Reviewer's report
Title:Predictors of persistent symptoms and reduced quality of life in treated
coeliac disease patients: a large cross-sectional study
Version: 2Date:9 March 2013
Reviewer: Fredrik Norström
Reviewer's report:
General comment
The authors have well taken care of my previous issues. Below is my response
to the issues that I still think can/should be improved. I have kept the headers
(major, minor and discretionary revisions) of the parts from my previous request
of revisions to make it easier to comment on the responses from authors. I
consider all my new requests (including the one for other reviewers request) as
minor or discretionary revisions.
Reviewer #1
Major compulsory revisions
Method 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.
Response: The aim was to identify subjects with persistent symptoms clearly
disturbing their daily life. Hence, we decided to use this fairly objective cut-off
value used also in previous studies. It is true that evidence supporting the
method is somewhat limited but, as shown in previous response, it turned out to
be quite accurate. This issue has now been further discussed as suggested (see
page 11, paragraph 1, lines 9-13) and two new references have been provided
(references 43 and 44).
Reviewer: My interpretation of the sentence “Nonetheless, it seemed that the
proportion of control subjects with increased symptoms was similar to that
previously seen in the general population [43, 44]” is that the references have
shown that GSRS and/or PGWB have shown similar results for control subjects
as in your paper. Neither of these measures was used in these references. My
other possible interpretation is that you want to show that the proportion of
control subjects with problems is similar in references as in your study. If so,
there is a lack of information about the rate of control subjects with problems in
your study and that information needs to be added if so. My concern in previous
review round has been taken care of without this statement. You can therefore
decide to either remove the sentence or rewrite it.
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.
Response: The requested threshold values have now been provided (see
Methods, page 5, paragraph 3, lines 9-11 and page 5, paragraph 4, line 6 to
page 6, paragraph 1, lines 1-2).
Reviewer: After some thinking I figured out that 2.55 is the threshold for the total
GSRS score as it corresponds to the control mean (1.9) + 1 SD (0.66). I suggest
that the text is rewritten so that this is easier to understand for the reader. The
problem is the same for the description of the threshold value for PGWB.
Discussion:
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.
Response: This information has now been provided (see Tables 2 and 3,
footnotes).
Reviewer: The suggested improvement is well done. I have another concern
regarding these tables that I failed to notice in previous revision round. There is
no information in any of the tables about how many that is in each row, i.e. how
many has had symptoms for 10 years or less and so on. This is relevant
information for the reader. It would also be valuable if the percentage of e.g.
participants with psychiatric disease was mentioned in these tables.
Minor Essential Revisions
Background:
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.
Response: This issue has now been clarified (see Results page 8, paragraph 1,
lines 3-5).
Reviewer: OK. However, grammar needs to be improved. Which instead of with
at line 3?
Discretionary Revisions
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?
Response: Both values have been used in the literature, but it is true that in this
case use of median would be more logical. However, in our study only a few
answers were missing, and this change had no impact on the results whatsoever.
Reviewer: I think that you well motivate the choice of mean values. Thank you for
the clarification.
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.
Response: This problem has now been further discussed as suggested (see
Discussion, page 8, paragraph 2, lines 2-5).
Reviewer: Updated text is good enough for me. However, I suggest that you
rewrite the sentences to get a better flow in the text.
Reviewer #2
3) Result section (page 7, line 9): It would be useful for the reader to define the
nature of gastrointestinal co-morbidities responsible for persisting symptoms in
treated coeliac disease. As stated in the discussion, irritable bowel syndrome is
probably a frequent cause, but what about gastro-esophageal reflux disease,
which, based on literature data, has been found in 66% of coeliac patients
(Barratt SM, Eur J Gastroenterol Hepatol 2011)? The Authors should specify the
nature of gastrointestinal co-morbidities and their relative occurrence in
determining the persistence of symptoms in treated coeliac disease.
Response: More detailed information for the gastrointestinal disorders has now
been provided (see Results, page 7, paragraph 2, lines 6-8).
Reviewer: You have stated “2% diverticulos (2%)” at row 7. 2% has accidently
been mentioned twice in this statement. I suggest that “(2%)” is removed from
the statement.
