France, Italy, Belgium stop hydroxychloroquine use for Covid-19 on safety fears(reuters.com)
reuters.com
France, Italy, Belgium stop hydroxychloroquine use for Covid-19 on safety fears
https://www.reuters.com/article/us-health-coronavirus-hydroxychloroquine/france-bans-hydroxychloroquine-to-treat-covid-19-amid-safety-concerns-idUSKBN233197
99 comments
If it had any effect on covid-19, it'd be very obvious by now. There isn't some massive conspiracy here, it just doesn't work. The reason trials have stopped is because France, Italy, Belgium & the UK have seen worse outcomes generally, directly because of it.
I don't get the 'it needs to be taken before symptoms!' argument - like we can possibly give a immunosuppressant with non-negligible side-effects (e.g. arrythmia) to billions of people with no scientific evidence of it working on covid at all.
I don't get the 'it needs to be taken before symptoms!' argument - like we can possibly give a immunosuppressant with non-negligible side-effects (e.g. arrythmia) to billions of people with no scientific evidence of it working on covid at all.
Not before symptoms, but after exposure, or early on during the course of the disease, like other antivirals.
I reinstate, before people think I'm some sort of HCQ defender: I am not. The effect size is probably very small. It may be as well that it doesn't work, and I would be happy even if it doesn't.
I just want to see a proper RCT done and sealed.
I reinstate, before people think I'm some sort of HCQ defender: I am not. The effect size is probably very small. It may be as well that it doesn't work, and I would be happy even if it doesn't.
I just want to see a proper RCT done and sealed.
You're not unique in wanting an RCT, but the decisions can't wait.
On currently-available evidence, the balance of risks is to not prescribe this drug for treatment of C19.
On currently-available evidence, the balance of risks is to not prescribe this drug for treatment of C19.
What decision can't wait for a RCT?
C19 will be with us for decades to come and there is no shortage of patients. An RCT does not stop development of other solutions.
This means that will be the forever-available evidence
It's obvious since end of February that the only usage is in prevention. Give to all risk persons 3 weeks before. That's the Indian advisory:
https://www.icmr.gov.in/pdf/covid/techdoc/V5_Revised_advisor...
https://www.icmr.gov.in/pdf/covid/techdoc/V5_Revised_advisor...
The first symptoms aren't necessarily the shortness of breath. In my case I had a week of mild fever before the shortness of breath kicked in. Fever isn't severe. Difficulty to breath is. You can have a policy to be treated when you get the first symptoms, but before these symptoms are severe.
The difficulty there is you're talking about giving it to a lot of people in an outpatient setting.
This is the worst case in terms of risk trade-offs:
Without being admitted as a patient, you will not be monitored as closely especially for coronary complications.
Since you'll be giving it to people before the onset of severe symptoms, you'll be risking side-effects giving it to people who might have been fine without it (and most people will survive with out it).
You'll be giving it to a lot of people which again just increases the chances of serious side-effects.
(PS I hope you're doing well now).
This is the worst case in terms of risk trade-offs:
Without being admitted as a patient, you will not be monitored as closely especially for coronary complications.
Since you'll be giving it to people before the onset of severe symptoms, you'll be risking side-effects giving it to people who might have been fine without it (and most people will survive with out it).
You'll be giving it to a lot of people which again just increases the chances of serious side-effects.
(PS I hope you're doing well now).
But then the side-effects are pretty low no? How long has it been in the WHO basic medicine category without concerns for its safety, 50 years or so?
Most of the side-effects aren't severe. The worst cited are usually blindness and deadly heart arrhythmia. The problem is when you start giving it out to a lot of people, you start to see those low-incidence side-effects increasingly often.
It is a basic and important medicine. It's not that there are no concerns about its safety; it's that the safety concerns are well-known. Those are distinctly different statements.
(As an aside, for example, Tylenol and aspirin can both be quite harmful, but under what conditions they're dangerous is well-known so they are widely used pretty safely. Even so, you still find people inadvertently destroying their livers with Tylenol/paracetemol when they don't realize two OTC medicines contain them and overdose).
So then the question is how much harm are you doing by giving people the drug (under some set of circumstances) vs how great a benefit might someone derive from it.
Clearly on one side, if you gave it to everyone as a prophylactic, that'd likely cause more harm than good. Perhaps, you give it to people who have tested positive but are not admitted to the hospital. Or you can give it to only those who are admitted. Or you can give it only to people who are doing poorly.
