Hydroxychloroquine Probably Isn’t the Answer
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France ex-IHU Marseille/AP-HP: 79160 cases, 7527 dead, mortality rate 9.5%
IHU Marseille/AP-HP: 3005 cases, 33 dead, mortality rate 1.1%
France doesn't use HCQ consistently yet. Didier Raoult who heads the IHU in Marseille has been using it systematically on all cases, even mild ones for more than 2 weeks. I doubt such a difference in mortality rate could be explained by a difference in number of tests performed or other parameters.
Everyone can have all sorts of opinions on the efficacy of the treatment but in the end, mortality rates don't lie. And no, differences in the level of care, health or other smaller factors cannot explain an 8x difference.
In addition to that, most patients seem to have elevated ferritin which would be a side effect of consuming too much iron. In this case, it is theorized that when the virus replicates, it creates non-essential proteins that take place of the iron in hemoglobin thus preventing red blood cell from carrying O2 and CO2 from and back to the lungs. Based on molecular simulations, it seems that HCQ can bond to those viral proteins preventing them from expelling iron from hemoglobin. It would also explain why it's useful to treat someone early on rather than later when their hemoglobin lost their iron... Source here: https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surf...
Regarding status, it seems the peak is being reached there [2]
[0] https://twitter.com/raoult_didier/status/1245978149206228992...
[1] https://twitter.com/raoult_didier/status/1242808646997880832...
[1] https://twitter.com/raoult_didier/status/1246003916325748736...
Maybe it is still a good number for their population age demographics and the treatment helps a lot, but it doesn't seem to be showing it to be anything like a game changer.
Of course it is a game-changer.
You eradicate the viral load after 6 days instead of 20+. Meaning :
- reduced contagion (avoiding big peak of infections), no confinement needed, so the better for the economy - you avoid complications, meaning less load on hospital, so you can save a lot of people who would have died otherwise. - people get better in less time so less damage to their finances.
There would be many less deaths if so.
Pennsylvania: 11510 cases, 150 deaths, mortality rate 1.3%
Is Pennsylvania also using HCQ systematically on all cases? I don't think these crude CFRs are useful.
Also, in your example, the crude CFR for the US is 2.9% right now, so only 2.2x that of Pennsylvania. We're talking about 8+ here.
Bouches-du-Rhône has ~3% of the French population and ~4% of the covid-19 hospitalizations.
The department of Paris has ~3% of the French population and ~10% of the hospitalizations.
That seems to indicate that Bouches-du-Rhône is behind Paris.
(used hospitalizations instead of cases only because I couldn't find a good source for case breakdown by department. numbers from https://dashboard.covid19.data.gouv.fr/)
Right now I choose to believe on MD in front line rather then in Health Societies, FDA, WHO and those bureaucrats who let the virus spread all around due to its incompetence
“Every patient showing symptoms and with CTs indicating the presence of Covid-19 are invited to join the protocol. We’ve discharged more than 200 patients”.
https://www.google.com.br/amp/s/noticias.uol.com.br/saude/ul...
Hospitals like Albert Einstein and Sirio Libanês are also using it but patients must sign a term and take full responsibility over any complications.
So I could reply that right now I choose to believe these MDs and ARNPs on front lines rather than commenters on HN. But that's not helpful compared to research.
This one is a mess, and the tiny sampling of articles we have are not definitive.
// Disclaimer: Lived in Africa for a decade, took anti-malarials. These and others can be nasty for a lot of people, some folks have to hunt to find things that aren't worse than the occasional bout of malaria. In fact, while my family took them, I never found anything tolerable. Curiously, the rest of the family got malaria, I did not.
https://www.gilead.com/stories/articles/an-update-on-covid-1...
That statement didn't clearly say whether they were going to donate those that they haven't produced yet. If they aren't donating that, this donation is like a ~10% discount (compared to the ~66% discount I had originally interpreted it in that case).
Correct. that’s against the thought right now. HCQ is great at preventing patients from getting to the serious pneumonia stage. Once they’re on a vent, they should be on another cocktail.
They are down from the normal 4.5k+ per week during this period to around 2.3k per week and they are falling parabolically as COVID-19 expands.
What could cause this?
Do you have any pointers?