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.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Predictors of persistent symptoms and reduced quality of life in treated
coeliac disease patients: a large cross-sectional study
Version: 2Date:9 March 2013
Reviewer: Fredrik Norström
Reviewer's report:
General comment
The authors have well taken care of my previous issues. Below is my response
to the issues that I still think can/should be improved. I have kept the headers
(major, minor and discretionary revisions) of the parts from my previous request
of revisions to make it easier to comment on the responses from authors. I
consider all my new requests (including the one for other reviewers request) as
minor or discretionary revisions.
Reviewer #1
Major compulsory revisions
Method 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.
Response: The aim was to identify subjects with persistent symptoms clearly
disturbing their daily life. Hence, we decided to use this fairly objective cut-off
value used also in previous studies. It is true that evidence supporting the
method is somewhat limited but, as shown in previous response, it turned out to
be quite accurate. This issue has now been further discussed as suggested (see
page 11, paragraph 1, lines 9-13) and two new references have been provided
(references 43 and 44).
Reviewer: My interpretation of the sentence “Nonetheless, it seemed that the
proportion of control subjects with increased symptoms was similar to that
previously seen in the general population [43, 44]” is that the references have
shown that GSRS and/or PGWB have shown similar results for control subjects
as in your paper. Neither of these measures was used in these references. My
other possible interpretation is that you want to show that the proportion of
control subjects with problems is similar in references as in your study. If so,
there is a lack of information about the rate of control subjects with problems in
your study and that information needs to be added if so. My concern in previous
review round has been taken care of without this statement. You can therefore
decide to either remove the sentence or rewrite it.
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.
Response: The requested threshold values have now been provided (see
Methods, page 5, paragraph 3, lines 9-11 and page 5, paragraph 4, line 6 to
page 6, paragraph 1, lines 1-2).
Reviewer: After some thinking I figured out that 2.55 is the threshold for the total
GSRS score as it corresponds to the control mean (1.9) + 1 SD (0.66). I suggest
that the text is rewritten so that this is easier to understand for the reader. The
problem is the same for the description of the threshold value for PGWB.
Discussion:
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.
Response: This information has now been provided (see Tables 2 and 3,
footnotes).
Reviewer: The suggested improvement is well done. I have another concern
regarding these tables that I failed to notice in previous revision round. There is
no information in any of the tables about how many that is in each row, i.e. how
many has had symptoms for 10 years or less and so on. This is relevant
information for the reader. It would also be valuable if the percentage of e.g.
participants with psychiatric disease was mentioned in these tables.
Minor Essential Revisions
Background:
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.
Response: This issue has now been clarified (see Results page 8, paragraph 1,
lines 3-5).
Reviewer: OK. However, grammar needs to be improved. Which instead of with
at line 3?
Discretionary Revisions
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?
Response: Both values have been used in the literature, but it is true that in this
case use of median would be more logical. However, in our study only a few
answers were missing, and this change had no impact on the results whatsoever.
Reviewer: I think that you well motivate the choice of mean values. Thank you for
the clarification.
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.
Response: This problem has now been further discussed as suggested (see
Discussion, page 8, paragraph 2, lines 2-5).
Reviewer: Updated text is good enough for me. However, I suggest that you
rewrite the sentences to get a better flow in the text.
Reviewer #2
3) Result section (page 7, line 9): It would be useful for the reader to define the
nature of gastrointestinal co-morbidities responsible for persisting symptoms in
treated coeliac disease. As stated in the discussion, irritable bowel syndrome is
probably a frequent cause, but what about gastro-esophageal reflux disease,
which, based on literature data, has been found in 66% of coeliac patients
(Barratt SM, Eur J Gastroenterol Hepatol 2011)? The Authors should specify the
nature of gastrointestinal co-morbidities and their relative occurrence in
determining the persistence of symptoms in treated coeliac disease.
Response: More detailed information for the gastrointestinal disorders has now
been provided (see Results, page 7, paragraph 2, lines 6-8).
Reviewer: You have stated “2% diverticulos (2%)” at row 7. 2% has accidently
been mentioned twice in this statement. I suggest that “(2%)” is removed from
the statement.
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.
