"Hydroxychloroquine:The Black Knight of treatments for COVID" Topic

From Dr. David Gorski's blog: link

Truly, hydroxychloroquine is the Black Knight of drugs to treat COVID-19. Monty Python fans will immediately know what I'm talking about, but for those who aren't familiar with the hilarious scene to which I refer, the Black Knight is a fictional character from Monty Python and the Holy Grail. In the film, King Arthur encounters him guarding a rather pathetic bridge and asks him to join his quest to seek the Holy Grail. The Black Knight refuses and then blocks Arthur's passage with a menacing, "None shall pass." The battle is joined, and Arthur, one by one, chops off all of the Black Knight's limbs in a truly warped comedy sequence. After losing each limb, the Black Knight says things like, "‘Tis but a scratch" and "I've had worse." Before his last leg is chopped off, the Black Knight proclaims (while hopping around), "I'm invincible," to which Arthur retorts, "You're a loony." After losing his last limb, the Black Knight finally concedes, "All right, we'll call it a draw." Then, as Arthur crosses the bridge and rides off, the Black Knight yells, "Oh. Oh, I see. Running away, eh? You yellow bastards! Come back here and take what's coming to ya! I'll bite your legs off!"

The reason the sketch is so funny and has become such a classic since the movie was released during 1970s, to the point that almost everyone recognizes it just by reference to the Black Knight, is, of course, due to the extreme disconnect between the Black Knight's overconfidence and his rapidly declining limb count. (The bleeding from each limb stump is also so obviously fake and absurd that it contributes to the ridiculousness of the entire scene.) If you apply the sketch to the situation with respect to hydroxychloroquine as a treatment for COVID-19, you can quickly see where I'm going with this. Initially (on the surface at least), like the Black Knight versus Arthur, hydroxychloroquine looked fairly formidable as a potential treatment for COVID-19 based on anecdotal evidence. It wasn't long, however, before the drip-drip-drip of negative studies soon rendered hydroxychloroquine a stump of a treatment, one limb at a time. Examples included the publication of a randomized controlled clinical trial of the drug as post-exposure prophylaxis that was entirely negative. This was followed by two more, first, a Spanish post-exposure prophylaxis trial that was also negative. Then there was the Recovery Trial from the UK. Most recently, last week the New England Journal of Medicine published a clinical trial of 667 patients with mild-to-moderate COVID-19 randomized to receive placebo or hydroxychloroquine (with and without azithromycin, yet!), with the primary outcome being clinical status at 15 days. It was completely negative. Two weeks ago yet another randomized controlled trial of hydroxychloroquine was published in Clinical Infectious Diseases. It was a Spanish trial of 293 non-hospitalized patients with mild COVID-19. Guess what? It was negative. No benefit was observed with hydroxychloroquine beyond the usual care. None of this stopped a Yale epidemiologist named Harvey Risch from publishing a risibly, embarrassingly inept defense of the evidence base for hydroxychloroquine, which I interpreted as the Black Knight losing his last leg.

So last week, the Black Knight was reduced to a stump. This week, we hit the part of the scene in which, as Arthur pretend-gallops off using coconuts to simulate the sound of horses' hooves, the Black Knight is yelling, "Oh. Oh, I see. Running away, eh? You yellow bastards! Come back here and take what's coming to ya! I'll bite your legs off!" Yes, the frenzied promotion of hydroxychloroquine for COVID-19 has gotten just that ridiculous, with the release on Monday of a video produced by Breitbart featuring a group of doctors portentously calling themselves "America's Frontline Doctors" that was viewed 17 million times on Facebook in just eight hours,

This Hydroxychloroquine saga will live in infamy…

Cheers,
Martin from Canada

Sorry, HQC works:

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Careful, there's no patent on HQC.