Presuming the harmfulness of the medicine is well known you can run some easy hypothetical numbers about how many people will have serious harm or death from receiving it on a wide scale. We have a rough idea of the range of people who will die or have serious cases of COVID. The only thing left is the possible benefit people may get from the medicine.
As of now there is no indication that the benefit is worth the harm to give it out to people in a wide-scale fashion. Additionally, the current studies don't even support giving it to people who are in-patients. In most studies, patients receiving it fare worse than those not.
It is a basic and important medicine. It's not that there are no concerns about its safety; it's that the safety concerns are well-known. Those are distinctly different statements.
(As an aside, for example, Tylenol and aspirin can both be quite harmful, but under what conditions they're dangerous is well-known so they are widely used pretty safely. Even so, you still find people inadvertently destroying their livers with Tylenol/paracetemol when they don't realize two OTC medicines contain them and overdose).
So then the question is how much harm are you doing by giving people the drug (under some set of circumstances) vs how great a benefit might someone derive from it.
Clearly on one side, if you gave it to everyone as a prophylactic, that'd likely cause more harm than good. Perhaps, you give it to people who have tested positive but are not admitted to the hospital. Or you can give it to only those who are admitted. Or you can give it only to people who are doing poorly.
Presuming the harmfulness of the medicine is well known you can run some easy hypothetical numbers about how many people will have serious harm or death from receiving it on a wide scale. We have a rough idea of the range of people who will die or have serious cases of COVID. The only thing left is the possible benefit people may get from the medicine.
As of now there is no indication that the benefit is worth the harm to give it out to people in a wide-scale fashion. Additionally, the current studies don't even support giving it to people who are in-patients. In most studies, patients receiving it fare worse than those not.
> If it had any effect on covid-19, it'd be very obvious by now.
Not directly in response to this, but a broader observation I ran across was that lockdowns effectively shut down a lot of data creation (infections) about the virus, so there are still a lot of things we don't know, it makes it hard to make informed decisions.
Not directly in response to this, but a broader observation I ran across was that lockdowns effectively shut down a lot of data creation (infections) about the virus, so there are still a lot of things we don't know, it makes it hard to make informed decisions.
Haha, then why did China, Russia and Japan use it so successfully? Let's not forget we live in geopolitically very interesting times, and that the WHO is pretty much under the influence of China.
It HCQ doesn't work, why is it the common first line of defense used internationally? Why does scholar.google.com list so many papers showing that it's effective?
Because it's a highly effective and widespread malaria (and RA/lupus) treatment?
The dose for malaria is 200mg. It's the higher doses that are associated with heart arythmia in covid patients. According to a trial reported in https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s129...
"No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation."
"Chloroquine is the most widely used antimalarial drug in history. It has a terminal elimination half-life of one month and an annual consumption of hundreds of tonnes for over 50 years, so it may be the drug to which humans have been exposed to most. Despite producing consistent QT prolongation, the only case reports of TdP and sudden death have been for its use for non-malaria indications such as systemic lupus erythematosus or rheumatoid arthritis, where high doses are used for much longer than in malaria treatment, or in overdose"
"No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation."
"Chloroquine is the most widely used antimalarial drug in history. It has a terminal elimination half-life of one month and an annual consumption of hundreds of tonnes for over 50 years, so it may be the drug to which humans have been exposed to most. Despite producing consistent QT prolongation, the only case reports of TdP and sudden death have been for its use for non-malaria indications such as systemic lupus erythematosus or rheumatoid arthritis, where high doses are used for much longer than in malaria treatment, or in overdose"
Unless I'm mistaken, this paper refers to chloroquine, not hydroxychloroquine.
They are often conflated in the media and colloquial reporting.
They are often conflated in the media and colloquial reporting.
Nothing is in the first line of defence against Covid - it's a novel virus
I don't know why I'm getting downvoted.
Anyone can verify what I'm saying if they go to scholar.google.com
Anyone can verify what I'm saying if they go to scholar.google.com
Because your statement is misleading. Some countries are are using it more frequently than the US, but Germany and the UK prescribe it much less. Italy had the highest prescription rates, but are no longer using it. While France prescribed it more often than the US but are also stopping.
Lastly, the argument of "if countries outside the US are prescribing it, it must work" is just nonsensical. Doctors prescribing a drug is not evidence a drug works.
https://www.google.com/amp/s/www.statista.com/chart/amp/2141...
