You are commenting on an article that is nearly as apolitical as I can imagine one being to say that politicization of this topic makes it impossible to have a debate rooted in science.
Isn’t this precisely an injection of politicization into a summary of scientific work?
Exactly! On one hand some scientists swear by these drugs and on the other hand other scientists are opposing it. It is science after all. It either works or it doesn't. There is no "probably isn't the answer" in this. It is almost like Big Pharma is fighting out their battles through these scientists.
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.
Unfortunately, while the whole world doesn't stop at the borders of the USA, neither does the political bullshit eminating from it. All the claims about what's effective or ineffective as a solution to Covid-19 that politicians and journalists latch onto for political reasons leech out into the rest of the world and cause trouble there too.
"If there was any effect of this drug on COVID-19, it was minimal. Hydroxychloroquine, whose toxicity is far lower, may be safer than chloroquine. But that doesn't matter if the drugs are ineffective."
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"?
To me, the headline reads like it's saying "this probably won't work" rather than "we don't yet have enough evidence to say that this works." If I had to headline this article, I probably would have written something like "Hydroxychloroquine data still inconclusive, don't get your hopes up yet" to better convey the meaning.
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.
It's resistance to people who are clearly out of their lane. He is not a medical doctor, yet he's recommending people take it. It's unremarkable that he's incompetent to give this advice, because most people are incompetent to give such advice. I am incompetent to give such advice. What is remarkable is he clearly thinks he's competent to give such advice, and that it's appropriate for him to give it without any qualification whatsoever.
https://mobile.twitter.com/atrupar/status/124655621931107942...
A fair amount of doctors tend to believe it is promising [1]. If I was in the hospital, of course I would want to take it regardless of how anecdotal the evidence is.
> A fair amount of doctors tend to believe it is promising
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.
I'm not so sure. Let's say it halves the number of deaths or halves the time it takes for someone to get better. But also it requires a certain dose to be most effective. How would you know in this fog of war? You'd still have many patients who are sick or dying.
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.
Of course it is. People just have Trump Derangement Syndrome and it's clouding their judgment. Get over it. Or not. Hey, in fact, if not, just don't take it. One less libtard voter.
Prevent Senior in Brazil, an health operator with mosts of its patients on risk groups (60+ yo) are using hydroxychloroquine on all its COVID-19 patients with tremendous success.
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”.
Doctors and clinicians on front lines in NYC and greater NYC area say it's not helping at all, that they've by and large given up on using it.
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.
This is the confusing thing about hidroxychloroquine right now. Two people looking at the same data, one saying it’s helping and one saying it’s doing nothing.
Agreed, also Hydroxychloroquine cost only few cents per pill, its probably too hard to swallow for big labs that want to sell $$$$$ treatment instead ... Poor them ...
Collectively, we need to get over the idea of all-or-nothing solutions to Coronavirus.
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.
Double blind peer reviewed trials are a good goal but in the middle of a crisis you can't let a desire for perfection get in the way of the good. There is enough imperfect evidence that this treatment stack (that is, several drugs used in combination with hydroxychloroquine) has benefits that it should be considered a potential part of a solution. Waiting a couple of years for perfect studies to be carefully conducted is waiting until the crisis is over and the treatment moot. What is well known are the side effects of this drug, their likelyhood, and how to ameliorate them.
> There is enough imperfect evidence that this treatment stack [...] has benefits that it should be considered a potential part of a solution.
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.
> 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.
Not to diminish the possible successes, but without a randomized control trial, there is no way the success can reliably be attributed to the medications.
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.
It's simply a problem of what is considered to be evidence in the scientific community. If everyone "got cured by a miracle drug", that implies you already have the compelling evidence in hand that the drug, in fact, is a cure. This is an example of begging the question.
Again, this is the very thing that needs to be shown. You're simply repeating the same mistake.
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!
> Again, this is the very thing that needs to be shown. You're simply repeating the same mistake.
"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?
I hardly know where to start with this. Parachutes are not a cliche example of anything other than engineered products that are the result of well understood principles of physics, knowledge which was hardly arrived at by magical intuition. And medicine lags far far behind in the maturity of the science (my understanding as a layman).
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?
Yes! I want to be sure that this miracle drug is 100% to eliminate all the other drugs that has nasty side effects and have a lower effectivity.
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.
Note that some cancers kill you very fast and other kill you in a very long time, so you have a chance of die from another cause.
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.
Of course, this would apply especially to a drug that hasn't been in regular use for 60 plus years.
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?
So you have a cancer that normally has a 90% fatality rate after a year. Someone gives you evidence that they gave this drug to everyone with this cancer in their hospital, and 70/73 survived for a year. Not properly randomized, not properly controlled. Would you really reject their data and find it unconvincing?
If the results are so good it would be impressive. But it will be necessary to take a look at the data. Dollar to doughnuts they have a horrible methodological mistake, like a bad classification of the patients, or using a weird definition of cure [1], or cherrypicking the patients that get cured.
