"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.
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.
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.
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.
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:
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.
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.
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.
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.
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.
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.
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.
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".
When this clusterfuck first started revealing itself, the forsythia plants in my town had just started flowering.
Every time this chloroquine stuff comes up I just hear Jude Law's character from Contagion in my head saying "forsythia" over and over again in different sentence fragments.
Unfortunately the SEC isn't going to send men to arrest anybody this time.
1 year ago, I'd have thought this movie was typical Hollywood hyperbole.
Watching it recently, the scene where Sanjay Gupta is facilitating an interview about the virus was like deja vu. He was literally on TV doing the same thing recently, but for real this time.
At the same time people who have diseases which actually require medicines that rely on similar component ingredients are unable to get them.
That's one of the biggest issues with talking up miracle cures. Since it's not been proven, no one is gonna actually put their money behind drastically increasing production (pharma companies, etc. are not gonna put tens of millions of dollars on manufacturing a hunch), but the run on the existing supply means that a lot of people who actually benefited from it (for whom that existing supply was intended) now dont have access to it.
It's a complete lose lose. Even the hoarders don't benefit if it turns out to be beneficial because if it does turn out to be beneficial, production will be ramped up extremely quickly (since it's a known product and process with know side effects, etc...)
Also, drugs like this have fairly elastic demands; a hoarder can go from no usage of a drug to buying up years worth of the stuff overnight.
Compare that to food, where every calorie you buy today is one fewer calorie you need to buy in the future. Your need for food doesn’t change drastically before and after quarantine.
The stark contrast is in reality it is the President that is trying to profit, not a regular joe.
edit: To clarify I do not mean to suggest that Trump profited financially like the fictional character in the movie, but rather Trump benefited by being able to tout a potential cure. Ie. Trump profited politically.
> The stark contrast is in reality it is the President that is trying to profit
Trump's stake in hydroxychloroquine (which is a generic, and a bit safer than the chloroquine mentioned) is held via a trust and a mutual fund (so no direct investment) and is valued at less than $1,305, basically pointless.
it's a relatively tiny amount as part of a mutual fund (chosen by someone else)
Now a real president would have liquidated his investments and put them into a blind trust, but Trump doesn't have that sort of integrity. But it's a tiny amount in the scheme of things, I suspect he's grasping at straws and wants to dangerously rush opening the economy because he's more worried about no one going to his hotels or using his golf courses, not because of this tiny investment.
The mutual fund isn't what I was referring to. Trump's lawyer has already been paid at least 1.2 million (likely much more) for pharma access to Trump.
Which they "never received" but still paid the full amount over time.
It's a childish attempt to be able to say, nuh uh we didn't do it. Turns out that's all you really need.
OK so that Novartis thing. Trump gets elected. According to the second article there Novartis tracks down Trump's lawyer and signs a contract for him to "advise" them on US health care policy matters.
Then after they sign the contract they meet with him and determine that he "would be unable to provide the services that Novartis had anticipated". Without details but it sounds like they said, "OK we gave you all this money, we don't really want legal advice, we want you to influence the President or tell us privileged information" and Cohen said "No way that is unethical." They then had to pay the rest of the contract since it could only be terminated for cause and "lawyer refuses to commit crimes" isn't valid cause.
So yeah, Novartis is one of many companies that makes generic HCQ and sells it at near cost. It's not a money maker for them at all. It definitely sounds like they were trying to do something unethical and illegal here, but how is the fact their lawyer refused to go along with it evidence of something wrong with Cohen or any of his other clients?
Thanks for that link. So that's a mutual fund that like most mutual fund includes some pharmaceutical companies.
Like most people with any 401k retirement savings or other stock holdings (includes most people in the US), I have a mix of mutual funds and indexed funds that include stocks I've never heard of and don't care to know anything about. I bet I own part of some company that makes HCQ as well. I probably also own Big Tobacco, Big Oil, Big Pharma, Defense, Offense, and a bunch of other horrible things, as probably nearly everyone that posts here does as well without realizing it.
I clarified my intent. Trump profited politically.
We have no evidence that Trump profited financially, but from what we know of past leaks from the whitehouse I'd be surprised if nobody profited financially as well.
COVID-19 is obviously very scary and I fully understand why we'd want to lessen some restrictions to allow novel treatments to be tried. But as bad as things are, I think people underestimate how much worse they could be if aren't careful when easing those restrictions. There seems to be a mentality that people are going to die anyway so we should be trying anything. That seems to underestimate the potential to make things worse, not just in terms of deaths but also in terms of quality of life for patients.
It irks me to see chloroquine and hydroxychloroquine being used interchangeably in the media. This study used chloroquine. Trump touted hydroxychloroquine.
