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I think IVM advocates started gaining popularity- with very loud lack of interest from most scientists- before the media started commenting.

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"I'm not 100% sure why Strongyloides emerged as the top contender"

From quick noodling around because it's often prevalent in a lot of places, prevalence is unrecognised, it causes a bunch of symptoms that can be mistaken for other things, and medical professionals don't tend to test for it regularly so are unaware if a patient is suffering from an infestation.

https://www.racgp.org.au/afp/2016/january-february/chronic-strongyloidiasis-don-t-look-and-you-won-t

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.... university administration, ....

That was hilarious. Thank you for that - made my day.

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Short rule of thumb for me. If Alex Jones is on the side of something, it isn't worth even considering. There is too much going on in life

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author

Have to sort of disagree with EY on this one.

You've got "stupidity" in the sense of a bad world model that produces random conclusions, but then you've also got "stupidity" in the sense that smart people have looked at an idea and think it's dumb. The first one isn't anti-correlated with reality, but the second one definitely is- and there are things that can selectively bias people in favor of that sort of thing. For example, when experts and credible sources disproportionately belong to a political class that you oppose, when you rely for your livelihood on the attention that comes from being contrarian, when you're enamored by the narrative of being a lone voice of truth in a world of illusions, and so on.

Alex Jones ticks enough of those boxes that him taking a stand on a controversial issue is pretty decent evidence that experts take the opposite stand- which is pretty decent evidence that his position is false.

Also, suppose you've already seen some evidence for and against a position, and have a lot of uncertainty about whether it's true. If you unexpectedly discover that there's a prolific and very dumb counter-culture promoting one side of the issue, shouldn't you wonder whether the evidence you've seen was biased by that group's efforts and adjust your credence accordingly? Reversed stupidity may not be intelligence for a blank slate, but if there's any chance you've been influenced by stupid, reversing it by a proportional amount just seems prudent.

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I'm surprised Scott didn't link to this instead:

https://slatestarcodex.com/2019/02/04/respectability-cascades/

Scott has better epistemic hygiene than Matt Ball.

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Feb 1, 2023·edited Feb 1, 2023

"They're turning the frogs gay!" isn't a theory that environmental endocrine disruptors are affecting sexual development in amphibian populations. It's a theory that the US government is using chemical warfare as a form of population control by feminizing men and turning them gay to stop procreation. One of the side effects of this plot is that now most frogs are homosexuals. Suffice it to say, Alex Jones is wrong about this.

Alex Jones was using a bit of pop coverage about a known scientific phenomenon, distorting it, and folding it into a ludicrous conspiracy theory. Being suspicious of Alex Jones endorsed conspiracies doesn't require you to dispute every single detail found in them, however strained.

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Feb 2, 2023·edited Feb 2, 2023

I don't know. How many? I suspect not a lot. I'm not sure the answer is greater than zero. The causality is oddly inverted here as Jones's conspiracy theories trade on popular media coverage of scientific findings.

What we have is a Scott Alexander anecdote where Scott brings up in polite company that what Alex Jones was talking bout was actually real and feels admonished for this. There's not much we can make of that, though it is notable that what Alex Jones was talking about wasn't real if you actually understand what his whole rant about the frogs being turned gay is about, so there's that.

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If you assumed that what Alex Jones says must be wrong, then you'd assume he was wrong about them turning the frogs gay (whether it's a side-effect or regardless of intentionality).

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Feb 2, 2023·edited Feb 2, 2023

Do you think the person was asserting that if Alex Jones believe it is a good idea to breath air, then Alex Jones must be wrong? I think we're able to give credit to how people colloquially communicate ideas and presume they probably mean that Alex Jones is apt to be on the wrong side of issues controversial issues that aren't conventionally accepted among people with greater credibility. That's usually what people mean when they express something like this.

If the response is, "But he wasn't wrong about the gay frog thing!," then I think it is worth noting that he was, in fact, wrong about that, both in the particulars of the assertion and what theory he was trying to communicate with that. That he loosely based it on a widely covered phenomenon that isn't all that controversial misses the point.

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Yes, but let's face it: This is some noise-ass, low-veracity Bayesian evidence, to be fair, and probably shouldn't budge your needle much in one direction or the other.

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If you know someone to be a pathological liar, disbelieving everything they say that you can't independently verify is not only a good bet, I would argue it's your ethical duty.

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No, it gives that pathological liar an easy means of convincing you of falsehoods.

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Feb 1, 2023·edited Feb 1, 2023

The key here is that there has to be another "side" in the argument that the pathological liar is diametrically opposed to. If propositions imply that one is false and one is true, you can make safe inferences on the other position based on which side the liar is on.

Obviously most issues aren't that clean, but as a heuristic, it could be a lot worse.

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The Nazis were well known for lying. And when they found a bunch of bodies in the Katyn forest and blamed it on the Soviets, the natural assumption would be the Nazis were blaming one of their own numerous massacres on another "side". But they were actually telling the truth in that instance, and your heuristic would repeatedly fail if you assumed the opposite side of a known liar must be a truthteller. It's entirely feasible for two liars to be opposed to each other.

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That's the other obvious failure mode of this heuristic, yes. But the majority of people are not outright liars, especially in the scientific community, so it's still useful in this instance and many others. (Also, it should go without saying that no individual failure of a heuristic makes it invalid; the existence of solar eclipses does not make the "dark outside -> it's night time" heuristic useless.)

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disbelieving != believing the opposite

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This was during the southeast Delta death surge…ivermectin as prescribed in Florida is clearly ineffective:

A recent study examining trends in ivermectin dispensing from outpatient retail pharmacies in the United States during the COVID-19 pandemic showed an increase from an average of 3,600 prescriptions per week at the pre-pandemic baseline (March 16, 2019–March 13, 2020) to a peak of 39,000 prescriptions in the week ending on January 8, 2021.1 Since early July 2021, outpatient ivermectin dispensing has again begun to rapidly increase, reaching more than 88,000 prescriptions in the week ending August 13, 2021. This represents a 24-fold increase from the pre-pandemic baseline. (Figure)

https://emergency.cdc.gov/han/2021/han00449.asp

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Unfortunately patient self advocacy is like playing chutes and ladders. Encounter a medical problem for you or your loved one and find out- there's no hand holding

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That's literally the same as arguing that eating sugar is bad because Hitler ate sugar. So if Alex Jones said that eating healthy is good then all reasonable people should go eat only fries at McDonalds 3 times a day 7 days a week?

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This is a false equivalence, because Alex Jones believes lots of true things he doesn't put on his show. What he chooses to put on his show is filtered for controversy and sensationalism. Nothing he puts on his show will be anything people generally agree is true.

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Well if you want to believe everything that people generally agree is true then you can just do that and cut out the Alex Jones involvement.

Believing everything that people generally agree is true is a pretty good strategy in life. You'll be right more often than you're wrong, and when you're wrong then at least you don't lose too many friends over it.

But if you're happy to just follow the believe-what-everyone-else-believes strategy then you needn't waste your time reading rationalist-adjacent blogs like this, which are about the often-quixotic struggle to do ever so slightly better than the general consensus.

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Feb 1, 2023·edited Feb 1, 2023

Well, I don't think that it's quite this simple these days, as compared to say 70 years ago. To an extent, there are now two mainstreams, the "establishment" and "anti-establishment" ones, to vaguely gesture at their essence. Many reasonable people believe that certain prevalent and high-status expert endorsed narratives are thoroughly wrong or "not even wrong". Arguably, Alex Jones serves a useful role in trawling through the "anti-establishment" thought-space and gathering all of its worst trash in one place. I wonder if there's an "establishment" equivalent.

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70 years ago there was also an establishment and an anti-establishment. The anti-establishment included Civil Rights activists, draft-resisters, folk/rock musicians, etc. And, admittedly, lots of wackos.

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I think the point is that Alex Jones generally airs the opposite of what people generally agree on, so it's still valuable information, thus you shouldn't cut out people like him. If you want to go for "believe everything people generally agree on", it's a lot less effort to watch AJones and believe the opposite, than to go around and ask everyone about what they believe on those same issues.

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Some things are only worth a rough heuristic.

