Reviewer's report
Title:Effectiveness and Safety of Ferric Carboxymaltose Treatment in Children
and Adolescents with Inflammatory Bowel Disease
Version:2Date:22 April 2014
Reviewer: Jayson Stoffman
Reviewer's report:
General comments:
An interesting paper, and a good discussion of a common problem in both
gastroenterology and hematology. I'm glad that you were able to review your
experience with this treatment method to show general efficacy and safety. You
have honestly discussed the limitations of the retrospective nature of this study,
and the possible impact on your interpretation of the data. Overall, it generates
important new questions to asks, and provides data supporting another way of
managing IDA.
Major compulsory revisions:
None
Minor essential revisions:
1. Abstract - Background: It should be 'orally given iron'
2. Abstract - Results: You do not need to say 'diagnosed, concomitant iron
deficiency anemia'. Saying concomitant is sufficient, since it implies diagnosed.
3. Abstract - Results: The sentence about the improved hemoglobin levels was
unclear to me after I read the paper. I thought the improved levels from 9.5 to
11.9 was the range of the final (improved) values, and not the change from
baseline to endpoint. This is clear in the paper, but should be clarified in the
abstract.
4. Background: In the first three paragraphs, you have used the terms 'iron
deficiency' and 'iron deficiency anemia (IDA)' somewhat interchangably, which
they really are not. IDA is one consequence of iron deficiency. The statistics in
your first paragraph describe patients who are iron deficient and those who were
also anemic. Your focus, and the inclusion criteria for your patient population, is
IDA. In the next paragraphs you discuss using hemoglobin to monitor and
manage iron deficiency, when I think you really mean IDA, and treating IDA to
relieve the acute symptoms of iron deficiency, which is generally asymptomatic
until the anemia is manifest. This is a bit of a splitting of hair, but my perspective
is as a hematologist, where we do consider iron deficiency without anemia and
IDA differently. I would suggest changing the language to IDA to avoid any
confusion.
5. Background - Paragraph 2: Good to point out the importance of acute
inflammation. I would add one word: '..such as C-reactive protein must 'also' be
taken...' It highlights that this is something else to consider.
6. Methods - Paragraph 6: The definition of baseline is confusing, and it was
unclear whether it was a distinct time point from the others. I interpreted it to be
either the pre-FCM or the first FCM, which are the two previously defined time
points. The graphs don't have a 'baseline', so it isn't a real timepoint. Might be
best to define day of first FCM as basline, with the comment that the pre-FCM
measure was used when first FCM was unavailable.
7. Results - Paragraph 1: The last sentence needs some grammar correction -
'37/72 (51.3%) patients were younger...'
8. Results - Paragraph 3: Add one word to the second sentence '...from a
baseline 'of' 9.5 ...'
9. Results - Paragraph 7: You don't need the parenthesis to explain that oedema
is swelling. Just say oedema of the palms and fingers of both hands. Your
readers should know what that means.
10. Results - Paragraph 7: You have a confusing double negative in the
discussion of the slow rate and high volume administered, which was not in
accordance with the instructions not to dilute below 2 mg/mL. It's much clearer in
the discussion that dilution went beyond manufacturer's recommendations.
11. Results - Paragraph 7: After changing your dilutions, only one further event
(not events) occurred.
12. Discussion - Paragraph 2: The paragraph ends with 'suggest a need for
additional iron to avoid repeat deficiency respectively anemia'. I don't know what
that is. I think you mean to say 'recurrent IDA', which is what you discuss in
Paragraph 4.
13. Discussion - Paragraph 6 - Same comment about oedema that I made in the
results section.
Discretionary revisions:
1. Results - Paragraph 2: I would suggest starting with a sentence stating the
total number of administrations. You've done this in the abstract, and it would
introduce the content of the paragraph well.
2. Results - Table 2: I don't think you need the first row, showing the indication for
100% was IDA. You've stated that clearly in the text, and it doesn't add to the
table.
3. Results - Paragraph 4: I wonder if you aren't overinterpreting the changes in
the WBC and platelet count. Both of these rise transiently and then fall, and the
changes are fairly minor. This may actually represent changes in myelopoeisis
with the management of the IDA. We often see increased platelet counts with
IDA because of increased bone marrow activity, which then increases further
when iron is provided for hematopoeisis. As the anemia improves, marrow
function returns to baseline, which may explain the drop in the counts. I don't
know for sure, and that doesn't address the CRP, but it's something to consider.