That's a verbatim quote from the article, and the point I was trying to make was that the article doesn't conflate them.
It says that the drugs are similar (which they are, both chemically and pharmacologically) and have both received some hype.
As for "politicizing the issue"...I'm a research scientist (and one who sometimes works with immunologists!). The data on CQ/HCQ make it look useless to me. The good trials show garbage effects and only the garbage "trials" seem to show any results. If you think insisting on careful analysis of data is political...good luck to you.
In-vitro results are worth following up on, but it is my understanding (as a non-expert) that it's very common that they don't pan out in actual humans. Turns out that human bodies and the way we interact with drugs are rather more complex than simple in-vitro situations.
It's really to soon to recommend either drug. Even with 0 side-effects there is a high risk of it being a massive waste of resources better spent elsewhere. This is just classic Trump afraid of being seen as not being on the top of the world in literally every situation.
> I also note that the half-maximal effective concentration (EC50) for blocking viral replication in vitro was 1.13 μM and the half-cytotoxic concentration (CC50) was greater than 100 μM. These are high concentrations for a drug, especially the CC50.
You need these high concentrations if you apply them too late. HCQ needs a few weeks to settle in the cells.
What I want to see are studies applying HCQ before the infection (that's what the Chinese measured, Lupus patients being immune), are at least when they were tested positive and sent home. Not when the shit already hit the fan, and the mucus is in the lungs causing bacterial infections all over. Because then it's too late already.
Wow, that's disturbing. The typical household variety isn't strong enough to do much more than give you a nasty upset stomach and maybe vomit a bit. I guess drinking a lot might cause irritation. But if quacks are peddling this, it's only a matter of time before someone gets creative and finds some of the 12% stuff in some hair dye kits and other beauty products. Internal chemical burns are pretty nasty stuff, and surviving the ordeal is option
Here in Brazil, for whatever reason, the president has been talking up chloroquine, while Trumps talking point is hydroxychloroquine.
I don't know how people who have no medical training or experience who are actively trying to undermine their advisors with such experience determine which of these medicines they're going to place their bets on, but given the lack of good results in either, it seems like either bet is as bad as the other.
COVID-19 kills anywhere between 0.7-4% of the people it infects. (Some countries like Italy saw a much higher mortality rate, nearing 15% in Italy, I believe, but that was due to the breakdown of the overwhelmed health services).
How would one even tell if any of the chloroquinine derivatives have been effective without a systematic study when 96 out of 100 people (at worst) would have recovered anyways? That's another thing that makes the 20 person French study which kicked off all this so much more ridiculous.
There was a 44% chance that they would have all recovered without any intervention. But it was probably higher for this group since they did have intervention, and they clearly had a high level of medical assistance.
> COVID-19 kills anywhere between 0.7-4% of the people it infects. (Some countries like Italy saw a much higher mortality rate, nearing 15% in Italy, I believe, but that was due to the breakdown of the overwhelmed health services).
That is mixing up IFR and CFR. We don't have any good way of knowing IFR yet, and it may be quite a while before we can get a good estimate. The denominator in CFR is confirmed cases, so Italy's inflated CFR could be (and probably is) entirely related to the lack of sufficient testing.
Italy has a very high IFR of 1%, the same rate as their every year flu epidemic. Or better very two years. The flu comes every two years.
Italy has traditionally the highest flu death rates in the world. This year, with COVID-19, it is still lower than in a bad flu year.
When you read 15% this might be the CFR, the case fatality rate. But only about a tenth is getting tested. So it means nothing.
You can only look the death numbers, and after it settled down at the excess death rate. From there you get the real IFR. So far we are at an IFR of 0.3 - 0.6. A little bit higher than the flu, but in absolute numbes lower than a bad flu year.
IIRC, Italy had a health care professional study that put their IFR at something around .35% or so. Similar for Germany, and the CDC just did a study of HCP's here and came up with 0.26% IFR (but the sample was 75% women).
Please check your calculations more carefully before posting a number. the 21% mortality rate represents a percentage of all closed cases in the worldmeters data, not the sum total of all cases both active and closed either through fatality or recovery. The CFR from worldmeters based on total cases counted so far and total deaths counted so far sits at about 6% (and bear in mind that the total count of cases on the site is far, far off from the probable real number of cases.
21% of people who have been confirmed to have the virus and don't anymore are dead. If the semantic argument hinges on the use of the CFR term, we don't need that term (though everything I've seen indicates CFR measures resolved cases, not total). People are using your small number to justify their belief that the virus is no worse than the flu. That does not reflect reality, and that belief is harmful.
I don't see anyone here arguing that. An IFR of 0.35, let's say, would be great news at the same time as it would be significantly worse than the flu. Using bad numbers to come up with a 21% CFR is not responsible, and is arguably fearmongering.