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It's not bad as a first approximation. But to then go on and say that a first approximation is all you need and no one should do further analysis, is stupid.

Jones is, in fact, right sometimes, even when he says controversial things. And some things he's wrong about have decent evidence for them.

Whether a drug has massive value against Covid is certainly a question worth more than a rough heuristic.

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You're giving Alex Jones a hell of a lot of power over you there.

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He seems to be a very powerful person, having caused a gigibucks worth of hurt feelings and all.

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A sensitive instrument is one that can pick up and amplify small signals that others miss, and no doubt this "sensitivity" has been an integral part of what has made your writing as successful as it has been. Getting overwhelmed more easily than you might otherwise be is the other side of that tradeoff, and it's great that you're not letting the tough side of that get in the way of giving things the response you know they're due.

Thanks for taking the time to respond to him, even though it hasn't been fun. I doubt I'm the only one that notices and appreciates the effort.

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> Dr. Ioannidis is known to be unusually rigorous and this is part of his pro-rigor crusade

I'm not familiar with all his work, but I think he deserves a reputation for self-promotion more than a reputation for rigor. I think his most famous essay is "Why Most Published Research Findings Are False", and I think this paper is notable for its sensational headline much more than for its careful analysis.

https://en.wikipedia.org/wiki/Why_Most_Published_Research_Findings_Are_False#Reception

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That's his most famous paper but it's not his most cited.

https://scholar.google.com/citations?user=JiiMY_wAAAAJ&hl=en

He was also involved in this fairly important early paper on COVID seroprevalence

https://pubmed.ncbi.nlm.nih.gov/33615345/

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An important but wrong paper on seroprevalence. That really tarnished his reputation.

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author

I took him to ask about that at https://slatestarcodex.com/2013/02/17/90-of-all-claims-about-the-problems-with-medical-studies-are-wrong/ but I do appreciate a lot of his work, and think that at that point he was one of the few people sounding the alarm at all.

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The early seroprevalence study had quite a few serious problems - but even worse he used it to generalize from non-representative sampling to wrongly characterize the virulence of COVID by a wide margin.

Also:

https://replicationindex.com/2019/01/15/ioannidis-2005-was-wrong-most-published-research-findings-are-not-false/

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And:

It's too perfect that this response to Ioannidis was co-authored by someone (Sander Greenland) who had positive things to say about Alexandros' analysis on Andrew Gelman's blog.

https://journals.plos.org/plosmedicine/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0040168

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Fabulous stuff, all of it.

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I didn't really have an opinion on Ioannidis before COVID times. But during the pandemic, I got a quite poor impression of him.

He was one of the early figures to warn that COVID might be an overrated problem, especially that mortality might be lower than common estimates, and gave his own, much lower estimates, of the problem. Even then I had the impression that his data looked rather cherry-picked. He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions, which would have been more alarming. That data was cleaner than what he took. But this was during the first few weeks of the pandemic, in a chaotic situation, and no data was really good, so that was still kind of ok.

But the real problem was that he didn't update when better studies came out. A year later, he would still stick to his old estimates in public interviews, even though there were much better studies by then, and his estimates were far out of the plausible range. Honestly, it was getting ridiculous.

I know that he deserves big praise for uncovering the replication crisis, but I really think that his performance during COVID was a scientific and Bayesian failure. Perhaps he became hyper-skeptical of studies after the replication crisis (or was so before, which made him detect it). But the issue is that he didn't just concluded "We don't know", but that he concluded "We don't know, so don't take the estimates from the literature, but take my own even more fishy estimates instead." And sticked with that.

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I agree the pandemic was not his best moment.

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Ah, interesting. I've never read SBM before but there's a pretty extensive criticism here

https://sciencebasedmedicine.org/what-the-heck-happened-to-john-ioannidis/

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Wow, thanks for sharing! I didn't know that it was so bad.

It's sad that such a brilliant mind can be trapped in some believe and totally disconnect from evidence about it. There are quite a few tragic cases like this, like physicist Roger Penrose or mathematician Michael Atiyah. Ioannidis is not there yet, but he might be heading that way.

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I'm not necessarily saying I agree with all of the criticism, just surprised to find it all in a neat little package here.

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I didn't really follow what Ioannides did, he isn't a public figure here in Europe. For example, I didn't know about his attacks on the PhD student.

But I noticed some bits, especially in March 2020, and later sporadically when he gave interviews to the news here, and my impression is pretty consistent with the article. It's just that the article contains a lot more of the same stuff.

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When you refer to the tragic case of Robert Penrose, what do you have in mind? His theory of Conformal Cyclic Cosmology, or something else?

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I was rather thinking of his concept of consciousness. He started with the idea that consciousness can impossibly be restricted by Gödel's incompleteness theorem, and thus computers can never become conscious. In more elaborate versions he insists that consciousness is impossible without resorting to quantum gravity effects in the brain. All this is completely detached from any evidence (in fact, there is lots of evidence against it) except for his gut feeling of what properties consciousness should have.

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I think the Penrose and Atiyah cases are somewhat different.

Penrose started going publicly off the rails about Consciousness And All That with "The Emperor's New Mind", published in 1989 when he was 58 and still (so far as I can tell) a genuinely brilliant mind.

Atiyah started going off the rails in his late 80s, when he was fairly clearly losing his mind. This wasn't a matter of a brilliant mathematician/physicist getting taken in by a bad idea, it was a matter of a _formerly_ brilliant mathematician/physicist no longer being able to tell good ideas from bad ones. A very different kind of tragedy.

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Fair point.

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"He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions"

This has probably been argued elsewhere, but cruise ship passengers tend to be older and fatter than the general population. Italy also has a lot of old people.

The sources may be clean from the point of view that the populations are isolated, but they aren't representative in other ways.

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True, and these things need to be accounted for. But this is possible and should be done, and the data should not be completely thrown out of the window. In the Bergamo region with about 1,000,000 people, the number of deaths in March 2020 was six times as high as in a normal month. So this March had half as many deaths as otherwise a whole year! Of course, this can become a bit less worse at other places if you adjust for age.

But Ioannidis arrived at the prediction:

"If we had not known about a new virus out there, and had not checked individuals with PCR tests, the number of total deaths due to “influenza-like illness” would not seem unusual this year. At most, we might have casually noted that flu this season seems to be a bit worse than average. The media coverage would have been less than for an NBA game between the two most indifferent teams."

Granted, this was mid-March 2020, but at this time preliminary death numbers from (smaller) parts of Bergamo were already available. There was just no way to arrive at his conclusion by "adjusting for age". Still, if he had corrected his estimates one or two months later, that would have been fine. But he sticked to them (and actively propagated them) long after the point where they were simply ridiculous.

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Feb 2, 2023·edited Feb 2, 2023

The general population isn't the primary comparison due to age. The cruise ship data WERE controlled by age - but they didn't control for factors like SES - which I think would likely make cruise passengers HEALTHIER (more active, better baseline health, more access to care, etc.) than their age-matched peers

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Feb 2, 2023·edited Feb 2, 2023

I had been quite a fan of Ioannidis.

As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):

https://youtu.be/NTXgbN6uB1I

And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:

https://statmodeling.stat.columbia.edu/2020/04/30/updated-santa-clara-study-of-coronavirus-infection/

Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.

OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.

And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.

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I'm repeating this comment because it appeared to get truncated above? (I'm not familiar with this comment interface)

I had been quite a fan of Ioannidis.

As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):

https://youtu.be/NTXgbN6uB1I

And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:

https://statmodeling.stat.columbia.edu/2020/04/30/updated-santa-clara-study-of-coronavirus-infection/

Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.

OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.

And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.

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typo: contraian

this (thankfully) isn't a typical post, but the extremely detailed, technical analysis of a minor current thing from 2 years ago is peak ACX energy

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This is still a major topic and will continue to be a major topic as long Covid generates millions of disabled ppl

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pedantic typo patrol: "...equal number of studies on both size."

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author

Thanks, fixed.

