Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients
sciencedirect.com
sciencedirect.com
> Several comorbidities were significantly less frequent in the HCQ group, including cardiovascular diseases, arterial hypertension, chronic renal disease, neurological and cognitive disorders, solid cancer, obesity as well as the proportion of active smokers.
IOW, doctors gave HCQ to healthier people, so you can't conclude much from the death rate being lower. There may be some value in this paper if you really dig into the details, but the overall death rate isn't a meaningful indication of whether HCQ helps.
>IOW, doctors gave HCQ to healthier people,
Literally the sentence after the one you quoted contradicts clarifies, though:
>> On the other hand, at admission, patients in the HCQ group appeared to be sicker as reflected by the higher frequency of radiological pneumonia, acute respiratory distress syndrome, ICU transfer within the 24h after admission and invasive ventilation support as well as the higher frequency of elevated LDH and CRP levels.
In this case, people arriving sicker at the hospital with a given disease is not necessarily an indication of the likelihood of death with no treatment. For instance, robust young people may wait until they are extremely sick before heading to the hospital, while old or immunocompromised people may go at the first sign of illness. In that case, you would expect death rate to be negatively correlated with how sick people are when they arrive at the hospital.
Non-randomized studies have wasted a lot of everyone's attention on this & related issues.
> patients in the HCQ group appeared to be sicker as reflected by the higher frequency of radiological pneumonia, acute respiratory distress syndrome, ICU transfer within the 24h after admission and invasive ventilation support as well as the higher frequency of elevated LDH and CRP levels.
But yes, it does not look good for this study that the HCQ group tended to be younger and healthier.
> "A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes."
The press release from June: No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19
https://www.recoverytrial.net/news/statement-from-the-chief-...
It would be interesting to see someone build an IPTW model to estimate the average treatment effect of HCQ in all these non-randomized studies. My guess is that the effect would be statistically indistinguishable from zero.
This is an obversational retrospective study.. Hydroxychloroquine is ineffective 100% of peer-reviewed randomized controlled trials,which is much more significative evidence..
Younger and sicker, actually:
>> patients in the HCQ group appeared to be sicker as reflected by the higher frequency of radiological pneumonia, acute respiratory distress syndrome, ICU transfer within the 24h after admission and invasive ventilation support as well as the higher frequency of elevated LDH and CRP levels.
Here's a tracker that lists studies: https://c19study.com/
> Hydroxychloroquine might be the most effective in reducing the duration of symptoms. Remdesivir has intermediate effectiveness and lopinavir-ritonavir could have intermediate effectiveness. The main limitations of the evidence are risk of bias and imprecision.
https://www.washingtonpost.com/health/2020/07/16/hydroxychlo...
FTA "The first randomized clinical trial testing hydroxychloroquine as an early treatment for mild covid-19 found the drug was no better than a placebo in patients who were not hospitalized."
So, maybe hcq has no effect on outcomes on mild cases. This does not mean it couldn't have an effect on severe/hospitalized patients.
Sure, but that's the exact opposite of the earlier narrative when the trials in Brazil were called off.
(paraphrasing) "Sure, it doesn't help people who are critically ill, but you should use it as a prophylactic to prevent milder cases from becoming more severe".
So... it doesn't work in patients with a mild, moderate or severe case; (per the earlier advice) it must be prescribed after infection but before symptoms develop; and it must be prescribed in doses that are known to cause heart problems in a significant portion of the population (so significant, in fact, that patients prescribed much lower doses of HCQ are normally required to be regularly monitored for the onset of said problems).
At what point do you admit that any positive effect of HCQ is just cherry-picking/p-value-hacking?
Mild cases in people who work high-risk jobs and were selected away if they're immunocompromised or especially susceptible to infectious disease.
This is a totally different, "cherry-picked" sample set than your average populace with diverse immune health.
I'm not sure if you read the whole article.
The other study is similar in design.
FTA "The new study was a companion to a randomized trial by the same researchers published last month. Those results showed the drug is not effective in preventing covid-19 in healthy people exposed to the coronavirus."
Sort of. Since Trump tweeted and mentioned the drug, hydroxychloroquine has become politicized.
Some scientists and doctors say it might have some use.
But the media is critical of it because Trump mentioned it.
Politician A does something outrageous for political gain. A's opponents in party B decry this outrageous action as being outrageous and done for political gain. Decrying things A does is to B's political advantage! Conclusions: everyone is politicizing this issue.
Maybe we need a better metric for evaluating political action than whether the actors see some political benefit.
What an odd conclusion to draw.
I think it would be more accurate to say: Trump is being criticized for hyping a medication that has not yet undergone medical trials.
There's an established method for bringing medication to market. Trump is ignorant of that method. That's why he's being criticized.