Bad numbers? Those are the numbers. How are you getting an IFR of 0.35? Where is the source for that? Does that source represent a projection or data coming from the results of tests being conducted?
My source for the CFR represents the totality of real information the world has presented us to date.
"A CFR can only be considered final when all the cases have been resolved (either died or recovered). The preliminary CFR, for example, during the course of an outbreak with a high daily increase and long resolution time would be substantially lower than the final CFR."
The epidemiologists are the ones projecting IFR at ~0.35. It's not responsible to use a crudely calculated CFR when you have ample evidence that the case rate is vastly underestimating the infection rate. It's also terrible to try and use 'recovered' numbers when a lot of localities do not track and report recovered cases.
Nobody here is arguing that it's no worse than the flu, least of all me. We still don't know the IFR of this virus and i'd be delighted if it was only half an order of magnitude worse than that of the flu but i'm certainly not claiming it is, and my "small number" of 6% is still huge, and in no way whatsoever an attempt to compare this to the flu. How could I with a massive 6% mortality rate? that would be than two orders of magnitude worse than the flu. No, what im very clearly and simply stating is the factual inaccuracy of claiming that the 21% from the worldmeters site is the CFR of Covid-19. As is made very obvious right on the site itself, this is not the case. Its CFR as a result of total cases to-date and total deaths to-date is sitting at around 6%.
This is not semantics, interpreting clearly stated numbers and definitions of basic terms badly to get a mortality rate that's almost four times larger than the case is simply wrong, and much more harmful than stating lower but more accurate numbers. I have no idea where you got your definition of CFR from or how you interpreted it like that, but CFR does not measure deaths as a percentage of resolved cases, it measures deaths as a percentage of all cases so far during a given period of time (in this case since the pandemic started). This is how it has been widely understood in discussions of CFR per country among all affected countries and you can find these figures on many different serious websites, with the percentages of fatalities clearly stated as CFR numbers that are based off all cases so far in any given country (Italy or Spain, for example). If this is mistaken, someone please do correct me and show me where it's claimed otherwise. If im wrong then, for example, nobody would be talking about Italy's CFR of 10%, they'd be discussing a different and considerably higher percentage derived only from resolved cases in that country vs its total deaths to-date.
> Some countries like Italy saw a much higher mortality rate, nearing 15% in Italy, I believe, but that was due to the breakdown of the overwhelmed health services
That's one factor. France and Britain have such extreme mortality rates vs case counts because of their very poor testing rates (which has been openly admitted by both nations, this isn't my opinion). Germany's mortality rate is so relatively low in part because of their vast testing program caught a lot more cases.
Britain has probably had between 5x-10x the positive cases that they've reported up to this point. They were only able to test 12,750 people per day as of a week ago. That's a minimum of 1/10th the rate they needed to be at. If the US has had 600,000 positive cases, it really has had 3+ million cases, given the poor rate of testing.
But the major problem with the french study was that they determined the outcome by testing throat swabs with RT-PCR test. But throat swabs become negative in the second week for most patients, indepedendent on the progress of symptoms of CoVid-19. As has been show by top German virologists, including Prof. Drosten, see https://www.nature.com/articles/s41586-020-2196-x_reference.....
So they measured in the french study something that would always go down.
From what I read [1], the Chinese "trail" (no data, only vague description) on chloroquine phosphate was mainly focused on mild - severe cases, not critical cases. These cases were not very likely going to die even without the drug. So fatality rate would not be a good metric to follow on. Metrics used in the "trail" also does not contains fatality rate, there were only something like "lung improvement rate in X days".
Another interesting point is China explicitly banned usage of macrolide antibiotics (which includes Azithromycin) together with chloroquine [2]. It was posted on Feb 26, 2020. I tried to use Wayback Machine to check whether they rewrote the history, but it seems like Wayback Machine only saved it recently. Another source (and with English translation) [3] indicate it is at least earlier than Mar 1 though. I did a Google search on key sentence "禁止同时使用喹诺酮类、大环内酯类抗生素及其他可能导致QT间期延长的药物" and found widespread reposting around March 1, so the date is likely genuine.
Experts that say that a solution in form of vaccine is 1 year out don't offer immediate help.
If some self-appointed expert claims to have a solution, a politician might take a bet on that solution and either later claim they were first to bet big on the solution or just move on to the next bet or blaming of someone else later.