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We have done an intensive study of viral load dynamics in our phase 2 platform trial. Ivermectin got dropped pretty quickly (pre-specified futility rule was met). In contrast, known effective antivirals such as casirivimab/imdevimab and remdesivir showed an effect on viral load dynamics pretty quickly.

https://www.medrxiv.org/content/10.1101/2022.07.15.22277570v1

https://www.medrxiv.org/content/10.1101/2022.10.17.22281161v1

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Alexandros blocked me on Twitter long ago just for repeatedly asking whether there was one good RCT supporting ivermectin. He apparently runs a startup, yet has the time to write a series of posts that literally total over 86,000 words (a sizeable non-fiction book!) just to respond to ONE blog post from Scott. And he did this over the space of a few months.

In other words, he has been engaged in a 24/7 side hustle--writing a full non-fiction book in a few months -- and moreover, it was all on a very narrow question about whether one particular blogger was mean about a particular drug that supposedly is a miracle cure for Covid (even though no rigorous study has ever shown that). Odd choice of priorities.

And despite aiming towards rationality, he is keen to write thousands of words nitpicking at the tiniest flaws in any negative ivermectin study, even while defending much worse studies or websites that defend ivermectin. Blatant double standard.

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PS, when I spent 5 minutes pasting Alexandros' blog posts into Microsoft Word, the result is 291 pages long (single spaced). Even if someone was unemployed, who has the energy for that kind of monomania?

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I do if it's called "Playing Civilization VI"

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Why not play a better one? Blegh.

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If he doesn't have two toddlers I can say from experience where that time might come from

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author

I think it's probably bad to make fun of people for spending too much time obsessively trying to get things right, even if you think they failed.

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I'd agree. But given the double standard (which you repeatedly and correctly note), he is not "trying to get things right." He's trying to defend ivermectin at all costs -- he comes up with the smallest nitpicks at any study showing that ivermectin doesn't work, while defending much lower-quality pro-ivermectin studies on the grounds that "but there's a STAT article" or "but this guy won a science competition" or some similarly one-sided argument.

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Okay, so what we're generally implying when we accuse somebody of having 'double standards' is that they're deliberately misinterpreting data. But when you're dealing with this much data, and a discourse that spans months, asymmetries in your application of epistemic rigor are bound to emerge.

In my submission, this doesn't really confirm a deliberate misinterpretation of the data. Scott does a reasonably good job being generous about that here.

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Yeah, especially since many here, including me, are prone to doing exactly that. And besides, I'm not sure it's a bad trait. It makes life harder for the person who has it, but it probably also makes them likelier to obsessively try to get something right, and succeed at doing so.

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To be clear, it's not bad to obsess over getting something right. But I think it's to obsess over defending a predetermined position at all costs (have you read my friend Julia Galef's book on the scout mindset?)

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Scott, I admire you for following through on writing this. My guess is that holding yourself to your pledged sucked, but you did it because you'd said you would, and also because you felt bad about some errors of yours Alexandros had pointed out. Jeez, write something you enjoy the hell out of next.

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I absolutely hate this kind of thing. Alexandros can invest his time however he likes. And blocking people for repeatedly tweeting the same thing at you is generally reasonable behavior.

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Yes, he can indeed invest his time in eminently ridiculous ways. Up to him. But it is still subject to ridicule by other people who are interested in what's actually true. If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence.

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I expect Scott put way more time into writing this response than he wanted to. In fact my guess is that working on it SUCKED, and that he held himself to doing so anyway because he said he would, and also because he felt bad about so genuine mistakes that Alexandros pointed out. Want to make fun of Scott's obsessiveness too?

"If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence."

Also, the thing none of us know about Alexandros is why he's persisting. Is he so invested in being Ivermectin Man that he can't allow himself to see how bad the case for it is? (That's my theory.) Does he know so little about research he can't tell good from bad? Does he know the evidence for Ivermectin's terrible, but he's cynically pretending it is not because he's profiting from being an advocate for the drug? But you're not addressing that question -- just throwing rotten eggs at him.

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Could be any or all of the above, but the thing is that even by you, there is no reasonable explanation. All of them are bad for Alexandros. So why are you so eager to keep weighing in on behalf of someone for whom there is no possible rational defense?

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Because I think that laughing at someone who's been bested is meanspirited. If the mockery is mixed with new information or a new take on what happens, then I experience it differently -- then it's an angry, substantive comment.

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Because I think that laughing at someone for making a lot of effort trying to get to what they think is the truth is incredibly toxic for everyone.

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But we don't have to pretend that everyone is trying to get at the truth. Alexandros is applying an absurd double standard whereby any negative ivermectin study has to be scrutinized for every tiny flaw whereas pro-ivermectin studies will be excused for far greater flaws.

There is plenty of room for good faith people to engage in discussions without always being derailed by the impulse to give the benefit of the doubt to people who don't deserve it.

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PS, I didn't repeatedly tweet the same thing at all. Here's how it ended. If someone had good evidence on their side, why wouldn't they cite it rather than blocking me? https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff08ee13f-d59f-4ffa-82af-1bb6e6b9685a_550x787.png

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Feb 1, 2023·edited Feb 1, 2023

Look, I'm no fan of Alexandros but I don't think you really score any points against him here. Why would he block you on Twitter for repeatedly asking whether there is one good RCT supporting Ivermectin? He thinks there are multiple good RCT's, doesn't he? Seems more likely that he pointed to studies that he considered good RCT's, you said, "no they're not because . . ." and he got tired of arguing with you.

Why does writing a full non-fiction book while running a start-up suggest that he or the contents of his book are not to be trusted? Maybe he's got lots of energy -- or maybe he's bad at time management -- or maybe he's just overinvested in winning the argument with Scott, even though the practical consequences of his winning or losing are small. All these possible personal failing of his seems kind of irrelevant in the context of a discussion of whether he's right about ivermectin, or whether he's arguing in good faith.

As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. I think he probably believes that.

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If you had multiple exchanges with him, there's no way I'm going to dig through the manure pile of Twitter for them. I did read the exchange you linked, and it's not clear what his view is about good RCT's existing. He once says "no good RCT's" but I don't know what he means -- is it agreement? a sarcastic gibe? If he really thought there were none, I'd expect him to say something like, "yes, OK, all the studies are imperfect, still if you look at the mass of evidence blah blah. . ." Then later he says something like "nothing would convince you." That could mean he's pointed to what he thinks are good RCT's and you dismiss them as not, or I suppose it could mean something else. So this exchange with Alexandros is far from solid evidence that he doesn't believe there are good RCTs. Actually, it's sort of like the case for Ivermectin's efficacy -- you can point to it as evidence for your view, but in fact it's full of holes.

Look, I hope it's clear that I do not think Ivermectin is useful against covid. I just don't like the way you're making fun of Alexandros. I get that he annoys the hell out of you, but if you want to go after him make good points, don't just snigger,

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No, he never pointed to even one good RCT. Earlier in the discussion, he pointed to ivmmeta.com (not a trustworthy website) and the Bryant meta-analysis (also not reliable because it included fraudulent studies). That's all he had.

But say, why are you trying to reconstruct Twitter history from 2021 to critique me on the grounds that Alexandros MIGHT have said something defensible back then? Why do you care so much, such that you're inventing alternative histories in which he had good RCTs to cite (which he didn't)? Why bend over backwards to give every possible benefit of the doubt to him rather than to me?

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Because you're the one trying desperately to defend a pointless smear, I'd wager.

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"As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. "

If he thinks that, he doesn't know what he's talking about, because it is objectively wrong. For example, the TOGETHER trial is not objectively worse than the Borody study -- quite the contrary.

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Hey, I agree that the case for Ivermectin is bad and the case against it is good. It's just not clear what point you're making about Alexandros by saying he's very critical of good studies and goes easy on bad ones. We're all aware of the thing you keep pointing to -- yep, ridiculously hypercritical of studies that weight against Ivermectin. And?

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|or maybe he's just overinvested in winning the argument with Scott

I'll note that Alexandros was clearly expending massive amounts of time and effort on ivermectin advocacy before Scott wrote anything on the subject.

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To give the other side of this thing, his company has produced this: <https://www.balena.io/etcher>, which is a really nice way to flash USBs and which has saved me a bunch of time in the past.

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Wait, really? Hilarious. I have to use that to create Homebridge images for my smart home setup.