Isolation should reduce all virus transmission and so reduce incidence of flu, etc.. We'll need 3 weeks minimum of isolation to reduce Covid19 transmissions, assuming everyone is actually doing it.
In the UK (just England I think, might be England & Wales) our Office of National Statistics says there were <500 deaths from flu (ICD codes J10-11, https://bit.ly/39DZPCo) in the most recent year of records (2017; from c.60M population).
The whole point of this article is that it's really hard to know without controlled, randomized trials. And I agree.
People just have a problem with a no-information-yet state, they'd rather talk about the unfounded rumor than acknowledge that people are hard at work and there is no definitive news yet.
https://www.sciencedirect.com/science/article/pii/S016635422...
https://www.who.int/bulletin/volumes/82/8/editorial30804html...
every dog, cat and horse that is on heartworm medication is already using it
It's supposed to be taken BEFORE you become seriously ill and develop ARDS.
In fact, many elites are put on a short course of HCQ/Z-Pak as soon as they show symptoms, even before the results of their tests come back (which can take days).
> https://www.cbsnews.com/news/coronavirus-treatment-drug-hydr...
Both ADAM17, which helps ACE2 shed from the cell, and ACE2 itself, are zinc finger proteins and use zinc as a cofactor.
We're not going to wake up one day with a "cure" for COVID-19. No one in the medical field actually expects Hydroxychloroquine to produce miraculous recoveries at this point. The idea is that any treatment that slows the progress of the infection will also buy the patient's immune system more time to fight the infection. If we can push the peak symptoms back even 1-2 days relative to untreated individuals, that gives the immune system that much extra time to mount an effective defense against the virus.
When we finally confirm which treatments, if any, are useful for slowing the progress of the infections, we can combine them with earlier testing and identification to help reduce the number of patients who require hospitalization. It won't look like a cure, but it will be making improvements in treatment outcomes and reducing the burden on hospitals.
At this scale, a small modification of disease severity can still be useful for minimizing the burden on hospitals, even if it doesn't fit the narrative of a miracle cure.
Is there any serious trial that shows that Hydroxychloroquine has any effect at all?
Is there any evidence? Do you have a link to the best evidence so far? Did someone tried a similar treatment and get the same result?
It is not necessary to have a perfect study, because there too little time. But how hard is to make a study with a randomized control group? You are not sure if this drug is better or worse, so giving only the standard treatment perhaps is better. I guess a double blind experiment is more difficult for logistic reasons, but if the patients have respirators and are sedated, it is almost a single blind experiment. And if the results are the number of death or an analysis in a lab by a machine (instead of self reports), they can be less influenceable.
Proven against SARS in vitro: https://www.ncbi.nlm.nih.gov/pubmed/15351731
And much evidence for efficacy against COVID-19 in humans: https://twitter.com/__ice9/status/1246549028382408706
Note that it is not peer reviewed
This part is strange:
> Normalization and mitigation criteria included the following: a. Body temperature ≤ 36.6 °C on the surface, ≤ 37.2 °C under the armpit and mouth or ≤ 37.8 °C in the rectum and tympanic membrane;
Is this a standard criteria? Why didn't they agree to use the same measurement method in all the study?
The part about counting coughs is not convincing for me, it looks too difficult to measure accurately. I prefer to ignore it.
But this part looks really interesting:
> Notably, a total of 4 of the 62 patients progressed to severe illness, all of which occurred in the control group not receiving HCQ treatment. For adverse effects, it should be noted that there were two patients with mild adverse reactions in the HCQ treatment group, one patient developed a rash, and one patient experienced a headache, none severe side effects appeared among them.
Plus it does have proven effect against SARS in vitro.
And this French treatment center seems to be getting good results.
That's not to say they should stop prescribing it, simply due to lack of formal trials. But the perceived benefits should not be taken at face value, yet.
That's non-sense, if everyone that had cancer got cured by a miracle drug, would you still demand a randomized control trial?
The post I was responding to really had no _point_, per se. It merely asserted that it's ridiculous to require such experiments because... miracle drug!
"This" being the idea that "compelling evidence" and "evidence from randomized controlled trials" are not the same thing? That has been shown. The cliche example is parachutes. We have compelling evidence that they save lives, even though nobody has ever done a proper trial.
