> The proportion of patients that had negative PCR results in nasopharyngeal samples significantly differed between treated patients and controls at days 3-4-5 and 6 post-inclusion (Table 2). At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologicaly cured comparing with 12.5% in the control group (p= 0.001).
The effect size is huge, even considering the potential biases.
One of the issues with the study is that they didn't use the clinical outcome as an endpoint, they just measured the virus concentration in the throat (and even that not properly for all cases as far as this HN post says).
Huge effect size doesn't matter at all when the effect is not the correct one. There is a significant risk that this surrogate endpoint is not telling the true story as the virus migrates to the lung, measuring in the throat could be very misleading.
Is there a reason to believe the viral load in the throat and the lungs would not follow the same trend? And you also forget to mention this (CQ and HCQ concentrate in certain organs):
> It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection.
Yes, that's one aspect discussed in the podcast with Christian Drosten that is linked in the blog post. This is the relevant part:
> We have a lot of experience. We have made the most precise description of an untreated patient cohort among the Munich patients. And at the Munich group, we saw how the virus concentration in both the throat and lungs behaved over time. And we can say that at the beginning of the disease the virus is in the throat and it goes away on its own through the - let's say - the first ten days of the disease. After that, many patients in the throat have little or only irregular evidence of the virus.
But that has nothing to do with how the virus behaves in the lungs. The virus is then really replicative in the lungs, especially in severe cases. And we can also say what the patient has in his throat, it has nothing to do with how the clinical development of the disease continues, whether the patient quickly gets well or only goes through a difficult phase. So what is being measured in this entire clinical study has nothing to do with the outcome of the disease, with the symptoms, but is only an initial indicator of how the disease starts. For all patients, the virus concentration drops in the first week, but if you now imagine that the group being treated will be included a little later and the untreated group being included earlier in this study, it is in nature the thing that with this group that was later included - they are already further in eliminating the virus from the throat - that the virus then goes down in the throat, faster. This disappears faster because they have simply been in the course of the disease for a long time. Whether this is due to the fact that they are treated, cannot be said at all from this entire study. Perhaps it would have been so if the groups had been put together as here, but if they hadn't given them chloroquine, but some headache pill, the study would have been the same.
Reducing viral load in the throat would make it less contagious though? In that case, wouldn't it be suitable to use for patients that are likely infected but don't need hospital treatment to reduce chances they'll infect others while quarantined?
Now here's the thing. Anyone with a basic understanding of probabilities could understand how to fake a study by doing just that. If I measure enough potentially interesting points over a small group of individuals, I will quite likely get at least one interesting correlation (aka, "drinking one glass of vodka a day helps to lose weight!"). But did anyone of the critics of that study ever try to do a follow-up? Did a single science journalist call the group and ask them about that study? How many measurements did they make? How did they actually chose the patients? Did these patients actually recover?
Funny how the super-rational HN crowd throws science out the window as soon as it starts to actually matter. I guess there really are no atheists in foxholes, nor statisticians in a pandemic.
The authors of this study excluded one patient from the study because they died, and several other because they were admitted to ICU.
Assuming the dead patient did not get run over by a car, not considering death as relevant information for your study seems... bold.
They switched outcomes from what they pre-registered.
They did not even measure viral load, their primary outcome, in the control group. They looked at the patient and went like “she’s really sick, that’s a 23 at least”.
This, and the other problems mentioned, make this study suspect. And at the point where actual fraud is a possibility, the top line numbers stop being meaningful.
So in that sense your comment is like my Grandmother’s insistence on Pascal’s wager: “I know there’s no God, but paradise sound too good not to try”
The HN crowd is not super-rational. For the most part, they are smart people with a contrarian bent, which is very dangerous when combined with topics outside of the area of their expertise. We’ve got a lot of armchair epidemiologists and doctors in these threads.
The problem with Pascal's wager (finite loss/infinite win) is that we can't calculate the probability of the existence of a God. If it is infinitesimally small, then there is no paradox.
By the same logic, you must stop eating carrots if I tell you that doing so will be infinitely rewarded after you die.
The control group is not randomized, and most of it was in others hospitals, so it's not clear that they have the same treatment and some prognosis.
They are not counting the 6 patients that they lost in the treatment group (1 just leave, 1 had too much nausea, 3 where transfer to ICU, 1 died). It is more strange that they didn't lost any patient in the control group.
In addition, what about long term effects? Curing someone now, and giving them a stroke six months later is not exactly desirable. That's why drug trials last for such a long time.
There's always possibility of interaction of a the drugs effects with disease state to cause new side effects. It may not be likely, but there's always a chance, which is why it would be monitored for as usage of a drug grows.
There's a likelihood of interaction in this case as they both have side effects on the heart. It should probably be monitored carefully in hospital this case.
As I understand it, this drug is used daily by people with conditions such as lupus so there’s some knowledge about long term effects at a given dosage.
The dosage rates are about the same as other use-cases and within safe boundaries.
Toxicity is typically tied to dosage rates or drug interactions. The bigger concern from the french study was the additional use of Azithromycin which is more dangerous/toxic. The dosage rates and toxicity of HCQ by itself is well known.
The other big risk is panicky people ignoring the recommended guidelines. Fortunately in the US (and Canada) both drugs require a prescription where both a doctor and pharmacist will provide this information, and it will be printed on the pillcase. What's more worrying is people buying it in countries where it's over the counter then not reading the side of the box and taking far too much (or worse reading the correct dose and thinking 2x the drug = 2x more effective or some nonsense).
It's (used to be?) a prophylactic for malaria. Literally billions of people took it. I did it myself when I was living in malarial areas. It does have secondary effect but they're very well-known and for most people the only ill effect is that it tastes incredibly foul.
It is a great question. As I understand it, we know a lot more about the long term effects of Hydroxychloroquine than we do about the long term effects of covid19.
