
Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients - Khelavaster
http://www.sciencedirect.com/science/article/pii/S0924857920303423
======
tlb
Not a randomized trial. In fact:

> Several comorbidities were significantly less frequent in the HCQ group,
> including cardiovascular diseases, arterial hypertension, chronic renal
> disease, neurological and cognitive disorders, solid cancer, obesity as well
> as the proportion of active smokers.

IOW, doctors gave HCQ to healthier people, so you can't conclude much from the
death rate being lower. There may be some value in this paper if you really
dig into the details, but the overall death rate isn't a meaningful indication
of whether HCQ helps.

~~~
Khelavaster
>>> Several comorbidities were significantly less frequent in the HCQ group,
including cardiovascular diseases, arterial hypertension, chronic renal
disease, neurological and cognitive disorders, solid cancer, obesity as well
as the proportion of active smokers.

>IOW, doctors gave HCQ to healthier people,

Literally the sentence after the one you quoted contradicts clarifies, though:

>> On the other hand, at admission, patients in the HCQ group appeared to be
sicker as reflected by the higher frequency of radiological pneumonia, acute
respiratory distress syndrome, ICU transfer within the 24h after admission and
invasive ventilation support as well as the higher frequency of elevated LDH
and CRP levels.

~~~
tlb
I wouldn't call that a contradiction or clarification. It's yet another
confound and there's no reason to believe it cancels out the other ones.

In this case, people arriving sicker at the hospital with a given disease is
not necessarily an indication of the likelihood of death with no treatment.
For instance, robust young people may wait until they are extremely sick
before heading to the hospital, while old or immunocompromised people may go
at the first sign of illness. In that case, you would expect death rate to be
_negatively_ correlated with how sick people are when they arrive at the
hospital.

------
lucd
Group treated with HCQ much younger and healthier..Study published in a paper
were the editor-in-chief works for Raoult Institute..more of less self-
publishing..

This is an obversational retrospective study.. Hydroxychloroquine is
ineffective 100% of peer-reviewed randomized controlled trials,which is much
more significative evidence..

~~~
Khelavaster
> Group treated with HCQ much younger and healthier..

Younger and sicker, actually:

>> patients in the HCQ group appeared to be sicker as reflected by the higher
frequency of radiological pneumonia, acute respiratory distress syndrome, ICU
transfer within the 24h after admission and invasive ventilation support as
well as the higher frequency of elevated LDH and CRP levels.

~~~
lucd
Healthier as less comorbidites..

------
srmatto
My experience with becoming infected with covid-19 and taking
Hydroxychloroquine, azithromycin, and Zinc sulphate for five days was
positive. My total time to recover from first sign of symptoms to becoming
healthy again was about 11 days. I obviously can't and therefore won't make
any claims that my experience is the direct result of taking those
medications.

Here's a tracker that lists studies:
[https://c19study.com/](https://c19study.com/)

~~~
lucd
You personal experience, despite being very important to you, isn't
significative as scientific proof. The site you mentioned is anonymous, a
collection of links with arbitrary ratings. This isn't a scientific paper,
this is marketing. Here is a real meta-analysis for the different covid-19
treatments:
[https://www.bmj.com/content/370/bmj.m2980](https://www.bmj.com/content/370/bmj.m2980)
In 100% of randomized controlled trials, the most significant kind of
scientific evidence, hydroxychloroquine is ineffective.
[https://threadreaderapp.com/thread/1291068395497062400.html](https://threadreaderapp.com/thread/1291068395497062400.html)

~~~
f154hfds
Thanks for the meta-analysis link! Looking at the other measures, it does
mention HCQ in duration of symptoms.

