Reviewer's report
Title:Predictors of persistent symptoms and reduced quality of life in treated
coeliac disease patients: a large cross-sectional study
Version: 1Date:10 December 2012
Reviewer: Fredrik Norström
Reviewer's report:
General comment
This is a well-written and interesting paper. The authors have performed a study
in which they attempt to find factors that explain persistent symptoms and a
reduced health-related quality of life despite a strict gluten-free diet. Few studies
have previously looked into this topic and the paper contributes with valuable
new information. The results from the study can therefore potentially help to
identify groups that are in need of more help with their disease after diagnosis. It
is also highly interesting that the authors conclude that early diagnosis is one of
the crucial parts to improve things for coeliac disease patients. This is in line with
many previous studies and highlights the importance of finding ways of detecting
the disease earlier.
Major Compulsory Revisions
Method section:
1. The selection of controls must be better described. Now it is unclear how, and
where, they were chosen so that they could be comparable with the coeliac
disease subjects. The reader needs to be informed about the criteria for being
selected as a control. If the only criterion was the currently mentioned (about no
first-degree relatives with coeliac disease), it needs to be specified that no
actions were taken regarding similarities between the populations in terms of e.g.
home district, age and sex. Depending on what is added to the method section it
is also likely that the limitations of the comparability between the coeliac disease
and the control population need to be mentioned in the discussion section.
2. The criterion # 1 SD is used to define both increased gastrointestinal
symptoms and a reduced health-related quality of life. It is not well motivated why
this criterion is used. You refer to studies by Häuser, Zeltzer and Wilt. The
papers by Häuser and Zeltzer (no knowledge about Wilt as it was not easily
accessible on internet) have not explicitly stated why they chose this criterion.
Even if it was well motivated by them, there is still a lack of information as why
this criterion is feasible for GSRS and PGWB, as they have used different
measurements in their studies (also the case for Wilt).
I have not used GSRS or PGWB myself. For that reason I have no
recommendation on methods for analyses of these measurements. Your analysis
method might be a good alternative. Thus, I do not dismiss the criterion used in
the paper, but it needs to be better formulated why it has been used. If you lack
good references you should try to motivate, and defend, the choice of criterion in
the discussion section.
3. The factors that are tested for a relation with both increased gastrointestinal
symptoms and a reduced health-related quality of life are not defined in the
method section. Some of the factors included in Table 2 and Table 3 might be
easily understood, but some of them are harder to judge on. The reader should
be informed about definitions in method section, and at least the less obvious
ones should be clarified also in Table 2 and Table 3.
For instance, I am unsure about how duration of symptoms is measured from the
article. It seems obvious that it was collected from the interview, and I also think
that it is measured from first experienced symptoms to diagnosis. It is also
unclear if you have asked about any symptom or if you have listed a few
symptoms. There is as well as a lack of definition to what group those with
exactly 10 years duration of symptom belong (it is possible with exactly 10 years
of symptom, isn’t it?). The definition of this factor might be the most unclear, but
there are also other variables where the definition is not clear.
Result section
4. The mean totals and ranges are specified for cases and controls, but not the
SD. Add the value of SD so that the threshold values for high GSRS and low
PGWB are available in the paper. Currently it is not even possible to guess the
thresholds. I also want it to be specified in the methods section if SD is derived
based on cases and/or controls. Currently it is only said that it is 1 SD higher
than the control mean. My interpretation is that SD is derived based on controls.
Discussion:
5. Page 9, paragraph 2. You mention that coeliac patients showed reduced
health-related quality of life while on a gluten-free diet. There is no such evidence
in the paper. You only present mean PGWB total score for study group and
controls. I suggest that you add such comparison for both GSRS and PGWS in
the result section and also specify the test for such comparison in method
section. I assume that such a test will give you evidence for your statement.
Tables:
6. No information about case criterion, i.e. # 1 SD higher or lower, in Table 2 and
Table 3. These tables are based on comparing cases and non-cases and this
information is too important to not include.
Minor Essential Revisions
Abstract:
1. “Patients with extraintestinal presentation at diagnosis had fewer current
symptoms”. Specify who you are comparing to.