[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.)
Valid issues, but you can have all of those problems in a randomized controlled trial too. That's not a very compelling argument that the non-random poorly-controlled version is any worse in this hypothetical.
For example if the "usual" death rate is 90% and you select some group of patients for security reasons, like 18<=age<=60, perhaps the death rate is reduced to 80%. If the testing and control group is randomized, then if there is no effect of the drug you will get the same 80% in both groups. If the group is not randomized, you can't be sure that any of the selection criteria is the cause of the improvement.
You can look at the selection criteria and perform an analysis. If the data is clear enough, you can still pull a signal out of the noise. I assume that's the reason you took a 70/73 survival rate in the hypothetical I posed and reduced it to 20% in your version. And to be clear, in my version it's a general hospital and they give the treatment to everyone that has this diagnosis. There are no intentional selection criteria, it's mostly just who lives in the area.
> 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.
Unless you did such a trial, you cannot be sure it actually was the drug that helped. But if everyone gets cured, such a trial should be easy to set up. Unfortunately, things are not that easy in real life. There is no miracle drug.
But you already have a control which is a statistic called "survival rate after x years". If you beat it with a large enough treatment group, then you can prove it works.
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.
The Danish Serum Institute runs a “sentinel” testing programme for the common flu, and they note in their report about covid-19 last week (available in Danish) that the common flu has mostly been eliminated since the social distancing and lockdown measure were implemented. They interpret this a leading indicator for the reduction in covid-19 since it has a similar transmission mechanism.
There’s an interesting docuseries on Netflix that is partially about a team that is working on a permanent 1-shot flu vaccine: https://www.netflix.com/title/81026143
Isolation (physical distancing) would cause this. Flu doesn't have a long incubation, and doesn't survive as well (AFAICT, not a medic) outside bodies.
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).
I'm guessing it's because the organization has been praised by a number of well-known people on the right (e.g., Steve Forbes, Ben Carson).
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.
A proprietary drug whose maker has said they will donate all 1.5 million doses that they currently have. That's more than they'll be able to produce over the next year (1 million) even after greatly increasing that production capacity.
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).
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...
It also doesn't count for confounding factors. Were all the patients of the same health? Did they all have the same supportive equipment? Did they all begin treatment at the same time after symptom onset? These are all questions that need to be addressed, the sooner the better.
It doesn't. We have to make a decision with uncertainty unfortunately. However, I don't think any of those questions could explain an 8x difference apart from the time of treatment. In Marseille, they treat you immediately independently of the severity of symptoms.
Each of the 3005 had proper full care and were closely watched. We don't know about the 79160. The difference in mortality could be a number of factors.
It's the most heavily tested area of the world [0], and also the only place where everyone who is positive gets a treatment (hydroxychloroquine + azithromycine). Other protocols are listed here [1]
Regarding status, it seems the peak is being reached there [2]
1% is about expected at that point, since there is a 14 day lag on average and CFR can only go up over time after new cases trail off, it should end up higher. Look how South Korea eventually rose from .7% to 1.8% (somewhat biased by lots of young people infected early, but most of the rise at least from 1% to 1.8% was just due to the lags involved).
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.
It's a narrow viewpoint to only see it through the lens of death percentage.
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.
Sorry, I misunderstood this, I thought the data was Marseille vs the rest of France based on the wording, not one hospital in Marseille vs others in Marseille.
That's the most interesting rebuttal I've heard but I don't think it's true. Everything else being equal, you could estimate the stage of the epidemic by the number of cases per capita. The Marseille department, Bouches-du-Rhône, has 3% of the French population and about 4% of cases.
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.
You didn't finish the comparison for cases for capita.
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/)
“ There is absolutely no evidence that HCQ or HCQ/azithromycin would have any effect on seriously ill patients with viral pneumonia.”
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.
Yes, once they're on a vent, your main problem is not even the viral load, but rather that the body reacts to the infection in desperate ways like cytokine storm [0] which destroys organs.
I have G6PD deficiency and there are mixed opinions on whether this form of chloroquine is safe for me to take. The deficiency affects about 400M people worldwide, surprised to see that this part of the discussion rarely gets brought up.
> There is absolutely no evidence that HCQ or HCQ/azithromycin would have any effect on seriously ill patients with viral pneumonia
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).
114 comments
[ 0.20 ms ] story [ 185 ms ] threadIsn’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.
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.
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.
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.
https://www.mediterranee-infection.com/covid-19/
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.
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?
an innocent answer, of course, is that physical distancing works.
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).
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
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.
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).
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/)
Both ADAM17, which helps ACE2 shed from the cell, and ACE2 itself, are zinc finger proteins and use zinc as a cofactor.
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.
[0] https://en.wikipedia.org/wiki/Cytokine_release_syndrome
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...