Lastly, the argument of "if countries outside the US are prescribing it, it must work" is just nonsensical. Doctors prescribing a drug is not evidence a drug works.
https://www.google.com/amp/s/www.statista.com/chart/amp/2141...
Lancet isn't the only paper that has raised issues with HCQ treatment.
Sciencemag [1] has this to say:
However, both HCQ and AZ have potential cardiac toxicity (QT prolongation, which can lead to fatal arrhythmia), and HCQ additionally has the potential for negative effects on the eye. Understanding risk-benefit ratios is paramount if these drugs are to become a standard of care for COVID-19. Several post hoc analyses carried out in the United States and Europe suggest modest benefit, at best, from HCQ monotherapy for COVID-19 patients; one large post hoc analysis among U.S. veterans suggests that there is harm to patients from HCQ. Given the mechanistic rationale but lack of well-designed clinical studies and potential for drug-induced toxicity, there is a key need for controlled, randomized trials to test the efficacy and safety of these drugs for COVID-19 patients.
[1]: https://science.sciencemag.org/content/sci/368/6493/829.full...
I don't think it's a "shame" that some have decided to stop wtih HCQ when other viable treatments seem to have less concerning side-effects. Either way, we will know very soon with greater certainty as ongoing randomized trials finish up.
Sciencemag [1] has this to say:
However, both HCQ and AZ have potential cardiac toxicity (QT prolongation, which can lead to fatal arrhythmia), and HCQ additionally has the potential for negative effects on the eye. Understanding risk-benefit ratios is paramount if these drugs are to become a standard of care for COVID-19. Several post hoc analyses carried out in the United States and Europe suggest modest benefit, at best, from HCQ monotherapy for COVID-19 patients; one large post hoc analysis among U.S. veterans suggests that there is harm to patients from HCQ. Given the mechanistic rationale but lack of well-designed clinical studies and potential for drug-induced toxicity, there is a key need for controlled, randomized trials to test the efficacy and safety of these drugs for COVID-19 patients.
[1]: https://science.sciencemag.org/content/sci/368/6493/829.full...
I don't think it's a "shame" that some have decided to stop wtih HCQ when other viable treatments seem to have less concerning side-effects. Either way, we will know very soon with greater certainty as ongoing randomized trials finish up.
Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus.
And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that.
EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).
And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that.
EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).
It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.
> It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process.
This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease.
This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself.
This calls more for extensive and early testing, IMO.
This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease.
This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself.
This calls more for extensive and early testing, IMO.
https://arstechnica.com/science/2020/05/the-antiviral-remdes...
participants who entered the trial more than 10 days after the onset of symptoms actually showed a better response to remdesivir than those who started being treated during the first 10 days of being symptomatic.
It's not a huge improvement, but it doesn't seem to be too dependent on starting treatment early.
participants who entered the trial more than 10 days after the onset of symptoms actually showed a better response to remdesivir than those who started being treated during the first 10 days of being symptomatic.
It's not a huge improvement, but it doesn't seem to be too dependent on starting treatment early.
Remdesivir doesn't have the sudden cardiac death side effect, though, does it?
HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
HCQ has been around for 70 years. Remdesivir's issue is that everyone gets to be the guinea pig. Sometimes it's better to go with the devil you know.
> HCQ has been around for 70 years.
Not in an antiviral context, and certainly not for SARS-CoV-2.
Not in an antiviral context, and certainly not for SARS-CoV-2.
So? The point here is the safety of it, plus there's research going back to 2006 about its effectiveness for other Coronaviruses. I mean do whatever you want to do, but there's a reason most people in government are taking it. In my country they privately take it, while publicly not endorsing it to prevent shortages
Same stories I've heard. Many doctors prescribing it for prophylactic treatment to friends and family immediately after diagnosis. Some government officials (in France, notably! While at the same time shutting down public use) taking it immediately after diagnosis.
As has been mentioned elsewhere, we'll have to answer soon, but power speaks with a forked tongue in this case. Too many anecdotal observations to be comfortable in the very loud politicization of the science.
The Lancet study and others cannot be accepted a conclusion to the safety & efficacy of early/prophylactic use. Let's wait for and encourage some proper, specific studies.
As has been mentioned elsewhere, we'll have to answer soon, but power speaks with a forked tongue in this case. Too many anecdotal observations to be comfortable in the very loud politicization of the science.
The Lancet study and others cannot be accepted a conclusion to the safety & efficacy of early/prophylactic use. Let's wait for and encourage some proper, specific studies.
