Reviewer ’s report  
 
Title: Prevalence of Paediatric Inflammatory Bowel Disease in Sweden: a Nationwide 
Population -Based Register Study  
 
Version: 0 Date: 16 May 2016  
 
Reviewer: Paul Henderson  
 
Reviewer's report:  
 
This is generally well -written and interesting study looking at the prevalence of paediatric IBD in 
Sweden. I have several comments with regard to the manuscript:  
 
Introduction:  
1. The authors should briefly explain the nature of IBD, as although this is a gastroenterology 
journal, some may not be familiar with it  
2. Do the authors have a more up to date reference for citation 1?  
3. I am unclear if the data presented in Table 1 is a result of a full systematic review, or just a 
general review of the literatu re. Also I feel that this is more part of the discussion, rather than 
introduction  
4. It is very confusing giving all prevalence figures as percentage/# per 100,000. The authors 
should use one method only (I would suggest number per 100,000)  
5. Line 68 - define early onset IBD (this usually means <10yrs in most literature)  
6. Line 69 - the authors should explain why it is "essential" to know prevalence figures  
7. I think that "period" prevalence, rather than "cumulative" prevalence is the preferred term  
8. Can the authors explain why they wished to examined EIM in these patients, without any 
review of the clinical notes. Is there not sufficient evidence to show that patients with IBD 
have more extra -intestinal manifestations than healthy controls?  
 
Methods:  
1. Line 81 - remove the word child (as already stated <18yrs)  
2. Why did the authors choose to study patients <18yrs when all commonly used classification 
systems (Montreal/Paris) use <17yrs?  
3. Line 90 - please use "period"  
4. I think it is difficult to u se patients with a listing of both IBD and CD in this study, although 
I appreciate that many patients change diagnosis.  
5. I think trying to estimate treatment from these records is difficult. What about patients 
treated with newer modalities such as anti biotics, or Crohn's patients treated with exclusive 
enteral nutrition; also clearly many patients treated with biologics are not included in this 
data.  I think that without case -note review of these patients this "estimate" is not of any use 
in this paper  
6. Although doing some sensitivity analysis is useful using this type of data, having several 
definitions and several age cut -off is very confusing for the reader.  
7. Line 103 - what was the definition of "time of first diagnosis" - endoscopy? If so, how was 
this determined?  
8. Although I appreciate that the authors used the differential diagnosis to improve sensitivity - 
I think this just confuses the paper somewhat  
 
Results:  
1. Was the age of children in 2010 normally distributed? If not then please use median and 
IQR, not mean and SD  
2. Line 148 - I have concerns about the "drug prescriptions" used here, given that many 
biologics, antibiotics and EEN are not included.  
3. From  the figures - did 223 patients with IBD not get seen at all by their IBD team in 2010?  
4. Can the authors discuss the 50%:50% split between CD and UC in this cohort - this is not in 
keeping with other published cohorts (often more CD)  
5. The differential diagnosis section of Table 2 is very confusing  
6. Can the authors explain the 5% surgery rate in their cohort? This is very low (usually 10 -
20%)  
7. Can the authors confidently include biologics data in Table 2?  
8. Using "Mixed diagnosis" in Table 2 is not a useful term  
9. I still do not understand the relevance of giving the differential diagnosis data. Many IBD 
patients suffer from concurrent IBS or other GI diagnoses (coeliac disease etc) so I am 
unclear how this adds to the data  
10. Line 163 - using phra ses like "patients with both diagnoses" is not acceptable  
11. Line 168 - how was follow up defined?  
12. The sensitivity analysis is very confusing, using multiple definitions, time frames, age cut -
offs etc. Having all these different prevalence figures doe s not really add to the data.  
13. Did the authors make any attempt to review the case -notes of their sample to see how good 
the coding was for diagnosis - this would be a far better sensitivity analysis.  
14. Line 187 - Did 16% of the paediatric population not get at least yearly follow up?  
15. Line 191 - why give mean and median time to diagnosis? They are very similar...  
16. Was follow up defined as "register identification" until last coded visit?  
17. Line 198 - define immunosuppressants  
18. Were the auth ors surprised at the finding of more EIMs in IBD patients compared to healthy 
controls?  
 
Discussion:  
1. Line 230 - the authors have not mentioned this at all in the methods. Why would longer data 
capture time improve identification of cases? Are cases not coded correctly initially?  
2. Line 234 - are the authors suggesting that at any one time 33% of paediatric IBD patients are 
on no treatment - this seems quite high....  
3. Line 237 - IBDU and IC are essentially the same, the former is used prior to colonic 
resection and IC historically used following resection where a diagnosis of UC or CD can 
still not be confirmed  
4. Line 273 - do the authors feel that a PPV of 85% is acceptable in a study of this kind? Is 
even missing 1 in 10 patients sufficient?  
5. Line 284 - the authors state that patients are closely monitored but ~15% aren't seen 
yearly....  
  
