Reviewer's report
Title:Xyloglucan for the treatment of acute diarrhea: results of a randomized,
controlled, open-label, parallel group, multicentre, national clinical trial
Version:5Date:21 July 2015
Reviewer: Laura Lamberti
Reviewer's report:
Minor Essential Revisions
1. English in the first sentence of the background is confusing and should be
rewritten (lines 74-76). If you delete “and increments in stool frequency,” the
sentence will make sense.
2. Line 78: replace the word “being” with the word “with”
3. Lines 83-86: From where did you get the 2.5 million deaths per year estimate?
You have listed reference #5, but this is a 2009 study focused solely on pediatric
patients in one site. In order to make this sort of statement about the global # of
diarrheal deaths across all age groups, you will need to cite different sources. For
example, “Global, regional, and national causes of child mortality in 2000–13,
with projections to inform post-2015 priorities: an updated systematic analysis” by
Li Liu et al. for deaths among children under 5 and “Estimating Diarrheal Illness
and Deaths Attributable to Shigellae and Enterotoxigenic Escherichia coli among
Older Children, Adolescents, and Adults in South Asia and Africa” for adults.
Although, I do not feel this paragraph is absolutely essential to the manuscript;
you may consider simply deleting it.
4. Lines 109-110: The editor should weigh in on this, but I believe the Bueno et
al. manuscript should be cited as the other references are (i.e. using a reference
# in brackets) and you can specify that it is in press in the reference section,
rather than the text.
5. Lines 98-102: I think you should include a reference here – perhaps the same
Bueno et al. reference or perhaps another study.
6. Lines 120-121: Delete. These findings should be reserved for the results and
discussion.
7. Lines 141-142: This sentence is confusing because it makes it seem as
though xyloglucan and diosemctite were administered to the same group of
patients. I believe you are missing a comma after the word “gelatin” (i.e. before
the word diosmectite) and that will resolve the issue.
8. Lines 262 & 266: The word ‘dehydration’ is spelled incorrectly.
9. Line 277-278: The sentence is phrased somewhat confusingly from a
grammatical standpoint and should be rephrased.
Major Compulsory Revisions
1. Why did you not include a placebo group? You should justify this decision in
your background, methods or discussion.
2. Lines 157-164: The methods are a bit confusing regarding the distinction
between what was recorded by the patients themselves and what was recorded
by investigators during each visit. It appears that the questionnaire on visit 1 was
self-administered, but it’s unclear whether patients recorded their own
observations of stool emissions/consistency/Bristol Stool Scale score etc. Please
make this clearer.
3. In addition to the antidiarrheals, were patients in all three groups also
administered oral rehydration therapy? As this is essential, it should be
mentioned somewhere in the methods.
4. Did you observe different rates of adherence to the 3-day regimen across the
three treatment groups? This should be reported in a table or at least mentioned
in the results section. In your description of the three treatments, it appears that
diosmectite had an orange-vanilla flavor, and I am wondering whether the
taste-masking improved adherence relative to the other groups. Please mention
in your results.
5. Please include p-values in Table 1 to indicate whether there are statistically
significant differences in the proportion female and the mean age across the
three groups.
6. Figure 1: The axis labels and point labels are unclear because they overlap.
Please restructure the figure so the labels are more easily understood. Also,
these figures should include some measure of statistical significance in
comparing the decrease of each outcome across the three groups.
7. Figure 3: Why is the prevalence of vomiting so much higher among xyloglucan
patients compared to the other two groups at visit 1? Visit 1 indicates the
presence of symptoms before treatment, correct? In your results, you mention
that all three treatments were efficacious in reducing vomiting, but the baseline
values are so different across the three groups that it makes a comparison
difficult. You should address this in your discussion.