You can't assume the top line effect size is real without critiquing the study design in detail. A lot of experienced drug developer think the data suggests that HCQ may be marginally effective, but Azt + HCQ seems promising. THere are others who are more skepticl
HCQ is already the recommended treatment for certain cases in many countries, including the US. Here is a super interesting conference call from UCSF: https://youtu.be/bt-BzEve46Y?t=3194
because nothing is known to work yet for covid-19, doctors are doing the best they can with limited data. this means using unproven drugs for which, to the best of our knowledge, the risk-beneift is favorable. HCQ for covid-19 is an exampel of this: we dont know if it works, but it might, and it seems safe enough
the goal of studies like this are to strengthen the evidence base and remove those unknowns, so physicians can make evidence-based decisions. if the study is sufficiently poorly designed, it does not accomplish this goal, and can even lead to misinformation
"we are not talking about some marginal level of efficacy here:"
Your above-statement, and then the quote suggests you have no idea how this actually works in the real world. The reality is that NO-ONE KNOWS whether there is great efficacy, no efficacy, or marginal efficacy. No one. And we will not until we have a properly designed trial. That link direct us to is horrifyingly badly designed (well, not designed at all). There are all sorts of confounding issues in their results.
> With my team, we believe we have found a cure. And in terms of medical ethics, I believe that I have no right as a doctor not to use the only treatment that has so far proven successful. I am convinced that in the end everyone will use this treatment. It's just a matter of time before people agree to eat their hats and say, this is the thing to do.
And in the Irish times:
>“In my field, I am a star, worldwide,” he boasted to La Provence newspaper.
Ugh. PCR can have false negatives, but in a clinical setting they can do this really crazy thing called "looking at the patient" or "asking them how they feel." So, if they were clearly sick, as they would be before getting to the hospital and into Chloroquine treatment, and they got qualitatively better, that is a good indication that the PCR result is correct.
It's difficult to due true double blind random studies in these cases because doctors are there to give everyone the best chance at recovery, not to pick half of a group to potentially do worse.
Hopefully we can ethically do well design studies on controlled groups with moderate symptoms, but until then this imperfect clinical data is very interesting.
If you're just looking at them to see if they got better you don't need an expensive test that has a 40% false negative rate.
But that's not what these doctors were doing, is it? They weren't looking at whether the patient got better or not. They were looking at viral load only.
Why are we so excited about the French trial? What about the Chinese treatment guidelines [0]?
The Chinese recommend chloroquine phosphate. They've had more experience than anyone else in this area and have had time to conduct actual trials. The disease has a ~2-4 week course so it should take about that long to gather compelling evidence; and they've been dealing with it since January.
The French are clever people, but we really should be looking to Asia for this information. People should be finding and quoting Chinese studies.
Another anti-malaria drug, methylene blue had been proven to work against coronavirus in blood plasma in 2005 [1].
It is used in photodynamic therapy to selectively kill some viruses (see below) / bacteria (e.g. mycoplasma) [2].
When entering the bloodstream, it binds selectively to the nucleus of the viruses it is effective against. It's the same mechanism why it's effective as a dye to stain microbes under microscope. Methylene blue best absorbs light at 660nm wavelength, which at the same time penetrates into human tissues deeply. When light is absorbed, methylene blue disintegrates to harmless molecules while releasing reactive oxygene species, killing the virus.
It is a very safe drug, so the same logic that bsaul mentioned could be applied, and therefore would be a responsible move. It is also beneficial to mitochondria and effective against fungus.
it also literally turns your bodily emissions blue, needs to be administered intravenously, and has some ugly side effects:
Common side effects include headache, vomiting, confusion, shortness of breath, and high blood pressure.[1] Other side effects include serotonin syndrome, red blood cell breakdown, and allergic reactions.[1] Use often turns the urine, sweat, and stool blue to green in color.[3]
The numerous* stories that I have read recently about medical professionals writing themselves prescriptions for hydroxychloroquine so that they can have it available for themselves and their families suggests to me that the French trial is not the only reason to be hopeful about hydroxychloroquine's efficacy against COVID-19.
Sure, medical professionals are not necessarily any kind of super-rational savants, but I think it's unlikely that all of the medical professionals who are trying to hoard hydroxychloroquine are being irrational hysterics. They might be engaging in ethically questionable acts by hoarding hydroxychloroquine, but that doesn't mean that they don't know what they're doing from a self-preservation standpoint.
That said, it's not that I think they are necessarily trying to hoard hydroxychloroquine because they are convinced that it works - it's probably more that they want it on hand in case it turns out that it works. However, some of them may also have directly seen it help people, or may have heard or read about it helping.
Given that hydroxychloroquine has already been used for, as I understand it, weeks in treating people ill with COVID-19, I am actually surprised that there is not more anecdotal evidence about its efficacy. But I probably have just not been reading in the right places.
*Edit: I probably shouldn't have said "numerous stories", since "numerous" implies more than the number that I actually have seen.
The vast majority of medical professionals are not researchers, and are not trained in evaluating clinical trial data. They are notoriously poor at assessing such information.
You can be a remarkable clinician without ever interacting with the primary literature. These are simply different things.
> The vast majority of medical professionals are not researchers, and are not trained in evaluating clinical trial data. They are notoriously poor at assessing such information.
Citation, please. This is a very strong statement.
As someone who works in drug development, this is very accurate.
Understanding, designing and executing clinical trials is an entire specialty within medicine. Your average doctor will be familiar with the concepts, but not necessarily adept at evaluating a clinical trial.
> The vast majority of software professionals are not researchers, and are not trained in evaluating computer science research. They are notoriously poor at assessing such information.
You absolutely cannot be a remarkable clinician without engaging primary literature. Not sure where that claim comes from. Physicians need to know how to interpret and criticize findings from clinical trials to incorporate into their practice and communicate with patients. Plenty get away without doing that, but they are not counted among the best of us.
Recently I learned you can be a doctor without getting a baccalaureate.
It may not still be a thing, but I happened to run across the factoid while reading the wikipedia page of a middle-aged and famous doctor that just got the coronavirus.
I feel like they'd start doing that even if they thought the chances were ~10% of it working. Its relatively inexpensive and they know its availability would drop dramatically as soon as more data is available.
> The numerous* stories that I have read recently about medical professionals writing themselves prescriptions for hydroxychloroquine
A doctor friend of mine showed me a Facebook group consisting entirely of prepper medical professionals trying to decide whether or not to buy guns (in Australia!) for self-defense.
Medical school tends to select for a personality type that is, shall we say, somewhat obsessive?
The doctors are likely doing the intelligent thing, not necessarily hoarding. They should know that antivirals tend to work only at disease onset or as preventives. The production of these drugs can be ramped up very quickly so the amount these doctors took from the supply should be immaterial - esp. in the US where testing is limited to later stage patients when antivirals are less likely to help.
I see many problems with all the caution around that study:
1/ chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of.