Toxicity is relative. I came across one mention that said it's 40% less cytotoxic. Overall, both drugs are supposed to be relatively safe at careful dosing levels, but both have significant risk if the dosing is just a little bit too high, and a therapeutic index for covid-19 has yet to be determined. Near as I can tell from a quick lit review, there's risk of blindness and also renal failure if renal systems are already weakened. Liver toxicity can also (but rarely) be a problem-- however, the cocktail proposed using antibiotics makes that more problematic, as antibiotics can also adversely impact liver function. Considering both liver risks are small at careful dosing, that may not be an issue if the risk is additive, but if it's potentiating then there's a real problem and we really need to understand if there are more at-risk people for those issues that will die from the cocktail than will die from covid-19 complications.
This is why the larger scale trials are necessary, and doctors should be extremely cautious in using any of these drugs unless the covid-19 trajectory looks to be trending towards death anyway. Outside of studies, they should probably not be prescribed for low or medium severity cases.
*Foot note: I'm not a doctor or medical professional. I'm well informed on these matters, but a little knowledge is dangerous. Take the above in that context.
He's not in any way medically or chemically trained either, and has a well established history of sometimes saying things that are not factually correct during briefings. Why would you rely on that as a source?
According to Trump's own words on the coronavirus, you can call it "a flu". During one of his daily press briefings, he listed off things you can call it, and that was on the list.
Influenza and coronaviruses are both categories of virus, but they are very different categories. They are not only not the same family, they are also not the same order, class, or phylum.
That's like if we were being attacked by horses, and Trump said, "You can call these horses many names... including octopus."
> This is this the more toxic variant though right? It’s meant to be hydroychloroquine
Hydroxychloroquine has fewer side effects than chloroquine which has fewer side effects than quinine which has fewer side effects than the bark it's made from that contains a bunch of other compounds including quinidine.
All quinine class drugs produce heart arrhythmia as a side effect in some patients, more so with increasing doses, and all come with warnings that they should not be used or should be used with caution in patients with heart conditions. These contraindications of these widely used drugs have been known for decades.
I wonder what happened with the WHO study: "20,000 healthcare workers [will receive] #chloroquine [and] will be tested daily as currently used in the treatment of rheumatoid arthritis for three months or until they are diagnosed with COVID-19."
Arrhythmia is a well know complication and contraindication of Chloroquine. This should have been identified by the doctors prescribing it and NOT PRESCRIBED IT for at risk patients.
Unfortunately, COVID may also be associated with hypokalemia, so even patients without comorbidities could be at risk for TdP. HCQ may have therapeutic or prophylactic benefits, but it’s definitely not without serious risks.
The body is the landscape where this battle gets fought. "Nuke it from orbit. It's the only way to be sure." is a treatment policy that should be expected to result in some patients dying.
Trump has been vociferous on the drugs’ potential benefits, but among those to contradict his views are his own top expert Anthony Fauci
Edit: I stand corrected. The above still horrifies me. I've edited out the inaccurate framing. It's absolutely not intended to make replies to me look dumb. Quite the contrary.
This comment has been extensively edited. Hopefully, this is the least worst handling of blurting something out that expresses my concerns badly.
Furthermore, the studies on chloroquine started at least a month before the US president ever mentioned hydroxycholoroquine in mid March. E.g. this one from early Feb: https://www.nature.com/articles/s41422-020-0282-0
So the research is not only being conducted because of the US president's promotion.
For starters, to call a compound "reactive" means it's eager to participate in chemical reactions. I'm unable to discern what you were trying to say, but I'm betting it isn't that.
To continue, yes, at the limit, a sufficient dose of anything will kill you. The difference between the therapeutic dose and the lethal dose is referred to as the therapeutic index: wide is good, narrow is dangerous.
(hydroxy)chloroquine has a fairly narrow therapeutic index at the doses being tested for acute COVID-19 intervention. That's not a property you want in a medicine. It would have to be that much more effective to make up for the risk it poses to the patient.
This title is misleading. They didn't halt the trial, they halted one treatment arm (the arm with a very high dose). They continued with the 'low' dose (2.7g - about the same dose as used to treat malaria). The high dose was over 4x more of the drug, at 12g.
I haven't looked farther than the linked article, but assuming their reporting is accurate:
> 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.
To me that reads as an increase of about 1.35x rather than 4x.
They were giving 1.2 grams a day to the patients that died. That is significantly higher than what is known to be a safe dose. CQ is also not indicated for anyone with underlying heart conditions. Since COVID-19 is known to cause heart damage as well as lung damage in the late stage of the disease using these drugs in the late stage of the disease has built in problems.
The article doesn't mention anyone in the lower dose group dying of heart problems, though heart attacks and related problems are things that are known to happen to people with COVID-19. The lower dose study is continuing and was not halted. Presumably there will be a subsequent study published with those results. I agree that it is a bad idea to be taking 1.2 grams a day of CQ. During the century of widespread CQ use the fatality rate due to side effects was certainly no where near what they managed to obtain by overdosing patients in this reckless study.