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Well, no. He's writing on a controversial topic that inspires fervent support amongst true believers. His comments show he's clearly attracted an audience, and he's baited Scott, who has a huge audience, into writing a long post in response. So whatever else he has done, his efforts have won him a big audience that he can than parlay into either a platform for his ideas or into some kind of monetary profit. You are being rather uncharitable to assume he did all over an obsessive need to prove Scott wrong.

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If you disagree with what he writes, please attack the writing directly, rather than "it is wrong to have a hobby while running a startup".

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If Alexandros had been right, that time would've been extremely well-spent. It's not like he spent any of your money on it.

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Scott's original post had so much stuff in it that if it was on any other subject we would have called it a Gish Gallop. It's unsurprising that responding to everything in it would take such a huge number of words.

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I don't think that's fair. The characteristic of a Gish gallop is that one throws out a large number of basically-independent claims without providing justification for any of them, taking advantage of the facts that (1) one can _state_ something much more quickly than _refuting_ it and (2) if you merely state something and someone else merely denies it, then to most people it looks as if you're in the right and they're in the wrong.

Scott's ivermectin post wasn't like that. It's mostly long because it's looking at a large number of studies, which ivmmeta can simply list in a big table but Scott had to look at in at least a paragraph's worth of detail.

Scott's post was the _exact opposite_ of a Gish gallop: it was very long because it was responding to something else that was long but didn't go into details.

(Maybe you could argue that he should have looked in _more_ detail at some of the studies. That would almost certainly have made his post longer, not shorter.)

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Feb 3, 2023·edited Feb 3, 2023

The important trait here is not how much detail it has, but that it has many arguments that would take a lot of time and space to respond to--so much that most people would give up because of the volume, regardless of whether the arguments have merit.

Complaining about Alexandros using a huge number of words to respond to Scott isn't fair; Scott said so much that in order to respond fully, he *had* to use a huge number of words.

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I agree that complaining about the length of AM's response to SA is likely unreasonable. (It depends on what that length actually consists of; I haven't looked myself.)

What I'm objecting to is something more specific: "if it was on any other subject we would have called it a Gish gallop". I hope we wouldn't, because "Gish gallop" doesn't just mean "very long thing", it means a particular _kind_ of very long thing, and Scott's post was unambiguously not that kind of very long thing.

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This analysis is great but I'd like to pay more attention to what our prior should be that some existing medication has a substantial benefit in treating a new disease when there isn't a strong theoretical basis supporting that use. My sense is that our prior should be very low. I mean, just ask yourself how much you'd be willing to bet about a large rigorous study showing a 10% drop in deaths from a random drug.

All the argument as to what direction the studies on ivermectin point is great and all, but even in the best case the evidence isn't very strong. I mean, it's not unusual in the slightest in medicine to see some initially suggestive studies only for the effect to turn out to be a mirage.

So while I think pinning down just how much evidence we have for ivermectin is important insofar as it should inform us whether to bother investing in yet more studies the idea that this should be enough to convince you to take the bet against the strongly theoretically supported side-effects (plus a reasonable prior that many drugs have them) seems like a big stretch.

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I agree. On the other hand, one thing Ivermectin has going for it is that it's cheap, easily accessible (and probably quick to make) and well-tolerated. And there weren't many other drugs that were: fluvoxamine and metformin were the only ones I heard about (and actually I don't know whether metformin is cheap or well-tolerated) .It would have been a great thing for the world if some drug like Ivermectin that did give some survival benefit, even a small one, had been discovered. The drug we finally came up with, Paxlovid, is highly effective for unvaccinated people, but it took a long time to develop, is not cheap, not easily accessible, and so unpleasant to take that many people bail before finishing the full course of medication. So I can see giving things like Ivermectin the benefit of the doubt in early research -- though I agree that the pro-Ivermectin people kept going long after it was time to give up.

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"and actually I don't know whether metformin is cheap or well-tolerated"

Reasonably so, there are generics of it available. Well-tolerated - the worst side effects are gastrointestinal and usually calm down in a couple of days (though some people get it worse and can't stay on it).

I've been taking metformin for several years now for Type II diabetes and it didn't stop me contracting Covid. Anecdotes are not data, but that is my lived experience 😁

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If it does anything it's not prevention of illness, it's improving outcomes. A number of studies found it reduces chance of ER visits and hospitalization, but some did not. Pros and cons are easy to find via google. Current official US guidelines are to not prescribe it for people with covid. A couple of the docs on medical Twitter whom I respect think that's a bad recommendation because metformin's way better than nothing. It's certainly not as helpful as Paxlovid, but Paxlovid's expensive and soon a lot of poor folks in the US will not have insurance that will allow them to get Paxlovid. Metformin was also available when Covid began. Paxlovid was ready to use about a year later, but the supply was limited for a while so it was 18 mos. until it was available for all. And of course Metformin could be used in parts of the world where nobody gets Paxlovid. Here are a couple of studies with positive findings:

https://www.nature.com/articles/s41598-022-09639-2

https://www.news-medical.net/news/20230111/Review-shows-metformin-usage-to-be-associated-with-better-COVID-19-outcomes.aspx

Who knows, maybe it reduced your illness severity.

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"Who knows, maybe it reduced your illness severity."

Hard to say, I had a murderous cough (so bad that once I nearly fainted from coughing so hard and not being able to catch my breath). Another family member had no cough but constant vomiting to the point of becoming severely dehydrated (couldn't even keep water down, anything they consumed came right back up). Two other family members just breezed through it like a bad cold.

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Feb 2, 2023·edited Feb 2, 2023

Especialy when it come to viral disease. There are very, very few effective antiviral drugs, and those that do exist and work are usually the results of a very long trail of arduous and expensive research.

The reason is completely obvious: bacteria have their own biochemistry, thousands of chemical reactions unique to them, which human cells do not use, and which are potential targets for chemical warfare. That's why there are tons of antiobiotics, and lots of compounds, both natural and artificial, show anti-bacterial properties. Viruses don't have any biochemistry at all, because they're not alive. They have *no* chemical reactions unique to them. An effective antiviral needs to interfere delicately but effectively in the chemistry of the invaded human cell, so that it blocks viral entry or reproduction -- which is carried out by human cell reactions -- but doesn't do bad things to the cell.

It's a miracle this is even possible at all, so delicate is the balance to be struck. So the baseline assumption about suggestions that any drug or herbal supplement or whatever is effective that *isn't* the result of some brain-straining enormous expensive effort should be skepticism bordering on incredulity.

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But drugs can help in other ways besides being antivirals My understanding is that metformin's mode of action (assuming it really does help covid patients) doesn't involve blocking viral entry or reproduction, but instead mitigating some of the effects downstream from that, eg cytokine storms. This article talks about that: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154087/

Of course such drugs are much harder to find -- seems almost a matter of luck. If you're looking for a covid antiviral you can just throw a drug in with some pseudovirus and see how well the drug blocks the virus. There's no simple way to find out which of the many drugs in use that do not qualify as antivirals slow down the processes by which covid does a lot of damage in those who are infected. In fact I have no idea how metformin was identified as possibly helpful. Nobody seems to be touting it as an antiviral.

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Sure. Supportive care is still all we've got in many cases, but it rarely changes outcomes in the kind of miraculous reversal way that you get with antibiotics and bubonic plague, say. It can't, because it's not getting at the root of the problem. I mean...if some people are going to go into full tinfoil-hat frenzy because Big Medicine is pooh-poohing folk remedy X that reduces the severity of symptoms or duration of disease by 15% it's just more of the shouting at the clouds that makes me think watching birds in the feeder in my backyard is a more productive use of my time than the Internet.

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But who's going into full tinfoil hat frenzy over this? Since I'm the only person in this discussion speaking up in favor of metformin & similar, it does feel a bit like you're talking about my view. I hope it's clear that I'm not even sure metformin works -- some think if does not. My point, made before you entered the discussion, was that having some cheap, widely available, well-tolerated drug would have made a lot of difference early on in the pandemic (which was when some, including Scott, were talking about fluvoxamine and metformin as a possible drug of that type). Something that at present does nothing more for a covid sufferer than shorten the illness a bit would have made a lot more difference than that early in the pandemic, when few people had immunity, there was no vax and there were no antivirals. And of course in some parts of the world there is still is little or no vax and no antivirals.

