Reviewer’s report  
Title: Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10  
years and under. Retrospective cohort study from t wo tertiary centres in the United Kingdom and  
in Italy.  
 
Version: 1 Date: 10 Dec 2015  
 
Reviewer: Abdul Elkadri  
Reviewer’s report:  
I have re -read the updates to the manuscript and the issues I have raised have been a ddressed 
adequately.  
 
On re -reading the manuscript, I have an issue that I would like to bring up as it has become more 
clear to me and I think it needs addressing: The two groups appear equivalent, up until the 
disease severity is compared. From the meas ured and reported variables, it's unclear why exactly 
that is, and that is ok, as long as it is taken into consideration. I'm specifically referring to Table 
2. PCDAI and PUCAI are significantly worse in the younger group (Group A). This appears 
driven by the British group only. If an analysis between Group A Britain and Group A Italy is 
performed, I expect that there to be a significant difference between the two (My quick 
calculations confirm this, but you should confirm as well). This also appears to be the case for 
Group B in the two locations. This would suggest that the British hospital sees "sicker" IBD 
patients than the Italian hospital (this is my conclusion from the data and no bias against either 
institute).  
 
So the issue is, if the above is true and patients described in the population from Britain are 
sicker, analysis attempting to compare the two as equivalent have the potential to be confounded. 
The Top -Down vs Step Up analysis is an example of this and I find it difficult to agree with 
using o utcome measures (such as relapse). One might argue that since the British patients are 
sicker, a step up approach appears to give the same outcomes and is therefore superior (I don't 
agree with this in reality, but this can be argued using the top -down vs step up logic).  
 
When looking into the remainder of the analysis, it appears that the multiple regression model 
has attempted to take this into account, but still, the issue appears to be real on univariate 
analysis. The fact remains: The two institutions see different sev erity of patients.  
 
My opinion remains that the manuscript is important in that this type of publication is not 
commonly found and it describes these two populations well, along with the fact that the analysis 
for the most part is done well. I feel that th e paper would benefit from toning down these 
arguments (top -down vs step up, steroids give worse relapses). These conclusions may actually 
be right, but they can't be supported by this analysis in my opinion. I would urge the authors to 
avoid drawing concl usions within the discussion stemming from this issue. I agree with the 
conclusion of this manuscript as it is written as it is supported by the data. I feel that paragraphs 
such as the one on page 26, starting at line 14 (second last paragraph) should be either a 
suggestion while taking into account the inherent differences in the two populations, or 
completely removed altogether.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please spe cify which controls 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 o r 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 recommend additional statist ical review  
 
Quality of written Engl ish 
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng 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, e ither now or in the future?  
 
2. Do you hold any stocks or shares in an organis ation that may in any way gain or lose 
financially from the publication of this manuscript, e ither 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 salary from an organization that 
holds or has applied for patents relating to the  content of the manuscript?  
 
5. Do you have any other fin ancial competing interests?  
 
6. Do you have any non -financial competing interests  in relation to this pa per? 
 
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 that 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 Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be inc luded 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: Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10  
years and under. Retrospective cohort study from t wo tertiary centres in the United Kingdom and  
in Italy.  
 
Version: 1 Date: 10 Dec 2015  
 
Reviewer: Abdul Elkadri  
Reviewer’s report:  
I have re -read the updates to the manuscript and the issues I have raised have been a ddressed 
adequately.  
 
On re -reading the manuscript, I have an issue that I would like to bring up as it has become more 
clear to me and I think it needs addressing: The two groups appear equivalent, up until the 
disease severity is compared. From the meas ured and reported variables, it's unclear why exactly 
that is, and that is ok, as long as it is taken into consideration. I'm specifically referring to Table 
2. PCDAI and PUCAI are significantly worse in the younger group (Group A). This appears 
driven by the British group only. If an analysis between Group A Britain and Group A Italy is 
performed, I expect that there to be a significant difference between the two (My quick 
calculations confirm this, but you should confirm as well). This also appears to be the case for 
Group B in the two locations. This would suggest that the British hospital sees "sicker" IBD 
patients than the Italian hospital (this is my conclusion from the data and no bias against either 
institute).  
 
So the issue is, if the above is true and patients described in the population from Britain are 
sicker, analysis attempting to compare the two as equivalent have the potential to be confounded. 
The Top -Down vs Step Up analysis is an example of this and I find it difficult to agree with 
using o utcome measures (such as relapse). One might argue that since the British patients are 
sicker, a step up approach appears to give the same outcomes and is therefore superior (I don't 
agree with this in reality, but this can be argued using the top -down vs step up logic).  
 