The researchers gave whopping doses of chloroquine to both groups:
(a) high dose chloroquine (600 mg chloroquine twice daily for 10 days or total dose 12g);
(b) low dose chloroquine (450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g)
In addition, all patients received ceftriaxone and azithromycin.
So group (a) got 1200 mg chloroquine the first day and group (b) got 900 mg chloroquine the first day. No wonder they had irregular heart rates! Luckily a review board stopped group (a) treatment before they killed all the patients.
In contrast, the regimen for Covid-19 _successfully_ used by Dr. Zev Zelenko on ~700 patients is:
1. Hydroxychloroquine 200mg twice a day for 5 days,
The zinc sulfate is _important_ because it raises the blood level of zinc (Zn++ ion). Chloroquine is a zinc Zn++ "ionophore" which marshals Zn++ across the cell's outer wall into the cytoplasm where the Zn++ can halt viral replication.
Some researchers seem to be missing the point that chloroquine and its analogs may play a different role here than in malaria, acting not directly against covid-19 but as a facilitator for Zn++, which then halts covid-19 replication.
Zelenko's use of an antibiotic(azithromycin = Z-Pak) is a prophylaxis against potential secondary bacterial infection; the antibiotic would not likely play a role against the viral infection directly.
Once again we see that randomized, double-blinded clinical trials can be more deadly and less informative than ad-hoc studies performed on the battlefield of medicine.
The remaining population of COVID patients is a good control group. Or, if you prefer, randomly select sub-populations with similar demographic statistics.
Yes, let's throw out valuable field evidence just because it doesn't fit some narrow definition of "valid experiment".
Compare 700 people who received a treatment to 700 demographically similar people who received the standard treatment in the same or similar hospital and you're going to get a useful result.
We can do your fancy RCT later when we aren't dying en masse from a novel and highly lethal virus.
I mean, people have tried doing studies like that for CQ/HCQ. They are riddled with questionable assumptions (that patient groups are similar or treatment regimens are equivalent) that make their conclusions completely unreliable.
In the end we will most likely find that all positive anecdotal evidence found was just confirmation bias. That's why RCTs are so important.
> Once again we see that randomized, double-blinded clinical trials can be more deadly and less informative than ad-hoc studies performed on the battlefield of medicine.
Can you elaborate?
I've always heard that it's unethetical to use unproven treatments and that the scientific method (rndm double-blind) was necessary to remove as much bias as possible.
Now such strict requirements obviously don't jam well with fighting on the front line of medicine.
I'm very interested to learn what "less deadly and more informative" ad hoc studies are in this context. (genuine, there is no irony in this comment, this is not my domain)
Austria stopped all uses of chloroquine/hydroxychloroquine for covid-19 a few weeks back citing bad outcomes and from what I can tell it's not the only country. I feel like the only reason trials are kept alive are the popularity in the US.
To be clear, because the title makes it ambiguous, 11 patients died because of the treatment, or 11 paitents died of covid-related/suspected causes despite elevated treatment? It's a crucial distinction. The article doesn't perfectly specify which either. Covid-19 is already becoming known for causing cardiac problems in some patients, so if they were killed by a fatal heart arrhythmia, how to be sure that the medication caused it to be fatal instead of the disease progression itself due to myocarditis or something related combining with said arrhythmia.
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[ 4.7 ms ] story [ 204 ms ] thread"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.
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.
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.
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.
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).
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...
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.
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.
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.
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.
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.
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.
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.
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
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".
Every time this chloroquine stuff comes up I just hear Jude Law's character from Contagion in my head saying "forsythia" over and over again in different sentence fragments.
Unfortunately the SEC isn't going to send men to arrest anybody this time.
https://www.youtube.com/watch?v=CHZ8wx6J36Q
Watching it recently, the scene where Sanjay Gupta is facilitating an interview about the virus was like deja vu. He was literally on TV doing the same thing recently, but for real this time.
Otherwise Contagion is actually quite accurate.
That's one of the biggest issues with talking up miracle cures. Since it's not been proven, no one is gonna actually put their money behind drastically increasing production (pharma companies, etc. are not gonna put tens of millions of dollars on manufacturing a hunch), but the run on the existing supply means that a lot of people who actually benefited from it (for whom that existing supply was intended) now dont have access to it.
It's a complete lose lose. Even the hoarders don't benefit if it turns out to be beneficial because if it does turn out to be beneficial, production will be ramped up extremely quickly (since it's a known product and process with know side effects, etc...)
Compare that to food, where every calorie you buy today is one fewer calorie you need to buy in the future. Your need for food doesn’t change drastically before and after quarantine.
edit: To clarify I do not mean to suggest that Trump profited financially like the fictional character in the movie, but rather Trump benefited by being able to tout a potential cure. Ie. Trump profited politically.