 
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 specify 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 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:  
 
Acceptable  
 
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 future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed 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 i n 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 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 websi te 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 name d 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 Paediatric Inflammatory Bowel Disease in Sweden: a Nationwide 
Population -Based Register Study  
 
Version: 0 Date: 16 May 2016  
 
Reviewer: Paul Henderson  
 
Reviewer's report:  
 
This is generally well -written and interesting study looking at the prevalence of paediatric IBD in 
Sweden. I have several comments with regard to the manuscript:  
 
Introduction:  
1. The authors should briefly explain the nature of IBD, as although this is a gastroenterology 
journal, some may not be familiar with it  
2. Do the authors have a more up to date reference for citation 1?  
3. I am unclear if the data presented in Table 1 is a result of a full systematic review, or just a 
general review of the literatu re. Also I feel that this is more part of the discussion, rather than 
introduction  
4. It is very confusing giving all prevalence figures as percentage/# per 100,000. The authors 
should use one method only (I would suggest number per 100,000)  
5. Line 68 - define early onset IBD (this usually means <10yrs in most literature)  
6. Line 69 - the authors should explain why it is "essential" to know prevalence figures  
7. I think that "period" prevalence, rather than "cumulative" prevalence is the preferred term  
8. Can the authors explain why they wished to examined EIM in these patients, without any 
review of the clinical notes. Is there not sufficient evidence to show that patients with IBD 
have more extra -intestinal manifestations than healthy controls?  
 
Methods:  
1. Line 81 - remove the word child (as already stated <18yrs)  
2. Why did the authors choose to study patients <18yrs when all commonly used classification 
systems (Montreal/Paris) use <17yrs?  
3. Line 90 - please use "period"  
4. I think it is difficult to u se patients with a listing of both IBD and CD in this study, although 
I appreciate that many patients change diagnosis.  
5. I think trying to estimate treatment from these records is difficult. What about patients 
treated with newer modalities such as anti biotics, or Crohn's patients treated with exclusive 
enteral nutrition; also clearly many patients treated with biologics are not included in this 
data.  I think that without case -note review of these patients this "estimate" is not of any use 
in this paper  
6. Although doing some sensitivity analysis is useful using this type of data, having several 
definitions and several age cut -off is very confusing for the reader.  
7. Line 103 - what was the definition of "time of first diagnosis" - endoscopy? If so, how was 
this determined?  
8. Although I appreciate that the authors used the differential diagnosis to improve sensitivity - 
I think this just confuses the paper somewhat  
 
Results:  
1. Was the age of children in 2010 normally distributed? If not then please use median and 
IQR, not mean and SD  
2. Line 148 - I have concerns about the "drug prescriptions" used here, given that many 
biologics, antibiotics and EEN are not included.  
3. From  the figures - did 223 patients with IBD not get seen at all by their IBD team in 2010?  
4. Can the authors discuss the 50%:50% split between CD and UC in this cohort - this is not in 
keeping with other published cohorts (often more CD)  
5. The differential diagnosis section of Table 2 is very confusing  
6. Can the authors explain the 5% surgery rate in their cohort? This is very low (usually 10 -
20%)  
7. Can the authors confidently include biologics data in Table 2?  
8. Using "Mixed diagnosis" in Table 2 is not a useful term  
9. I still do not understand the relevance of giving the differential diagnosis data. Many IBD 
patients suffer from concurrent IBS or other GI diagnoses (coeliac disease etc) so I am 
unclear how this adds to the data  
10. Line 163 - using phra ses like "patients with both diagnoses" is not acceptable  
11. Line 168 - how was follow up defined?  
12. The sensitivity analysis is very confusing, using multiple definitions, time frames, age cut -
offs etc. Having all these different prevalence figures doe s not really add to the data.  
13. Did the authors make any attempt to review the case -notes of their sample to see how good 
the coding was for diagnosis - this would be a far better sensitivity analysis.  
14. Line 187 - Did 16% of the paediatric population not get at least yearly follow up?  
15. Line 191 - why give mean and median time to diagnosis? They are very similar...  
16. Was follow up defined as "register identification" until last coded visit?  
17. Line 198 - define immunosuppressants  
18. Were the auth ors surprised at the finding of more EIMs in IBD patients compared to healthy 
controls?  
 
Discussion:  
1. Line 230 - the authors have not mentioned this at all in the methods. Why would longer data 
capture time improve identification of cases? Are cases not coded correctly initially?  
2. Line 234 - are the authors suggesting that at any one time 33% of paediatric IBD patients are 
on no treatment - this seems quite high....  
3. Line 237 - IBDU and IC are essentially the same, the former is used prior to colonic 
resection and IC historically used following resection where a diagnosis of UC or CD can 
still not be confirmed  
4. Line 273 - do the authors feel that a PPV of 85% is acceptable in a study of this kind? Is 
even missing 1 in 10 patients sufficient?  
5. Line 284 - the authors state that patients are closely monitored but ~15% aren't seen 
yearly....  
  