From last week's editorial column in JAMA: [emphasis mine] link

Several recent experiences in the public arena exemplify concerns about a cacophony of scientific claims regarding candidate therapeutics. In the case of hydroxychloroquine, initial reports of benefit were followed by the initiation of multiple clinical trials using randomization across the spectrum of relevant populations. While these trials were accruing, multiple observational studies were published, claiming to show either no benefit or harm, and one very large published study received sharp criticism from experts and immediate calls for retraction due to methodological flaws and concerns about data provenance.6

However, despite the refrain that RCTs are needed, the lay and scientific press amplified various estimates of treatment effect, while at the same time hydroxychloroquine was promoted in the global political arena. The fact that a high-profile study incorporating observational data was later retracted6 is in some ways less relevant: during the brief interval when the study data were thought to be valid, many (including some international regulators) were duped by the method, turning the conclusion of "evidence from RCTs is needed" into a movement of "RCTs should cease." However, several pragmatic RCTs were conducted, and definitive findings of no benefit for hydroxychloroquine in hospitalized patients with COVID-19 have been announced.7,8

At the moment the best reliabe evidence states that HQC is no better than quackery such as Traditional Chinese Medicine and Homeopathy. That's not good company.

Should have read HCQ.

No patent, just proven effectiveness.

no better than quackery such as Traditional Chinese Medicine

What was that about xenophobia and sinophobia?

So according to that article, are we to jail Dr. Fauci due to his incompetence as a doctor? He failed to comprehend the studies he recently quoted in public? Or do we jail him because he has effectively murdered thousands of Americans by deliberately denying (for some reason) the effectiveness of this drug?

wmyers +1

Silurian
And no we shouldn't jail him for incompetency, but we should certainly fire him.

I could see class-action law suits being considered and prepared.

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TCM started as a stopgap after the Chinese revolution to cover for the lack of doctors in China. When Mao was sick at the end of life, he went for western style medicine over TCM.

Unfortunately, the government also looks at traditional Chinese medicine (TCM) as part of their cultural pride. This is very much in line with Chairman Mao who engineered the resurgence of TCM and instituted the barefoot doctor program, to fill the gap in medical care for the Chinese people.

In essence, China could not provide actual medical care for its population (well, decided no to allocate proper resources to do so), and instead leveraged cultural pride to convince people that what they really wanted was TCM.

TCM is a collection of pre-scientific practices based in superstition – the Eastern equivalent of blood letting and drilling holes in the skull to release evil spirits. Modern TCM has tried to sand down some of the rough edges, but it is still nonsense all the way down. link

More specifically, TCM is the same boat as Homeopathy in that they routinely fail to show any effect in double-blind RCTs. My bias against TCM isn't because it comes from China, but rather that it fails to show results. Reminds me of a joke an MD I know keeps saying: "What do you call alternative medicine that works? Medicine.".

Wow. So there is exactly zero evidence for HCQ being effective, and yet people are pumping for it here on a gaming site?

What the actual heck? How is this not politics of the first order? The only argument for this drug's effectiveness is political!

Why is this even being discussed here?

+1 Dave. The science boards have been political for many months.

More like years – started with AGW.

We can debate whether or not hydroxychloroquine helps COVID but we cannot debate on whether or not it is safe.

It is FDA approved and has been around for 65 years.

They give it to pregnant women.

After a certain USA president endorsed it, political opponents launched a full scale attack.

They conducted a test by giving patients three times the recommended dose. If you give a toxic dose, you're going to get a toxic result. They falsified the results to support their political agenda.

But I believe multiple tests, repeatable with all the correct controls, have been conducted around the world.

It also can cause problems for people with heart trouble. It has been studied again and again and there is zero evidence that is effective against Covid. Certain presidents are pretty much the only people pushing it.

So how is discussing it not political and what possible relevance does it have to miniatures wargaming?

So how is discussing it not political and what possible relevance does it have to miniatures wargaming?

+10!

The "what does this have to with miniature wargaming query" is a horse than has long left the barn. It's a ship that has long sailed.
The Plus boards were set up specifically to cover that.