2/ we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare.
3/ people are oversaturating ICU right now. And as such, it is an emergency situation. We should take the reverse reasoning we usually take : if there's no suscipicion this drug could cause new problems, we should have people massively use it whenever possible and look at the result after 6 days (since that's the time the original study says it takes for the first results to show).
> 3/ people are oversaturating ICU right now. And as such, it is an emergency situation.
From what I can gather chloroquine is already used as a first line treatment in Italian hospitals (at least it is indicated as such by the COVID treatment guidelines published by the society of Italian infectious disease specialists [0], and has been for quite some time - this document is from 10 days ago, but an earlier revision was not different regarding chloroquine). If this is the case, it's pretty clear that this is no miracle cure - it has at best a marginal effect.
The number of patients already overwhelmed the healthcare system.
Per some interview with some Chinese doctors who battled COVID19, they said that for many critical patients, their viral load is actually low, but the virus had caused damages to all parts of their bodies thus antiviral isn't going to do anything significant at that stage.
This might suggest chloroquine could be helpful at earlier stage of COVID19, to help prevent patients developing into server/critical stage, which would still be a very good thing if hold true.
It might be, we don't know how the Italian system would cope without it. Due to increasing but low test numbers, we don't know how many infected patients there are in Italy. The situation in some hospitals is severe, but it has been for ~2 weeks.
I believe with the number of patients they have, they would've updated the guideline if it wasn't effective at all. But how effective it is we don't know. If a large percentage of some areas is already infected but the health system is still in the state it's in now, it could actually be a good sign. If the current numbers are realistic (which I don't believe at a positive test rate of >30%), it's probably not. We simply cannot know.
Thanks for this reference, it seems they are proposing 2 potential treatments (p. 13) for the more severe patients
> Il trattamento deve essere accompagnato da trattamento antivirale (lopinavir/ritonavir o remdesivir + clorochina/idrossiclorochina) e/o steorideo (desametasone)
This is from the 13th of March so I guess there will be still some days until we see results of this (either positive or negative)
For the record since that decision day, the growth rate in the number of deaths in Italy has fallen in half[1]. In the 9 days from March 13 to March 22 the daily number of deaths grew 160% from 250 to 651. Prior to that, the same level of growth occurred in 4 days between March 9 (96 deaths) to March 13.
That seems like pretty strong evidence that the new treatment protocol is drastically decelerating the pandemic in Italy.
This does not make much sense to me. If it was effective, it should decrease the lethality rate, not the growth in the number of deaths which is much more affected by the actual number of cases. In the page you link you can see that lethality rate has not fallen. Also, as I wrote I'm pretty sure that I saw an earlier version of that document, dating IIRC to the beginning of the month, that prescribed more or less the same combination of chloroquine and antivirals as a first line treatment.
I have no clue how much it is actually used, couldn't find any info and fortunately I don't have any direct experience yet. If it is used, the lethality rate in Italian hospital definitely show it's not incredibly effective, at least in the way they are using it.
> we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare.
This is very wrong; we have good aggregate statistics across lots of different hospitals, but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect.
This is doubly true as health care varies as sites get overwhelmed, and healthcare workers get increasingly strained from long shifts. There will be far more variability as time goes on.
And for how small we expect the effect to be, based on the data in the paper, we really should include controls.
All that said, I think that the publication of this flawed study is very good, and why pop-science takes that excoriate science as "most research finding are false" really communicate the wrong way to think about science, and limit its applicability. Flawed datasets like this still give us clues, and publishing flawed data is still useful to others to accelerate the pace of science. Which is why we need to take the attitude that publications are point in time guesses at what's going on, and only rarely does one come out that can be considered on its own as definitive, and that it's good to have mostly "here's some data and analysis but we don't have a complete theory yet"-type-papers. Without those intermediate publications, science would grind to a halt.
> but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect.
The simple solution is to spread it over enough sites so that the law of large numbers quantifies that variability into the dataset. For example if we run trials over 10 hospitals in 20 different states, 200 sites in the dataset would almost certainly capture inter-site variance.
That only normalizes natural variances in your patients, not artificial biases introduced by the healthcare system. Pump and other hardware measuring out dosages might come from different manufacturers or be calibrated and serviced by different technicians. Maybe the study includes one too many hospitals in a region dominated by one manufacturer whose hardware tends to error more in one direction than other manufacturers. The generics used by pharmacies and hospitals might be slightly different because of local relationships. Exercise, ability to have visitation in quarantine, and other amenities in hospitals will have differing impacts on confounding factors like exercise and morale. And on and on.
There are a bunch of "contract research organizations" all over the world, quite a few of them making billions of dollars a year, who specialize only in running clinical trials because these things are so complicated. The documentation for clinical trials are often thousands of pages long describing tiny details like device calibration across hospitals trying to eliminate as many risks as possible. These organizations tend to have long standing relationships with hospitals and host many different trials in each one with a bunch more subcontractors who do patient selection.
As I said, drugs just have effects. Humans then look at the results, decide which are good and bad, and then label the bad ones "side effect". So I think the real question is: why do you think 100% of the novel effects will be later put in the "good" bucket?
Opinions like this seem to be popular these days, but they're dangerous. Because this is an emergency we want reliable information.
Think about it like this: If these researchers had done a proper trial - and there's absolutely no reason to think that they couldn't have done that in the same amount of time with the same amount of effort - then we'd actually know something useful now. With that trial - we don't.
Agreed, this kind of thinking comes from fear and desperation (and another kind is denial of reality - this can't be happening so it isn't. My neighbours still don't realise it's actually happening).
If we want to deal with covid we should have started years ago. As ever, we didn't.
They are in a war zone in Italy and presumably in the US very soon. If hydroxychloroquine is safe (except for some people with a known predisposed genetic condition), then we should be giving it widely and early. We can worry about the science and studies later on, but right now we need to save lives and decrease ICU overload.
> chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of.
I mean, you could say the same of practically any older drug. It's a fairly well-understood, cheap, somewhat dangerous drug.
> we do have a lot of statistics now on the outcome of patient not treated with that drug.
Sure. We also have a lot of statistics on the outcome of patients not treated with thalidomide, and morphine, and basically any other cheap somewhat dangerous drug you care to mention.
> if there's no suscipicion this drug could cause new problems
While I don't think there are, there's the certainty that it will cause the usual old problems that this drug causes. Which you probably don't want when you also have covid-19.