> Hydroxychloroquine might be the most effective in reducing the duration of
> symptoms. Remdesivir has intermediate effectiveness and lopinavir-ritonavir
> could have intermediate effectiveness. The main limitations of the evidence
> are risk of bias and imprecision.

~~~
lucd
Yes mean difference −4.5 days,with a low certainty.. They also say:
Hydroxychloroquine might increase the risk of adverse events compared with the
other interventions And no evidence for reduction in death, except for
glucocorticoids.. I would expect an effective treatment to reduce mortality..

------
AaronFriel
I'm unfortunately completely unprepared to read a study like this and
criticize it, but I do think that there's reason to believe the effect is
close to zero. Why? Because more than one randomized controlled trial have
produced zero effects compared to placebo.

[https://www.washingtonpost.com/health/2020/07/16/hydroxychlo...](https://www.washingtonpost.com/health/2020/07/16/hydroxychloroquine-
studies-show-drug-is-not-effective-early-treatment-mild-covid-19/)

~~~
underdown
I have no idea if hcq is effective, but I'm not sure that study you linked was
meaningful.

FTA "The first randomized clinical trial testing hydroxychloroquine as an
early treatment for mild covid-19 found the drug was no better than a placebo
in patients who were not hospitalized."

So, maybe hcq has no effect on outcomes on mild cases. This does not mean it
couldn't have an effect on severe/hospitalized patients.

~~~
labcomputer
> So, maybe hcq has no effect on outcomes on mild cases. This does not mean it
> couldn't have an effect on severe/hospitalized patients.

Sure, but that's the exact opposite of the earlier narrative when the trials
in Brazil were called off.

(paraphrasing) "Sure, it doesn't help people who are critically ill, but you
should use it as a prophylactic to prevent milder cases from becoming more
severe".

So... it doesn't work in patients with a mild, moderate or severe case; (per
the earlier advice) it must be prescribed after infection but before symptoms
develop; and it must be prescribed in doses that are known to cause heart
problems in a significant portion of the population (so significant, in fact,
that patients prescribed much lower doses of HCQ are normally required to be
regularly monitored for the onset of said problems).

At what point do you admit that any positive effect of HCQ is just cherry-
picking/p-value-hacking?

~~~
Khelavaster
> So, maybe hcq has no effect on outcomes on mild cases.

Mild cases in people who work high-risk jobs and were selected away if they're
immunocompromised or especially susceptible to infectious disease.

This is a totally different, "cherry-picked" sample set than your average
populace with diverse immune health.

------
cdiamand
This seems like good news. Is hydroxychloroquine currently being prescribed
widely?

~~~
rs999gti
> This seems like good news. Is hydroxychloroquine currently being prescribed
> widely?

Sort of. Since Trump tweeted and mentioned the drug, hydroxychloroquine has
become politicized.

Some scientists and doctors say it might have some use.

But the media is critical of it because Trump mentioned it.

~~~
bradford
> But the media is critical of it because Trump mentioned it.

What an odd conclusion to draw.

I think it would be more accurate to say: Trump is being criticized for hyping
a medication that has not yet undergone medical trials.

There's an established method for bringing medication to market. Trump is
ignorant of that method. That's why he's being criticized.

~~~
gizmo
HCQ is not a new drug. It's widely available globally. It has been used as an
antiviral therapeutic and to prevent malaria since the 50s or so.

~~~
bradford
Right, It's not a new drug, but its efficacy for treating COVID-19 has not
been established. Using it to treat COVID-19 prior to completion of medical
trials is premature and has the potential to cause more harm than good.

"widely available globally" and "has been used as an antiviral therapeutic" is
not the correct criteria to use here.

~~~
gizmo
When you're dealing with a new disease there are no best practices for
treatment. This is tautologically true. That's why doctors have to use their
best judgement and try different things and write down what seems to work and
what doesn't. Often they get it wrong, with very bad consequences. For
instance putting covid patients prematurely on mechanical ventilators had
catastrophic health implications. When this became apparent ventilator policy
changed. People died and now we know better. It's ugly, but that's how you
learn about treating a new(ish) disease. Waiting for the results of multiple
randomized controlled trials is, frankly, fantasy. Covid has almost entirely
ran its course and we aren't close to having solid treatment results from
randomized controlled trials. Premature and ad-hoc treatment is how we've
muddled through the pandemic, and it's how we'll muddle through the next
pandemic, too.

~~~
manicdee
> When you're dealing with a new disease there are no best practices for
> treatment.