Experiments don't have to be perfect to provide valid data. And there are things you can learn from observation even without an explicit experiment.
Nobody is suggesting that we would take an unknown drug and call it a miracle drug without evidence. When someone has a miracle drug in a hypothetical, pretend they're holding a bottle of penicillin and they've gone to a country where nobody has ever heard of penicillin. How should that country react when it immediately cures almost everyone with a certain disease? Do they really need a randomized trial to be confident it works?
And your final example of showing up in scientifically illiterate society wielding a miracle drug and declaring that they need no evidence of its efficacy, ignoring the fact that such evidence was all on you prior to arriving there? Sorry, I don't see how this is productive.
We know they work. We have evidence of efficacy. But this evidence does not come from randomized controlled trials.
If it was a pill, the standards for evidence should not change.
Randomized controlled trials make things easier to prove. But they are not the only way to collect evidence of efficacy.
> And your final example of showing up in scientifically illiterate society wielding a miracle drug and declaring that they need no evidence of its efficacy, ignoring the fact that such evidence was all on you prior to arriving there?
No evidence?? That's the exact opposite of what I'm trying to say.
Your objections... okay, would a better thought experiment be an invention of a new antibiotic?
There is no existing proof of anything.
I go to the nearest town and give the pill to every single resident with gonorrhea, 50 of them, and a few days later only 48 of them have the disease any more.
They otherwise took no drugs they hadn't already been taking for months.
I didn't randomize at all, and I didn't set up a control group.
But it's statistically impossible for that to happen by chance.
Also, I and a team of respected researchers searched for confounding factors just as hard as someone performing a randomized controlled trial, and we could not find any.
Did I provide evidence of efficacy? If not, why not?
Let's pick some terminal ill patients. I think cancer metastasis in the brain has a very bad prognosis, like less than a year of life expectancy [1]. Let's make a one year trial: 100 patients in the control group that receive the usual treatment and a placebo. 100 patients in the treatment group that receive the miracle drug instead of the placebo. Obviously a double blind study.
If the terminal patients selection was good enough, after a year you will get 90 death in the control group (there are some lucky guys) and only 5 death in the treatment group (someone died in a car accident). That would be very convincing and in a few years (with a few additional studies) it will remove all the current drugs from the market.
Without a serious study, some doctors will believe in the miracle drug and some will have the gut feeling that another drug or drug combination is better and continue using the old treatment. The lack of a convincing study kill people.
And also, there is the risk of snake oil. Some doctors are convinced that a drug cures 100% of the patients and push it to be applied to everyone. Sometimes they are wrong, without a study it is impossible to separate the good and the bad ideas. The lack of a convincing study kill people.
[1] Unless it a metastasis of breast cancer and is affected by hormones? I think there a few exceptions, but it is usually very bad.
If the study in a small group proves that the miracle drug is ineffective and moreover it reduces the life expectancy to 1/2, then by not giving it to everyone avoid the nasty effect of reducing the life expectancy of a lot of people.
Take a look at some "miracle" cures of cancer of the past, like https://theincidentaleconomist.com/wordpress/the-rise-and-fa...
Also, since a few years in Prostate Cancer the recommendation is not to treat all cases after detection https://en.wikipedia.org/wiki/Prostate_cancer#Management
Side effects of HCQ are well known, and safe dosage has long been established. If it saves some lives, why deny it to patients knocking on death's door?
[1] We have a big announcement of a miracle cure in Argentina in 1986. It was crotoxina [links bellow] that is a part of the venom of some snakes. One of the problems was that they were comparing CT from different angles and finding fake reductions in the size of the tumors. (Other parts of the study were just frauds.)
https://translate.google.com/translate?sl=auto&tl=en&u=https...
https://translate.google.com/translate?hl=&sl=es&tl=en&u=htt...
https://translate.google.com/translate?hl=&sl=es&tl=en&u=htt...
> If the data is clear enough, you can still pull a signal out of the noise.
It is theoretically possible, but very difficult. Unless you use a lot of people in the trial, but then you must ensure that the measurements are done in a consistent way.
> in my version it's a general hospital and they give the treatment to everyone that has this diagnosis
Does it include pregnant women and babies with less than 1 year? Does it include people with more than 90 years? Does it include people that goes to the hospital in an ambulance because they are almost dying, like a hearth attack? Does it include someone that had one of the lungs removed and is under a chemotherapy treatment?