We know the side effects for a healthy individual or those with malaria, but how do we know for certain this won't cause new problems in those with COVID-19?
This is irresponsible. This drug has severe side effects, it makes absolutely no sense to prescribe it for a completely different disease without first confirming in clinical trials that it has positive effects.
> if there's no suscipicion this drug could cause new problems, we should have people massively use it
That's not how evidence-based medicine works. The drug is known to cause new problems because of the side effects. Clinical trials are needed to determine whether these are outweighed in patients by positive health effects.
You do not prescribe medicine on the basis of hunches.
> This is irresponsible. This drug has severe side effects
What are you talking about? The severe side effects are known and are usually associated with chronic usage of that drug. Chloroquine is taken for prophylaxis against malaria (daily) in many places in the southern hemisphere. Usual regimen is at least for 8 continuous weeks!
The suggestion on the table is to give this drug to extremely ill patients who suffer from a new viral disease on the basis of anecdotal evidence and without clinical trials. The suggestion was to massively prescribe it.
What health authorities want to do is to allow physicians to use the drug if the patient agrees, but only in a controlled setting in which data is collected and there is a control group. So at least afterwards we could draw conclusions about whether it killed more people or helped saving people. Does that not make sense to you?
There are actually several suggestions, which were repeatedly discussed a decade ago in multiple SARS studies (see my post below).
First is prophylaxis for front line health care workers, who are suffering grave infections likely exacerbated by long hours and low morale. Long term use of chloroquine or alternatives is a concern for this audience. There were fatalities last time, just like this time.
The second is for the patients themselves, who will otherwise endure uncontrolled viral replication for up to two weeks until the adaptive immune response recognizes the pathogen. Reducing transmission requires an earlier end to this stage.
Is the data from the previous studies worthless for these goals?
I feel like this thread and the arguments contained in it are a microcosm of what's going on in the world at large right now, and also explains why people were so slow to respond. Perfect is the enemy of good, after all.
In medicine, bad is the enemy of good. Improperly studied medicine rushed into a clinical setting can make things worse and are perfectly capable of making things worse on a grand scale, regardless of how terrible people's understanding of statistics and variance are.
Doctors have the authority in many countries to prescribe it off label based on their own review of the evidence and their patient's consent. That's the best we can do right now without risking something much worse.
As noted in the original post you replied to we don't really need a control group because we already have a lot of experience with people who didn't get any drugs. Quoting that post: "all that is needed is a proper categorization".
The goal here is to get enough evidence the treatment works or doesn't work. Conducting double blind studies is not the most efficient and fastest way to do that when you already have a lot of preexisting knowledge about both the patients not receiving any drugs and the safety profile of the drug in question.
This is again a situation where statisticians should be asked for help as medical professionals very often operate on very simplistic model (double blind or gtfo) which we just don't have time for this time around.
It does, but why can't one can have the control groups at the same as blanket prescribtion? In times like this when the health care apparatus is overwhelmed, is it a good alternative to do that, since side effects are well-known and given the fact that the drug might be ineffective if used late in the infection cycle [0]?
i absolutely don't see the need for a control group. We just need to monitor which patient had the treament and which didn't, globally. But if a doctor wants to prescribe all its patient with it, he should be allowed to, as long as it doesn't go against the traditional counter-indication for this very well known and very widely used on a global scale drug.
> We just need to monitor which patient had the treament and which didn't, globally
And you just described the reason for a control group. We simply do not have that information. Things are moving too fast and treatments have not been standardized yet, not to mention the built in variability between locations. If you want to know if a treatment is effective, you must have to comparable groups. The point of the control group is to gather that information. Just because there are many, many, global cases doesn’t mean you actually have been able to capture the data for a control. Things are moving that fast.
> But if a doctor wants to prescribe all its patient with it, he should be allowed to
And what about the supply of these drugs? There are people who do need these drugs for other conditions (I’ve read Lupus patients sometimes need it). These patients need the drug and the supply is getting scooped up by people who don’t know (a) if they have the virus and (b) if the treatment is effective. And if it is effective, is it effective for treatment of infection or prophylactically? Just because a drug is widely used does not mean that there is enough supply to distribute it to anyone who wants to try it.
These are major issues that can be answered with proper clinical trials. We know how to do this and they can (and are) being done as fast as possible.
I saw a retweet the other day by a Lupus patient who couldn't get their prescription refilled. That's going to make a crappy situation much worse for a whole class of people.
That is a fallacy right there, discredit the source of the argument instead of the argument itself. People should have the right to discuss things openly, even without credentials. They should not, however, actively act upon it causing actual harm. This is the realm of the specialists. As long as we have these distinctions, let people discuss.
Trouble is opinions can take on a life of their own. Not everyone is sensible enough to read opinions as just that. A lot of these articles are written with a tone of authority; espessially the ones from data scienctists. Discussion is fine, but bear in mind that its adding to a lot of unecessary noise.
You imply there is a necessary noise in the conversation. Who are we to define what credentials should be used to define what is noisy and what is not? I think the best way is to attack the argument itself, not where it is coming from.
If the discourse become authoritative and biased, we shut it, disregard it pointing out the flaws. But we have to be careful not to be authoritative ourselves when we don't even give the chance for the writer to be wrong because he lacks the right credentials.
Easy, in a pandemic like this only listen to medical professionals. Like I said, the time for amateur to examine and draw conclusions is after the pandemic is over.
I guess I should have articulated an argument instead of venting and using sarcasm.
Basically, I've seen my share of unqualified people (not that I'm qualified myself) building ridiculous models of exponential growth and predicting catastrophes, commenting on drug research protocols without necessarily understanding the details and so on.
What's the point of pollution the conversation with useless ill informed fake-authoritative opinions that no one should act upon? This isn't "I tried Python and had a lot of problems with dynamic types", it's uninformed specualtion on an arbitrary sample of information the they haven't trained to understand.
then use that against the argument. Break it for what it is not worth, but don't attack the person itself and the right to free speech. Where would you draw the line for defining what is polluting the conversation and what is not? Can you see the danger there? This trend of checking someones credentials before hearing the argument can become elitist real fast. Careful to not become the censorship we condemn
The problem is even for hydroxychloroquine the most at risk patients for serious COVID-19 illness (People with Diabetes and Heart issues) are under the well established precautions in using the hydroxychloroquine. To build publics faith in the idea that one medication is going to really come through is haphazard at best.