Background:
2. You have written “even well-treated coeliac patients have often failed to attain
well-being similar to that of the population in general”. Besides Hallert [1998] and
Usai [2007], that you refer to, I can only identify Häuser [2006] that have shown
this for quality of life, while Casellas [2008], Gray [2010], Kolsteren [2001],
Nachman [2009], Norström [2011], Tontini [2011], van Koppen [2010], and
Zarkadas [2006], have all shown similar quality of life between coeliac disease
patients and the general population. For other issues related to well-being have
comparisons rarely been done with persons without coeliac disease diagnosis.
My interpretation is therefore that this sentence needs to be rewritten.
3. The main aim of the paper is to find predictors for poorer health-related quality
of life in those with coeliac disease. You have referred to Kurppa [2011]. It would
add value to the paper if you mentioned the most notable of these factors already
in the background section, and then with most focus on the ones you chose to
look at yourself.
Method section:
4. On first occasion that you use SD write the word in full form. I am unsure if the
standard deviation at individual level or the standard deviation for the mean
(commonly called standard error of the mean) is used for comparisons. If the
standard error of the mean is used is SD not a proper short form as it is generally
referred to the standard deviation at individual level. Could be worth giving both
the standard deviation and the threshold value in result section to avoid any
doubts on the definition of it.
Result section:
5. Second row at page 7, “food intolerance and gastrointestinal or any” should be
“food intolerance, other gastrointestinal disease, and any”, or a similar phrasing.
6. Row 8-9 at page 7. You show that both the group <10 years and >10 years
with symptoms have worse health-related quality of life than those without
symptoms. You have written “long duration of symptoms”, which needs to be
corrected as both short and long duration give evidence of a worse health-related
quality of life according to Table 3.
Discussion:
7. At top of page 10 you write “well-defined study cohort”. As also mentioned
later in same paragraph you admit a limitation in your selection, which potentially
could cause a selection bias. This contradicts the phrasing “well-defined”. Are
you referring to members of your cohort having a well-defined coeliac disease
diagnosis? If that is the case you should rewrite the sentence or else you
reasonably should remove the word “well-defined”.
Tables:
8. Specify in table 2 and table 3 that you have used bivariate logistic regression.
References:
9. Add dots to surnames also for other authors than Mäki, e.g. Ström and
Grännö.
Discretionary Revisions
1. Some of the references in the background section are a bit out of date. I think
that the authors should consider updating with more recent and relevant
references.
2. You replace missing with mean value of the item for PGWB and GSRS. How
do you motivate this? Maybe it might be an alternative to replace with median
values instead?
3. At start of the discussion section you refer to more symptoms being shown by
Cranney et al. They have not defined symptoms in a similar way as your paper
as far as I can interpret it. Is your statement valid? It is also hard to compare with
Midhagen et al as they seem to lack a definition on how they define symptoms in
their paper. They do report a higher proportion though with same measurement
as yours.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Reviewer's report
Title:Predictors of persistent symptoms and reduced quality of life in treated
coeliac disease patients: a large cross-sectional study
Version: 1Date:10 December 2012
Reviewer: Fredrik Norström
Reviewer's report:
General comment
This is a well-written and interesting paper. The authors have performed a study
in which they attempt to find factors that explain persistent symptoms and a
reduced health-related quality of life despite a strict gluten-free diet. Few studies
have previously looked into this topic and the paper contributes with valuable
new information. The results from the study can therefore potentially help to
identify groups that are in need of more help with their disease after diagnosis. It
is also highly interesting that the authors conclude that early diagnosis is one of
the crucial parts to improve things for coeliac disease patients. This is in line with
many previous studies and highlights the importance of finding ways of detecting
the disease earlier.
Major Compulsory Revisions
Method section:
1. The selection of controls must be better described. Now it is unclear how, and
where, they were chosen so that they could be comparable with the coeliac
disease subjects. The reader needs to be informed about the criteria for being
selected as a control. If the only criterion was the currently mentioned (about no
first-degree relatives with coeliac disease), it needs to be specified that no
actions were taken regarding similarities between the populations in terms of e.g.
home district, age and sex. Depending on what is added to the method section it
is also likely that the limitations of the comparability between the coeliac disease
and the control population need to be mentioned in the discussion section.