8. Discussion: You should include a paragraph or two on the implications of
these findings and suggestions for next steps. For example, are your findings
sufficient to change current treatment guidelines or is further research
warranted? How generalizable is this study – to other populations and
geographic settings and to children?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Xyloglucan for the treatment of acute diarrhea: results of a randomized,
controlled, open-label, parallel group, multicentre, national clinical trial
Version:5Date:21 July 2015
Reviewer: Laura Lamberti
Reviewer's report:
Minor Essential Revisions
1. English in the first sentence of the background is confusing and should be
rewritten (lines 74-76). If you delete “and increments in stool frequency,” the
sentence will make sense.
2. Line 78: replace the word “being” with the word “with”
3. Lines 83-86: From where did you get the 2.5 million deaths per year estimate?
You have listed reference #5, but this is a 2009 study focused solely on pediatric
patients in one site. In order to make this sort of statement about the global # of
diarrheal deaths across all age groups, you will need to cite different sources. For
example, “Global, regional, and national causes of child mortality in 2000–13,
with projections to inform post-2015 priorities: an updated systematic analysis” by
Li Liu et al. for deaths among children under 5 and “Estimating Diarrheal Illness
and Deaths Attributable to Shigellae and Enterotoxigenic Escherichia coli among
Older Children, Adolescents, and Adults in South Asia and Africa” for adults.
Although, I do not feel this paragraph is absolutely essential to the manuscript;
you may consider simply deleting it.
4. Lines 109-110: The editor should weigh in on this, but I believe the Bueno et
al. manuscript should be cited as the other references are (i.e. using a reference
# in brackets) and you can specify that it is in press in the reference section,
rather than the text.
5. Lines 98-102: I think you should include a reference here – perhaps the same
Bueno et al. reference or perhaps another study.
6. Lines 120-121: Delete. These findings should be reserved for the results and
discussion.
7. Lines 141-142: This sentence is confusing because it makes it seem as
though xyloglucan and diosemctite were administered to the same group of
patients. I believe you are missing a comma after the word “gelatin” (i.e. before
the word diosmectite) and that will resolve the issue.
8. Lines 262 & 266: The word ‘dehydration’ is spelled incorrectly.
9. Line 277-278: The sentence is phrased somewhat confusingly from a
grammatical standpoint and should be rephrased.
Major Compulsory Revisions
1. Why did you not include a placebo group? You should justify this decision in
your background, methods or discussion.
2. Lines 157-164: The methods are a bit confusing regarding the distinction
between what was recorded by the patients themselves and what was recorded
by investigators during each visit. It appears that the questionnaire on visit 1 was
self-administered, but it’s unclear whether patients recorded their own
observations of stool emissions/consistency/Bristol Stool Scale score etc. Please
make this clearer.
3. In addition to the antidiarrheals, were patients in all three groups also
administered oral rehydration therapy? As this is essential, it should be
mentioned somewhere in the methods.
4. Did you observe different rates of adherence to the 3-day regimen across the
three treatment groups? This should be reported in a table or at least mentioned
in the results section. In your description of the three treatments, it appears that
diosmectite had an orange-vanilla flavor, and I am wondering whether the
taste-masking improved adherence relative to the other groups. Please mention
in your results.
5. Please include p-values in Table 1 to indicate whether there are statistically
significant differences in the proportion female and the mean age across the
three groups.
6. Figure 1: The axis labels and point labels are unclear because they overlap.
Please restructure the figure so the labels are more easily understood. Also,
these figures should include some measure of statistical significance in
comparing the decrease of each outcome across the three groups.
7. Figure 3: Why is the prevalence of vomiting so much higher among xyloglucan
patients compared to the other two groups at visit 1? Visit 1 indicates the
presence of symptoms before treatment, correct? In your results, you mention
that all three treatments were efficacious in reducing vomiting, but the baseline
values are so different across the three groups that it makes a comparison
difficult. You should address this in your discussion.