Beyond its standard antiviral and immunomodulatory activity, it's thought that hydroxychloroquine protects red blood cells' heme molecules from having their iron ripped out by Covid.
"widely available globally" and "has been used as an antiviral therapeutic" is not the correct criteria to use here.
That doesn't give you carte blanche to claim that your drug does wonderful things for condition X when the evidence supporting your claim is non-existent, extremely weak, or obviously fraudulent.
> That's why doctors have to use their best judgement and try different things and write down what seems to work and what doesn't.
Which is completely different to POTUS recommending HCQ because he or his friends have financial interest in a company that makes that drug.
It's also extremely negligent to try popularising a particular drug which is already in short supply and needed by people with existing life-threatening conditions. If something looks promising, you finance some trials to provide more certainty, and then you look at ways to ramp up production because you know demand is going to increase.
It talks about the history of the HCQ debacle and in the process taught me quite a lot about medical study methodology/epistemology.
The article if anything is about epistemology - so the sneer is in reference to doctors assuming they 'know' the only correct ways to draw conclusions (and the article did take a dark twist indeed referencing the opioid epidemic). As a layman though, I don't know what it is referring to about Europe's relationship to homeopathy. I would be curious for a more knowledgeable person to weigh in on that.
It's stupid to believe in miracle cures. But it's also stupid to discard out of hand things for which evidence is unclear just because your opponent is irrationally keen on it.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-c...
[1]https://twitter.com/SpoxHHS/status/1298001649798197248?s=20
Also see.. FDA Walks Back Claim of Dramatic Benefit From Covid Therapy https://www.bloomberg.com/news/articles/2020-08-24/fda-trump...
Trump mentions it and suddenly it’s the worst idea in the world.
I have zero problems with calling out Trump on his hyperbole. It's not helpful at all. But it would be nice if the MSM didn't bash things these previously praised just because Trump said something.
You have a ton of studies that says "no" and a few that say "maybe". But you want us to what? Keep studying until it finally says "yes"?
"Check this out, it shows promise"
"Ok." "Oh, it's not as effective as initially thought"
"Ok, but this study says it might be"
"Ok, but we just did a full study that says it's not"
"Ok, but this study"
And on and on. At what point do you say, "Ok, I guess we should move on".
It was never discarded out of hand.
If someone says "Take this magical cure, maybe it could work... but I don't have any evidence of it yet", it's not so terrible to start from a position of skepticism. Could hcq work? Maybe, although with every randomized trial it seems less likely. But the people who initially pushed it did so from a position of wishful thinking, not actual science. This might have been a hoax of ignorance not evil, but in the end, I say it's still a hoax.
No, there were Chinese, French and other reports and observational studies during the pandemic that supported use of HCQ:
>"Wuhan was the epicenter, and the Chinese physicians at the People’s Hospital of Wuhan University told their Western counterparts that they got the idea of using HCQ because none of the 178 patients they had admitted for COVID-19 had lupus—a surprise, since lupus is an immune disease, and some thought it might have made these patients especially vulnerable. They wondered why this might be, and whether HCQ, which these patients had been taking for this preexisting condition, might in some way be protecting them against COVID-19."<
taken from "Hydroxychloroquine: A Morality Tale":
https://www.tabletmag.com/sections/science/articles/hydroxyc...
At that time, the only responsible answer, and the answer that any biomedical scientist with integrity would give is: "Early results show X, though further follow up studies would be needed to replicate these results to confirm their validity"
But that's not what we got. What we got was a binary split between miracle cure and worse than homeopathy, depending on which side of the political divide you were on.
I argue that when someone declares, without evidence, that "X works", that is a hoax and should be criticized. Even if later evidence shows it works! Because it's easy to make a random guess, and it's hard to fight the collateral damage that wrong guess can cause.
There are a million things that might be the covid miracle cure (colloidal silver? high protein diet? grapeseed extract? etc, etc, etc). If I pick one of these on a hunch and start pushing it as a cure, I would rightly deserve to be called out.
Now that some monthes have passed, at least five peer-reviewed RCTs were conducted. In each of them hydroxychloroquine is ineffective.
Trump isn't pushing sound science.
He's hoping to buffalo people (like you) into thinking he's on to something. AND THE MEDIA IS SO AGAINST HIM. EVEN THO IT REALLY HELPS THE FAKE NEWS JUST WANTS TO HURT HIM. BECAUSE THEY LOVE HILLARY
Dr. Zelenco was working with the FDA to get a trial of his protocol. The FDA director provided some help to get his trial started. The director got criticism for helping. Something about a small trial not being worth his time. I don’t know where this criticism/pressure came from. But this has politics written all over it.