And the study I linked to did find considerably more benefit than a 15% redux in symptoms or duration. There was a substantial difference in death rate between metformin users and nonusers.

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I must admit that I scrolled straight to the conclusions, and even that felt like a strain at this stage of the ivermectin conversation. The graph of likely false positive results at the end of the post was quite interesting, and I admire Scott's dedication to this topic. Otherwise, I'm hoping we can all move on to other topics!

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Feb 1, 2023·edited Feb 1, 2023

I guess that Scott wrote this in large part because there's a bigger and always relevant meta-topic of what to belive in the absence of "settled science", and how easy it is to make the mistake of thinking that you've gleaned a valuable insight from the messy landscape.

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You seem to be missing the positive results in the MedinCell trial and the new paper on hemagglutination showing that IVM both prevents and reverses RBC clotting associated with poor outcomes.

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This was primarily about the studies we discussed in 2021, with me only mentioning a few especially large and well-done studies since then. Still, those seem interesting - can you give me links to those studies?

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Yeah, Bret Weinstein did a video on those results recently. I thought Scott's original article was a net win for Team Ivermectin in any case- even being right for the wrong reasons makes a case for having a public debate.

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That MedinCell trial also seems very fishy on its face. It randomized 399 people to ivermectin or placebo, and measured how many got infected with Covid in 28 days. https://www.medincell.com/wp-content/uploads/2023/01/PR-results-TTG-VF-EN.pdf In the placebo group, they claim that 105 out of 199 people got a Covid infection in 28 days. Really? Unless this was a challenge trial, it is hard to imagine that over half of people came down with Covid in a 4-week period.

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I'd totally believe those numbers if they'd come from, say, China last December.

MedinCell says they did the study in Bulgaria "between March and November 2022"; I don't know about infection rates there, so off the top of my head I'd say it's questionable but not totally unbelievable.

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Never mind, I missed a line showing that they were studying people who had been close contact with an infected person in the prior 5 days.

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I agree with these conclusions a lot more than those from your original post.

One quibble: what does "clinically significant effects" mean? Is the burden "better than a placebo"? "Better than Paxlovid"? "Better than no placebo"? The differences in efficacy between those thresholds are large enough to drive a truck through.

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Feb 1, 2023·edited Feb 1, 2023Author

I originally framed it as d > 0.3, but as mentioned in the quote in 7B, Alexandros preferred to talk about a 10%+ drop in mortality for high-risk patients.

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I think there might be a typo in the phrase "not for excess mortality in the control group" in the Cadegiani et al section

If they were hypothetically going to condemn him for giving unhelpful drugs to people, wouldn't that involve them complaining about excess mortality in the treatment group, not the control group?

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Outside of the technical arguments, you deserve credit for taking the high road in responding to Alexandros.

If nothing else, his bad faith characterizations of you made it clear that he's not very strictly bound by the available evidence. No one is perfectly in control all the time, especially when there's strong disagreement - but getting as far out over his skis as he did in impugning your motivations is a strong tell for "motivated reasoning." Unless he's got mind-reading skills which he hasn't yet explicated.

But the bottom line is that accountability is the key - and you've demonstrated accountability here.

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I don't think he was especially bad faith. I accused him of being bad in a few ways, he accused me of being bad in a few ways, we mostly disagree with each other, but this seems within the normal range.

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Maybe - but normal range is a pretty low standard, imo.

I'm not going to go back and look and I could be wrong, but my recollection was that there was a difference in that he explicitly attributed conscious mal-intent and impugned your motivations in ways that required mind-probing, whereas you (perhaps foolishly) observed on sub-optimal behavior.

I see a distinction there as the one set of actions is unnecessary and counterproductive, whereas the other reflects fallacious (or motivated) reasoning.

That might seem like semantics but as an observer, for me it reflects a meaningful category difference. Of course, we can and do all cross that line at times; the question then becomes about frequency and more importantly accountability.

On accountability, I recall trying to engage with him on the fallaciousness of his process of attributing motivation and intent on your part, and him being totally unaccountable/unreflective

It would be interesting to go back and see if my characterization of my exchange with him isn't correct, as that would reveal a form of bias on my part. But it would be take too long a time to find it.

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I think not so much Alexandros as his fanboys, who kept popping up here to pester Scott about "why haven't you answered Alexandros yet, huh? huh? have you read this new study, huh? huh? why won't you admit you were wrong and he was right, huh? huh?"

They annoyed me, anyway.

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Feb 2, 2023·edited Feb 2, 2023

You thought he was not engaging in good faith and was dishonest, at least at first. But yeah, the normal range is wide

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I doubt Ivermectin works, happy to be convinced with stronger evidence.

What I found most alarming was how politicized Ivermectin became, most glaringly with the CDC, pretending as if Ivermectin was only for livestock with their infamous "you are not a horse" tweet [1] which may (?) have encouraged people like Dr Jason McElyea to make up fictitious stories about people "clogging up hospital beds because they are OD'ing on Ivermectin" [2]

Meanwhile, the CDC suggests ivermectin off-label to treat lice, even though there are plenty of FDA approved OTC and prescription treatments [3]. I quote:

"Given as a tablet in mass drug administrations, oral ivermectin has been used extensively and safely for over two decades in many countries to treat filarial worm infections. Although not FDA-approved for the treatment of lice, ivermectin tablets given in a single oral dose of 200 micrograms/kg or 400 micrograms/kg repeated in 9-10 days has been shown effective against head lice"

_____

[1] https://twitter.com/us_fda/status/1429050070243192839

[2] https://reason.com/2021/09/06/ivermectin-overdoses-oklahoma-hospitals-rolling-stone-hoax/

[3] https://www.cdc.gov/parasites/lice/head/treatment.html

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Also scabies, especially in parts of the world where the first-line treatment, permethrin, is not easily available.

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I think it should probably have been made available over the counter, instead of being heavily suppressed. At the very least that wouldn't have fed the fire of conspiracy theories as much, and it's probably safer for people who want to take it not to have to rely on veterinary or questionable sources.

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I’ve always leaned towards explaining Ivermectin’s apparent success in the developing world as a case of a low-resource medical team throwing everything they got free from WHO at a novel infection, which then got written up as, “My 20yo cousin got broad-spectrum antivirals AND Ivermectin and lived….my 80yo uncle only got the antivirals and died…must have been the Ivermectin,” with a small side order of parasite load.

A lot of the stories in 2020 were of the, “We really don’t know much…here’s a handful of straws to clutch at…” variety.

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Exactly. With the survival rate between 99 and 99.9 for people under 50, it's difficult to separate placebo from cure without large scale double blind RCT, then replicate those RCTs.

What was so sad the last 3 years was how political ideology dictated which were the favorable placebos, which allowed absolutely terrible studies to get praised. Case in point, consider "Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff" which somehow made it into NEJM to promote cloth masking toddlers.

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I think part of the problem also was the various 'miracle cures' were being peddled alongside "don't get vaccinated, take this instead" like Dr. Cadegiani and his co-authors:

Lucy Kerris is a paid consultant for both Vitamedic, an ivermectin manufacturer, and is co-founder, as well as acting as a paid consultant, for Médicos Pela Vida (MPV), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination.

Flavio A. Cadegiani was a paid consultant (USD 1,600.00) for Vitamedic, an ivermectin manufacturer. Dr. Cadegiani is a founding member of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19.

Pierre Kory is the President and Chief Medical Officer of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Dr. Kory reports receiving payments from FLCCC. In February of 2022, Dr. Kory opened a private telehealth fee-based service to evaluate and treat patients with acute COVID, long-haul COVID, and post-vaccination syndromes. Dr. Kory expresses personal points of view against COVID-19 vaccination.

Jennifer A. Hibberd is a co-founder of the Canadian Covid Care Alliance and World Council for Health, both of which discourage vaccination and encourage ivermectin as a treatment for COVID-19.

Juan J. Chamie-Quintero is a contributor to the Front Line COVID-19 Critical Care Alliance (FLCCC), lists the FLCCC as his employer on his LinkedIn page, and expresses personal points of view against COVID-19 vaccination."