8. Discussion: You should include a paragraph or two on the implications of
these findings and suggestions for next steps. For example, are your findings
sufficient to change current treatment guidelines or is further research
warranted? How generalizable is this study – to other populations and
geographic settings and to children?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Xyloglucan for the treatment of acute diarrhea: results of a randomized,
controlled, open-label, parallel group, multicentre, national clinical trial
Version:5Date:21 July 2015
Reviewer: Laura Lamberti
Reviewer's report:
Minor Essential Revisions
1. English in the first sentence of the background is confusing and should be
rewritten (lines 74-76). If you delete “and increments in stool frequency,” the
sentence will make sense.
2. Line 78: replace the word “being” with the word “with”
3. Lines 83-86: From where did you get the 2.5 million deaths per year estimate?
You have listed reference #5, but this is a 2009 study focused solely on pediatric
patients in one site. In order to make this sort of statement about the global # of
diarrheal deaths across all age groups, you will need to cite different sources. For
example, “Global, regional, and national causes of child mortality in 2000–13,
with projections to inform post-2015 priorities: an updated systematic analysis” by
Li Liu et al. for deaths among children under 5 and “Estimating Diarrheal Illness
and Deaths Attributable to Shigellae and Enterotoxigenic Escherichia coli among
Older Children, Adolescents, and Adults in South Asia and Africa” for adults.
Although, I do not feel this paragraph is absolutely essential to the manuscript;
you may consider simply deleting it.
4. Lines 109-110: The editor should weigh in on this, but I believe the Bueno et
al. manuscript should be cited as the other references are (i.e. using a reference
# in brackets) and you can specify that it is in press in the reference section,
rather than the text.
5. Lines 98-102: I think you should include a reference here – perhaps the same
Bueno et al. reference or perhaps another study.
6. Lines 120-121: Delete. These findings should be reserved for the results and
discussion.
7. Lines 141-142: This sentence is confusing because it makes it seem as
though xyloglucan and diosemctite were administered to the same group of
patients. I believe you are missing a comma after the word “gelatin” (i.e. before
the word diosmectite) and that will resolve the issue.
8. Lines 262 & 266: The word ‘dehydration’ is spelled incorrectly.
9. Line 277-278: The sentence is phrased somewhat confusingly from a
grammatical standpoint and should be rephrased.
Major Compulsory Revisions
1. Why did you not include a placebo group? You should justify this decision in
your background, methods or discussion.
2. Lines 157-164: The methods are a bit confusing regarding the distinction
between what was recorded by the patients themselves and what was recorded
by investigators during each visit. It appears that the questionnaire on visit 1 was
self-administered, but it’s unclear whether patients recorded their own
observations of stool emissions/consistency/Bristol Stool Scale score etc. Please
make this clearer.
3. In addition to the antidiarrheals, were patients in all three groups also
administered oral rehydration therapy? As this is essential, it should be
mentioned somewhere in the methods.
4. Did you observe different rates of adherence to the 3-day regimen across the
three treatment groups? This should be reported in a table or at least mentioned
in the results section. In your description of the three treatments, it appears that
diosmectite had an orange-vanilla flavor, and I am wondering whether the
taste-masking improved adherence relative to the other groups. Please mention
in your results.
5. Please include p-values in Table 1 to indicate whether there are statistically
significant differences in the proportion female and the mean age across the
three groups.
6. Figure 1: The axis labels and point labels are unclear because they overlap.
Please restructure the figure so the labels are more easily understood. Also,
these figures should include some measure of statistical significance in
comparing the decrease of each outcome across the three groups.
7. Figure 3: Why is the prevalence of vomiting so much higher among xyloglucan
patients compared to the other two groups at visit 1? Visit 1 indicates the
presence of symptoms before treatment, correct? In your results, you mention
that all three treatments were efficacious in reducing vomiting, but the baseline
values are so different across the three groups that it makes a comparison
difficult. You should address this in your discussion.
8. Discussion: You should include a paragraph or two on the implications of
these findings and suggestions for next steps. For example, are your findings
sufficient to change current treatment guidelines or is further research
warranted? How generalizable is this study – to other populations and
geographic settings and to children?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
assistant