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Comment by GenerocUsername | Hacker News Reader

From the article:

"The Brazil study was undertaken with 81 patients at a hospital in Manaus, in Amazonas state. As well as chloroquine, patients were also given azithromycin, an antibiotic also being used in the U.S., often paired with chloroquine. However, higher dose use of chloroquine (600 milligrams as opposed to 450 milligrams) was stopped after just six days, after 11 of patients who were given the greater dose died."

So they canceled a test with higher doses, not tests with regular doses.

Meanwhile they touched several times on the fact that Trump touted the drug. If trump recommended hugs, the media would write an article about how choking people is bad.

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It's not that trump said he likes to breath air, so everyone became fixated on that. It's that this is one of many (dozens at least) of things he has said were solutions, cures, miracles that would deal with covid-19. These went through the fox news world and now my elderly relatives are fixated on getting it (they are otherwise healthy). Because fox news and all these other non-medical people keep harping on it, the elderly people, the same ones preyed upon by certain news sources get the wrong idea about this.

nick_kline>"and now my elderly relatives are fixated on getting it(HCQ/CQ)."

Do you think Trump and Fox News are your elderly relatives only source of information? Do you think this behavior is limited to your elderly relatives? You can't shake an MD today w/o HCQ/CQ, zinc and ZPAK pills falling out of their pockets. Why is that?

Firstly, because it works.

Secondly, doctors (and dentists, and everyone who could write prescriptions and wasn't living in Tibet) spread the word of using HCQ/CQ+ZINC+ZPAK as a prophylactic measure among themselves. They wrote prescriptions for themselves and theirs, so much so that for awhile they sucked up all the HCQ/CQ in the supply chain.

If you think your "elderly relatives" are "fixated", then you must also think that most MDs are also "fixated".But maybe your "elderly relatives" know something you don't know. Perhaps you're the "fixated" one - fixated on false ideas of how to best judge from social behavior in the heat of possible disaster what most likely works and what does not work.

In this situation "doing what the doctors are doing" makes sense. The poor lost soul by the side of the road, waving a red flag and saying "But what about randomized controlled double-blind trials? I must have real science!" is the person that Darwin's theories will leave behind.

There are two stories here: One is whether one of the most promising drugs to stop the pandemic is actually dangerous, and the other is what Trump said and whether he was right to say it blah blah blah.

Thanks to the inclusion of Trump in this article by National Post, anyone who has strong views about Trump (most people in North America) are now focused on the second story, instead of the first.

Best I can tell, the article doesn't even mention the cause of death. :-) Did they die because they were given HCQ or did they die in spite of being given HCQ? We'll never know.

And the paper itself (https://web.archive.org/web/20200413181618/https://www.medrx...) doesn't say that either, and mentions that this study's randomization was flawed in that older patients with heart disease were assigned to the high dosage arm of the experiment.

They saw people were getting heart arrhythmias in the original Brazil study. Anecdotally, a doctor I know has been seeing an increase in arrhythmias on patients treated with HCQ at lower doses if they already have a pre-existing circulatory problem. What is really irking me is that we still don't even know if it's really doing anything.

At the same time, my elderly parent is taking HCQ for arthritis and appears to think she is invincible, going to the store each day in the middle of Queens, the world epicenter. She tried to send me links to Trump's touted Dr. Zelenko about how it's a miracle cure.

Alot of people touting this stuff dismiss or are in denial about their own condition.

I have a friend yakking about this topic and dismissing things like "pre-existing circulatory problems". This particular individual has had high blood pressure since we were in high school, is overweight, pre-diabetic and has some other problems. It doesn't dawn upon him that he is in the bullseye of people who are high risk for both the disease and the experimental, potential treatment option.

We don't even know if eggs and butter are "good for you" so I'm not surprised we know jack squat about HCQ beyond anecdotal evidence, which most studies you will find in the press seem to either ignore, or set their studies up s.t. they fail. In particular, per anecdotal evidence HCQ+Zpak+Zinc is the most effective combination, and only if given at the onset of symptoms. Yet routinely we see either just HQ or HCQ alone, or HCQ (with or without Zpak) given to patients that are so far gone it's unlikely to make any difference. Just read the original study fer chrissakes, it's publicly accessible. Sure it's not "randomized" or "principled", but at the very least _try_ what Raoult did in the first place, maybe? Exactly as he did it?

It looks like Azithromycin is for clearing bacterial pneumonia. Certainly this is a possible and probably common complication of viral pneumonia caused by COVID-19, but I'm sure doctors are well aware of ways to treat secondary bacterial pneumonia.

Just looking at what doctors are saying about Zinc, it seems like there could be something to it, especially if an individual is Zinc deficient, but it's not at all clear it's anything like a silver bullet.

https://www.medicinenet.com/script/main/art.asp?articlekey=2...

We have no idea what the mechanism of action if for HCQ. My doctor friend tried looking it up and it seemed like there are many possible pathways, many of which are still being researched, that modify immune response. There was one statement that speculated if HCQ could act directly on viral particles by changing pH near a key molecule. My attitude is, great if it works, but we still are very far from knowing that for certain.

One thing that I think is worth keeping in mind is that if a medicine kills 1% of the people we give it to, and we give it to a large number of people relatively indiscriminately, it's about as bad as COVID, which kills 1-5% of victims (though as much as 15% for high risk patients).

tehjoker says>"We have no idea what the mechanism of action if for HCQ. "<

Here's one paper showing that chloroquine allows Zn++ ions to pass into the cell cytoplasm where viral replication takes place. Zinc halts viral replication:

"Chloroquine Is a Zinc Ionophore":

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/

(PDF version) https://journals.plos.org/plosone/article/file?id=10.1371/jo...

