blithedale

Truvada is PREP. PRE exposure prophylaxis.

PEP =/= PREP. PEP is after the fact treatment, there's more than just Truvada in that protocol.

PEP is typically much harder on the body than PREP.

Most every gay man I know takes PREP with few or no side effects.

Findings: In this double-blind, randomized, placebo-controlled trial involving 240 hospitalized patients with severe COVID-19, a single dose of 200,000 IU of vitamin D3 supplementation was safe and effective in increasing 25-hydroxyvitamin D levels, but did not significantly reduce hospital length of stay (hazard ratio, 1.12) or any other clinically-relevant outcomes compared with placebo.

Thanks for clarifying comments here, much appreciated.

I have to think my initial comment was overly harsh as well, given Supplement 3.

I think all I can say is that it may be possible for this issue to affect their data once they have OS stats accumulated in five years, but it was unlikely to do anything to yield differences in adherence with these kinds of patients over this kind of follow-up length.

I'm not convinced the 2/3 dropout rate of the FMD didn't simply select for people with less aggressive tumors, given that the Intention-To-Treat analysis found no difference in response rate, and that this paper is telling a nice story that actually happens to reverse cause and effect.

Basically, this?

   HAS AGGRESSIVE TUMOR ---> CANNOT DO THE FMD

   HAS SLOW-GROWING TUMOR ---> ABLE TO MAINTAIN FMD

Since you're researcher in this field and I'm just a weirdo who likes watching scientists argue on Twitter, I'll ask: Anything you can see in the paper that would give a clearer picture regarding possible bias that might have snuck in?

Good stuff.

Also of note is tumor heterogenity. Not only are cancers different between cell origin and across different patients, cancer is not one uniform genetic entity even inside a single person.

Why? The cancer's ability to repair DNA mutations is crap, so different chunks of tumor can rapidly evolve different mutations.

You might be able to drug one portion of the tumor based on a fancy receptor/biomarker, but that tumor chunk will get outcompeted by a different cancer blob that doesn't express that.

Their "better response rate" touted at the top ignores the 2/3 of women who couldn't carry out the assigned FMD.

When you fold back in those 2/3 of people on that arm, the response rate is the same:

   "The overall pCR rate was 11.7% and did not differ between the two groups (10.8% in FMD group versus 12.7% in control group; OR 0.830, 95% CI 0.282–2.442, P = 0.735)."

This is like making people with cancer do an Ironman triathalon.

People about to enter hospice and pass on in a few weeks are gonna be way less able to complete it than someone who has months left to live.

But all you've done is stratify your patients.

The triathalon doesn't make anyone live longer.

A lot of people might think "Ah, well, fasting is clearly effective for the 1/3 that are able to carry it out, just gotta make sure you have the willpower to be the 1/3."

But hold on. Slow down. There's a good chance the "women who fasted had better chemo responses" story completely REVERSES cause and effect. Here's how:

    WOMEN 1 - Has indolent biology, slower growing tumor than your average breast cancer at this stage.
 - Symptoms: Less pain, neuropathy, less swelling, tumors not affecting distant organs as much

    WOMEN 2 - Has aggressive biology, faster growing tumor than your average breast cancer at this stage.
 - Symptoms: More pain, neuropathy, more swelling, tumors begin to affect distant organs

So ask yourself: Which women is more likely to be able to follow a strictly regimented diet?

Clearly WOMEN 1.

ARGH. ARGH ARGH ARGH.

Almost no one reads these papers when stuff like this gets posted on HN.

And there is shameful statistical fuckery afoot in this paper. People are only repeating the hype statistics at the top of the paper.

Their "pathological response" rates touted at the top of paper only come from the 1/3 of women able to actually carry out the diet. This is the "per-protocol" language in the abstract. An honest evaluation here would be "intention to treat" and analyze chemo responses in every assigned to each arm.

And they do that evaulation, but bury it later in their paper. Turns out when you account for the 2/3 of women who can't do that fasting, there's NO DIFFERENCE in response rate:

   "The overall pCR rate was 11.7% and did not differ between the two groups (10.8% in FMD group versus 12.7% in control group; OR 0.830, 95% CI 0.282–2.442, P = 0.735."

Argh...

Except the dosing in this study is a massive supra-physiological bolus that's something like 50x the daily RDV.

Welcome to every Vitamin D study done ever. I follow some PHD/RD combination researchers on Twitter and they all get together each time one of these studies is done and bang their heads against a wall.

Thank you thank you thank you. There is a craze for popping Vitamin D related to the raft of observational studies, here... so many of which never find a causal link.

Take my own particular condition: an inherited vascular dysplasia which causes frequent nose and GI bleeds. People with low Vitamin D seem to have a worse time of it in OBSERVATIONAL studies.

But people with GI bleeds so bad they have daily diarrhea from hemorrhages and anemia that disables them to the point they can't work aren't going to be out in the sun, and aren't going to be able to absorb as many vitamins in their gut due to the havoc the hemorrhaging is yielding.

Thinking really hard about the direction the arrow of causality runs here is massively important. Is it:

LOW VITAMIN D ---> BAD BLEEDING?

Or:

BAD BLEEDING ---> LOW VITAMIN D

And as the consequences of overdosing show, this isn't like popping an extra Metamucil cracker a day or something - dire stuff can happen.