Declaration of competing interests:
I declare that I have no competing interests
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: 2Date:9 March 2013
Reviewer: Fredrik Norström
Reviewer's report:
General comment
The authors have well taken care of my previous issues. Below is my response
to the issues that I still think can/should be improved. I have kept the headers
(major, minor and discretionary revisions) of the parts from my previous request
of revisions to make it easier to comment on the responses from authors. I
consider all my new requests (including the one for other reviewers request) as
minor or discretionary revisions.
Reviewer #1
Major compulsory revisions
Method 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.
Response: The aim was to identify subjects with persistent symptoms clearly
disturbing their daily life. Hence, we decided to use this fairly objective cut-off
value used also in previous studies. It is true that evidence supporting the
method is somewhat limited but, as shown in previous response, it turned out to
be quite accurate. This issue has now been further discussed as suggested (see
page 11, paragraph 1, lines 9-13) and two new references have been provided
(references 43 and 44).
Reviewer: My interpretation of the sentence “Nonetheless, it seemed that the
proportion of control subjects with increased symptoms was similar to that
previously seen in the general population [43, 44]” is that the references have
shown that GSRS and/or PGWB have shown similar results for control subjects
as in your paper. Neither of these measures was used in these references. My
other possible interpretation is that you want to show that the proportion of
control subjects with problems is similar in references as in your study. If so,
there is a lack of information about the rate of control subjects with problems in
your study and that information needs to be added if so. My concern in previous
review round has been taken care of without this statement. You can therefore
decide to either remove the sentence or rewrite it.
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.
Response: The requested threshold values have now been provided (see
Methods, page 5, paragraph 3, lines 9-11 and page 5, paragraph 4, line 6 to
page 6, paragraph 1, lines 1-2).
Reviewer: After some thinking I figured out that 2.55 is the threshold for the total
GSRS score as it corresponds to the control mean (1.9) + 1 SD (0.66). I suggest
that the text is rewritten so that this is easier to understand for the reader. The
problem is the same for the description of the threshold value for PGWB.
Discussion:
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.
Response: This information has now been provided (see Tables 2 and 3,
footnotes).
Reviewer: The suggested improvement is well done. I have another concern
regarding these tables that I failed to notice in previous revision round. There is
no information in any of the tables about how many that is in each row, i.e. how
many has had symptoms for 10 years or less and so on. This is relevant
information for the reader. It would also be valuable if the percentage of e.g.
participants with psychiatric disease was mentioned in these tables.
Minor Essential Revisions
Background:
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.
Response: This issue has now been clarified (see Results page 8, paragraph 1,
lines 3-5).
Reviewer: OK. However, grammar needs to be improved. Which instead of with
at line 3?
Discretionary Revisions
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?
Response: Both values have been used in the literature, but it is true that in this
case use of median would be more logical. However, in our study only a few
answers were missing, and this change had no impact on the results whatsoever.
Reviewer: I think that you well motivate the choice of mean values. Thank you for
the clarification.
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.
Response: This problem has now been further discussed as suggested (see
Discussion, page 8, paragraph 2, lines 2-5).
Reviewer: Updated text is good enough for me. However, I suggest that you
rewrite the sentences to get a better flow in the text.
Reviewer #2
3) Result section (page 7, line 9): It would be useful for the reader to define the
nature of gastrointestinal co-morbidities responsible for persisting symptoms in
treated coeliac disease. As stated in the discussion, irritable bowel syndrome is
probably a frequent cause, but what about gastro-esophageal reflux disease,
which, based on literature data, has been found in 66% of coeliac patients
(Barratt SM, Eur J Gastroenterol Hepatol 2011)? The Authors should specify the
nature of gastrointestinal co-morbidities and their relative occurrence in
determining the persistence of symptoms in treated coeliac disease.
Response: More detailed information for the gastrointestinal disorders has now
been provided (see Results, page 7, paragraph 2, lines 6-8).
Reviewer: You have stated “2% diverticulos (2%)” at row 7. 2% has accidently
been mentioned twice in this statement. I suggest that “(2%)” is removed from
the statement.
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.
Declaration of competing interests:
I declare that I have no competing interests
assistant