Reviewer's report
Title:"Treatment of acute pancreatitis with protease inhibitors: an updated
systematic review and meta-analysis."
Version: 1Date:13 October 2013
Reviewer: Anubhav Mittal
Reviewer's report:
Major Revisions
1. Why were trials where protease inhibitors given oral, intra-arterial or via
intra-abdominal infusions excluded? Certainly the title of the paper does not
suggest that the method of giving anti-protease therapy would be a limiting
factors. The authors need to explain the reasons and also modify the title
accordingly.
2. Why was the administration of FFP an exclusion factor?
3. Also exclusion criteria 11 seems very global and could introduce bias. The
authors need to clarify which papers were removed due to this exclusion criteria
and why?
4. One of the problems with studies in acute pancreatitis is that each RCT uses
differing definitions of severity. This leads to misclassification of patients into
mild, moderate or severe pancreatitis and makes any meta-analysis difficult. How
did the authors deal with this problem? How many different definitions of severity
were used in the 17 RCTs?
5. Outcome measures should be separated into primary and secondary.
6. GRADE – it was mentioned in the letter but where is the analysis? It would be
nice to know how the body of evidence stacks up in terms of quality.
7. Not enough is made of the fact that protease therapy did reduce mortality with
low heterogeneity in the subgroup of patients with severe acute pancreatitis. This
needs to be discussed further. Perhaps antiprotease therapy is indicated in this
subgroup of patients? A Forest plot would be helpful for this subgroup analysis.
8. The conclusion is nihilistic. There is recent animal research showing that
perhaps targeting anti-proteases to mesenteric lymph may be a way forward.
Certainly, there should be a paragraph in the discussion about where to from
here? New directions in research should be discussed rather than shutting the
door forever on this type of therapy.
Minor Revisions
The language and style of writing can be improved throughout the manuscript.
Level of interest: An article of importance in its field
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:"Treatment of acute pancreatitis with protease inhibitors: an updated
systematic review and meta-analysis."
Version: 1Date:13 October 2013
Reviewer: Anubhav Mittal
Reviewer's report:
Major Revisions
1. Why were trials where protease inhibitors given oral, intra-arterial or via
intra-abdominal infusions excluded? Certainly the title of the paper does not
suggest that the method of giving anti-protease therapy would be a limiting
factors. The authors need to explain the reasons and also modify the title
accordingly.
2. Why was the administration of FFP an exclusion factor?
3. Also exclusion criteria 11 seems very global and could introduce bias. The
authors need to clarify which papers were removed due to this exclusion criteria
and why?
4. One of the problems with studies in acute pancreatitis is that each RCT uses
differing definitions of severity. This leads to misclassification of patients into
mild, moderate or severe pancreatitis and makes any meta-analysis difficult. How
did the authors deal with this problem? How many different definitions of severity
were used in the 17 RCTs?
5. Outcome measures should be separated into primary and secondary.
6. GRADE – it was mentioned in the letter but where is the analysis? It would be
nice to know how the body of evidence stacks up in terms of quality.
7. Not enough is made of the fact that protease therapy did reduce mortality with
low heterogeneity in the subgroup of patients with severe acute pancreatitis. This
needs to be discussed further. Perhaps antiprotease therapy is indicated in this
subgroup of patients? A Forest plot would be helpful for this subgroup analysis.
8. The conclusion is nihilistic. There is recent animal research showing that
perhaps targeting anti-proteases to mesenteric lymph may be a way forward.
Certainly, there should be a paragraph in the discussion about where to from
here? New directions in research should be discussed rather than shutting the
door forever on this type of therapy.
Minor Revisions
The language and style of writing can be improved throughout the manuscript.
Level of interest: An article of importance in its field
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:"Treatment of acute pancreatitis with protease inhibitors: an updated
systematic review and meta-analysis."
Version: 1Date:13 October 2013
Reviewer: Anubhav Mittal
Reviewer's report:
Major Revisions
1. Why were trials where protease inhibitors given oral, intra-arterial or via
intra-abdominal infusions excluded? Certainly the title of the paper does not
suggest that the method of giving anti-protease therapy would be a limiting
factors. The authors need to explain the reasons and also modify the title
accordingly.
2. Why was the administration of FFP an exclusion factor?
3. Also exclusion criteria 11 seems very global and could introduce bias. The
authors need to clarify which papers were removed due to this exclusion criteria
and why?
4. One of the problems with studies in acute pancreatitis is that each RCT uses
differing definitions of severity. This leads to misclassification of patients into
mild, moderate or severe pancreatitis and makes any meta-analysis difficult. How
did the authors deal with this problem? How many different definitions of severity
were used in the 17 RCTs?
5. Outcome measures should be separated into primary and secondary.
6. GRADE – it was mentioned in the letter but where is the analysis? It would be
nice to know how the body of evidence stacks up in terms of quality.
7. Not enough is made of the fact that protease therapy did reduce mortality with
low heterogeneity in the subgroup of patients with severe acute pancreatitis. This
needs to be discussed further. Perhaps antiprotease therapy is indicated in this
subgroup of patients? A Forest plot would be helpful for this subgroup analysis.
8. The conclusion is nihilistic. There is recent animal research showing that
perhaps targeting anti-proteases to mesenteric lymph may be a way forward.
Certainly, there should be a paragraph in the discussion about where to from
here? New directions in research should be discussed rather than shutting the
door forever on this type of therapy.
Minor Revisions
The language and style of writing can be improved throughout the manuscript.
Level of interest: An article of importance in its field
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
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