 
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 specify 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 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:  
 
Acceptable  
 
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 future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed 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 i n 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 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 websi te 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 name d 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 Paediatric Inflammatory Bowel Disease in Sweden: a Nationwide 
Population -Based Register Study  
 
Version: 0 Date: 16 May 2016  
 
Reviewer: Paul Henderson  
 
Reviewer's report:  
 
This is generally well -written and interesting study looking at the prevalence of paediatric IBD in 
Sweden. I have several comments with regard to the manuscript:  
 
Introduction:  
1. The authors should briefly explain the nature of IBD, as although this is a gastroenterology 
journal, some may not be familiar with it  
2. Do the authors have a more up to date reference for citation 1?  
3. I am unclear if the data presented in Table 1 is a result of a full systematic review, or just a 
general review of the literatu re. Also I feel that this is more part of the discussion, rather than 
introduction  
4. It is very confusing giving all prevalence figures as percentage/# per 100,000. The authors 
should use one method only (I would suggest number per 100,000)  
5. Line 68 - define early onset IBD (this usually means <10yrs in most literature)  
6. Line 69 - the authors should explain why it is "essential" to know prevalence figures  
7. I think that "period" prevalence, rather than "cumulative" prevalence is the preferred term  
8. Can the authors explain why they wished to examined EIM in these patients, without any 
review of the clinical notes. Is there not sufficient evidence to show that patients with IBD 
have more extra -intestinal manifestations than healthy controls?  
 
Methods:  
1. Line 81 - remove the word child (as already stated <18yrs)  
2. Why did the authors choose to study patients <18yrs when all commonly used classification 
systems (Montreal/Paris) use <17yrs?  
3. Line 90 - please use "period"  
4. I think it is difficult to u se patients with a listing of both IBD and CD in this study, although 
I appreciate that many patients change diagnosis.  
5. I think trying to estimate treatment from these records is difficult. What about patients 
treated with newer modalities such as anti biotics, or Crohn's patients treated with exclusive 
enteral nutrition; also clearly many patients treated with biologics are not included in this 
data.  I think that without case -note review of these patients this "estimate" is not of any use 
in this paper  
6. Although doing some sensitivity analysis is useful using this type of data, having several 
definitions and several age cut -off is very confusing for the reader.  
7. Line 103 - what was the definition of "time of first diagnosis" - endoscopy? If so, how was 
this determined?  
8. Although I appreciate that the authors used the differential diagnosis to improve sensitivity - 
I think this just confuses the paper somewhat  
 
Results:  
1. Was the age of children in 2010 normally distributed? If not then please use median and 
IQR, not mean and SD  
2. Line 148 - I have concerns about the "drug prescriptions" used here, given that many 
biologics, antibiotics and EEN are not included.  
3. From  the figures - did 223 patients with IBD not get seen at all by their IBD team in 2010?  
4. Can the authors discuss the 50%:50% split between CD and UC in this cohort - this is not in 
keeping with other published cohorts (often more CD)  
5. The differential diagnosis section of Table 2 is very confusing  
6. Can the authors explain the 5% surgery rate in their cohort? This is very low (usually 10 -
20%)  
7. Can the authors confidently include biologics data in Table 2?  
8. Using "Mixed diagnosis" in Table 2 is not a useful term  
9. I still do not understand the relevance of giving the differential diagnosis data. Many IBD 
patients suffer from concurrent IBS or other GI diagnoses (coeliac disease etc) so I am 
unclear how this adds to the data  
10. Line 163 - using phra ses like "patients with both diagnoses" is not acceptable  
11. Line 168 - how was follow up defined?  
12. The sensitivity analysis is very confusing, using multiple definitions, time frames, age cut -
offs etc. Having all these different prevalence figures doe s not really add to the data.  
13. Did the authors make any attempt to review the case -notes of their sample to see how good 
the coding was for diagnosis - this would be a far better sensitivity analysis.  
14. Line 187 - Did 16% of the paediatric population not get at least yearly follow up?  
15. Line 191 - why give mean and median time to diagnosis? They are very similar...  
16. Was follow up defined as "register identification" until last coded visit?  
17. Line 198 - define immunosuppressants  
18. Were the auth ors surprised at the finding of more EIMs in IBD patients compared to healthy 
controls?  
 
Discussion:  
1. Line 230 - the authors have not mentioned this at all in the methods. Why would longer data 
capture time improve identification of cases? Are cases not coded correctly initially?  
2. Line 234 - are the authors suggesting that at any one time 33% of paediatric IBD patients are 
on no treatment - this seems quite high....  
3. Line 237 - IBDU and IC are essentially the same, the former is used prior to colonic 
resection and IC historically used following resection where a diagnosis of UC or CD can 
still not be confirmed  
4. Line 273 - do the authors feel that a PPV of 85% is acceptable in a study of this kind? Is 
even missing 1 in 10 patients sufficient?  
5. Line 284 - the authors state that patients are closely monitored but ~15% aren't seen 
yearly....  
  
 
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 specify 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 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:  
 
Acceptable  
 
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 future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed 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 i n 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 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 websi te 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 name d 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