> You do not prescribe medicine on the basis of hunches.
Nor on the basis of panic; we should be able to manage this pandemic as long as people stick to the measures in place. Stay at home, limit your shopping, don't take the piss. I mean panic right now is causing more problems - e.g. hoarding and people trying to make a quick buck.
This thing is mainly a big problem because people can't keep calm and rational. Or they think they're rational, as in, "I should buy enough toilet paper because I should stay indoors for a while".
How long is a while? What happens if our supply chain is impacted? Grocery stores are open now, but isn't it possible for there to be outbreaks in the stores? What will become of the economy if this continues?
These are very real concerns for which no one has answers. People are stockpiling because of the uncertainty, which could be seen as a very rational stance in hindsight if this goes on for quite some time.
Hydroxycholoquine is very safe and is prescribed to lupus patients daily. The Korean recommended dose (400mg/day) is the same as what is prescribed to lupus patients. Chloroquine is a bit more dangerous, but only in high doses and over long periods of time. Patients would be on either for 10-20 days maximum which is much less than what it takes to be dangerous.
I'm not sure if any of what you wrote is accurate.
The drug is 90 years old, has been used by millions, has relatively modest side effects, is relatively well-understood, has shown efficacy against coronavirus in vitro.
Yes--in plain English, the trade-offs are different in different places. It's not a recreational drug so there is (usually) little risk it will get taken or abused unless it is really needed. That does not mean the drug has no risks and can be taken as a free-for-all.
And it's not just for drugs. It's also why DDT continues used in some countries but is illegal in others.
Exactly. Since the risks and side-effects are well-established, it’s more ethical at this point to experiment on humans with an “off label” usage. Doctors do that all the time with other meds.
Yes, doctors should experiment with the drug and I am certain, a lot of those, who have the necessary conditions to perform a proper experiment, will do.
What should not happen now is, that the general public starts taking the drug as a precaution, just because it might work. The known side-effects are too severe (e.g. blindness) and also, there are already shortages of the drug for those who already require it as part of their medical treatment (e.g. immune-supressed).
"Risk for toxicity is less with <5.0 mg/kg real weight/day for hydroxychloroquine and <2.3 mg/kg real weight/day for chloroquine[2]. Patients are at low risk during the first 5 years of treatment."
And management is as simple as stopping the drug if it starts affecting your vision:
"At the first signs of retinal toxicity, hydroxychloroquine should be stopped to prevent further retinal damage and visual loss[2]. "
I'd note that the phrase "further retinal damage and visual loss" implies that retinal damage and visual loss has already occurred... how much of that you are willing to tolerate is up to you, I suppose: I'd prefer 0 unless necessary. If the retinal damage is saving me from a death at the hands of COVID-19 maybe it's worth it, but if it's not...
Did you just read the list of side-effects without checking how often they happen? With that mindset any over the counter medicine will read like description of Zyklon B.
Being sick with a disease like Covid-19 could absolutely alter how a medication works on a person. The drug might be safe to a person with a certain profile and it has been tested against those, but each underlying issue is a new profile which it should be tested against as separately as possible.
Based on that reasoning, we shouldn't give any pharmaceuticals to coronavirus patients. Even simple fever relievers, like acetaminophen, or oral rehydration fluids should be prohibited because we just don't have enough data to know how they'll interact with COVID-19 specifically.
I think this is the fairest counter-argument I've heard so far about safety of HCQ in Covid-19. I still think the background of "you're in a house burning down, some tests tentatively indicate this may be effective..." weigh more against the risk of side-effects or worse progression due to CQ/HCQ. We ought to be able to devise some experiments to add certainty, using mainly retrospective data now available.
Most SLE/Lupus patients take HCQ, and reportedly none in the cohort of the doctor I know have sufficiently severe symptoms to qualify for pCR testing to even establish if they have Covid19. This is Spain with (currently) 708 cases per MM. Of course, caveats like absence of evidence is not (necessarily sufficient) evidence of absence. It may be that SLE or other immuno-modulation treatments have some effect - someone should do analysis with matched non-SLE HCQ and non-HCQ prophylaxis cohorts. But back to my main point with the house burning metaphor for exponential infection - the risk landscape demands we take more risk, give HCQ widely instead of waiting for the conclusion of prospective studies. We can withdraw it if it is shown to be no better than placebo or worsens outcomes when enough data is available to conclude.
2) It complicates the treatment of the patients who will experience the worst cases of COVID-19 causing panic... people above 65 with diabetes and heart conditions.
3) Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19
Having Grandpa John walk in for COVID-19 and roll out for death by QT elongation is not something the public will have to litigate.
> Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19
Except those precautions are at least two orders of magnitude less than the case fatality rate for coronavirus infection.
Equivalently, there are scenarios where a seatbelt can decapitate you or trap you in a drowning car. But you'd still be a fool to drive without one, because buckling is a thousand times more likely to save you than kill you.
The most serious cases of COVID-19 affect all the people who have the underlying conditions that have precautions listed using H-Chloroquine.
That makes the normal ICU case of COVID-19 more difficult (time consuming) to manage because now you have to spend time managing / monitoring: The condition, COVID-19, the side effects of H-Chloroquine on vital body systems already impaired, already being attacked by COVID.
Throw the magnitude two out the window like a lucky car crash victim while these patients suffer the crash in the hospital. Not even Bernie was going to pay for the specialty concierge care needed to manage such a patient and yet you some how assume that is how it works.
It isn't vitamin C. It has a lot of side effects, including serious psychiatric ones in limited cases. If you give it to 100 people you're going to get new health issues that you didn't have before in that population.
You cannot pour a drug into the populace that will cause side effects on a mass scale that might also overwhelm the healthcare system. It is nice to imagine we have the medicine already, that we can simply wave our hands distribute the pills and everything can go on as it was before this. But we do not and can not go back.
> There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare.
This is very difficult to do. In this study all the patients in the treatment group are from a hospital and most of the patients in the other hospital are from other hospital. Do the population of both hospitals have the same median income? Usually a low income cause a bad diet that may cause bad health that has a worse prognosis.
Are the patients in the other countries classified by income? Does the difference in income cause more/less consumption of milk? Bottled milk has an additional amount of vitamin D, and some unconfirmed reports say that the lack of vitamin D is bad for covid19. Does this difference depend on the country? For historical/genetic reason, French drink more milk that Chinese. What about wine, is the consumption of wine important?