So whatever the virtues of ivermectin (which remain to be proven re: covid), the publicising of it as a cure was being done with a side of "vaccines bad, don't trust Big Pharma, don't trust the authorities!" which is not going to make the authorities trying to grapple with a new pandemic trust your take or look favourably on your miracle cure, hence the "it's horse paste".

Especially if people were going on Youtube with 'hacks' about "if your doctor won't prescribe it for you, buy it off veterinary stores" which is risky enough - maybe ivermectin won't do you harm, but in general don't take animal medicines, stick with human formulations. For animals (rat studies in this case, but warnings for dogs as well on another site):

"Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality."

Okay, that's overdosing, but someone taking medications made for (yes) horses might indeed overdose as well.

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Fantastic comment with some background on these people I wasn't even aware of.

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The ones who work for ivermectin manufacturers do seem suspect, but aren't you (ahem) putting the cart before the horse on the FLCCC (and similar) people?

They *formed* these organizations in response to their impressions that ivermectin was super-helpful in treating Covid, and in opposition to people promoting vaccines *because they thought ivermectin works*.

While they may be factually wrong in this, if they were correct then agitating for ivermectin and making it easier for people to get would be morally admirable, if not imperative.

I don't know much about most of these people, but Kory in particular is a long-time ICU doctor with a pretty impressive research background -- I can't see how the grift would be worth the squeeze for somebody like that.

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Considering the sums of Money big pharma slings around that 1600$ consulting fee sounds laughable. Especially considering the risk a lot of these people took going against the FDA/CDC and a lot of the mainstream. If they are financially motivated they are pretty stupid about it.

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Yeah, the CDC definitely lost a lot of respect in my eyes over the past couple years. Utterly shameful behavior on several fronts. -.-

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I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one. He does seem to have had a knack for a) picking investments in engineering companies to buy* or start, and b) hiring good engineers to work for him. But those are not engineering.

* One of his main mistakes with Twitter seems to be his belief that it's an engineering company, rather than a media company.

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I'm not sure where I saw it, maybe I can dig it up, but I saw a pretty good round up for sources that basically all said "No, Elon really was the head engineer - or at least one of the top ones - at SpaceX."

I'm not a huge Musk fan, but I think a lot of people are overcorrecting wrt to his competence.

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I would like to see those sources. Musk has no formal engineering education, and from what I've seen so far, he shows no appreciation of how absurd (or at least absurdly difficult) many of the things he promises are. The vibe I'm getting is much more "this sounds good, let's sell it and let my dudes figure out how to implement it" than "I have a genius solution to a really hard problem, here is why we can do what no one else can".

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I think this is the list I'm thinking of: https://www.reddit.com/r/SpaceXLounge/comments/k1e0ta/evidence_that_musk_is_the_chief_engineer_of_spacex

I'm sure that subreddit isn't exactly unbiased, but it seems a pretty solid list including a decent section of non-employees.

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Thanks.

That is surprising, and at odds with everything I've heard about the man in the last years.

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FWIW, before he was such a public figure, I read a lot of people claiming first-hand knowledge that he's a brilliant engineer and was indeed responsible for a lot of rocket science at SpaceX. I have no sources or whatever, so take it for what it's worth.

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I'm not surprised it's at odds with what you've heard, lots of people in media love to hate on Musk, probably because Musk comes across as self-important and self-aggrandizing in many ways. I think only time will tell for sure.

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My mental model of the guy isn't some charismatic business guy who "LARPs as an engineer", (to borrow eleventhkeys terminology), but that he's actually more of a dubiously charismatic engineer who ended up running large businesses, and frankly has a certain amount of distain and disinterest in the business side of things.

This is at least part of the impression I got from him when he came on Dan Carlin's Hardcore History Addendum feed last year - he doesn't come across as particularly charismatic but spends a lot of the time "nerding out" about the technical details of WWII fighter jets.

I don't deny there's certain some level of intentional hype-building in his process, but it's hard for me to judge how much, and overall his track record on technical stuff seems pretty good? (SpaceX, EVs, and Starlink all seem like fairly clear 'wins') Maybe I'm just not familiar with some of the 'absurd promises' he's made? (He's definitely proven over-optimistic about self-driving timeline)

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My mental model is that he's a brilliant manipulator and neither a good engineer nor a good businessman per se, but very good at pretending to be both - good enough to fail upward far enough that it becomes difficult to doubt his capabilities.

Regarding the absurd promises, here are a few:

- the Hyperloop

- the Loop (digging lots of tunnels for battery-powered pods to "solve traffic")

- rockets for passenger transportation between cities

- a battery-powered hypersonic jet

- Mars colonies any time within the next decade

That stuff is so transparently daft and Sci-Fi-y, it makes my head burst with cognitive dissonance.

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Feb 6, 2023·edited Feb 7, 2023

> That is surprising, and at odds with everything I've heard about the man in the last years.

Well, discourse online about him is utterly absurd. Sth that especially gets me is people who compulsively include "Emerald mine" thing.

Link to a fragment of Lex Fridman episode featuring John Carmack, who talks about Elon: https://www.youtube.com/watch?v=IQro0rkg2DE

Quote (I've broken it into chunks and slightly cleaned up, but there's ~no interpunction):

i think in many corners he does not get the respect that he should about being a wealthy person that could just retire and he went all in where he was really going to.

you know he could have gone bust and there's plenty of people you look at the you know the sad uh athletes or entertainers that had all the money in the world and blew it he could have been the business case example of that

but the things that he was doing space exploration electrification of transportation uh solar city type things these are big world level things and i have a great deal of admiration that he was willing to throw himself so completely into that

because in contrast with myself i was doing armadillo aerospace with this tightly bounded... it was john's crazy money at the time that had a finite limit on it. it was never going to impact me or my family if it completely failed and i was still hedging my bets working at id software at the time when he had been you know really all in there

i have a huge amount of respect for that and people do not

the other thing i get irritated with is people that say it's like oh elon's just just a business guy you know he just was gifted the money and he's just kind of uh investing in all of this

when he was really deeply involved in a lot of the decisions you know not all of them were perfect but i know he cared very much about engine material selection propellant selection and for years he'd be kind of telling me things like "get off that hydrogen peroxide stuff, liquid oxygen is the, it's the only proper oxidizer for this

like the times that i've gone through the factories with him we're we're talking very detailed things about how this weld is made how this sub assembly goes together, what are like startup shutdown behaviors of the different things

so he is really in there at a very detailed level and i think that he is the best modern example now of someone that tries to that can effectively micromanage some decisions on things on both tesla you know and spacex to some degree where he cares enough about it

i worry a lot that he is stretched too thin; you get boring company and neuralink and twitter and all the other possible things there where i know i've got i i've got limits on how much i can pay attention to

i have to kind of box off different amounts of time and i look back at my aerospace side of things it's like i did not go all in on that i did not commit myself at a level that it would have taken to be successful

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Feb 2, 2023·edited Feb 2, 2023

Perhaps also you overestimate what being an engineer implies wrt skills and knowledge.

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I'm pretty sure I saw the same list of sources praising Musk, and it was almost exclusively people that currently worked for him. I can't imagine any of Musk's employees being allowed to say "Oh sure, my billionaire boss is actually kind of useless as an engineer".

I think Musk is an exceptional CEO, who for some reason wants to be known, instead, as a genius inventor and engineer. He's a great businessman who wants to LARP as Tony Stark.

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That doesn't work, because Tony Stark is LARPing as Elon Musk.

https://www.esquire.com/entertainment/movies/a40871355/tony-stark-iron-man-elon-musk/

Or maybe they're caught in an infinite feedback loop?

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...and that's how the world ends.

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We Software Engineering types love to smack talk Bill Gates, but back when all he did was sling code he was astonishingly good at it.

The people who only know his current persona never knew “Microsoft Bill” or numerous business flubs. Sure Bill himself lucked into IBM’s miscalculation as to the potential of personal computing, but if he couldn’t make his code work on an (iirc) 4k ROM, he’d just be another Harvard dropout.

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> I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one

Everyone who has claimed this has never met Elon, while every engineer or scientist who has actually met him agrees he's an engineer. As an engineer myself, I know which sounds more plausible to me.

