Reviewer ’s report  
 
Title: The impact of diagnosis on health -related quality of life in people with coeliac disease: a 
UK popu lation -based longitudinal perspective  
 
Version: 1 Date: 27 Jan 2019  
 
Reviewer: GIUSEPPE MAGAZZU  
 
Reviewer's report:  
 
In their study the Authors  report on a large UK nationwide survey of people with CD, conducted 
in 
2015, which largely replicated a previous survey that was conducted in 2006, aiming at assess ing 
changes over time in prevalence of CD symptoms/associated medical conditions, time to 
diagnosis, and quality of life before and after diagnosis.  
According to what the Authors state in the first sentence of the Discussion, patient reported 
outcome measu res are increasingly recognised as valuable tools in assessing the burden of 
disease and the impact of intervention and for this reason the Authors should to be congratulated.  
Apart from the revisions that the Authors already made on the original version o f the paper (and 
title) there are other critical issues that should be addressed.  
- Relying  the diagnosis of CD still on histology,  the "cases" to be considered in the study 
should be  only 85.5% of the respondents who were diagnosed through either a bio psy 
(53.2%; 842/1584) or blood test and biopsy (32.3%). There is no proof that 15% of cases 
met diagnostic criteria for CD  
 
- The outcome  measures should be calculated separately for those diagnosed through a 
biopsy, that are 52%, and those through blood t est and biopsy.  Who underwent biopsy only 
and had a villous atrophy in absence of positive serology  it is probable that  may have a 
different QoL,  affected by different diagnostic workup.  As a matter of fact in order to have 
a diagnosis of CD in people  with villous atrophy further biopsy, at least,  after a gluten free 
diet and, possibly, after a gluten challenge should be offered . Looking up the questionnaire 
of  the previous paper (reference 6) - that was used in the present paper with some further 
information collected  that should be specified -  no question concerned the number of  
intestinal biopsies. This issue is not relevant  only  for sound ascertainment of cases (that is 
important in order to have a homogenous study cohort) but especially for  the QoL, that is the 
most relevant outcome measured and that is presumably affected by the need to undergo 
further intestinal biopsy and, in the event of a challenge wth gluten, by different diet 
regimen.   
- There were 12.8% of cases under 18 years of ag e: the outcomes should be estimated  as 
subgroup.  
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.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are yo u 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.  
 
Not relevan t to this manuscript  
 
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 o f 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 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 included i n 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: The impact of diagnosis on health -related quality of life in people with coeliac disease: a 
UK popu lation -based longitudinal perspective  
 
Version: 1 Date: 27 Jan 2019  
 
Reviewer: GIUSEPPE MAGAZZU  
 
Reviewer's report:  
 
In their study the Authors  report on a large UK nationwide survey of people with CD, conducted 
in 
2015, which largely replicated a previous survey that was conducted in 2006, aiming at assess ing 
changes over time in prevalence of CD symptoms/associated medical conditions, time to 
diagnosis, and quality of life before and after diagnosis.  
According to what the Authors state in the first sentence of the Discussion, patient reported 
outcome measu res are increasingly recognised as valuable tools in assessing the burden of 
disease and the impact of intervention and for this reason the Authors should to be congratulated.  
Apart from the revisions that the Authors already made on the original version o f the paper (and 
title) there are other critical issues that should be addressed.  
- Relying  the diagnosis of CD still on histology,  the "cases" to be considered in the study 
should be  only 85.5% of the respondents who were diagnosed through either a bio psy 
(53.2%; 842/1584) or blood test and biopsy (32.3%). There is no proof that 15% of cases 
met diagnostic criteria for CD  
 
- The outcome  measures should be calculated separately for those diagnosed through a 
biopsy, that are 52%, and those through blood t est and biopsy.  Who underwent biopsy only 
and had a villous atrophy in absence of positive serology  it is probable that  may have a 
different QoL,  affected by different diagnostic workup.  As a matter of fact in order to have 
a diagnosis of CD in people  with villous atrophy further biopsy, at least,  after a gluten free 
diet and, possibly, after a gluten challenge should be offered . Looking up the questionnaire 
of  the previous paper (reference 6) - that was used in the present paper with some further 
information collected  that should be specified -  no question concerned the number of  
intestinal biopsies. This issue is not relevant  only  for sound ascertainment of cases (that is 
important in order to have a homogenous study cohort) but especially for  the QoL, that is the 
most relevant outcome measured and that is presumably affected by the need to undergo 
further intestinal biopsy and, in the event of a challenge wth gluten, by different diet 
regimen.   
- There were 12.8% of cases under 18 years of ag e: the outcomes should be estimated  as 
subgroup.  
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.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are yo u 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.  
 
Not relevan t to this manuscript  
 
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 o f 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 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 included i n 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: The impact of diagnosis on health -related quality of life in people with coeliac disease: a 
UK popu lation -based longitudinal perspective  
 
Version: 1 Date: 27 Jan 2019  
 
Reviewer: GIUSEPPE MAGAZZU  
 
Reviewer's report:  
 
In their study the Authors  report on a large UK nationwide survey of people with CD, conducted 
in 
2015, which largely replicated a previous survey that was conducted in 2006, aiming at assess ing 
changes over time in prevalence of CD symptoms/associated medical conditions, time to 
diagnosis, and quality of life before and after diagnosis.  
According to what the Authors state in the first sentence of the Discussion, patient reported 
outcome measu res are increasingly recognised as valuable tools in assessing the burden of 
disease and the impact of intervention and for this reason the Authors should to be congratulated.  
Apart from the revisions that the Authors already made on the original version o f the paper (and 
title) there are other critical issues that should be addressed.  
- Relying  the diagnosis of CD still on histology,  the "cases" to be considered in the study 
should be  only 85.5% of the respondents who were diagnosed through either a bio psy 
(53.2%; 842/1584) or blood test and biopsy (32.3%). There is no proof that 15% of cases 
met diagnostic criteria for CD  
 
- The outcome  measures should be calculated separately for those diagnosed through a 
biopsy, that are 52%, and those through blood t est and biopsy.  Who underwent biopsy only 
and had a villous atrophy in absence of positive serology  it is probable that  may have a 
different QoL,  affected by different diagnostic workup.  As a matter of fact in order to have 
a diagnosis of CD in people  with villous atrophy further biopsy, at least,  after a gluten free 
diet and, possibly, after a gluten challenge should be offered . Looking up the questionnaire 
of  the previous paper (reference 6) - that was used in the present paper with some further 
information collected  that should be specified -  no question concerned the number of  
intestinal biopsies. This issue is not relevant  only  for sound ascertainment of cases (that is 
important in order to have a homogenous study cohort) but especially for  the QoL, that is the 
most relevant outcome measured and that is presumably affected by the need to undergo 
further intestinal biopsy and, in the event of a challenge wth gluten, by different diet 
regimen.   
- There were 12.8% of cases under 18 years of ag e: the outcomes should be estimated  as 
subgroup.  
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.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are yo u 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.  
 
Not relevan t to this manuscript  
 
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 o f 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 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 included i n 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