Dr Zelenco made one mistake stating that he had FDA approval to run the trial. The truth is that he had his hospital approval. The district attorney was looking to prosecute him for this mistake. I believe it was a simple mistake. He is not versed in running trials. He was told his trial was approved. He failed to distinguish who made the approval. The DA getting involved is more politics. His trial never got run, probably because of DA pressure. I believe he is a good doctor and has not been discredited. Railroaded by politics more likely. You should be asking why no one wants to test HCQ+Zinc. Why is HCQ condemned without running this most obvious of necessary trials. Why is there no urgency to run a trial on HCQ+Zinc. Why is the media silent on the lack of Zinc in the trials. It might not work, but a trial is more than warranted.
He did one other thing I’m aware of which was to tell his community the current scientific projections of mortality of Covid19. Those projections have proven wrong, and his community blames the messenger.
https://respectfulinsolence.com/2020/04/03/zelenko-smith-aba...
What ethics violations? Please provide a cite that says "Zelenko has been thoroughly disgraced for ethics violations" or even charged with any ethics violations. You're slandering him.
And why are doctors giving untested treatments to patients?
But there are plenty of reasons why antibiotics are given to people with Covid-19 to deal with secondary infections.
> And why are doctors giving untested treatments to patients?
This seems a pretty bad-faith comment. In the early days of COVID-19 there was no "tested" treatment, so doctors use reasoning to try to find something. This is a completely normal thing to do.
Doctors are not researchers and they shouldn't be.
It's not a bad-faith comment.
"Azithromycin Induces Anti-Viral Responses in Bronchial Epithelial Cells" has over 220 citations. (https://pubmed.ncbi.nlm.nih.gov/20150207/)
This is a weird question. By "we" do you mean the media or politicians or scientists?
Politician should not ever be making claims that aren't backed up by strong studies. It's fine to say "I'm hopeful this will prove useful" etc, but to advocate for treatment using unproven medicines is irresponsible.
The media has a pretty difficult job here. Medical studies (particularly early ones) on treatments are rarely decisive (because doctors are trying anything to save someone's life, and that creates co-founding factors. Generally trying for balance ("this is a good study with promising results. Others show different results, and the differences are X and Y. Specialist Dr ABC says "XXXX") is about the best someone can do.
Scientists should keep studying it until we understand what is causing the different responses.
To keep studying it would be to appease either the politicians or media.
In science, failure is actually an option.
Well results seem conflicted on this. This very study (the one linked here!, ie[1]) shows a significant result.
It's an observational study, but that is a normal part of the scientific process during medical research.
There are plenty of other studies showing no result. But this is hardly the only one showing positive results.
So I don't think the science is settled on this (and it would be astonishing if it was in the 4 months since this process started!). I think Trump's behaviour on this has been atrocious and has caused harm, but that doesn't mean anything regarding if it works or not.
[1] https://www.sciencedirect.com/science/article/pii/S092485792...
This site has a good summary of all the studies that have been done on HCQ treatment of Covid-19.
Some smart French guy debunked this site https://threadreaderapp.com/thread/1284493669895041024.html And c19trials, another disinformation piece from the same authors.. https://threadreaderapp.com/thread/1291126570392924160.html
I think given that Doctors such as Simone Gold are being fired simply for stating that there's scientific evidence that HCQ can treat Covid-19 it's somewhat expected that sites such as this will be done anonymously.
Only a fool or someone just looking for confirmation would take an anonymous sham of meta-analysis seriously.
2. No mention of zinc supplements, which seems to be the key to make the Hydroxychloroquine effective
Clearly not.
Zinc has antiviral properties. It has been shown to stop Sars Cov2 replication in-vitro. Cells limit their Zinc intake. HCQ facilitates Zinc getting into cells.
So I'll see, for example, some otherwise-highly-credible UCSF researchers mention a bunch of evidence they think puts the potential of HCQ to help to rest, without any mention of Zinc considerations (even in passing, or to ridicule, or to share why they don't think the link credible). But even coincident upon the very 1st discussions of HCQ as having potential, Derek Lowe shared an anecdote about how carrying-Zinc seemed essential to Chloroquine-related-compoounds' bioactivity (https://blogs.sciencemag.org/pipeline/archives/2020/03/20/ch...).
And, in many parts of the world, HCQ – as a cheap drug that, in moderate doses with proper monitoring, is very low-risk – is already considered part of the Covid-19 "standard-of-care". So, it's given even to the 'control' arms of trials for other compounds – making both its effects, and those other compounds' effects, harder to disentangle.
All I want now is true randomized trials - and can't at least one of those monitor, or vary the supplementation of, Zinc as well?
In vitro results are much less meaningful than in vivo results. It can be a useful early validation step, but is far from telling us anything about real world efficacy.
There's enough in vivo studies at this point that in vitro studies should no longer be part of the conversation.