4. Discussion - Paragraph 5 - Given my previous comments about the falling
WBC and platelets, I found your reference to similar findings in other studies
interesting. It might be helpful to add one sentence describing their interpretation
of that finding.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Effectiveness and Safety of Ferric Carboxymaltose Treatment in Children
and Adolescents with Inflammatory Bowel Disease
Version:2Date:22 April 2014
Reviewer: Jayson Stoffman
Reviewer's report:
General comments:
An interesting paper, and a good discussion of a common problem in both
gastroenterology and hematology. I'm glad that you were able to review your
experience with this treatment method to show general efficacy and safety. You
have honestly discussed the limitations of the retrospective nature of this study,
and the possible impact on your interpretation of the data. Overall, it generates
important new questions to asks, and provides data supporting another way of
managing IDA.
Major compulsory revisions:
None
Minor essential revisions:
1. Abstract - Background: It should be 'orally given iron'
2. Abstract - Results: You do not need to say 'diagnosed, concomitant iron
deficiency anemia'. Saying concomitant is sufficient, since it implies diagnosed.
3. Abstract - Results: The sentence about the improved hemoglobin levels was
unclear to me after I read the paper. I thought the improved levels from 9.5 to
11.9 was the range of the final (improved) values, and not the change from
baseline to endpoint. This is clear in the paper, but should be clarified in the
abstract.
4. Background: In the first three paragraphs, you have used the terms 'iron
deficiency' and 'iron deficiency anemia (IDA)' somewhat interchangably, which
they really are not. IDA is one consequence of iron deficiency. The statistics in
your first paragraph describe patients who are iron deficient and those who were
also anemic. Your focus, and the inclusion criteria for your patient population, is
IDA. In the next paragraphs you discuss using hemoglobin to monitor and
manage iron deficiency, when I think you really mean IDA, and treating IDA to
relieve the acute symptoms of iron deficiency, which is generally asymptomatic
until the anemia is manifest. This is a bit of a splitting of hair, but my perspective
is as a hematologist, where we do consider iron deficiency without anemia and
IDA differently. I would suggest changing the language to IDA to avoid any
confusion.
5. Background - Paragraph 2: Good to point out the importance of acute
inflammation. I would add one word: '..such as C-reactive protein must 'also' be
taken...' It highlights that this is something else to consider.
6. Methods - Paragraph 6: The definition of baseline is confusing, and it was
unclear whether it was a distinct time point from the others. I interpreted it to be
either the pre-FCM or the first FCM, which are the two previously defined time
points. The graphs don't have a 'baseline', so it isn't a real timepoint. Might be
best to define day of first FCM as basline, with the comment that the pre-FCM
measure was used when first FCM was unavailable.
7. Results - Paragraph 1: The last sentence needs some grammar correction -
'37/72 (51.3%) patients were younger...'
8. Results - Paragraph 3: Add one word to the second sentence '...from a
baseline 'of' 9.5 ...'
9. Results - Paragraph 7: You don't need the parenthesis to explain that oedema
is swelling. Just say oedema of the palms and fingers of both hands. Your
readers should know what that means.
10. Results - Paragraph 7: You have a confusing double negative in the
discussion of the slow rate and high volume administered, which was not in
accordance with the instructions not to dilute below 2 mg/mL. It's much clearer in
the discussion that dilution went beyond manufacturer's recommendations.
11. Results - Paragraph 7: After changing your dilutions, only one further event
(not events) occurred.
12. Discussion - Paragraph 2: The paragraph ends with 'suggest a need for
additional iron to avoid repeat deficiency respectively anemia'. I don't know what
that is. I think you mean to say 'recurrent IDA', which is what you discuss in
Paragraph 4.
13. Discussion - Paragraph 6 - Same comment about oedema that I made in the
results section.
Discretionary revisions:
1. Results - Paragraph 2: I would suggest starting with a sentence stating the
total number of administrations. You've done this in the abstract, and it would
introduce the content of the paragraph well.
2. Results - Table 2: I don't think you need the first row, showing the indication for
100% was IDA. You've stated that clearly in the text, and it doesn't add to the
table.
3. Results - Paragraph 4: I wonder if you aren't overinterpreting the changes in
the WBC and platelet count. Both of these rise transiently and then fall, and the
changes are fairly minor. This may actually represent changes in myelopoeisis
with the management of the IDA. We often see increased platelet counts with
IDA because of increased bone marrow activity, which then increases further
when iron is provided for hematopoeisis. As the anemia improves, marrow
function returns to baseline, which may explain the drop in the counts. I don't
know for sure, and that doesn't address the CRP, but it's something to consider.