HCQ is marvelous in treating malaria and lupus.
For Covid, it has never shown any real statistical value.
Just like leeches are fine for treating swelling in plastic surgery, but not for diabetes.

But, hey! This is the TMP Science Board! Believe what you want.
It certainly is not as important as JAMA or The Lancet.

Howdy,

I found the article below quite interesting.

- snipped – There are now 53 studies that show positive results of hydroxychloroquine in COVID infections. There are 14 global studies that show neutral or negative results -- and 10 of them were of patients in very late stages of COVID-19, where no antiviral drug can be expected to have much effect. Of the remaining four studies, two come from the same University of Minnesota author. The other two are from the faulty Brazil paper, which should be retracted, and the fake Lancet paper, which was.

Millions of people are taking or have taken hydroxychloroquine in nations that have managed to get their national pandemic under some degree of control. Two recent, large, early-use clinical trials have been conducted by the Henry Ford Health System and at Mount Sinai showing a 51% and 47% lower mortality, respectively, in hospitalized patients given hydroxychloroquine. A recent study from Spain published on July 29, two days before Margaret Sullivan's strafing of "fringe doctors," shows a 66% reduction in COVID mortality in patients taking hydroxychloroquine. No serious side effects were reported in these studies and no epidemic of heartbeat abnormalities.

This is ground-shaking news. Why is it not being widely reported? Why is the American media trying to run the U.S. pandemic response with its own misinformation? – end snip -

realclearpolitics.com/articles/2020/08/04/an_effective_covid_treatment_the_media_continues_to_besmirch_143875.html?fbclid=IwAR0HdwccdMQ0jxWdVhKnuwP1A2MsFQxKhdcEIBFdT2-sWUheePTtk66EHEA

Ponder on,

JAS

The Henry Ford study had poor design, it's a retrospective study without blinding, ignores/fails to model multiple confounding variables (DNR orders, frailty of the patient, severity of malady(Paper suggests that worst cases were given palliative care rather than medical intervention)). Until you get a proper double blind random controlled trial trial that shows promise, this is simply a loud anecdote. And if anecdotes were useful, the field of statistics wouldn't exist ;-).

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The Henry Ford study had poor design.

…

this is simply a loud anecdote. And if anecdotes were useful, the field of statistics wouldn't exist ;-).

Please remind us what your area of study is again?

This is ground-shaking news. Why is it not being widely reported? Why is the American media trying to run the U.S. pandemic response with its own misinformation? – end snip -

I just read a piece that I think is directly related to your question.

Dr James Todaro has launched a website called Medicine Uncensored. He states that "The influence that the pharmaceutical industry wields over media outlets is no secret…An estimated 70% of all news advertising in the US came from pharmaceutical companies."

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medicineuncensored.com

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When discussing "America's Frontline Doctors"

In addition, there were several other doctors, including an ophthalmologist and founder of a cryptocurrency company named Dr. James Todaro; a emergency medicine doctor named Dr. Simone Gold known for promoting hydroxychloroquine; another emergency medicine doctor named Dr. Dan Erickson, co-owner of a chain of urgent care centers in Bakersfield, CA who made a name for splash in April with a poorly conceived and carried out "study" full of bad epidemiology that concluded that COVID-19 was far more widespread than thought and that the infection fatality rate was far lower than thought; Dr. Joseph Ladapo, an associate professor of medicine at UCLA and an ardent proponent for the "open up the economy" message who has downplayed the lethality of COVID-19; and Dr. Robert C. Hamilton, a Santa Monica pediatrician who argued for reopening the schools in the fall based on cherry picked studies and information and also made his political orientation very clear with a gratuitous swipe at teachers' unions in his part of the video (Gizmodo later reported on a letter he wrote in the 1990s expressing anti-homosexual bigotry); and Dr. Richard Urso, an ophthalmologist who has been touting hydroxychloroquine for COVID-19 and claims never to have seen a patient with a heart issue attributable to the drug.