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My direct evidence is his series of interviews with the everyday astronaut where he ends up giving an impromptu 30min technical presentation about the raptor engine.

I've met my share of pointy-haired-bosses and they didn't know that level of detail on their own product.

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Feb 6, 2023·edited Feb 6, 2023

> I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one

I know John Carmack (who has a rather high credibility) doesn't. What explains this?

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Feb 1, 2023·edited Feb 1, 2023

> …but am generally not impressed.

Same. AM’s Twitter is mostly a dumpster. He’s clearly trying to ride Ivermectin into the spotlight.

Yet I still find these posts valuable due diligence. Thanks.

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"My usual heuristic is that when studies contradict, I trust bigger studies, more professionally done studies, and (as a tiebreaker) negative studies - so I leaned towards the studies finding no effect."

The debate really comes down to the validity of that heuristic. Trusting bigger, more professionally done studies would be a great heuristic if we assume corporate money does not corrupt scientific research. But this is of course a false assumption. I trust small studies done by doctors trying to treat patients in a third world country over large, professionally done studies brought to you by Pfizer.

I believe BigPharma is completely corrupt, and countless civil lawsuits and corporate criminal prosecutions bear this out. These corporations also corrupt the regulators, universities, and contractors who rely directly or indirectly on their patronage. In short, I rely on the Upton Sinclair heuristic - “It is difficult to get a man to understand something, when his salary depends on his not understanding it.”

Leaning towards negative studies would be a good heuristic in the case of patented and thus potentially lucrative drugs, but not in the case of generic drugs threatening a BigPharma income stream. Based on the foregoing, I don't have a strong belief that Ivermectin is effective as a Covid treatment, but I do lean in that direction based on the Upton Sinclair heuristic. You can go into all the studies and present critiques and counter-critiques until the cows come home, but it really just comes down to which heuristic you apply.

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1. Big ivermectin studies have failed pretty consistently over long periods. You would need pharma companies to have meddled with studies from before their own drugs were ever approved, in the hopes that their drug would be approved later. And then after their drug had become standard of care, in order to prevent the previous meddling from being found out.

2. About 50% of Phase III trials fail. These are the big studies where pharma companies have already invested tens of millions of dollars into a drug, and now they have one big study to prove to the FDA that it really works. These studies are usually done by the pharma company itself, albeit with FDA oversight. If pharma companies can't even fix their own studies of their own drugs when tens of millions of dollars are on the line, why do you think they would so consistently bring out all the stops for a drug that *might* compete with their drugs later on?

3. Why did pharma companies let corticosteroids look good in studies and become standard of care for COVID?

4. I mentioned in Part 7 that using IVMMeta's methodology, basically every drug and supplement is a miraculous COVID cure (see https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F3e83bb87-2893-4c69-b71c-604782896641_717x671.png ). Do you believe Big Pharma is suppressing all of these, or just ivermectin?

5. Several of the big studies that failed weren't American - do you believe US pharma companies were able to rig these too?

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1. I don't understand this claim. My understanding is a bunch of small trials showed promising results, then the Together trial was put forth as ending the question once and for all. Meanwhile, the Oxford trial ended under suspicious circumstances with no results forthcoming. I'm unaware of big early IVM trials repeatedly failing in the early days of Covid. And everything about the Together trial stinks. Putting forth an initial protocol of a single low dose of ivermectin cannot be reconciled with an intent to discover the truth in the best interests of patients. The initial Together ivermectin protocol was such obvious bad faith that one can't help but become extremely skeptical of the whole industry and everything that comes out of it.

2. BigPharma can only do so much. Obviously I'm not claiming there are zero checks. There are just inadequate checks and lots of ways around them. I would guess of the 50% of Phase III trials that succeed, most of those are actually garbage drugs, as most drugs are actually garbage drugs. I've been prescribed all kinds of garbage drugs (and now take none and am healthier than ever). Vioxx is of course exhibit A for garbage drugs getting through the system, and there's no reason to believe it was a real outlier. There's no reason to believe the Vioxx trials were conducted in a dramatically different way than other trials. In support of claim that most drugs are garbage, see, e.g., https://www.newscientist.com/article/2209477-why-most-new-medicines-are-no-better-than-existing-treatments/, https://studyfinds.org/big-pharma-fail-no-evidence-of-added-benefit-in-most-new-drugs-study-finds/. A high percentage of the "successful" trials are showing benefits that do not exist in the real world.

3. BigPharma can't tank every study. Sometimes real science happens, even in medicine.

4. I don't know why ivermectin became the target of BigPharma, the regulators, and the media to the extent it did, as opposed to other drugs and supplements. The whole campaign against ivermectin was bizarre, even if one accepts that it is an ineffective treatment. I'm not aware of similar campaigns against other treatments, and I have no explanation for the absence of such campaigns.

5. BigPharma is global. Yes, BigPharma can manipulate studies conducted in other countries.

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Huh, I thought that the reasons for the media frenzy were obvious. The other side of the culture war happened to take ivermectin as their rallying banner, so the usual weapons were deployed.

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Sure, but there were many other popular treatments. Indeed, the popular FLCCC protocol consisted of a cocktail of supplements and generic drugs, not just ivermectin. But ivermectin became the leading target.

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I guess that the "horse dewormer" dig was just too good to pass up.

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"The whole campaign against ivermectin was bizarre, even if one accepts that it is an ineffective treatment. I'm not aware of similar campaigns against other treatments, and I have no explanation for the absence of such campaigns."

Were any other medications touted as a miracle cure by as many people as ivermectin was, with as little biological plausibility to support it? If you got a big fire, you need the big hose to put it out.

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It seems to me that there is an isolated demand for rigor that was applied to Ivermectin that was not applied to the Pfizer vaccine, even though Ivermectin has a much lower side effect profile. Call me cynical, but I suspect this has to do with profitability.

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The side effect profile is secondary when there are fundamental doubts about the efficacy of the stuff. A medication can be as cheap and safe as it wants - if it doesn't work, and the promise of it working keeps people from taking a vaccine that has been shown to reduce mortality by an order of magnitude, that is a problem (especially at a time while the earlier variants were circulating, which were deadlier, but more effectively suppressed by the vaccine than Omicron).

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The Pfizer trial showed more deaths in the experiment group than the ontrol group.

(And Pfizer has a long history of fraudulent medical research.)

And in many cases, the jabs were pushed on people without informed consent. But please do link the evidence that the jabs reduced mortality by an order of magnitude along with the longterm safety data.

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The side effect profile is crucial here. There’s no question that ivermectin is safe. Accordingly, there was no fire that needed putting out, anymore than there needs to be a war on vitamin C supplements. The proposition that ivermectin caused “vaccine hesitancy” is unfounded. True, many of the same people who believed ivermectin was effective also believed the jabs were dangerous. But this is a correlative relationship, not causal. Both beliefs are secondary to distrust of the establishment.

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"Putting forth an initial protocol of a single low dose of ivermectin cannot be reconciled with an intent to discover the truth in the best interests of patients."

For the conventional use of ivermectin, a study found that a single dose rather than multiple doses was the best method. This may be why that was the initial protocol used.

https://pubmed.ncbi.nlm.nih.gov/31558376/

"Interpretation: Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis."

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I suppose that could be put forth as a justification, but I don’t find it persuasive. Groups of doctors were putting forth specific ivermectin protocols, most notably the FLCCC protocol. The matter of public interest was whether those protocols were effective. All of those protocols called for much more than a single low dose. To deviate dramatically from those protocols and then offer your trial as debunking those protocols strikes me as bad faith.

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With respect to Big Pharma, Big Studies, and the priors we should place on them, I think its imperative to consider the unitaid/Hill/Lawrie audio tapes.

Not only do we know of at least one high profile instance of monied interest putting their thumbs on the scale in a way that would make the most cartoonish-villain tobacco executive blush; what was perhaps more damning was the deafening silence around it. Not only can you do these things; we live in a world where you can do these things with zero consequences.

Its that silence in particular, that causes me to update strongly away from the Big Studies; which are the natural targets of monied interests, over the plethora of small independent studies.

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Agree completely. Well said.