Trump's stake in hydroxychloroquine (which is a generic, and a bit safer than the chloroquine mentioned) is held via a trust and a mutual fund (so no direct investment) and is valued at less than $1,305, basically pointless.
https://www.businessinsider.com/trump-small-financial-ties-h...
Edit: Love how I'm getting downvoted for pointing out facts.
Which seems like an unreasonable leap to make given the copious evidence that he's acted to provide plausible deniability for Trump in the past.
Now a real president would have liquidated his investments and put them into a blind trust, but Trump doesn't have that sort of integrity. But it's a tiny amount in the scheme of things, I suspect he's grasping at straws and wants to dangerously rush opening the economy because he's more worried about no one going to his hotels or using his golf courses, not because of this tiny investment.
Which they "never received" but still paid the full amount over time.
It's a childish attempt to be able to say, nuh uh we didn't do it. Turns out that's all you really need.
https://www.reuters.com/article/us-usa-trump-russia-novartis...
https://www.cnbc.com/2018/05/09/novartis-paid-trumps-lawyer-...
https://www.cbsnews.com/news/novartis-michael-cohen-1-2-mill...
Then after they sign the contract they meet with him and determine that he "would be unable to provide the services that Novartis had anticipated". Without details but it sounds like they said, "OK we gave you all this money, we don't really want legal advice, we want you to influence the President or tell us privileged information" and Cohen said "No way that is unethical." They then had to pay the rest of the contract since it could only be terminated for cause and "lawyer refuses to commit crimes" isn't valid cause.
So yeah, Novartis is one of many companies that makes generic HCQ and sells it at near cost. It's not a money maker for them at all. It definitely sounds like they were trying to do something unethical and illegal here, but how is the fact their lawyer refused to go along with it evidence of something wrong with Cohen or any of his other clients?
Like most people with any 401k retirement savings or other stock holdings (includes most people in the US), I have a mix of mutual funds and indexed funds that include stocks I've never heard of and don't care to know anything about. I bet I own part of some company that makes HCQ as well. I probably also own Big Tobacco, Big Oil, Big Pharma, Defense, Offense, and a bunch of other horrible things, as probably nearly everyone that posts here does as well without realizing it.
We have no evidence that Trump profited financially, but from what we know of past leaks from the whitehouse I'd be surprised if nobody profited financially as well.
TL;DR - The FDA only approved it for emergency investigation, not treatment. (as of 2020-03-31):
https://www.forbes.com/sites/rachelsandler/2020/03/30/fda-ap...
"Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro" https://www.nature.com/articles/s41421-020-0156-0
"The similar drugs chloroquine and hydroxychloroquine have been pushed by Trump as a possible partial solution to the pandemic..."
[Folks, the point is not about Trump here. The point is that the article's author clearly knows that CQ and HCQ are separate but related drugs].
Ah, yes, Trump, the world's leading expert in antiviral medicine.
Stop politicizing this issue. Stop feeding the trolls and the demagogues. Let science find things out.
It says that the drugs are similar (which they are, both chemically and pharmacologically) and have both received some hype.
As for "politicizing the issue"...I'm a research scientist (and one who sometimes works with immunologists!). The data on CQ/HCQ make it look useless to me. The good trials show garbage effects and only the garbage "trials" seem to show any results. If you think insisting on careful analysis of data is political...good luck to you.
In-vitro results are worth following up on, but it is my understanding (as a non-expert) that it's very common that they don't pan out in actual humans. Turns out that human bodies and the way we interact with drugs are rather more complex than simple in-vitro situations.
It's really to soon to recommend either drug. Even with 0 side-effects there is a high risk of it being a massive waste of resources better spent elsewhere. This is just classic Trump afraid of being seen as not being on the top of the world in literally every situation.
> I also note that the half-maximal effective concentration (EC50) for blocking viral replication in vitro was 1.13 μM and the half-cytotoxic concentration (CC50) was greater than 100 μM. These are high concentrations for a drug, especially the CC50.
What I want to see are studies applying HCQ before the infection (that's what the Chinese measured, Lupus patients being immune), are at least when they were tested positive and sent home. Not when the shit already hit the fan, and the mucus is in the lungs causing bacterial infections all over. Because then it's too late already.
Lots of things work in vitro. Many things don't work when pumped into bodies.
However, this drug is all about politics, so i think it's pointless to discuss it here
I don't know how people who have no medical training or experience who are actively trying to undermine their advisors with such experience determine which of these medicines they're going to place their bets on, but given the lack of good results in either, it seems like either bet is as bad as the other.
How would one even tell if any of the chloroquinine derivatives have been effective without a systematic study when 96 out of 100 people (at worst) would have recovered anyways? That's another thing that makes the 20 person French study which kicked off all this so much more ridiculous.