> The point here is the safety of it
Yes, which is why all of the studies keep saying that it's too dangerous to use as treatment for covid-19.
Yes, which is why all of the studies keep saying that it's too dangerous to use as treatment for covid-19.
Too dangerous (or even ineffective) to use it with patients with severe COVID-19. Whether it may be the same or not in a prophylaxis regime or for outpatient use (mild to moderate that does not require hospitalization) is yet unknown at this point (most papers that I've read are on hospitalized patients).
It may be too toxic, it may not cause a noticeable effect, but currently it is a big question mark.
It may be too toxic, it may not cause a noticeable effect, but currently it is a big question mark.
You'd take the risk for people with severe Covid-19 because it might[1] save their life. You can't justify taking that risk in other people because they're probably not going to be killed by covid-19. Balancing harm from medication against not much harm from covid comes out against the meds.
[1] Except now we know (and we always thought this) that it won't save their life; it'll increase their risk of death.
[1] Except now we know (and we always thought this) that it won't save their life; it'll increase their risk of death.
Agree but the rationale is that you reduce the contamination by testing people early and giving them drugs that reduce the viral charge, hence the contagiousness.
> Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus.
To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started.
This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.
To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started.
This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.
For the purposes we're discussing here, Raoult et al. are front-line clinicians working to save lives under extreme uncertainty, with every decision scrutinized with the benefit of hindsight. You shouldn't hold them to the same standard as pure research scientists.
Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day.
The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.
Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day.
The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.
Agree this isn't an RCT, but why would this be an "over-reaction"? It's not like the default reaction is to administrate millions of doses of a medicine that has yet to be proven effective. (and could potentially do more harm than good)
The studies supposedly proving HCQ's effectiveness have much bigger caveats (tiny sample size and/or manipulation of the groups in a dishonest way, like Raoult removing severe cases from the treatment group whereas the control group had none)
The studies supposedly proving HCQ's effectiveness have much bigger caveats (tiny sample size and/or manipulation of the groups in a dishonest way, like Raoult removing severe cases from the treatment group whereas the control group had none)
> PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news.
And the RCTs are still going and will finish, unless there is a major negative effect noticed in them, which is not the case so far.
And the RCTs are still going and will finish, unless there is a major negative effect noticed in them, which is not the case so far.
Indeed, there is hope that a definitive answer will come out (at this point, given how politicized the discourse is, any answer in either direction willl be fine).
FTR, the U of Minnesota trials used normal dosages and (according to its PI) did not report any cardiotoxicity so far.
FTR, the U of Minnesota trials used normal dosages and (according to its PI) did not report any cardiotoxicity so far.
“India has so far made the right decision on HCQ and that this decision has been based on evidence,” Preeti Sudan, Secretary, Ministry of Health and Family Welfare, was quoted as saying by The Hindu.
The government late last week extended the use of HCQ for paramilitary and police personnel involved in COVID-19 management, besides direct health care providers for positive patients.
Soumya Swaminathan, Chief Scientist at WHO also told The Hindu that WHO is not advising stopping all HCQ trials but has only dropped HCQ from the Solidarity Trial, and that many prophylaxis trials using HCQ are ongoing or about to start.
The government late last week extended the use of HCQ for paramilitary and police personnel involved in COVID-19 management, besides direct health care providers for positive patients.
Soumya Swaminathan, Chief Scientist at WHO also told The Hindu that WHO is not advising stopping all HCQ trials but has only dropped HCQ from the Solidarity Trial, and that many prophylaxis trials using HCQ are ongoing or about to start.
Yes, i'm not a proponent of HCQ, not without RCT as some of my previous post might tell you, but the "raw" data of the Lancet study seems pretty well harmonized for raw data, i wouldn't trust this study for my national policies.
I can't take HCQ as i already have extrasystole and a allergies treatment that already can cause arythmia, so i hope this won't be the "best" treatment, but really this paper, while interesting, should not be used to take decisions.
I can't take HCQ as i already have extrasystole and a allergies treatment that already can cause arythmia, so i hope this won't be the "best" treatment, but really this paper, while interesting, should not be used to take decisions.
As I wrote elsewhere (check my post history) I personally think that if the effect is there, it is small. I don't really mind if HCQ doesn't work, but I get mad when people say "follow the science", and the most basic thing to do for science (a RCT) is not done.
Let's see if the U of Minnesota trial is published soon. The PI of the study tweeted he had sent revisions to the manuscript, and hoped for a publication this week (and he however added that he thought the same last week).