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@Scott Are you planning on adding Biber to your mistakes page? Anything where you have to write "I was egregiously wrong, and I apologize to the study authors and to you." probably qualifies. I'm not writing this as any kind of attack; I just want to see that page remain up to date because I think it is one of the keystones of your credibility: I can trust you because you will tell me when you've been wrong (and not just in the depths of some post that I might not have read, though that's already an impressive and unfortunately rare step).

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Thanks, I've added it in.

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I feel like this is the best post that could have been written about a debate so full of sound and fury (and in many dimensions, not signifying nothing). At one point I felt like my eyes were bleeding from the point by point depths of discussion. At another I was blessed by the novel exposure to funnel plots and their interesting and likely significance. And at another by the graph that doesn't think it's about publication bias. At all points by the way this all works as a parable about how to debate and how well meaning people can perhaps go wrong and what it looks like to keep doing it

I was familiar with Alexandros' arguments before your original post and I respect his general capacity and attitude. I always doubted ivermectin but I was interested in the debate and nowhere else did I encounter actual debate. You two win by default, but also by a mile. It's quite understandable that someone with a high personal stake in something so high stakes made some personal remarks - but it would be worthy if he took them back

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There are no personal remarks from my end. Scott has slung several insults towards me, and he is aware that I don't believe I have ever personally attacked him, even if he has done it. He still chose to leave that language in this article. Make of that what you will.

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Feb 1, 2023·edited Feb 1, 2023

Nothing much to say about ivermectin at this point, though I still find it amazing how ivermectin was able to get 100s of times more interest and noise than fluvoxamine, which was probably the better hypothesis among the possible repurposing candidates, and was being researched around the same time period.

In any case, I find it weird that you would call your own mistake "offensive". I know these days being offended is kind of fashionable, but what on earth is offensive about a honest mistake in the middle of a best attempt at an objective take on a complicated and hot topic?

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Yeah I wonder why Ivermectin is the one that took off and got popular, developed a legion of believers and scientist defenders. Was wondering if it's because it would be better known in rural areas . Fluvoxamine, on the other hand, is an OCD drug, sometimes also used for depression -- so maybe people in blue states are more likely to know about Luvox, people in red about Ivermectin?

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I'd guess it's more that the "haha stupid vax deniers are taking horse medicine" angle that made it a lot more inflammatory and memetic.

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My impression is the vax deniers started talking about IVM before the most of the Left became aware they were doing so.

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One reason could be that people can buy ivermectin for veterinary use without a prescription, whereas there's no legal way to get fluvoxamine without seeing a doctor.

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> would I bet even money that they'd see "statistically significant" 10% reduction in mortality? Thinking about it as hard as I can, If I felt I could trust the scientists to not pull any dirty tricks, I think I still would, yes.

I am impressed to see an answer that's not a panacea complex.

This is so different than what IVM fans were saying in 2021. Bret and Pierre were talking about using IVM to drive covid to extinction on Rogan that year. Pierre was going further saying it's likely to be a general purpose antiviral.

If people had said "take this in reasonable doses and maybe it shaves a few days off" the 2021 discussions would have went so much more smoothly.

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Youre confusing the use of ivm as prophylactic against the earliest variants in a seronegative population with the use of ivermectin against omicron as early treatment in a mostly seropositive population.

That said, the extinction thesis was probably wrong when it was articulated, even just considering sars-cov-2 had spread to animals such as deer.

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Not confusing them, comparing a reasonable take on its potential for treatment to the much much more unreasonable “not only is it a treatment, it’s a general use antiviral.”

Point being, if you had went on JRE in 2021 and said I think there’s a 50/50 chance of IVM lowering mortality in a very well-designed study, I would of had zero problem with that statement.

The avatars of ivermectinism were making much grander statements than that much earlier on.

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Sure. Just keep in mind that essentially everyone recommending ivermectin was doing so as part of an extensive multi-drug protocol, so the various hyperbolic statements you've probably heard are ones selectively taken out of context, or ones corrected shortly after they were made, and were always contradicted by what was being recommended to people.

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I mean, maybe. I never heard Bret or Pierre formally update their positions from JRE 1671: https://open.spotify.com/episode/7uVXKgE6eLJKMXkETwcw0D

That podcast was perhaps the exact moment where I went from being a Bret fan to being like"OH MY GOD BRET WHAT THE FUCK HAPPENED TO YOU!?" And that was when I stopped paying much attention to him and others in that camp. There might have been some value in continuing to track their intellectual progress, but there's only so many hours in a day and I wanted to find the best signal to noise ratios in the pandemic. I hope he updated and I hope he can let go of some of the pandemic takes.

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I have no idea what specifically you are referring to, so I couldn't tell you.

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"I wish other people would do this so I could stay in my lane of sniping at people with bad opinions about antidepressants."

I'm interested in reading this sniping about antidepressants. Any links to SSC/ACX posts on that topic?

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For all who could use a little comic relief at this point, here are 3 DALL-E images of the Ivermectin debate. The prompt was "two men having an intense debate about a medication for intestinal parasites."

steampunk: https://i.imgur.com/VlmdSZX.png

surrealist: https://i.imgur.com/iItysT1.png

And, Scott, especially for you:

stained glass: https://i.imgur.com/mKcsP8J.png

Might look elegant as a dining room window.

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Good heavens - what a waste of time on balderdash and trying to play it through disagreements on statistics.

Where the hell were you when the Pfizer and Moderna info had to be forced by a judge to release it within 75 years ?

You can say what you believe and I will continue to believe what I/ we my spouse and 7 members of a Vet’s coffee group have experienced.

We have been on prophylaxis dose of IVM for nearly three years, surrounded by Covid victims in our daily lives, close contact with positive testing individuals.

A coffee group meeting every MWF every week for many years - 7 members have all gone thru their 3-4 x Covid infections and all have treated with IVM at proper 0.2 - 0.4 - 0.6 mg/kg doses as per flccc.net protocols excepting they took the 0.6 mg when having Covid to get over it but then stopped the regular dosage after getting well with a 5 - 7. day course of therapy, only to gain another Covid infection several months again later.

You can browbeat and try stats to kill off IVM but we will continue our usage for prophylaxis for as long as the idiocy continues.

You would be better served and maybe be accepted more readily if you chose to use the fraudulent results

Of Pfizer, Moderna et.al 60 day trials which more align your thoughts.

You keep your results and we will keep ours and obviously never the twain shall meet.

But we know our friends and fellow IVM users will be around to meet again and again as against the bullshit you keep trying to kill it off while ignoring the works of RCT’s with proper dosage and protocols.

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"You can browbeat and try stats to kill off IVM but we will continue our usage for prophylaxis for as long as the idiocy continues." Jeez, miner, if you really think the stuff protects you I don't think you should only keep taking it as long as "idiots" like Scott keep making the case Ivermectin doesn't work. That would be a sign you are mostly taking it to defy Scott -- you know, like a teenage guy dying his hair pink to upset his mom. I really think you should keep taking Ivermectin as long as you believe your health is in danger.

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You might take notice that I could take this post, replace ivermectin with some alternative medicine thing you don't believe in, and you would probably laugh at it.

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I also haven't gotten COVID at all in the past three years, even though my wife and almost all my friends did. Sometimes you just get lucky.

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I think you misread his comment as saying he never got COVID but he actually got it 3 or 4 times, he just didn't die from it (what I assume he means by 'covid victims')

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Feb 1, 2023·edited Feb 1, 2023

Do you think that not having gotten it at all is more likely at this point than an undetected asymptomatic case?

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Wow, a coffee group! Yeah, that beats everything else for rigour and repeatability!

Look, I'm glad you and your friends didn't get sick. Except for those of your friends who did get sick.

I and other family members also got sick. We didn't use ivermectin and we got better the old-fashioned way (by suffering through it for a week or ten days, then it cleared up). It hit us all differently, for a couple it was no worse than a cold, for others it had worse symptoms but different ways.

So seven of your group got recurrent infections and got better again within a week. Just like the ordinary way of getting better. This doesn't mean ivermectin cured them.

Keep taking the cattle drench, it won't do you much harm and at least you'll be free of worms!

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I take paxlovid for worms. What's good for the goose.....

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Hmmm - has anyone tried infecting people with worms to see if that shifts covid?

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