4. Discussion - Paragraph 5 - Given my previous comments about the falling
WBC and platelets, I found your reference to similar findings in other studies
interesting. It might be helpful to add one sentence describing their interpretation
of that finding.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Effectiveness and Safety of Ferric Carboxymaltose Treatment in Children
and Adolescents with Inflammatory Bowel Disease
Version:2Date:22 April 2014
Reviewer: Jayson Stoffman
Reviewer's report:
General comments:
An interesting paper, and a good discussion of a common problem in both
gastroenterology and hematology. I'm glad that you were able to review your
experience with this treatment method to show general efficacy and safety. You
have honestly discussed the limitations of the retrospective nature of this study,
and the possible impact on your interpretation of the data. Overall, it generates
important new questions to asks, and provides data supporting another way of
managing IDA.
Major compulsory revisions:
None
Minor essential revisions:
1. Abstract - Background: It should be 'orally given iron'
2. Abstract - Results: You do not need to say 'diagnosed, concomitant iron
deficiency anemia'. Saying concomitant is sufficient, since it implies diagnosed.
3. Abstract - Results: The sentence about the improved hemoglobin levels was
unclear to me after I read the paper. I thought the improved levels from 9.5 to
11.9 was the range of the final (improved) values, and not the change from
baseline to endpoint. This is clear in the paper, but should be clarified in the
abstract.
4. Background: In the first three paragraphs, you have used the terms 'iron
deficiency' and 'iron deficiency anemia (IDA)' somewhat interchangably, which
they really are not. IDA is one consequence of iron deficiency. The statistics in
your first paragraph describe patients who are iron deficient and those who were
also anemic. Your focus, and the inclusion criteria for your patient population, is
IDA. In the next paragraphs you discuss using hemoglobin to monitor and
manage iron deficiency, when I think you really mean IDA, and treating IDA to
relieve the acute symptoms of iron deficiency, which is generally asymptomatic
until the anemia is manifest. This is a bit of a splitting of hair, but my perspective
is as a hematologist, where we do consider iron deficiency without anemia and
IDA differently. I would suggest changing the language to IDA to avoid any
confusion.
5. Background - Paragraph 2: Good to point out the importance of acute
inflammation. I would add one word: '..such as C-reactive protein must 'also' be
taken...' It highlights that this is something else to consider.
6. Methods - Paragraph 6: The definition of baseline is confusing, and it was
unclear whether it was a distinct time point from the others. I interpreted it to be
either the pre-FCM or the first FCM, which are the two previously defined time
points. The graphs don't have a 'baseline', so it isn't a real timepoint. Might be
best to define day of first FCM as basline, with the comment that the pre-FCM
measure was used when first FCM was unavailable.
7. Results - Paragraph 1: The last sentence needs some grammar correction -
'37/72 (51.3%) patients were younger...'
8. Results - Paragraph 3: Add one word to the second sentence '...from a
baseline 'of' 9.5 ...'
9. Results - Paragraph 7: You don't need the parenthesis to explain that oedema
is swelling. Just say oedema of the palms and fingers of both hands. Your
readers should know what that means.
10. Results - Paragraph 7: You have a confusing double negative in the
discussion of the slow rate and high volume administered, which was not in
accordance with the instructions not to dilute below 2 mg/mL. It's much clearer in
the discussion that dilution went beyond manufacturer's recommendations.
11. Results - Paragraph 7: After changing your dilutions, only one further event
(not events) occurred.
12. Discussion - Paragraph 2: The paragraph ends with 'suggest a need for
additional iron to avoid repeat deficiency respectively anemia'. I don't know what
that is. I think you mean to say 'recurrent IDA', which is what you discuss in
Paragraph 4.
13. Discussion - Paragraph 6 - Same comment about oedema that I made in the
results section.
Discretionary revisions:
1. Results - Paragraph 2: I would suggest starting with a sentence stating the
total number of administrations. You've done this in the abstract, and it would
introduce the content of the paragraph well.
2. Results - Table 2: I don't think you need the first row, showing the indication for
100% was IDA. You've stated that clearly in the text, and it doesn't add to the
table.
3. Results - Paragraph 4: I wonder if you aren't overinterpreting the changes in
the WBC and platelet count. Both of these rise transiently and then fall, and the
changes are fairly minor. This may actually represent changes in myelopoeisis
with the management of the IDA. We often see increased platelet counts with
IDA because of increased bone marrow activity, which then increases further
when iron is provided for hematopoeisis. As the anemia improves, marrow
function returns to baseline, which may explain the drop in the counts. I don't
know for sure, and that doesn't address the CRP, but it's something to consider.
4. Discussion - Paragraph 5 - Given my previous comments about the falling
WBC and platelets, I found your reference to similar findings in other studies
interesting. It might be helpful to add one sentence describing their interpretation
of that finding.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
assistant