Let's see if the U of Minnesota trial is published soon. The PI of the study tweeted he had sent revisions to the manuscript, and hoped for a publication this week (and he however added that he thought the same last week).
> most basic thing to do for science (a RCT) is not done.
Randomised Controlled Trials are the gold standard but not the "most basic thing". They are the ideal we'd like to have but often simply aren't an option.
One of the most obvious reasons we often can't do a trial is that we have good reason to believe it would be unreasonably dangerous, which is why these trials stopped.
The opposite scenario happens sometimes too. If all patients treated with Hydroxychloroquine magically got better they'd stop the trial and recommend immediately using it on similar patients.
Randomised Controlled Trials are the gold standard but not the "most basic thing". They are the ideal we'd like to have but often simply aren't an option.
One of the most obvious reasons we often can't do a trial is that we have good reason to believe it would be unreasonably dangerous, which is why these trials stopped.
The opposite scenario happens sometimes too. If all patients treated with Hydroxychloroquine magically got better they'd stop the trial and recommend immediately using it on similar patients.
Meh. It wouldn't surprise me if these trials are being run by the makers of Remdesivir or some other drug, and they're purposely killing folks to make their treatment look more effective. It's a pretty common tactic in the pharma industry for drug makers to do trials with enormous doses of their competitors products to make them look more dangerous by comparison, and given that this whole thing has turned into a multi-billion dollar cash grab I would assume that that's what's happening here unless proven otherwise.
It's the same thing with famatodine, where someone observed that folks taking it for heartburn have a lower risk of death. So rather than doing an RCT with giving folks 10mg orally (a normal dose), someone started doing an RCT with like 140mg injected.
Just thinking about it logically, why would you ever give someone a drug that ostensibly works by blocking viral replication when they've already had the virus for multiple weeks? It makes zero sense, which tells you there is something shady going on.
It's the same thing with famatodine, where someone observed that folks taking it for heartburn have a lower risk of death. So rather than doing an RCT with giving folks 10mg orally (a normal dose), someone started doing an RCT with like 140mg injected.
Just thinking about it logically, why would you ever give someone a drug that ostensibly works by blocking viral replication when they've already had the virus for multiple weeks? It makes zero sense, which tells you there is something shady going on.
Fuck you are right, remember just reading that Gilead gave some 250K to the author of one of the studies against HCQ. IF that is not a conflict of interest then what is?
Nice, if you can find the source I'd love to see that.
edit: I'm assuming this: https://www.thenewamerican.com/usnews/health-care/item/35547...
edit: I'm assuming this: https://www.thenewamerican.com/usnews/health-care/item/35547...
Yeah, not exactly that one but similar. A thing that this one misses is that the author of the study did not do a proper disclosure of the conflict of interest.
The thing is it's pretty evident it works and also why many governments and leaders around the world are taking it as prophylaxes. Anecdotally (doctors in the family), it is being used in private hospitals in my country quite successfully.
The thing is it's pretty evident it works and also why many governments and leaders around the world are taking it as prophylaxes. Anecdotally (doctors in the family), it is being used in private hospitals in my country quite successfully.
Particularly in the case of a 1950s drug that has been consumed by millions of people, and which as far as I know was available without prescription until covid. It’s like saying aspirin is dangerous. Sure. At a certain dosage.
Quinine-based drugs are no small thing. They are neurotoxic even at low dosages, for example (the somewhat-related antimalaric drug mefloquine very often causes really bad nightmares, at the very low prophylactic dosage, and it has a long half life so they persist even a few weeks after you've stopped taking it).
We are talking about HCQ. Perhaps its use is strange in the US, but in India its commonly prescribed for malaria (and also lupus, arthritis). My entire extended family (ex-military) has taken HCQ at one point of time or another. No ill-effects for millions of people. Heavy dosages should be avoided of-course.
Exactly. And the dosage being given for COVID-19 patients is comparable to the dosage given for patients with chronic conditions such as lupus, only the COVID-19 patients are given the drug for something like a week, while the chronic patients are given the drug indefinitely.
Meanwhile, drugs like benzodiazepines are basically just dumped on a largely unwitting populace with the tacit blessing of these very same people who are fretting about hydroxychloroquine. There is more than simply the disinterested caution of science going on here.
Meanwhile, drugs like benzodiazepines are basically just dumped on a largely unwitting populace with the tacit blessing of these very same people who are fretting about hydroxychloroquine. There is more than simply the disinterested caution of science going on here.