What about people that can't sign the form for the experimental treatment? Just signing a form is a selection of people that is not toooooooooooooooooooo bad.
What about asymptomatic people? Does your are has the same policy to test everyone/someone/noone than the region you are comparing with? What about the effects of temperature or humidity?
What about diet? Poor people may have a bad diet, with a low amount of vitamins and that can affect the illness. Some countries drink a lot of milk and some very few, some countries add vitamins to the milk.
What about the median income? If the city has a few hospitals, there will be one closer to the poor area and other closer to the rich one. Some people has health plan that include one hospital(s) but not other hospital(s). How does it affect the selection of people in the hospital? Different countries have a different definition of poor.
Some hospital are famous and get more of the strange/difficult cases after the standard hospitals give up or realize it is a complex case.
I may be missing other factor, or overestimating some of them, but it is very difficult to be sure that you know all the things that change the cure rate and that you can correct the result.
If you don't control who gets the treatment, who gets a placebo, and who gets the current state of the art treatment, you cannot really exclude your results are biased. There are some ideas about how to reason with observational data but your conclusion are still weaker as with experimental data.
In the real world, science comes after engineering has succeeded to explain why (and ideally, how) something the engineers are doing successfully actually works.
To validate the "science", you then test what the scientists came up with by taking their "why/how" explanation and doing some new engineering based on it. If the new engineering also works, the science is solid. If it fails, the science is wrong. In both cases though: the original approach is still successful for the engineers.
I wish we had an "I Fucking Love Engineering" crowd. Would solve a lot of problems with how people think about the world, and the advancement of knowledge in general.
Isn’t this precisely an injection of politicization into a summary of scientific work?
No, not really. What the criteria for starting/stopping treatment are (e.g. is it being given to early or late stage patients), what other treatments/drugs are also used, what dosage is used, etc can all effect this.
What's political about that?
The whole idea that if there were a simple and cheap cure that it would be politicized to the point where it won't see widespread application is ridiculous.
Then why does the title say that Hydroxychloroquine "probably" isn't the answer? It either works or it doesn't. If the drugs are ineffective just say so. Why beat around the bush with a "probably"?
From reading it, what the article actually supports is that we have seen two trials that are inconclusive. This is the meat of it in my view -
==
A French study of HCQ suggested that it had was effective in decreasing the viral load from nasal secretions. When azithromycin was added the magnitude of the effect was larger.
[...]
And a Chinese study of 30 patients doesn't prove that HCQ worked. Or that it doesn't. But the two groups, control and treated, showed no difference in the amount of virus in the throat on day seven, the length of time for the fever to go away. There was an apparent difference in the progression of the infection (determined by x-ray), in the two groups but this means little since 5/15 treated patients got worse vs. 7/15 in the control group. This effect could easily be by chance and nothing to do to the drug. Furthermore, this trial did not include azithromycin, so it cannot be compared to the French trial.
There's an almost perfect correlation between reaction to these drugs and Trump support.
[1] https://www.washingtontimes.com/news/2020/apr/2/hydroxychlor...
There are a couple of red flags about that article. No peer-reviewed (or otherwise) papers are mentioned and no clinical trials are discussed. The article does not even attempt to evaluate the truth of whether it's an effective therapy.
Even judged on its own terms, the article is a weak. After looking at that survey they're flogging, it'd be pretty interesting to hear from Spanish doctors, since that's where most of the enthusiasm seems to be coming from, but they don't even attempt to talk to anyone. Well... it's the Washington Times.
> of course I would want to take it
"Of course?" I hope you would at least consider the opinion of the physician treating you.
Sure. But if I was dying, "of course" I would want to try something with even anecdotal evidence of efficacy.
And because the question of whether or not this drug works, or even should be used at all, seems to have become highly politicized. I think I read that at least one US governor threatened to pull the medical license of any doctor that used it.
I don't have any idea whether this drug might be useful, but I think our most boring, apolitical scientists should be making that call. It could well end up that it sort of works, some of the time, perhaps in combination with other drugs or factors. Conceivably this will be solved the way AIDS ultimately was, slowly zeroing in on a set of treatments that mostly work.