What is the effect of temperature and humidity in the no-hydroxychloroquine group? The average climate conditions change from country to country and from place to place and from month to month.
To be included in the testing group the patient must give consent. Probably they have not to be too wasted to be able to read it. Probably not been to wasted is a good sign.
There are a lot of factors, and not all of them are known, not all of them are easy to measure, not all of them are measured. So you need a control group.
Many doctors are already actively prescrbign this. I heard that it is basically de facto standard of care in France. Doctors recognize that when eveidence based medicine doesn't provide an adequate treatment, they need to improvise. Off-label prescribing is very common
The point of these studies is to help the evidence catch up to improvised clinical practice. If the studies are poorly designed, that goal is not achieved
It is being used in several countries already (US and Europe, not sure about Asia). If you are interested in details, here is a video of a conference call at UCSF:
This is not some crazy experimental new drug that was unknown until past week. It's an experimental treatment, it's not an experimental drug, with unknown side effects. For a condition where time is critical.
Of course, we should also be quick to discard unpromising drugs, and not only focus on one promising drug.
In particular, if it turns out to reduce infection rate, taking it prophylactically will save the lives of everyone who would otherwise die for lack of a ventilator, or who would die even with one. If it does not turn out to reduce infection rate, no harm done.
If it turns out to shorten the illness, everyone sick, and also everyone taking it prophylactically who is actually infected but asymptomatic, will reduce their contagion rate by joining the ranks of the non-contagious sooner, reducing everyone's risk. If it does not turn out to shorten the illness, no harm done.
Chloroquine is well-known. If it caused an unacceptable rate of liver failure we would already know.
I see suggestions that it takes a very high doses to work. But that might be so only for the already severe infections they are using it on. It should be easy enough to discover whether low doses work prophylactically, and safe enough to try them while waiting on results.
Yeah, it's important to have it available if it's needed and it's important to conduct at least some sort of trial. Because the drug, combined with azithromycin is so fast acting, we should see the first results in a few days. Worst thing that can happen is it doesn't work. Best thing that can happen is we can save 1.8 trillion dollars and restart the economy. Under these circumstances one would be an idiot not to give it a try.
Coughing your lungs out but feel like CNN is not lying to you? Easy! Refuse the drug. Nobody can force you to take it.
Worst thing that can happen with a chloroquine and azithromycin combination is that it causes heart arrhythmia and sudden death in a patient that would not have otherwise died.
Studies of patients taking this combination of meds include daily EKGs, which is something the general population at home isn't going to have access to.
That's why they are starting with a trial, and not a full scale roll out. Other countries are using this combination of drug, and it's not because they're huge fans of Trump, I can assure you. We also have literally millions of devices out there capable of detecting arrhythmia - they're called Apple Watch.
That's like saying construction N95 masks can't be used in the medical setting just because they lack appropriate certification. That old shibboleth has been defenestrated weeks ago.
I bet it can, if FDA is beat over the head with a shovel, which it will be if the need arises. It's a real ECG verifiably capable of detecting irregular hearth rhythm, and it costs a tiny fraction of what a big-ass ECG machine would, and therefore can be deployed at a much larger scale. Just because it could only get approval to detect atrial fibrillation duing "peacetime" doesn't mean it can't be pressed into service for other things.
I have 0 clues about clinical trials and the procedures. My questions is: Why are so few studies done on this?
I think so far we have 2 studies. (from China and France).
However, we've had hundreds of hospitals around the world with thousands of patients. And the drug is cheaply available.
What is preventing us to have studies around this in tens of different hospitals? Wouldn't WHO be able to budget this, or actually send people to conduct these studies all across the globe and report back day to day, so within 2 weeks we get a pretty significant set of data?
This drug has actually been mentioned in several past clinical studies on the closely-related SARS. The particular study below has been circulating in several areas online, and has citations to several more:
Despite the role of the pH-sensitive endosomal protease cathepsin L in the entry pathway (151, 300), viral culture does not require pretreatment with trypsin. However, this pH-sensitive cathepsin L may be a target for agents such as chloroquine, which elevates endosomal pH (174, 341).
The chemical pathway that allows the virus to enter the cell changes based on the pH of the cell. Chloroquine changes the pH of that pathway and therefore may slow/stop the entry of the virus into the cell.
I guess it could be time shortage? You need to bring researchers and doctors together, doctors need to increase documentation on treatment at a time where they are already over capacity, studies need to be approved by regulators and ethic boards etc. The system is not designed to start massive amounts of studies within a week and I'm not sure how much of the red tape can be cut without endangering lives.
It seems this man was treated with lopinavir–ritonavir ... Unfortunately according to this recently published study, it seems inefficient against Covid19.
I found this "Some centers and even national guidelines, such as those in Italy, have recommended treatment with lopinavir-ritonavir for patients with COVID-19 infection."
Not sure what to make of this. Can this to some extent explain the huge differences in death rate between Italy and Germany?
> Can this to some extent explain the huge differences in death rate between Italy and Germany?
Italy has a couple severe disadvantages compared to Germany:
- since the financial crisis young ppl are forced to live with their parents and often enough grandparents in cramped conditions due to exploded rents - which means that symptomless infected can spread coronavirus in their families
- Italy's healthcare system has been wrecked by forced austerity after the financial crisis - it's exactly what everyone warned of back at the time.
- many young nurses and other medical staff have fled to Germany and other countries for better pay
As far as the netherlands are concerned, Lopinavir is now removed from their interim guidelines. The first line treatement is now hydroxichloroquine/chloroquine with maybe remdesivir for severe cases.
I like facts. Article says only French study exists but at least a couple of other studies exist from China. I wish when someone makes a very important argument to check all internet sources.
This is the kind of idiocy that pie-in-the-sky theatrical crap like this causes. People are going to end up seriously harming if not killing themselves by taking this stuff.
Regarding randomization, the HCQ + Azithromycin study showed good results despite the control group being 14 years younger. Sex was about equal so no male/female imbalance. It’s clear that older patients have worse outcomes, but this study measures viral load which also can change depending on the stage of the disease.
There were 6 patients in that group. No mention of how they were selected. Some patients dropped out of the treatment group because they died or went to the ICU. These could affect the numbers significantly.
Yes it seems they have 100 on one dosage, 100 one a different dosage and 100 in a placebo group.