Shh, don't mention the opiate / benzo crisis. We know this disproportionately affects Middle America, and therefore is not something we can bring up as a serious topic of conversation.
To be honest, dosage varies a lot across countries. The trials in Brazil gave very high dosage, which can probably explain the deaths from cardiotoxicity there.
The risk of treating patients with pain-reducing levels of ASA (aspirin) is actually a significant issue, and it's not hard to find papers covering this issue, and reporting data on it. It's usually in older populations who are more likely to be in pain and also more likely to die from a stomach bleed.
Yeah. But like every drug in the world has contraindications. By this standard all drugs are dangerous and should be banned from trials.
I think I misunderstood you. I thought you were suggesting we should give drugs to people regardless of the fact that the randomized controlled trials say that the drug doesn't provide any significant benefit. Giving widespread ASA to a population that wouldn't benefit from it would be a bad idea.
Well I am personally in favour of doing randomized control trials, not to cancel them based on what appear to be a weak statistical analysis. There was an argument to not wait at the peak of the epidemic rather than not treating (and some of these trials are only starting, which baffles me). But these trials should have been done from the outset.
Doctors in the heat of the moment cannot wait for a randomized trial. They started keeping patients off intrusive ventilators without doing a randomized trial, based on annecdotal evidence.
But these trials still need to happen.
Doctors in the heat of the moment cannot wait for a randomized trial. They started keeping patients off intrusive ventilators without doing a randomized trial, based on annecdotal evidence.
But these trials still need to happen.
According to most of the countries mentioned in the article, trials of HCQ are still going on. The WHO put its trial on pause. Other countries are just stopping the use of HCQ outside of approved trials.
I wish it would be the case but for instance in France the drug authority seems to be determined to stop all trials [1]
[1] https://www.midilibre.fr/2020/05/26/coronavirus-lagence-du-m...
[1] https://www.midilibre.fr/2020/05/26/coronavirus-lagence-du-m...
[deleted]
Aspirin can be deadly if used to treat patients with an hemorrhage. Likewise, treating patients that are infected by a virus is not like preventing malaria in heathy people might to be exposed to a deadly virus like malaria, especially when most deaths are from older people which might be more sensitive to side effects.
Maybe this is pedantic, but malaria isn't caused by a virus. It's caused by a single-celled group of eukaryots called Plasmodium.
This is not the only sabotaged study being done on HCQ.
As I pointed out on Twitter over a month ago, the bill gates foundation was doing a study on HCQ for preventing covid19.
The "inert" placebo they decided to use in the control group? VITAMIN C.
That's right, one of the most potent and documented immune boosters is now being assumed to be "inert".
https://depts.washington.edu/covid19pep/about/
As I pointed out on Twitter over a month ago, the bill gates foundation was doing a study on HCQ for preventing covid19.
The "inert" placebo they decided to use in the control group? VITAMIN C.
That's right, one of the most potent and documented immune boosters is now being assumed to be "inert".
https://depts.washington.edu/covid19pep/about/
A cardiotoxicity paper from the WHO in 2017 said the following:
"Despite hundreds of millions of doses administered in the treatment of malaria, there have been no reports of sudden unexplained death associated with quinine, chloroquine or amodiaquine, although each drug causes QT/QTcinterval prolongation. Unfortunately, there are relatively few prospective studies of the electrocardiographic effects of these drugs."
Link to paper: https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxi...
Link to Chris Martenson's video where I first heard about the 2017 paper: https://www.youtube.com/watch?v=rN_YpFhdii4
Chris Martenson is doing an awesome job staying on top of the science in an apolitical manner.
"Despite hundreds of millions of doses administered in the treatment of malaria, there have been no reports of sudden unexplained death associated with quinine, chloroquine or amodiaquine, although each drug causes QT/QTcinterval prolongation. Unfortunately, there are relatively few prospective studies of the electrocardiographic effects of these drugs."
Link to paper: https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxi...
Link to Chris Martenson's video where I first heard about the 2017 paper: https://www.youtube.com/watch?v=rN_YpFhdii4
Chris Martenson is doing an awesome job staying on top of the science in an apolitical manner.
Having ACE2 receptors depleted increases blood pressure and changes the properties of blood itself (probably the source of the weird clotting issues), so it makes sense that there would be more risk with Covid-19. Plus many or most Covid patients are probably already polypharming with 5+ drugs already given their age, unlike people going on vacation to Bali or wherever.