2. The criterion # 1 SD is used to define both increased gastrointestinal
symptoms and a reduced health-related quality of life. It is not well motivated why
this criterion is used. You refer to studies by Häuser, Zeltzer and Wilt. The
papers by Häuser and Zeltzer (no knowledge about Wilt as it was not easily
accessible on internet) have not explicitly stated why they chose this criterion.
Even if it was well motivated by them, there is still a lack of information as why
this criterion is feasible for GSRS and PGWB, as they have used different
measurements in their studies (also the case for Wilt).
I have not used GSRS or PGWB myself. For that reason I have no
recommendation on methods for analyses of these measurements. Your analysis
method might be a good alternative. Thus, I do not dismiss the criterion used in
the paper, but it needs to be better formulated why it has been used. If you lack
good references you should try to motivate, and defend, the choice of criterion in
the discussion section.
3. The factors that are tested for a relation with both increased gastrointestinal
symptoms and a reduced health-related quality of life are not defined in the
method section. Some of the factors included in Table 2 and Table 3 might be
easily understood, but some of them are harder to judge on. The reader should
be informed about definitions in method section, and at least the less obvious
ones should be clarified also in Table 2 and Table 3.
For instance, I am unsure about how duration of symptoms is measured from the
article. It seems obvious that it was collected from the interview, and I also think
that it is measured from first experienced symptoms to diagnosis. It is also
unclear if you have asked about any symptom or if you have listed a few
symptoms. There is as well as a lack of definition to what group those with
exactly 10 years duration of symptom belong (it is possible with exactly 10 years
of symptom, isn’t it?). The definition of this factor might be the most unclear, but
there are also other variables where the definition is not clear.
Result section
4. The mean totals and ranges are specified for cases and controls, but not the
SD. Add the value of SD so that the threshold values for high GSRS and low
PGWB are available in the paper. Currently it is not even possible to guess the
thresholds. I also want it to be specified in the methods section if SD is derived
based on cases and/or controls. Currently it is only said that it is 1 SD higher
than the control mean. My interpretation is that SD is derived based on controls.
Discussion:
5. Page 9, paragraph 2. You mention that coeliac patients showed reduced
health-related quality of life while on a gluten-free diet. There is no such evidence
in the paper. You only present mean PGWB total score for study group and
controls. I suggest that you add such comparison for both GSRS and PGWS in
the result section and also specify the test for such comparison in method
section. I assume that such a test will give you evidence for your statement.
Tables:
6. No information about case criterion, i.e. # 1 SD higher or lower, in Table 2 and
Table 3. These tables are based on comparing cases and non-cases and this
information is too important to not include.
Minor Essential Revisions
Abstract:
1. “Patients with extraintestinal presentation at diagnosis had fewer current
symptoms”. Specify who you are comparing to.
Background:
2. You have written “even well-treated coeliac patients have often failed to attain
well-being similar to that of the population in general”. Besides Hallert [1998] and
Usai [2007], that you refer to, I can only identify Häuser [2006] that have shown
this for quality of life, while Casellas [2008], Gray [2010], Kolsteren [2001],
Nachman [2009], Norström [2011], Tontini [2011], van Koppen [2010], and
Zarkadas [2006], have all shown similar quality of life between coeliac disease
patients and the general population. For other issues related to well-being have
comparisons rarely been done with persons without coeliac disease diagnosis.
My interpretation is therefore that this sentence needs to be rewritten.
3. The main aim of the paper is to find predictors for poorer health-related quality
of life in those with coeliac disease. You have referred to Kurppa [2011]. It would
add value to the paper if you mentioned the most notable of these factors already
in the background section, and then with most focus on the ones you chose to
look at yourself.
Method section:
4. On first occasion that you use SD write the word in full form. I am unsure if the
standard deviation at individual level or the standard deviation for the mean
(commonly called standard error of the mean) is used for comparisons. If the
standard error of the mean is used is SD not a proper short form as it is generally
referred to the standard deviation at individual level. Could be worth giving both
the standard deviation and the threshold value in result section to avoid any
doubts on the definition of it.
Result section:
5. Second row at page 7, “food intolerance and gastrointestinal or any” should be
“food intolerance, other gastrointestinal disease, and any”, or a similar phrasing.