That doesn't give you carte blanche to claim that your drug does wonderful
things for condition X when the evidence supporting your claim is non-
existent, extremely weak, or obviously fraudulent.

> That's why doctors have to use their best judgement and try different things
> and write down what seems to work and what doesn't.

Which is completely different to POTUS recommending HCQ because he or his
friends have financial interest in a company that makes that drug.

It's also extremely negligent to try popularising a particular drug which is
already in short supply and needed by people with existing life-threatening
conditions. If something looks promising, you finance some trials to provide
more certainty, and then you look at ways to ramp up production because you
know demand is going to increase.

------
f154hfds
This fascinating article was posted on HN a few days ago:
[https://news.ycombinator.com/item?id=24251718](https://news.ycombinator.com/item?id=24251718)

It talks about the history of the HCQ debacle and in the process taught me
quite a lot about medical study methodology/epistemology.

~~~
jimhefferon
It appears to, at one point, just as a sideline, sneer at those who assert
that homeopathy is quackery. To at least my layman's mind, that considerably
drops the credibility of anything else it says.

~~~
f154hfds
I looked for homeopathy in the article to understand what you were getting at.
To disregard a long article such as this on one sentence doesn't seem fair.

The article if anything is about epistemology - so the sneer is in reference
to doctors assuming they 'know' the only correct ways to draw conclusions (and
the article did take a dark twist indeed referencing the opioid epidemic). As
a layman though, I don't know what it is referring to about Europe's
relationship to homeopathy. I would be curious for a more knowledgeable person
to weigh in on that.

~~~
jimhefferon
Well, as I say, I am a layman. To a person like me, trying to judge from what
I _do_ know, that was a show-stopper.

------
nl
It's such a pity how politicised hydroxychloroquine has become.

It's stupid to believe in miracle cures. But it's also stupid to discard out
of hand things for which evidence is unclear just because your opponent is
irrationally keen on it.

~~~
refurb
Indeed. Look at the convalescent plasma news. Numerous article pumping it up,
then Trump makes his announcement and suddenly it's questionable. All from the
same MSM newspaper.[1]

[1][https://twitter.com/SpoxHHS/status/1298001649798197248?s=20](https://twitter.com/SpoxHHS/status/1298001649798197248?s=20)

~~~
lucd
"scientists express doubts about coronavirus treatment touted as breakthough
by Trump " What is the problem with this Washington Post headlines? Didn't
scientists express doubts about this treatment? Didn't Trump didn't tout is as
breakthrough?

Also see.. FDA Walks Back Claim of Dramatic Benefit From Covid Therapy
[https://www.bloomberg.com/news/articles/2020-08-24/fda-
trump...](https://www.bloomberg.com/news/articles/2020-08-24/fda-trump-
officials-misrepresent-key-statistic-on-covid-therapy?sref=yYYRek8e)

~~~
refurb
Did you look at the Tweet? 4 articles a few months back touting plasma as a
promising therapy. All positive.

Trump mentions it and suddenly it’s the worst idea in the world.

I have zero problems with calling out Trump on his hyperbole. It's not helpful
at all. But it would be nice if the MSM didn't bash things these previously
praised just because Trump said something.

------
jdoliner
[https://c19study.com/](https://c19study.com/)

This site has a good summary of all the studies that have been done on HCQ
treatment of Covid-19.

~~~
lucd
This is a collection of links with arbitrary ratings from anonymous authors. A
propaganda piece. Here is a real meta-analysis..
[https://www.bmj.com/content/370/bmj.m2980](https://www.bmj.com/content/370/bmj.m2980)

~~~
jdoliner
What makes you say the ratings are arbitrary? Can you point to any of the
papers in which the rating is out of sync with the conclusion of the linked
paper?

~~~
lucd
No methodology, anonymous authors, no peer-reviewing, related to the account
@covidanalysis, which is known to push pro-hcq propaganda.. Are you kidding?
Why should we waste time with this propaganda piece while there are real
scientific papers available? No methodology, anonymous authors, no peer-
reviewing, related to the account @covidanalysis, which is known to push pro-
hcq propaganda.. Are you kidding?

Some smart French guy debunked this site
[https://threadreaderapp.com/thread/1284493669895041024.html](https://threadreaderapp.com/thread/1284493669895041024.html)
And c19trials, another disinformation piece from the same authors..
[https://threadreaderapp.com/thread/1291126570392924160.html](https://threadreaderapp.com/thread/1291126570392924160.html)