According to the register, the study execution time should be "2020-01-31 To 2020-02-29"
But nobody seems to have any insight on the final results. But I would recommend this article with comments of the study leader (Dr Zhang Zhan). The article also explains how they initially discovered the efficiency of the drug by just noticing there were no lupus patients (who were under chronic treatment of hydroxichloroquine) infected with covid19.
"As of 23 March 2020, it seems that Japan and China have issued an export ban on the substance. Japan and China are the only countries in which favirapir is produced and approved as a medical compound." [1]
And I guess setting up factories to produce millions of doses of new meds can take a while. At the same time, each new manufacturer has to negotiate terms with the patent holder. Using an existing cheap generic drug means that production facilities are already up and running and that any company could start if they have the means to produce it.
Apparently a 1-month dose costs £5 in the UK, so there doesn't seem to be a large hurdle to produce it.
Do governments have a good reason not to suspend patents for the time of emergency? Emergency rules break a lot of other businesses, and pharma is probably one of the few industries not in danger?
When thinking about this I always assume it is the same reason countries tended not to reach for national security provisions¹ despite how attractive they are, it just isn't clear how to put the genie back in the bottle when you've broken it with the biggest-and-most-crushy hammer you can find.
If you dig around in the other exceptions in the document I've linked you'll see there are multiple places where patent protection and protection of human life are discussed.
I know where I sit on the patent validity continuum already, but I also know other people are furiously bouncing on the other end of that seesaw.
Since it ends in mab I assume it's a monoclonal antibody. Those are expensive as fuck because they're so difficult to make. I wonder whether we could scale production up to meet pandemic demand.
mabs are not a straight small molecule synth. Scale as much as you want, growing them takes a while even in parallel.
(this is more or less also why vaccine timelines are so long; chicken eggs take a bit of time to get going, and that's the best breeding ground we have!)
The way the authors have analyzed their data it tells us this is a promising drug. Had they done an intention to treat analysis very likely the opposite would've been the result.
The only thing that trial tells us is that if you do a bad trial you're as clueless as before.
I am not a doctor, just a physicist, so I know about experimental data, but of course not about this study in detail. But as several sources dealing with this study confirm, it doesn't really tell us anything. So really at best it can be seen as reason to conduct a proper study, but the data itself does not yield any conclusion.
There's a lot in medicine that goes into publication that has results not even borderline as meaningful as this. I would be careful to label this as "it doesn't really tell us anything". Especially since another study in China reached a similar conclusion.
a) The quality, or lack of quality, of other studies does not affect the quality of the discussed study.
b) The availability of another study with similar results, does not affect the quality of this study.
A lot of people are eager to say chloroquine is the answer and say, "forget the small details, look at that p-value!". But this article raises a bunch of important points. The important ones IMO are:
1) 6 / 26 of the individuals in the experimental group got removed from the stats because their condition got worse and the treatment ceased. One of them died.
2) The metric used to test the efficacy is viral load. You can get a negative on this and still have the disease. This is going to be a function of how long you've had the disease, which isn't controlled in the study.
1) The combination of HCQ and AZ was hyped as superior because all 6 patients did better. But looking at the data there is no significant difference in viral load outcomes between both drugs and just HCQ.
2) Many of the author's claims of statistical significance disappear if you use more conservative estimates for when people were supposed to be PCR positive except for Day 6 (now 0.01 instead of 0.001).
3) The paper turnaround was incredibly fast, with less than 24 hours for peer review. One of the authors of the paper is an editor of the journal in which it was published. Could be indicative of poor study controls.
I hope this turns out to be useful. I would not be surprised if it did not. Regardless, the best case takeaway of THIS information does not inform us about how the drug performs in the most critical area (severe ICU patients).
If you're a non-bio programmer please try to recognize that saying the current paper is good enough to justify mass distribution of chloroquine tablets to everyone is about on par with the cliche clueless product manager making bold decisions about how to move forward with your codebase despite having no clue how it works themselves.
Unfortunately, all those waiting patiently for "confirmed results of double blind trials" will make up a significant percentage of those visiting the pearly gates by the time those trials are ever completed.
Look, the risk is fairly low for chloroquine, mild side effects in a very well done Danish study were only ~15%, serious side effects were ~1.5%.
Reported Side Effects to Chloroquine, Chloroquine plus ...
academic.oup.com › jtm › article-pdf › jtm7-0079
Now, what's the risk of serious side effects/death from coronavirus for those over 70 years old ? Like >10%.
And a recent report out of Hong Kong is stating that lung scarring from coronavirus is being found in all ages (radiological imaging), like 20 to 30% loss of lung function, shortness of breath reported by recovered patients just from fast walking - - - is that going to be permanent in all ages ? Are you willing to take that risk ?
A glaring fact is that chloroquine / hydroxychloroquine have been on the WHO's list of essential medicines for decades . . . . why so, if they were too toxic to recommend ?
Just like the rush on buying ammo, would you prefer to have "the likely treatment" before the problems comes to you - - or, would you prefer to fail to find it after all the shops and stores are completely sold out and the unemployed "zombies" are all over your property and smashing down your door while your family is cowering under the table screaming and crying for help ? I already got my supply of it, best of luck for all the naysayers.
BTW, what is your Gov't offering you right now in the way of proven drugs ? Nothing. All the while the rich in NY are reported in the news media as cashing in on favors to secure reservations for hospital beds in case they need them - - and buying ventilators . . . under the counter.
Nothing quite like a site titled "Better Science" with the disclaimer:
"While I understand the basics of a clinical trial, I’d like to point out that I am no medical scientists. Most of the issues here were spotted by other people and I have linked to the sources."
You cannot make this s@#t up!
Put on your critical thinking caps folks -- there's a lot of bad info out there.
I've noticed that too. I think it might be due to all of the doomsday predictions going around on cable news scaring people. If you've just liquidated your 401k into cash at market lows, you're going to want reassurance that it was the correct thing to do
It's funny, because as a scientist I though "why in the word is anybody even talking about this paper, it's way too preliminary to be of general interest." No other tiny, flawed study like this would generate hype unless it had been picked up by some rumor machine.
And I guess the reason is that we have a terrible executive that doesn't understand basic science and has weaponized his followers to politicize science to their own ends.
To have the President is the US be the source of rumors is such a shame. We have fallen so far as a country, to such pitiable depths of poverty of mind.