6. Row 8-9 at page 7. You show that both the group <10 years and >10 years
with symptoms have worse health-related quality of life than those without
symptoms. You have written “long duration of symptoms”, which needs to be
corrected as both short and long duration give evidence of a worse health-related
quality of life according to Table 3.
Discussion:
7. At top of page 10 you write “well-defined study cohort”. As also mentioned
later in same paragraph you admit a limitation in your selection, which potentially
could cause a selection bias. This contradicts the phrasing “well-defined”. Are
you referring to members of your cohort having a well-defined coeliac disease
diagnosis? If that is the case you should rewrite the sentence or else you
reasonably should remove the word “well-defined”.
Tables:
8. Specify in table 2 and table 3 that you have used bivariate logistic regression.
References:
9. Add dots to surnames also for other authors than Mäki, e.g. Ström and
Grännö.
Discretionary Revisions
1. Some of the references in the background section are a bit out of date. I think
that the authors should consider updating with more recent and relevant
references.
2. You replace missing with mean value of the item for PGWB and GSRS. How
do you motivate this? Maybe it might be an alternative to replace with median
values instead?
3. At start of the discussion section you refer to more symptoms being shown by
Cranney et al. They have not defined symptoms in a similar way as your paper
as far as I can interpret it. Is your statement valid? It is also hard to compare with
Midhagen et al as they seem to lack a definition on how they define symptoms in
their paper. They do report a higher proportion though with same measurement
as yours.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Please review this paper.
user
Reviewer's report
Title:Predictors of persistent symptoms and reduced quality of life in treated
coeliac disease patients: a large cross-sectional study
Version: 1Date:10 December 2012
Reviewer: Fredrik Norström
Reviewer's report:
General comment
This is a well-written and interesting paper. The authors have performed a study
in which they attempt to find factors that explain persistent symptoms and a
reduced health-related quality of life despite a strict gluten-free diet. Few studies
have previously looked into this topic and the paper contributes with valuable
new information. The results from the study can therefore potentially help to
identify groups that are in need of more help with their disease after diagnosis. It
is also highly interesting that the authors conclude that early diagnosis is one of
the crucial parts to improve things for coeliac disease patients. This is in line with
many previous studies and highlights the importance of finding ways of detecting
the disease earlier.
Major Compulsory Revisions
Method section:
1. The selection of controls must be better described. Now it is unclear how, and
where, they were chosen so that they could be comparable with the coeliac
disease subjects. The reader needs to be informed about the criteria for being
selected as a control. If the only criterion was the currently mentioned (about no
first-degree relatives with coeliac disease), it needs to be specified that no
actions were taken regarding similarities between the populations in terms of e.g.
home district, age and sex. Depending on what is added to the method section it
is also likely that the limitations of the comparability between the coeliac disease
and the control population need to be mentioned in the discussion section.
2. The criterion # 1 SD is used to define both increased gastrointestinal
symptoms and a reduced health-related quality of life. It is not well motivated why
this criterion is used. You refer to studies by Häuser, Zeltzer and Wilt. The
papers by Häuser and Zeltzer (no knowledge about Wilt as it was not easily
accessible on internet) have not explicitly stated why they chose this criterion.
Even if it was well motivated by them, there is still a lack of information as why
this criterion is feasible for GSRS and PGWB, as they have used different
measurements in their studies (also the case for Wilt).
I have not used GSRS or PGWB myself. For that reason I have no
recommendation on methods for analyses of these measurements. Your analysis
method might be a good alternative. Thus, I do not dismiss the criterion used in
the paper, but it needs to be better formulated why it has been used. If you lack
good references you should try to motivate, and defend, the choice of criterion in
the discussion section.
3. The factors that are tested for a relation with both increased gastrointestinal
symptoms and a reduced health-related quality of life are not defined in the
method section. Some of the factors included in Table 2 and Table 3 might be
easily understood, but some of them are harder to judge on. The reader should
be informed about definitions in method section, and at least the less obvious
ones should be clarified also in Table 2 and Table 3.
For instance, I am unsure about how duration of symptoms is measured from the
article. It seems obvious that it was collected from the interview, and I also think
that it is measured from first experienced symptoms to diagnosis. It is also
unclear if you have asked about any symptom or if you have listed a few
symptoms. There is as well as a lack of definition to what group those with
exactly 10 years duration of symptom belong (it is possible with exactly 10 years
of symptom, isn’t it?). The definition of this factor might be the most unclear, but
there are also other variables where the definition is not clear.