Thanks for the link. I looked around and I saw that 2 uM Zinc inhibited SARS-CoV-1 in vitro, while human cellular concentrations of zinc are typically in the tens to hundreds mM range.

As a non-expert, there are two things that occur to me. That either something weird is going on, or zinc is very tightly controlled by the body and the range is really important. This means that taking extra dietary zinc without an ionophore probably wouldn't do much. So maybe CQ would help promote additional Zinc. According to one review article I was reading, Zinc concentration is naturally increased during immune response unless the virus hijacks the Zinc system.

This information makes me open to the possibility CQ is doing something, but so far the real world results have been unclear. One study showed that CQ had no effect on patients in France. If it's the Zinc that's making the difference and they didn't give Zinc, that would possibly explain the results, but the body also has abundant supplies of Zinc and adjusting intracellular concentration by 2/1000 of the ambient concentration shouldn't be a big deal.

Likely died form heart attacks. Both HCQ and azythro lengthen QT's.

> Likely died from heart attacks.

The paper does not support this assertion: https://web.archive.org/web/20200413181618/https://www.medrx...

> Both HCQ and azythro lengthen QT's.

The paper does support this assertion.

It also says "Several ongoing trials have been addressing the early use of CQ, in which the anti-inflammatory properties could be more helpful. That information is urgently needed." and also " Unfortunately, this study’s randomization, probably due to the low sample size, assigned older patients with heart disease to the high dosage arm." Uh-oh.

TL;DR of the paper: if we give as much CQ as the Chinese recommend, people seem to have heart related side effects, so we had to stop treating them with the drug. And if we select older patients with heart disease for the high dosage arm, they tend to experience more side effects.

It’s a random study so very significant evidence points to because.

Any high level official recommending it is a bad thing in itself.

The major issue is that there isn't enough evidence there for drug companies to put in money to ramp up supply. Heck, there wasn't enough evidence for Trump, who had just signed a trillion dollar stimulus, to divert a few tens of millions of dollars to ramp up supply.

Yet, you are telling a bunch of people who may never be able to make use of it to go buy the existing supply on the market. This existing supply exists because there are people who have actual proven needs of the drug, and as a result now you've also made the drug unavailable for uses where it's actually been proven to work.

Sorry to say but this sounds like a Darwin award. People always worry about the stupidest in society but if it wasn't one thing it would be another for them. If the danger of something is that stupid people act stupidly then I don't see it as a danger at all. This is why people can sell cure all homeopathic drinks that only succeed in making you relieve your bowels or "cleanse your body" as they would say. In this case the people are doubly stupid because not only do they believe something wrong, but they believe it wrong not from a lie, but because they are interpreting "promising trials" as something already working.

It was a multi-drug combination therapy without real control arm as far as I saw. Also the 95% confidence intervals were overlapping, and the probablity of the high dosage being more lethal is not published.

So you think they were mistaken to stop the trial? Or what?

No, when we are talking about taking away human lives, even with a little bit of data it’s immoral to continue a human trial.

The problem is with the binary reporting that doesn’t get into the nuances of the data that we’re getting.

People are getting confused and disappointed, because it looks like there’s a new miracle cure every day. And at the end cynical people are wright when it comes to this kind of binary reporting. And then cynism can lead to bad decisions.

> Meanwhile they touched several times on the fact that Trump touted the drug.

I did notice that. There were articles and some research before and everyone seemed interested and noticed as soon as he mentioned it the majority opinion almost immediately switched to "it's dangerous", "let's avoid it", "it probably won't work" while all the other alternatives seem to be still "interesting" and "worth studying" etc.

> I did notice that. There were articles and some research before and everyone seemed interested and noticed as soon as he mentioned it the majority opinion almost immediately switched to "it's dangerous", "let's avoid it", "it probably won't work" while all the other alternatives seem to be still "interesting" and "worth studying" etc.

The fact that a politician is pushing an (yet) unproven drug has to be viewed with skepticism. The flip side is that it caused a cascade of reactions from other governments trying to control the drug's supply. They may have reasoned that a world leader has information they do not. And other governments (see this article) started pushing it as a treatment too.

Additionally, now people are pushing the drug as a political issue. By people, I mean the average joe. This is damaging.

Regardless, science is doing its thing. Trials are ongoing, as this article shows. But politicians should refrain from making baseless statements about subjects they know zero about.

Notably on Feb 4th China announced their researchers were recommending testing chloroquine, about a month and a half(?) before Trump mentioned it:

http://www.whiov.ac.cn/kyjz_105338/202002/t20200204_5497136....

https://www.nytimes.com/2020/02/06/health/coronavirus-treatm...

https://www.nature.com/articles/s41422-020-0282-0

This was the original study which I believe influenced the French study and Dr. Zelenko (who seemed to be the nexus to Trump).

The UK banned export of CQ around Feb 26th (I believe the first country to do so):

https://ihsmarkit.com/research-analysis/uk-bans-parallel-exp...

From Google's custom date searches is looks like Trump first mentioned it in a press conference on March 19th:

https://twitter.com/cspan/status/1240672025989001221

It helps that he mentioned it just a couple of days before some studies (more controlled than what have been done before) finished and posted their non-results in preprint.

I mean... When scientists start discovering that a drug probably doesn't work, it's natural that people change their opinion from "I hope this works" to "it probably doesn't work".

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