There was a 44% chance that they would have all recovered without any intervention. But it was probably higher for this group since they did have intervention, and they clearly had a high level of medical assistance.
That is mixing up IFR and CFR. We don't have any good way of knowing IFR yet, and it may be quite a while before we can get a good estimate. The denominator in CFR is confirmed cases, so Italy's inflated CFR could be (and probably is) entirely related to the lack of sufficient testing.
When you read 15% this might be the CFR, the case fatality rate. But only about a tenth is getting tested. So it means nothing. You can only look the death numbers, and after it settled down at the excess death rate. From there you get the real IFR. So far we are at an IFR of 0.3 - 0.6. A little bit higher than the flu, but in absolute numbes lower than a bad flu year.
[0] https://www.worldometers.info/coronavirus/
My source for the CFR represents the totality of real information the world has presented us to date.
"A CFR can only be considered final when all the cases have been resolved (either died or recovered). The preliminary CFR, for example, during the course of an outbreak with a high daily increase and long resolution time would be substantially lower than the final CFR."
https://en.wikipedia.org/wiki/Case_fatality_rate
This is not semantics, interpreting clearly stated numbers and definitions of basic terms badly to get a mortality rate that's almost four times larger than the case is simply wrong, and much more harmful than stating lower but more accurate numbers. I have no idea where you got your definition of CFR from or how you interpreted it like that, but CFR does not measure deaths as a percentage of resolved cases, it measures deaths as a percentage of all cases so far during a given period of time (in this case since the pandemic started). This is how it has been widely understood in discussions of CFR per country among all affected countries and you can find these figures on many different serious websites, with the percentages of fatalities clearly stated as CFR numbers that are based off all cases so far in any given country (Italy or Spain, for example). If this is mistaken, someone please do correct me and show me where it's claimed otherwise. If im wrong then, for example, nobody would be talking about Italy's CFR of 10%, they'd be discussing a different and considerably higher percentage derived only from resolved cases in that country vs its total deaths to-date.
That's one factor. France and Britain have such extreme mortality rates vs case counts because of their very poor testing rates (which has been openly admitted by both nations, this isn't my opinion). Germany's mortality rate is so relatively low in part because of their vast testing program caught a lot more cases.
Britain has probably had between 5x-10x the positive cases that they've reported up to this point. They were only able to test 12,750 people per day as of a week ago. That's a minimum of 1/10th the rate they needed to be at. If the US has had 600,000 positive cases, it really has had 3+ million cases, given the poor rate of testing.
So they measured in the french study something that would always go down.
Another interesting point is China explicitly banned usage of macrolide antibiotics (which includes Azithromycin) together with chloroquine [2]. It was posted on Feb 26, 2020. I tried to use Wayback Machine to check whether they rewrote the history, but it seems like Wayback Machine only saved it recently. Another source (and with English translation) [3] indicate it is at least earlier than Mar 1 though. I did a Google search on key sentence "禁止同时使用喹诺酮类、大环内酯类抗生素及其他可能导致QT间期延长的药物" and found widespread reposting around March 1, so the date is likely genuine.
[1] http://www.scio.gov.cn/xwfbh/xwbfbh/wqfbh/42311/42568/xgbd42...
[2] http://www.nhc.gov.cn/yzygj/s7653p/202002/0293d017621941f6b2...
[3] https://www.chinalawtranslate.com/en/chloroquine-phosphate/
Source: https://www.medrxiv.org/content/10.1101/2020.04.10.20060699v...
Discussion: https://news.ycombinator.com/item?id=22879361
https://news.ycombinator.com/item?id=22879361
This is why the larger scale trials are necessary, and doctors should be extremely cautious in using any of these drugs unless the covid-19 trajectory looks to be trending towards death anyway. Outside of studies, they should probably not be prescribed for low or medium severity cases.
*Foot note: I'm not a doctor or medical professional. I'm well informed on these matters, but a little knowledge is dangerous. Take the above in that context.
No, it isn't. Chloroquine and hydroxychloroquine are not the same drug.
We need to invent a drug that increases people's ability to detect irony.
Influenza and coronaviruses are both categories of virus, but they are very different categories. They are not only not the same family, they are also not the same order, class, or phylum.
That's like if we were being attacked by horses, and Trump said, "You can call these horses many names... including octopus."
Anyone who finished highschool should un Know that the two are different chemicals. The first has hydroxy the second doesn't.
As a side note: a quick google search indicates that the one with hydroxy is an improvement and is less toxic and brings less side effects.
Hydroxychloroquine has fewer side effects than chloroquine which has fewer side effects than quinine which has fewer side effects than the bark it's made from that contains a bunch of other compounds including quinidine.
