I’ve read with attention the paper of Davis et al. that is potentially of interest. The background and aim of the study have been clearly defined.

The methodology applied is overall correct, the results are reliable and adequately discussed.

However, the study duration is too short and the sample size too small to confirm the acute observations on the middle-term. This is more than relevant, considering that both tested treatment should be administered on years of exposition.

Then, even if the treatment sequence was randomized, the patient sample size was too short to exclude any carry-over effect on some patients.

All the reviewers have raised serious concerns on the patient sample size. I agree with them.

Even if the study is a pilot and is interesting, the enrollment of 8 patients only (6 men. 2 women) exposed to the treatment for a very short time (and with an even shorter washout period) limits the interest for the study.