I wouldn't trust the trials showing that it's dangerous, but I wouldn't assume it's safe either.
I wouldn't trust the trials showing that it's dangerous, but I wouldn't assume it's safe either.
From the linked paper:
Summary of findings and proposed recommendations
1. Apart from halofantrine, antimalarial medicines thatprolong the QT/QTc interval,such as quinine, chloroquine, artesunate-amodiaquine and dihydroartemisinin-piperaquine,have beenassociated with a low risk of cardiotoxicity.
This seems to indicate that there is a risk, albeit low. The risk is for cardiotoxicity, not sudden deaths.
Summary of findings and proposed recommendations
1. Apart from halofantrine, antimalarial medicines thatprolong the QT/QTc interval,such as quinine, chloroquine, artesunate-amodiaquine and dihydroartemisinin-piperaquine,have beenassociated with a low risk of cardiotoxicity.
This seems to indicate that there is a risk, albeit low. The risk is for cardiotoxicity, not sudden deaths.
The data from those hundreds of millions of doses were on people who did not have COVID-19. It's not contradictory to say that the drug does not tend to cause these effects generally, but does cause these effects in a specific context. Like, say, a deadly disease wrecking havoc on your oxygen levels. Maybe it does, maybe it doesn't. Hard to know anything.
Also, the dosage may be different
This is essentially the Andrew Wakefield fiasco on speedrun, isn't it?
My skepticism was founded entirely on seeing who was promoting this idea, and it is slowly being vindicated.
My skepticism was founded entirely on seeing who was promoting this idea, and it is slowly being vindicated.
> My skepticism was founded entirely on seeing who was promoting this idea
The proponent has no effect on the null hypothesis. What was needed was a RCT: no results are out for any, at this point.
The proponent has no effect on the null hypothesis. What was needed was a RCT: no results are out for any, at this point.
If the snake oil salesman presents a new, improved brand of snake oil, skepticism is wise.
I disagree from a statistical point of view. Of all possible hypothesis we choose to study, for the great majority we will fail to reject the null hypothesis. (For most things we study, we will find the treatment has no discernible effect.)
If some unstudied hypothesis is being promoted at random by vested interests, the chance that it is in fact an effective treatment is low because most treatments we would try are ineffective. And a vested interest will use every rhetorical tool at its disposal to promote what it is selling, including citing studies and scientists. If those do not exist or seem low-quality then skepticism is warranted. We should be wary of all medical claims till they are supported by high quality evidence.
If some unstudied hypothesis is being promoted at random by vested interests, the chance that it is in fact an effective treatment is low because most treatments we would try are ineffective. And a vested interest will use every rhetorical tool at its disposal to promote what it is selling, including citing studies and scientists. If those do not exist or seem low-quality then skepticism is warranted. We should be wary of all medical claims till they are supported by high quality evidence.
You are describing a decision making framework with no real world applicability.
Like, how do we decide which things to study with RCTs? We ask experts...
Like, how do we decide which things to study with RCTs? We ask experts...
This is what I appreciate in YC feed. You got far more better information gathered in one than the MSN article shared initially.
For better information, I would suggest following the credentialed scientific experts on Twitter. You can get information straight from the very best people in their field.
Here, I feel it's a bit of a crap shoot, and half the comments are misinformed & happy to share it.
Here, I feel it's a bit of a crap shoot, and half the comments are misinformed & happy to share it.
Haha, damned Poe's law, hope this was sarcasm!
During Galileo's time most credentialed experts believed the sun to spin around the earth.
During Galileo's time most credentialed experts believed the sun to spin around the earth.
I think it’s always good to be wary of relying uncritically on experts. Nobody’s infallible, but there’s valuable perspective that comes from “person actively involved in the process” vs. “Armchair Hacker News expert”
"coronavirus is what happens when you put the reproducibility crisis in charge of the planet"
-- @mwilcox[0]
[0] https://twitter.com/mwilcox/status/1260458110596120576
[0] https://twitter.com/mwilcox/status/1260458110596120576
Can someone please elaborate on this? What is the "reproducibility crisis" in this case?
Reproducibility crisis is well known, especially in social sciences. However, it affects other science fields as well.
In a nutshell, the crisis is that there is far more incentive to churn out a new publication/study than reproduce an existing one. So we have tons of studies that are the only one of its kind that have not been reproduced. The crisis part comes in where attempts to reproduce the results of these studies fail which throws into question the legitimacy of the entire field's publications.
