Reviewer's report
Title:Acetaminophen-cysteine adducts during therapeutic dosing and following
overdose.
Version: 1Date:22 December 2010
Reviewer: Laura K Schnackenberg
Reviewer's report:
The authors provide a well-written report on the measurement of
acetaminophen-cysteine adducts as a potential diagnostic tool for
acetaminophen toxicity. Acetaminophen toxicity is the number one cause of
acute liver failure in the United States and ALT is not necessarily a reliable
marker of acetaminophen-induced toxicity. Further, the rapid metabolism of the
parent compound renders measurements of acetaminophen useless as a
diagnostic tool. However, the authors clearly demonstrate that APAP-Cys is
present even after acetaminophen dosing has ceased. The authors took care in
obtaining data in a number of different populations in order to assess the effects
of different conditions on APAP-Cys concentrations. Overall, this was a nicely
written report. A few minor discretionary revisions follow:
Discretionary Revisions:
1. For Clinical Trial 2, why were only two timepoints acquired?
2. Why was there no placebo arm for Trial 1?
3. On p. 11, in the paragraph starting, “Mean APAP-Cys concentrations tended to
increase…”, it is noted that samples were also collected 1 and 4 days after
dosing ceased in Trial 1 and on days 1 and 3 in Trial 3, however, this does not
seem to be reflected in Table 1.
4. In Table 2, it would be more clear if a column for peak ALT and time to NAC
could be added rather than having all of the information under the Case
description.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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:Acetaminophen-cysteine adducts during therapeutic dosing and following
overdose.
Version: 1Date:22 December 2010
Reviewer: Laura K Schnackenberg
Reviewer's report:
The authors provide a well-written report on the measurement of
acetaminophen-cysteine adducts as a potential diagnostic tool for
acetaminophen toxicity. Acetaminophen toxicity is the number one cause of
acute liver failure in the United States and ALT is not necessarily a reliable
marker of acetaminophen-induced toxicity. Further, the rapid metabolism of the
parent compound renders measurements of acetaminophen useless as a
diagnostic tool. However, the authors clearly demonstrate that APAP-Cys is
present even after acetaminophen dosing has ceased. The authors took care in
obtaining data in a number of different populations in order to assess the effects
of different conditions on APAP-Cys concentrations. Overall, this was a nicely
written report. A few minor discretionary revisions follow:
Discretionary Revisions:
1. For Clinical Trial 2, why were only two timepoints acquired?
2. Why was there no placebo arm for Trial 1?
3. On p. 11, in the paragraph starting, “Mean APAP-Cys concentrations tended to
increase…”, it is noted that samples were also collected 1 and 4 days after
dosing ceased in Trial 1 and on days 1 and 3 in Trial 3, however, this does not
seem to be reflected in Table 1.
4. In Table 2, it would be more clear if a column for peak ALT and time to NAC
could be added rather than having all of the information under the Case
description.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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:Acetaminophen-cysteine adducts during therapeutic dosing and following
overdose.
Version: 1Date:22 December 2010
Reviewer: Laura K Schnackenberg
Reviewer's report:
The authors provide a well-written report on the measurement of
acetaminophen-cysteine adducts as a potential diagnostic tool for
acetaminophen toxicity. Acetaminophen toxicity is the number one cause of
acute liver failure in the United States and ALT is not necessarily a reliable
marker of acetaminophen-induced toxicity. Further, the rapid metabolism of the
parent compound renders measurements of acetaminophen useless as a
diagnostic tool. However, the authors clearly demonstrate that APAP-Cys is
present even after acetaminophen dosing has ceased. The authors took care in
obtaining data in a number of different populations in order to assess the effects
of different conditions on APAP-Cys concentrations. Overall, this was a nicely
written report. A few minor discretionary revisions follow:
Discretionary Revisions:
1. For Clinical Trial 2, why were only two timepoints acquired?
2. Why was there no placebo arm for Trial 1?
3. On p. 11, in the paragraph starting, “Mean APAP-Cys concentrations tended to
increase…”, it is noted that samples were also collected 1 and 4 days after
dosing ceased in Trial 1 and on days 1 and 3 in Trial 3, however, this does not
seem to be reflected in Table 1.
4. In Table 2, it would be more clear if a column for peak ALT and time to NAC
could be added rather than having all of the information under the Case
description.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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