Unsurprisingly, MedPage Today reported that there's no evidence that any of the doctors in the video got near the "COVID front lines". Over several days last week, the claims of these doctors were thoroughly refuted, in particular the claim that hydroxychloroquine is, in essence, a cure for COVID-19 that eliminates the need for social distancing and masks to prevent the spread of coronavirus. In fact, more and more, the evidence is trending strongly in the direction that hydroxychloroquine doesn't work. What this incident demonstrated very clearly is that, not only are most people unable to evaluate medical claims, but there are a lot of actual physicians out there who are similarly unable to evaluate certain medical claims. It is very telling that these physicians consisted of ophthalmologists, emergency medicine doctors, and doctors who don't actually have any expertise in virology, epidemiology, clinical trials, or the treatment of COVID-19. This is not a knock on ophthalmologists, emergency medicine doctors, etc., but rather an observation I use to make a point. Even experts in medicine frequently go astray when they wander outside of their field of expertise, particularly when the belief that they want to accept is linked somehow with their sense of self. In this case, it was the politics. These physicians all support President Trump, and President Trump has promoted hydroxychloroquine, downplayed the seriousness of COVID-19, and strongly pushed for the schools reopening, even when there is still doubt about whether it is safe to do so in many areas where the virus is still running rampant.

Basically, like any lay person, when faced with beliefs that they wanted to embrace, "America's Frontline Doctors" engaged in motivated reasoning and sought out observations, evidence, and cherry-picked studies to give them a reason to support the belief, regardless of whether science actually did support the belief or not. Worse, they very intentionally used their status as physicians to promote those beliefs and persuade lay people to believe them, too. It worked to some extent, as well, although it would have worked a lot better if "America's Frontline Doctors" had left Dr. Immanuel out of their membership. Her history of claims involving alien DNA and that gynecological problems like cysts and endometriosis are in fact caused by people having sex in their dreams with demons and witches led the hashtag #DemonSperm to trend on Twitter and provided an easy approach to debunking and discrediting her and, thus, the entire group. (It didn't help that she called doctors doubting hydroxychloroquine fake doctors and the negative studies of the drug "fake studies," all while accusing those same doctors of being like the "good Germans, the good Nazis" who "watched Jews get killed" and didn't speak up.) Indeed, it wasn't long before Dr. Hamilton sent out an open letter to the parents of his patients disavowing Dr. Immanuel's hydroxychloroquine claims and the claims of other doctors that facemasks are of "no value" in combatting the spread of COVID-19.

Please remind us what your area of study is again?

Financial Geographer, with research interests in institutional investment, spatial stats and big data.

Please remind us what your area of study is again?

Ok. Martin has done what you asked. Asked and answered.
It means that he knows how to look up stuff, and dig deeper than … the usual sensational sites.

Your turn now. What's your field of expertise?

Nice to see you again John the OFM.

Oh, it's not whether or not Martin should be able and capable of looking something up. It is completely whether or not he is a qualified expert in the field, by his own standards, and should therefore even be commenting; based upon his own standards.

Unfortunately, a lot of the recent problems afflicting TMP have been stated to be because of a "toxic environment".

Sadly, it seems many (some have stated most) posts are simply belittling others and throwing around phrases that ridicule, etc.

One example is going off and trying to claim that a colleague had no business talking about AGW because he tried to claim he was completely unqualified to do so, when one of his areas of expertise is paleoclimatology.

TMP link

Of course, it seems perfectly fine when the shoe is on another foot…

Oh, it's not whether or not Martin should be able and capable of looking something up. It is completely whether or not he is a qualified expert in the field, by his own standards, and should therefore even be commenting; based upon his own standards.

Where have I claimed any medical expertise? I've leaned heavily on experts outside of my own field of expertise, but I always make sure to put links in my posts. Let me tell you, relying on argumentum ex-culo would save me a large amount of time, but I don't since it's not an honest way to debate.

One example is going off and trying to claim that a colleague had no business talking about AGW because he tried to claim he was completely unqualified to do so, when one of his areas of expertise is paleoclimatology.