~~~
jdoliner
I'm not sure what you're saying. Every paper has named authors listed next to
it. And it explicitly states which ones have been peer-reviewed and which
haven't (most, but not all, have been). Clicking through gets you full papers
in the medical journals they were published in which includes the methodology.

~~~
lucd
Please tell me who are the authors of the website you mentioned and tell me
what is the methodology they used for selecting the studies and rating them.

~~~
jdoliner
I think that's a somewhat valid criticism. However, everything the site claims
is something that you can verify for yourself by simply clicking the links
they offer. This doesn't account for studies that should be in this list, but
aren't. I'd be interested in hearing about which studies those are.

I think given that Doctors such as Simone Gold are being fired simply for
stating that there's scientific evidence that HCQ can treat Covid-19 it's
somewhat expected that sites such as this will be done anonymously.

~~~
lucd
Where was Simone Gold fired from? If you look at her LinkedIn profile she is
working as a concierge physician for 9 years, she worked as a congressional
fellow.. never worked as an emergency physician. Claiming to have been fired
is part of her whistle-blower narrative.. [https://www.linkedin.com/in/simone-
gold-md-jd-4636a87](https://www.linkedin.com/in/simone-gold-md-jd-4636a87)

Only a fool or someone just looking for confirmation would take an anonymous
sham of meta-analysis seriously.

------
validuser
1\. Not a low dose (400mg/week should be enough from what I've read)

2\. No mention of zinc supplements, which seems to be the key to make the
Hydroxychloroquine effective

~~~
JumpCrisscross
> _No mention of zinc supplements, which seems to be the key to make the
> Hydroxychloroquine effective_

Clearly not.

~~~
jbritton
To my knowledge there has not yet been a trial completed with HCQ+Zinc. There
are several doctors stating positive observational results with HCQ+Zinc. I’m
waiting for this study to complete:
[https://clinicaltrials.gov/ct2/show/NCT04370782](https://clinicaltrials.gov/ct2/show/NCT04370782)

Zinc has antiviral properties. It has been shown to stop Sars Cov2 replication
in-vitro. Cells limit their Zinc intake. HCQ facilitates Zinc getting into
cells.

~~~
gojomo
Yes, it's been amazing to me how nearly everyone with continuing interest in
HCQ has emphasized Zinc as an important factor, while so many studies have
ignored it: neither supplementing it nor even checking enrolled patients for
zinc deficiencies (which may be especially prevalent in the aged or those with
known Covid comorbidities).

So I'll see, for example, some otherwise-highly-credible UCSF researchers
mention a bunch of evidence they think puts the potential of HCQ to help to
rest, without any mention of Zinc considerations (even in passing, or to
ridicule, or to share why they don't think the link credible). But even
coincident upon the very 1st discussions of HCQ as having potential, Derek
Lowe shared an anecdote about how carrying-Zinc seemed essential to
Chloroquine-related-compoounds' bioactivity
([https://blogs.sciencemag.org/pipeline/archives/2020/03/20/ch...](https://blogs.sciencemag.org/pipeline/archives/2020/03/20/chloroquine-
past-and-present)).

And, in many parts of the world, HCQ – as a cheap drug that, in moderate doses
with proper monitoring, is very low-risk – is already considered part of the
Covid-19 "standard-of-care". So, it's given even to the 'control' arms of
trials for other compounds – making both its effects, and those other
compounds' effects, harder to disentangle.

All I want now is true randomized trials - and can't at least one of those
monitor, or vary the supplementation of, Zinc as well?

------
chunsj
Why this kind of lie keeps up?

------
edgriebel
I'm sure people are going to find some link between sciencedirect.com and the
Trump administration so we can ignore it, since it doesn't fit with our
worldview of Orange Man Bad