All quinine class drugs produce heart arrhythmia as a side effect in some patients, more so with increasing doses, and all come with warnings that they should not be used or should be used with caution in patients with heart conditions. These contraindications of these widely used drugs have been known for decades.
https://www.who.int/blueprint/priority-diseases/key-action/R...
(The city is on fire! Those hacks at the fire department failed to predict the earthquake! Fire them all!)
The body is the landscape where this battle gets fought. "Nuke it from orbit. It's the only way to be sure." is a treatment policy that should be expected to result in some patients dying.
Trump has been vociferous on the drugs’ potential benefits, but among those to contradict his views are his own top expert Anthony Fauci
Edit: I stand corrected. The above still horrifies me. I've edited out the inaccurate framing. It's absolutely not intended to make replies to me look dumb. Quite the contrary.
This comment has been extensively edited. Hopefully, this is the least worst handling of blurting something out that expresses my concerns badly.
The article is describing a trial in Brazil, not the US.
Also, the trial used chloroquine, not hydroxychloroquine. They're not the same.
So the research is not only being conducted because of the US president's promotion.
For starters, to call a compound "reactive" means it's eager to participate in chemical reactions. I'm unable to discern what you were trying to say, but I'm betting it isn't that.
To continue, yes, at the limit, a sufficient dose of anything will kill you. The difference between the therapeutic dose and the lethal dose is referred to as the therapeutic index: wide is good, narrow is dangerous.
(hydroxy)chloroquine has a fairly narrow therapeutic index at the doses being tested for acute COVID-19 intervention. That's not a property you want in a medicine. It would have to be that much more effective to make up for the risk it poses to the patient.
You can construct scenarios where LD50 of water is relevant, say, but it isn't easy to see them in practice I imagine.
> 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.
To me that reads as an increase of about 1.35x rather than 4x.
450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g
The article doesn't mention anyone in the lower dose group dying of heart problems, though heart attacks and related problems are things that are known to happen to people with COVID-19. The lower dose study is continuing and was not halted. Presumably there will be a subsequent study published with those results. I agree that it is a bad idea to be taking 1.2 grams a day of CQ. During the century of widespread CQ use the fatality rate due to side effects was certainly no where near what they managed to obtain by overdosing patients in this reckless study.
(b) low dose chloroquine (450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g)
In addition, all patients received ceftriaxone and azithromycin.
So group (a) got 1200 mg chloroquine the first day and group (b) got 900 mg chloroquine the first day. No wonder they had irregular heart rates! Luckily a review board stopped group (a) treatment before they killed all the patients.
In contrast, the regimen for Covid-19 _successfully_ used by Dr. Zev Zelenko on ~700 patients is:
1. Hydroxychloroquine 200mg twice a day for 5 days,
2. Azithromycin 500 mg once a day for 5 days,
3. Zinc sulfate 220 mg once a day for 5 days.
https://www.freerepublic.com/focus/f-news/3829492/posts
The zinc sulfate is _important_ because it raises the blood level of zinc (Zn++ ion). Chloroquine is a zinc Zn++ "ionophore" which marshals Zn++ across the cell's outer wall into the cytoplasm where the Zn++ can halt viral replication.
"Chloroquine Is a Zinc Ionophore":
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/
(PDF) https://journals.plos.org/plosone/article/file?id=10.1371/jo....
Some researchers seem to be missing the point that chloroquine and its analogs may play a different role here than in malaria, acting not directly against covid-19 but as a facilitator for Zn++, which then halts covid-19 replication.
Zelenko's use of an antibiotic(azithromycin = Z-Pak) is a prophylaxis against potential secondary bacterial infection; the antibiotic would not likely play a role against the viral infection directly.
Once again we see that randomized, double-blinded clinical trials can be more deadly and less informative than ad-hoc studies performed on the battlefield of medicine.
For all we know, it was a successful placebo. Anecdotal evidence does not constitute scientific fact.
~700 pieces of anecdotal evidence is a study.
Compare 700 people who received a treatment to 700 demographically similar people who received the standard treatment in the same or similar hospital and you're going to get a useful result.
We can do your fancy RCT later when we aren't dying en masse from a novel and highly lethal virus.
In the end we will most likely find that all positive anecdotal evidence found was just confirmation bias. That's why RCTs are so important.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1232869/
Can you elaborate?
I've always heard that it's unethetical to use unproven treatments and that the scientific method (rndm double-blind) was necessary to remove as much bias as possible.
Now such strict requirements obviously don't jam well with fighting on the front line of medicine.
I'm very interested to learn what "less deadly and more informative" ad hoc studies are in this context. (genuine, there is no irony in this comment, this is not my domain)
600mg WILL kill you. I don't even understand who approved that!