However, what Dr Pratt has said completely fails to engage with the consensus literature nor does he say where or why the consensus literature is wrong. Since the onus is on Dr. Pratt to challenge the consensus literature, it can easily be dismissed. I'm not casting aspersions to Dr. Pratt's professional expertise in identifying various forms of fossilized worms and trilobites, or examining the evidence for ancient earth quakes, but I am casting aspersions on his climate work for failing to interact with the consensus literature.

I hope you notice an underlying theme. Science (human and natural) is a highly complex system of evaluating Truth, and for all of the scientific method's flaws and institutional blindspots, it is the least bad method we have devised for approaching asymptotically towards Truth. Outside of my area of financial geography, I know that I do not have the lifetime of knowledge (nor the time needed to get up to speed) to properly evaluate statements. Therefore, I rely on scientific consensus – and that only exists when the overwhelming majority of experts in a field hold the same professional opinion. When we "do our own research", what we're really doing is scouring the web for tidbits that confirm our suspicions or cast our interlocutor's position in the worst possible light.

But don't take my word for it. Ethan Siegel has a really good article (with a horrible title, but that's usually the editor's job not the author) on this called "You Must Not ‘Do Your Own Research' When It Comes To Science" on Forbes a few days ago.
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All I can say about this is anecdotal. My wife's close friend Martinha from Brasil developed COVID. She started getting worse and was hospitalized on Sunday. The doctors there put her on Hydroxycholroquin along with 2 other medicines. WITHIN 3 HOURS she had greatly improved and felt that she could breathe fairly normally. She was able to go home the next day to be quaranteed at home. She called my wife and talked to her normally yesterday. She is a relatively healthy woman in her mid 40s. What she can't stand right now is the fact that she cannot taste anything.

One other thing I know about the drug is that my dad took it everyday when he was in Vietnam to prevent Malaria. So it was considered safe in late 60s. I took it when I went to the Pantanal in Western Brazil in the late 90s and it was safe then. (The Pantanal is a swamp that is bigger than France!) It seems that it has only developed major health dangers in the past 5 months.

Study: c19study.com

Wolfhag

"We need to act out of science," not out of a generated fear.

When the information is changed to a narrative that is then controlled, cancel culture becomes the consensus.

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Alternative view, Media is finally realsing that when lives are on the line they need to do their jobs as gatekeepers and keep quakery out of the news.

None of "America's Frontline Doctors" have first hand experience with treating COVID-19 (link, link ), they don't have any relevant expertise in infectious disease or epidemiology (ibid), their advice runs contrary to the public health consensus for medical and non-medical intervention (ibid).

At the end of the day, not everybody deserves a platform, and giving somebody that is pants on head equal billing with a bonafide expert is simultaneously giving the crank too much credit and denigrating the expertise of the expert. I'm not say that debate should be verboten, but rather there's a time and place for it – science journals and conferences, not mainstream media or social media.

Best not to make statements that you cannot verify.

Martin, both of those fringe links are part of the problem you identified.

The former is an opinion piece with no verified information and the other seems like your way of trying to slip in some AGW alarmism into another subject area.

There were other frontline doctors you made the same claims about:

YouTube link

Wow, you're going with the Bakersfield Quacks as your rebuttal? Talk about putting the puck in your own net. These two clown made the "elementary mistake" of not using a representative sample, and then extrapolated from there. This wouldn't cut it from an undergrad. The proper term for this is selection bias.

There are mathematical workarounds – for example, re-weighting their data to match the population – but they give no hints of doing this in the first place, and even then, the re-weighting is a tricky to nigh impossible to do without a strong prior on which to base your underlying distribution.

