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Comment by zamfi | Hacker News Reader

To be clear, all patients received these supplemental drugs, as at the time they were considered the best standard of care. (Also to be clear: they're not anti-virals.)

Of the 75 patients in the trial, 50 people received additionally Vitamin D3 supplementation (in the form of calcifediol), and 25 did not.

Notably, though, diabetes and high blood pressure were substantially more frequent in the control group, which are HUGE risk factors. Also they didn't track BMI or obesity.

Still, check out table 2. Even with these limitations, seems powerful.

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Diabetes and high blood pressure are significant risk factors, but I wouldn't go as far as calling them huge, certainly not capital-letter huge.

https://www.nature.com/articles/s41586-020-2521-4

Wow! That link suggests diabetes doubles your risk, but that high blood pressure actually lowers your risk — but turns out to be only for folks over 70. Super weird!

> We similarly investigated the change in the hypertension hazard ratio (from 1.09 (1.05–1.14) adjusted for age and sex, to 0.89 (0.85–0.93) with all covariates included), and found that diabetes and obesity were principally responsible for this reduction (HR 0.97 (0.92–1.01) adjusted for age, sex, diabetes and obesity). Given the strong association between blood pressure and age we then examined the interaction between these variables; this revealed strong evidence of interaction (P < 0.001), with hypertension associated with a higher risk up to the age of 70 years and a lower risk above the age of 70 (adjusted HRs 3.10 (1.69–5.70), 2.73 (1.96–3.81), 2.07 (1.73–2.47), 1.32 (1.17–1.50), 0.94 (0.86–1.02) and 0.73 (0.69–0.78) for ages 18–39, 40–49, 50–59, 60–69, 70–79 and 80 or over, respectively). The reasons for the inverse association between hypertension and mortality in older individuals are unclear and warrant further investigation, including detailed examination of frailty, comorbidity and drug exposures in this age group.

Thanks for sharing this!

> Notably, though, diabetes and high blood pressure were substantially more frequent in the control group

How did this happen? Just bad luck with randomization?

That's the implication from the paper.

ack those could definitely affect this, isn't that why they normally try to select otherwise healthy patients as a baseline? Bring in the unhealthy people for the big studies and they'll most likely be spread much more evenly

Hydroxychloroquine was never the "best standard of care". It's a quack treatment that was pushed by some bad studies.

Reading Hydroxychloroquine mentioned in this study should make one very suspicious.

This is a substantial oversimplification.

Hydroxychloroquine looked promising for a while, and was being studied in an RCT, but that RCT was ended before completion because of the release of an observational study that suggested strongly negative outcomes from Hydroxychloroquine.

Later, that observational study was retracted because it was discovered to be based on falsified data.

So, unfortunately, we don't know very much about Hydroxychloroquine's effectiveness and risks in use -- but we do know that it has become a massive political hot potato, as your comment indicates.

> but we do know that it has become a massive political hot potato

I posted this a few days ago and got an interesting swing of votes on that comment since then:

> So, unfortunately, we don't know very much about Hydroxychloroquine's effectiveness and risks in use

For effectiveness it looks like we actually do, thanks to an experiment Switzerland accidentally ran on their population over May and June [0]. On May 27, they banned use of hydroxychloroquine, and 13 days later the death rate among resolved cases nearly tripled. Just after the spike began, on June 11 they reversed the ban and 13 days later the death rate drops back down. The graph from that article [1] is very stark, comparing the rate from late March through early July.

[0] http://www.francesoir.fr/societe-sante/covid-19-hydroxychlor...

[1] http://www.francesoir.fr/sites/francesoir/files/20200713_fs_...

That is quite a spike! Unfortunately the sharpness of the edge makes it pretty likely that a change in therapy is the cause -- time to death from hospital admission has a median of 10-12 days, but this is not a "wall", it's a median. The actual distribution is probably somewhat normal -- you'd expect a gradual increase and decrease around the intervention. We don't know how or when the Hydroxychloroquine was administered, but the mechanism of action seems to be prevention of infection early in the course of infection, generally before hospitalization.

To me, this seems more likely coincidental or a reporting change.

Ahhh I meant to say "pretty unlikely that a change in therapy is the cause" above.

The "HCQ doesn't work"-narrative is entirely political, not scientific.

The original "quack treatment", which is prophylactic zinc+HCQ (as an ionophore) for at-risk groups, has never been shown to be ineffective in an RCT. It is still being studied.

Of course the studies that show it to be effective aren't of the best quality, but they aren't entirely meaningless either.

Logically, the treatment ought to be for exposed people who aren't yet showing symptoms. Prime candidates would be family members of infected people.

This was presumably done a while ago, when hospitals were trying all sorts of weird things.

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