Result section
4. The mean totals and ranges are specified for cases and controls, but not the
SD. Add the value of SD so that the threshold values for high GSRS and low
PGWB are available in the paper. Currently it is not even possible to guess the
thresholds. I also want it to be specified in the methods section if SD is derived
based on cases and/or controls. Currently it is only said that it is 1 SD higher
than the control mean. My interpretation is that SD is derived based on controls.
Discussion:
5. Page 9, paragraph 2. You mention that coeliac patients showed reduced
health-related quality of life while on a gluten-free diet. There is no such evidence
in the paper. You only present mean PGWB total score for study group and
controls. I suggest that you add such comparison for both GSRS and PGWS in
the result section and also specify the test for such comparison in method
section. I assume that such a test will give you evidence for your statement.
Tables:
6. No information about case criterion, i.e. # 1 SD higher or lower, in Table 2 and
Table 3. These tables are based on comparing cases and non-cases and this
information is too important to not include.
Minor Essential Revisions
Abstract:
1. “Patients with extraintestinal presentation at diagnosis had fewer current
symptoms”. Specify who you are comparing to.
Background:
2. You have written “even well-treated coeliac patients have often failed to attain
well-being similar to that of the population in general”. Besides Hallert [1998] and
Usai [2007], that you refer to, I can only identify Häuser [2006] that have shown
this for quality of life, while Casellas [2008], Gray [2010], Kolsteren [2001],
Nachman [2009], Norström [2011], Tontini [2011], van Koppen [2010], and
Zarkadas [2006], have all shown similar quality of life between coeliac disease
patients and the general population. For other issues related to well-being have
comparisons rarely been done with persons without coeliac disease diagnosis.
My interpretation is therefore that this sentence needs to be rewritten.
3. The main aim of the paper is to find predictors for poorer health-related quality
of life in those with coeliac disease. You have referred to Kurppa [2011]. It would
add value to the paper if you mentioned the most notable of these factors already
in the background section, and then with most focus on the ones you chose to
look at yourself.
Method section:
4. On first occasion that you use SD write the word in full form. I am unsure if the
standard deviation at individual level or the standard deviation for the mean
(commonly called standard error of the mean) is used for comparisons. If the
standard error of the mean is used is SD not a proper short form as it is generally
referred to the standard deviation at individual level. Could be worth giving both
the standard deviation and the threshold value in result section to avoid any
doubts on the definition of it.
Result section:
5. Second row at page 7, “food intolerance and gastrointestinal or any” should be
“food intolerance, other gastrointestinal disease, and any”, or a similar phrasing.
6. Row 8-9 at page 7. You show that both the group <10 years and >10 years
with symptoms have worse health-related quality of life than those without
symptoms. You have written “long duration of symptoms”, which needs to be
corrected as both short and long duration give evidence of a worse health-related
quality of life according to Table 3.
Discussion:
7. At top of page 10 you write “well-defined study cohort”. As also mentioned
later in same paragraph you admit a limitation in your selection, which potentially
could cause a selection bias. This contradicts the phrasing “well-defined”. Are
you referring to members of your cohort having a well-defined coeliac disease
diagnosis? If that is the case you should rewrite the sentence or else you
reasonably should remove the word “well-defined”.
Tables:
8. Specify in table 2 and table 3 that you have used bivariate logistic regression.
References:
9. Add dots to surnames also for other authors than Mäki, e.g. Ström and
Grännö.
Discretionary Revisions
1. Some of the references in the background section are a bit out of date. I think
that the authors should consider updating with more recent and relevant
references.
2. You replace missing with mean value of the item for PGWB and GSRS. How
do you motivate this? Maybe it might be an alternative to replace with median
values instead?
3. At start of the discussion section you refer to more symptoms being shown by
Cranney et al. They have not defined symptoms in a similar way as your paper
as far as I can interpret it. Is your statement valid? It is also hard to compare with
Midhagen et al as they seem to lack a definition on how they define symptoms in
their paper. They do report a higher proportion though with same measurement
as yours.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
assistant