And the misericorde though the eye slit – to keep with the Black Knight theme:

AAEM-ACEP Joint Statement on Physician Misinformation

The American Academy of Emergency Medicine (AAEM) and the American College of Emergency Physicians (ACEP) jointly and emphatically condemn the recent opinions released by Dr. Daniel Erickson and Dr. Artin Massihi. These reckless and untested musings do not speak for medical society and are inconsistent with current science and epidemiology regarding COVID-19. As owners of local urgent care clinics, it appears these two individuals are releasing biased, non-peer reviewed data to advance their personal financial interests without regard for the public's health.

COVID-19 misinformation is widespread and dangerous. Members of AAEM and ACEP are first-hand witnesses to the human toll that COVID-19 is taking on our communities. AAEM and ACEP strongly advise against using any statements of Drs. Erickson and Massihi as a basis for policy and decision making.

Approved: 4/27/2020
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And Dr. David Gorski's take on those two clowns with MDs.
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So, YouTube link

Odd isn't how a drug take daily by millions for over 5 decades isn't safe when new expansive drugs are being touted?
As they say, follow the money.

If I get it if I have to get to Mexico to get HCQ I will.

Odd isn't how a drug take daily by millions for over 5 decades isn't safe when new expansive drugs are being touted?
As they say, follow the money.

It's a matter of risk vs reward. For example a competent surgeon can open you up and physically examine your liver and sew you back up and you're probably not worse for wear 6 months from now. However, if a non-invasive test would give your physician the same info, the ethical thing to do is order up the non-invasive test over ordering up the surgery since the non-invasive test has less downside risk, and doesn't put exploratory surgery off the table. HQC has some non-insignificant side effects, and when the situation demands it (IE. lupus or severe rheumatoid arthritis), consensus amongst physicians is that it's worth it.

However, with regards to COVID-19, HQC has the same number of positive double blind randomized control studies as acupuncture and homeopathy – which is none.

Also, good luck crossing international borders with a communicable disease.

consensus amongst physicians

You can only have consensus when all are allowed to fairly participate and not be cancelled.

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good luck crossing international borders with a communicable disease

Just how do you think we got to where we are in the world today?!

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So let me get the facts here, Dr. Kulvinder Gill is a doctor that specializes in Pediatrics – not infectious disease – and is currently at odds with College of Physicians and Surgeons of Ontario jumped on the crazy train to Hydroxychloroquine. Professional organizations do serve an important gatekeeping role in protecting the public from quacks. From the CBC article:

In an email to CBC News, the CPSO said it doesn't comment on ongoing investigations.

"It's important that physicians recognize the influence they may have on social media, particularly when it comes to public health. The CPSO believes questioning the value of vaccinations or countering public health best practices during COVID-19 represents a risk to the public and is not acceptable behaviour," wrote a spokesperson for the CPSO.

"Physicians who are found to be spreading misleading medical information that may bring harm towards patients can face practice restrictions or suspension for their actions."

So let me get the facts here, Dr. Kulvinder Gill is a doctor that specializes in Pediatrics – not infectious disease

As you said, let's get the facts straight here. You specialize in what?

And you're criticizing her?

quacks

So when is the time to raise concerns about a rushed vaccine?

But apparently, someone will report you for that …

She is the President of the Concerned Ontario Doctors (COD) and has been for a number of years. COD represents about 10,000 frontline doctors.

carenotcuts.ca

Based on your comments, you obviously think you know more about medicine?

So when is the time to raise concerns about a rushed vaccine?

Look at Steven Salzberg's evolution vis-a-vis the bypassing stage 3 trials.

I wrote a blog post over the weekend that has generated tremendous pushback, including an op-ed in the New York Times as well as thousands of comments on Twitter.

In my previous post, I suggested that while we're pursuing Phase 3 testing of several promising Covid-19 vaccines, we could simultaneously offer those same, unapproved vaccines to a wider community of volunteers, as long as those volunteers were fully informed. The benefits of moving quickly, I argued, would outweigh the risks.

I was wrong. After reading many of the responses to my article, some of them outlining the risks in greater detail, I have concluded that (1) the risks are greater than I presented them, and (2) the benefits are not as great as I had thought.

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