  
i. Wo uld the authors consider adding a paragraph outlining the importance of identifying FD 
subtypes and overlap with other syndromes in the overall management of such pediatric patients?  
ii.Please consider adding a paragraph with the strengths and limitations of the present study.  
 
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 controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in t he manuscript or would you recommend 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 indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received 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 futu re? 
 
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 salary 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 answer 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 I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand 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 C reative 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: Prevalence of overlap syndromes and symptoms in pediatric functional dyspepsia  
 
 
Version: 0 Date: 16 May 2016 
 
 
Reviewer: Efstratios  Saliakellis  
 
 
Reviewer's report:  
 
In the present manuscript the authors present a very interesting study that explores the prevalence 
of overlap syndromes and symptoms in pediatric functional dyspepsia (FD).  
FD remains an enigmatic clinical entity, not fully understood in terms of pathophysiology, which 
in turn reflects on the diagnostic and therapeutic limitations encountered in this condition.  
 
A few issues need to be addressed prior to considering this articl e for publication:  
 
1. Style of references: please adopt the one proposed by the journal e.g. use brackets instead of 
parentheses and place the references before full stop.  
 
2. Abstract:  
i. Please include the first sentence of the 'methods' paragraph in the 'results' paragraph as this 
actually presents results of the study (e.g. number of patients enrolled and age range). In this 
sentence you may also consider adding the number of male or female participants.  
 
3. Methods:  
 
Study cohort and exclusion criteria:  
i. Please comment on the two -week acid reduction treatment (e.g. PPIs, Histamine -2 receptor 
antagonists, dosing scheme).  
ii. Except for the upper gastrointestinal (GI) endoscopy did th e authors perform any pH -
impedance studies to assess for non -acid reflux after acid reduction treatment failures? was a pH -
impedance study considered to evaluate patients with symptoms such as excessive 
belching/burping?  
iii. Please comment on the values used by the pathologist to exclude  eosinophilic GI disease; I 
do note that the authors comment on the values used for the esophagus but there is no additional 
data for the stomach and the duodenum.  
iv. Apart from the enumeration of eosinophils, were the b iopsy samples assessed for mast cells?  
 
GI and systemic symptoms:  
i. Please change narration from present to past tense;  
ii. L33 add 'to' ('...sample was selected to complete...');  
iii. Omit questions 1 and 2 from the text;  
iv. Regarding the evaluation  for systemic symptoms: many of them may be present as 
extraintestinal manifestations in children with gastrointestinal food allergy; were the patients 
assessed for food allergies? was any of the v. patients on a food elimination diet?  
vi. Patients presen ting with red flag symptoms e.g. weight loss, were they further investigated for 
organic disease?  
vii. Were patients who presented with symptoms such as vomiting, nausea, early satiety and 
bloating, further investigated with a gastric emptying study?  
viii. Were patients who presented with abdominal pain that increased with eating, further 
investigated with an upper GI contrast study?  
tables do not appear in the manuscript with their numerical order i.e. tables 3, 4 appear in page 6 
whereas tables 1,2 in pag e 7. 
ix. Please merge tables 1 and 2; please do not include in the manuscript tables 3 and 4.  
 
 
 
Statistical analysis:  
i. Please clearly define 'age groups';  
ii. L57 -59: please rephrase as the meaning is not clear and also add a relevant reference.  
 
4. Resu lts: 
i. Please present your results in tables (e.g. one for demographics and another for overlap 
syndromes/symptoms).  
ii. Could the authors provide additional epidemiological data for their cohort (e.g. gestational age 
of the study participants; early life events related to functional GI disorders)?.  
iii. Page 7 L57 -59: was age used as a continuous (t -test) or categorical  variable (chi -square test)? 
if it was used as a categorical variable then please specify the age groups.  
iv. Page 9 ('discussion' section) L4 -9: the authors use the term 'interaction' while interpreting 
their results; could you please specify whether you have analysed your data by performing a 
regression analysis with an interaction variable (gender*age in this case)? if this is true then you 
need to mention it in the 'statistical analysis' section and present the results accordingly.  
 
5. Discussion:  
i. Wo uld the authors consider adding a paragraph outlining the importance of identifying FD 
subtypes and overlap with other syndromes in the overall management of such pediatric patients?  
ii.Please consider adding a paragraph with the strengths and limitations of the present study.  
 
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 controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in t he manuscript or would you recommend 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 indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received 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 futu re? 
 
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 salary 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 answer 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 I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand 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 C reative 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