mycabbages

The link to the follow up study seems to be split, but I was able to pick together the link There are two major differences between the two studies: 1. The first one looked at mitral valves, and this one studied aortic valves; 2. The target INRs were different, although given the difference between aortic and mitral valves, both correspond to an INR 0.5 points lower than standard targets.

In your case, given the risks involved, a mechanical valve sounds like the best choice. I mostly see valve replacements in the elderly, so there's my personal observational bias. I'm from the US. From what I can tell about our warfarin recommendations, On-X aortic valves do get warfarin and aspirin at lower INR targets. In contrast, there is no such recommendation for On-X valves in the mitral position (yet).

I think your interpretation is correct, no conclusion can be drawn from the results of this study.

If a similar study were repeated and adequately powered, I wouldn't consider it p-hacking. The larger sample should only decrease the uncertainty in the primary outcome. P-hacking would be like if they set out to measure like 20 different outcomes to see if some turn out to be statistically significant by pure chance.

As an aside, I think it might be hard to gather enough participants for an adequately powered study given how close the outcomes were in this study. I'm no cardiac surgeon, but I think mechanical heart valves are generally less favored compared with bioprosthetics. Furthermore, the addition of aspirin to warfarin may cut down the number of participants as well, as aspirin is not routinely recommended.

I realize this is going to apply to a small fraction of people, but there is an additional caution I would like to add about kratom. There are two compounds in kratom that work as mu-opioid receptor partial agonists. I think of it like a natural analog of buprenorphine. As such, try to avoid taking kratom with full opioid agonists.

Anecdotally, this became relevant one time in my experience. I saw someone undergo elective orthopedic surgery, and he was using large doses of kratom up to the day of surgery. 24 hours after the surgery, when the nerve block had worn off, his usage of oxycodone and hydromorphone skyrocketed due to uncontrolled pain. And even then, he looked like he was going through opioid withdrawal.

At that time, it was hypothesized that some of the kratom had been eliminated from his system to have him go into withdrawal, but enough remained to block the action of the regular opioid medication. The pain crisis period eventually passed, but man did he have a really bad time.

https://dndi.org/press-releases/2023/worlds-first-clinical-trial-for-mycetoma-shows-efficacy-new-promising-treatment/ This is based on pre-publish results from a phase II randomized-controlled trial comparing fosravuconazole and itraconazole. It's odd that the 300 mg dose would perform worse than 200 mg, but it could be due to randomness; they don't give the sample size or ratio of bacterial vs fungal infection. Hopefully I remember to check back in a few weeks to read the published paper