So you can imagine how putting your faith into covid-19 related studies (such as effects of hydroxychloroquine) that were rushed and results not reproduced independently can result in problems down the road.
Science is probably the best tool we have for determining truth. However, it takes a long time and a lot of effort to converge on the truth and people put far more faith than they ought to in the results of fresh publications that have results they like (or fear).
In a nutshell, the crisis is that there is far more incentive to churn out a new publication/study than reproduce an existing one. So we have tons of studies that are the only one of its kind that have not been reproduced. The crisis part comes in where attempts to reproduce the results of these studies fail which throws into question the legitimacy of the entire field's publications.
So you can imagine how putting your faith into covid-19 related studies (such as effects of hydroxychloroquine) that were rushed and results not reproduced independently can result in problems down the road.
Science is probably the best tool we have for determining truth. However, it takes a long time and a lot of effort to converge on the truth and people put far more faith than they ought to in the results of fresh publications that have results they like (or fear).
"Most published research findings are false" (not reproducible)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/
This is an excellent read: https://slatestarcodex.com/2014/12/12/beware-the-man-of-one-... -- basically says one has to be very skeptical of trusting a study that suits the narrative, and how studies can be cherry-picked to align with your narrative.
“reproducibility crisis” is a euphemism for “fake science”, which now, by the numbers, accounts for the majority of mainstream establishment science.
Prove me wrong.
Prove me wrong.
"Fake science" implies intent to mislead. The reproducibility crisis is usually attributed to selection bias due to only positive results getting published.
You could have five times the accuracy by simply flipping a coin to answer any yes or no question, compared to the level of accuracy in the “reproducibility crisis”. I don’t think this can be explained by “selection bias”, and, if it can, and I do believe that could also qualify the entire industry as “fake science”, if the industry cannot even get close to as accurate as a coin toss.
If you'd read the literature on the reproducibility issue, you'd understand the selection mechanism can easily create the observed phenomenon.
By calling it "fake science" you're touching on the idea of a paradigm shift, that periodically the community changes its beliefs about what enables someone to know something or to be certain about something.
By calling it "fake science" you're touching on the idea of a paradigm shift, that periodically the community changes its beliefs about what enables someone to know something or to be certain about something.
My thinking is that, if he’s published papers are a large part of the means by which we share scientific knowledge, then, regardless of the underlying mechanism to be blamed (e.g., selection bias), the entire institution has become corrupted.
To illustrate, the literature that you’re describing is presumably in the form of meta-analyses published in Nature. How can we even trust that to be “reproducible” (aka correct)?
I think the correct reaction to this situation is to completely stop trusting scientists and their papers, in general. Not trusting scientists add their papers doesn’t mean disbelieving science in general; it just means the established institutions do not know how to do science correctly, and I believe this has been the case since the beginning of modern science. That means we can learn things by reading between the lines and using some common sense, but we can’t simply rely on institutions to tell us the correct answer to anything whatsoever.
To illustrate, the literature that you’re describing is presumably in the form of meta-analyses published in Nature. How can we even trust that to be “reproducible” (aka correct)?
I think the correct reaction to this situation is to completely stop trusting scientists and their papers, in general. Not trusting scientists add their papers doesn’t mean disbelieving science in general; it just means the established institutions do not know how to do science correctly, and I believe this has been the case since the beginning of modern science. That means we can learn things by reading between the lines and using some common sense, but we can’t simply rely on institutions to tell us the correct answer to anything whatsoever.
> presumably
Incorrect. It's in the form of math. Deductive, not inductive.
> completely stop trusting scientists and their papers ... since the beginning of modern science
You are using a computer right now. You don't trust it? Now you're just trolling me.
Incorrect. It's in the form of math. Deductive, not inductive.
> completely stop trusting scientists and their papers ... since the beginning of modern science
You are using a computer right now. You don't trust it? Now you're just trolling me.
[deleted]
Interestingly enough, the french military are still using it to treat their personnel.
They have only confirmed ordering some in case it is proven to be useful. (this was 1 month ago)
https://factuel.afp.com/oui-larmee-francaise-sest-procure-de...
https://factuel.afp.com/oui-larmee-francaise-sest-procure-de...
And this before the results of the Minnesota trial are out. At this point I hope those are negative, so that it does not show that countries are overreacting.
[1] https://statmodeling.stat.columbia.edu/2020/05/25/hydroxychl... and related posts
[2] https://twitter.com/StevePhillipsMD/status/12638995692528967...
PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news.