It was talked about a fair bit before Trump got on to it. You may have noticed there is a pandemic going on many deaths so it's natural to be interested in remedies.
The data - 100% of the azithromycin + hydroxychloroquine group better after 6 days is promising even if it's a small sample.
You're just witnessing the old joke IRL: If Trump could walk on water, the Left would complain that he can't swim.
I'm not saying this works, but it does seem to me that for severely ill patients there's no harm in doing a large-ish field trial. Prophylactic use should receive more scrutiny.
They do in fact "give it to those willing to try" in Italy, France, and China at a minimum. Probably elsewhere as well. Here in the US we're instead engaging in purely partisan bickering as to whether or not it should be available (which is not the same thing as pervasive use).
He never called virus itself a hoax. He called the accusations that the administration's response was ineffective a "hoax". There's a difference. Didn't read the rest of your partisan drivel, sorry.
You were extremely lucky to read only the one point that has been in the news as not entirely correct, missing the other dozen or so that are difficult or impossible to refute.
Like supporters of Oberan, Erdogan, Bolsonaro, Modi, Putin, Duterte and Maduro, any damning direct quotes will always be claimed to mean something else entirely.
The larger issue is that the leader's supporters know what he is and his relationship to the truth. They know when he looses the popular vote, has consistent majority disapproval and acts with dubious legality. These things don't mater. If fact, that he can retain power in spite of these things is considered a virtue.
They elected him because of single minded ruthlessness and willingness to break laws to permanently eradicate liberalism and the viability of opposing parties. The mere promise of this is so thrilling to them that any action the leader takes is defended or obfuscated unwaveringly even when the defenders don't fully believe or aren't really comfortable with it themselves.
This works both ways though. I hope you're smart enough recognize that. There's literally nothing Trump can say or do to earn the approval of those suffering from TDS. He could say "water is wet" and you'd still argue that's not the case.
Even before he was president, his calls for infrastructure were praised by democrats. And many on the left praised his calls for tariffs.
But after leading chants to lock up political rivals and repeatedly calling the free press the "enemy of the people"[1], there is indeed nothing any politician from any party with any agenda could ever do to become normalized by democratically minded people.
But they are "the enemy of the people" figuratively speaking. They lie _all the time_, they're routinely caught and called out, and they continue to lie. The only two journalists that I know of who point out this sorry state of affairs are Matt Taibbi and Glenn Greenwald. Neither is a fan of Trump in the least. Everyone else is perfectly OK with it. Far fewer people trust the press than the president.
They are supposed to inform. Instead, most of the time, they push disinformation to fit a predefined agenda. Jeff Zucker literally tells CNN talking heads what to say in his 9AM meeting. This is not "free press". This is a fucking disgrace, and it is actively harmful to "the people", especially when there's a crisis.
Let me give you an example: https://www.cnn.com/2020/03/23/health/arizona-coronavirus-ch.... Unless you read the article carefully, you will get the impression that the man medicated himself with the actual chloroquine pills. This is NOT what happened: he ate god damn aquarium cleaner by the spoonful.
The front page of CNN is FULL of this bullshit. Literally all of the liberal outlets reprint these stories _knowing_ they are fake or misleading (just serarch Google for "chloroquine" and see for yourself, today - it'll be full of the same dude who ingested aquarium cleaner). And that's before we even mention lying by omission, which also happens all the time.
Your example wouldn’t even constitute a lie. It would be “misleading” at best.
But it’s not that, either. You’re making up a completely fact-free accusation:
The aquarium is mentioned in the headline
The second sentence is:
“It does not appear they took the pharmaceutical version of the drug, but rather "an additive commonly used at aquariums to clean fish tanks," Banner Health said in a statement.“
If that constitutes „lying“ to you, it’s beyond hope.
#1: in context is a clearly forward looking statement, since the text surrounding it speaks of significant testing capacity coming online in the near future. Which it did. Currently labs in e.g. WA (original epicenter of the infection) are operating under capacity: https://twitter.com/UWVirology/status/1241953101076037632. NY is still challenging, but ramped up tremendously since then. I mean, you can armchair quarterback all you want, but those are facts. Capacity was promised, capacity is being delivered.
#2. Yeah, I will concede that this one wasn't the best wording. That's how he deals with clearly partisan hacks in the audience. If you think anybody in his opposition would publicly accept blame for _anything_ you're sorely mistaken. Do I need to remind you what the Congress has spent the entire January and half the February on?
#3. We've been over this.
#4. He's right, they are doing whatever they can to freak people out as much as possible, whether or not there's a reason to freak out. The risk was low to the average American at the time, and at below 150 cases per million it remains so even now. Moreover, if you conservatively (by which I mean all the currently active cases there end in a fatality, which is unlikely) extrapolate S. Korea numbers to 7x the population, you'll end up with fewer than 50K deaths. We could realistically end up in that situation, given that we have a comparable level of medical care, and given that Korea is perhaps the only country for which extensive, reliable test data is available.
#6. This is from Jan 22. First case in the US was identified just 3 days before: https://www.nejm.org/doi/10.1056/NEJMoa2001191. It did at the time seem that this could be "under control", especially considering that he was planning to shut down flights just 9 days later (something he was called a "racist" for at the time). You can say it ain't so with the benefit of the hindsight, but I bet you didn't think of this much in January, and if I told you several states would be in full lockdown, you wouldn't believe me.
7. In terms of the number of infections per million, the level of response, and the number of fatalities, we are in a "great" shape compared to most other places, including Korea, which is widely acknowledged to be a "success" as far as response measures and containment go. One thing we did fuck up is testing. That's being fixed as quickly as humanly possible: https://www.politico.com/interactives/2020/coronavirus-testi...
Why (from his point of view) would it be either/or? The latter claim could overlap with or imply the former. In principle, it doesn't have to, but saying the response was adequate certainly doesn't imply that liberals were correct about the magnitude of the threat.
Right, so based on what I know, I can't speak to the state of his mind or all the things he said that indicate it. So if you think some people are wrong and your opinion is right, you might consider explaining why.
https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v...
> The proportion of patients that had negative PCR results in nasopharyngeal samples significantly differed between treated patients and controls at days 3-4-5 and 6 post-inclusion (Table 2). At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologicaly cured comparing with 12.5% in the control group (p= 0.001).
The effect size is huge, even considering the potential biases.