When looking into the remainder of the analysis, it appears that the multiple regression model 
has attempted to take this into account, but still, the issue appears to be real on univariate 
analysis. The fact remains: The two institutions see different sev erity of patients.  
 
My opinion remains that the manuscript is important in that this type of publication is not 
commonly found and it describes these two populations well, along with the fact that the analysis 
for the most part is done well. I feel that th e paper would benefit from toning down these 
arguments (top -down vs step up, steroids give worse relapses). These conclusions may actually 
be right, but they can't be supported by this analysis in my opinion. I would urge the authors to 
avoid drawing concl usions within the discussion stemming from this issue. I agree with the 
conclusion of this manuscript as it is written as it is supported by the data. I feel that paragraphs 
such as the one on page 26, starting at line 14 (second last paragraph) should be either a 
suggestion while taking into account the inherent differences in the two populations, or 
completely removed altogether.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please spe cify which controls 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 o r 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 recommend additional statist ical review  
 
Quality of written Engl ish 
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng 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, e ither now or in the future?  
 
2. Do you hold any stocks or shares in an organis ation that may in any way gain or lose 
financially from the publication of this manuscript, e ither 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 salary from an organization that 
holds or has applied for patents relating to the  content of the manuscript?  
 
5. Do you have any other fin ancial competing interests?  
 
6. Do you have any non -financial competing interests  in relation to this pa per? 
 
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 that 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 Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be inc luded 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: Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10  
years and under. Retrospective cohort study from t wo tertiary centres in the United Kingdom and  
in Italy.  
 
Version: 1 Date: 10 Dec 2015  
 
Reviewer: Abdul Elkadri  
Reviewer’s report:  
I have re -read the updates to the manuscript and the issues I have raised have been a ddressed 
adequately.  
 
On re -reading the manuscript, I have an issue that I would like to bring up as it has become more 
clear to me and I think it needs addressing: The two groups appear equivalent, up until the 
disease severity is compared. From the meas ured and reported variables, it's unclear why exactly 
that is, and that is ok, as long as it is taken into consideration. I'm specifically referring to Table 
2. PCDAI and PUCAI are significantly worse in the younger group (Group A). This appears 
driven by the British group only. If an analysis between Group A Britain and Group A Italy is 
performed, I expect that there to be a significant difference between the two (My quick 
calculations confirm this, but you should confirm as well). This also appears to be the case for 
Group B in the two locations. This would suggest that the British hospital sees "sicker" IBD 
patients than the Italian hospital (this is my conclusion from the data and no bias against either 
institute).  
 
So the issue is, if the above is true and patients described in the population from Britain are 
sicker, analysis attempting to compare the two as equivalent have the potential to be confounded. 
The Top -Down vs Step Up analysis is an example of this and I find it difficult to agree with 
using o utcome measures (such as relapse). One might argue that since the British patients are 
sicker, a step up approach appears to give the same outcomes and is therefore superior (I don't 
agree with this in reality, but this can be argued using the top -down vs step up logic).  
 
When looking into the remainder of the analysis, it appears that the multiple regression model 
has attempted to take this into account, but still, the issue appears to be real on univariate 
analysis. The fact remains: The two institutions see different sev erity of patients.  
 
My opinion remains that the manuscript is important in that this type of publication is not 
commonly found and it describes these two populations well, along with the fact that the analysis 
for the most part is done well. I feel that th e paper would benefit from toning down these 
arguments (top -down vs step up, steroids give worse relapses). These conclusions may actually 
be right, but they can't be supported by this analysis in my opinion. I would urge the authors to 
avoid drawing concl usions within the discussion stemming from this issue. I agree with the 
conclusion of this manuscript as it is written as it is supported by the data. I feel that paragraphs 
such as the one on page 26, starting at line 14 (second last paragraph) should be either a 
suggestion while taking into account the inherent differences in the two populations, or 
completely removed altogether.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please spe cify which controls 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 o r 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 recommend additional statist ical review  
 
Quality of written Engl ish 
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng 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, e ither now or in the future?  
 
2. Do you hold any stocks or shares in an organis ation that may in any way gain or lose 
financially from the publication of this manuscript, e ither 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 salary from an organization that 
holds or has applied for patents relating to the  content of the manuscript?  
 
5. Do you have any other fin ancial competing interests?  
 
6. Do you have any non -financial competing interests  in relation to this pa per? 
 
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 that 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 Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be inc luded 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