@AlexandrosM's banner p

AlexandrosM


				

				

				
2 followers   follows 0 users  
joined 2022 September 15 22:05:51 UTC

				

User ID: 1219

AlexandrosM


				
				
				

				
2 followers   follows 0 users   joined 2022 September 15 22:05:51 UTC

					

No bio...


					

User ID: 1219

Hey there -- the JAMA paper made the claim that hyperinfections had a substantial effect on the mortality of ivermectin RCTs. This is the claim I focused on. And no, the studies did not test for strongyloides, as they did not test for a million other things that were not considered relevant at the time that the studies were put together.

I am not sure which studies you're talking about. No doubt some of the studies are bad, while others are very good (e.g. the Biber et al. study from israel). This kind of variation can be found in any field of inquiry (as is a certain amount of junk papers). I did not choose the studies in the JAMA paper, I simply investigated whether strongyloides could be seen as causal for the deaths in their control groups as the hypothesis stated.

If you have specific criticisms, please let me know.

You do realize that there are thousands of hypotheses that are similar to the strongyloides one that could be raised against any conceivable drug or other health intervention? Let me give you some examples:

What if toxoplasmosis is responsible for the effectiveness of ivermectin? Afterall, toxo makes covid worse, and some studies report ivm helps with toxo. Do people have to debunk this too before using ivm?

Or, what if fluvoxamine doesn't help with covid, but instead helps with depression? Afterall, depression makes COVID a lot worse, and fluvoxamine is known to help with depression. Further, women suffer more from depression, and in several studies, the benefit of fluvoxamine seems to be disproportionately concentrated towards women. Do people have to debunk this before using fluvoxamine?

And what if there is some other, unknown effect, that Paxlovid has, which we are unaware of, which confounds or mediates the results of its clinical trials? How much research has been done on that question?

You see where I'm going with this. How is it not yet another isolated demand for rigor?

(1) You'll be interested to hear that it's super unclear if worms help or harm in terms of COVID. Even the study that Scott quoted to illustrate how worms can harm the response to covid, has another section that discusses how worms might help by boosting the immune system.

(2) Yes, this is one of the things ivermectin does. For instance, did you know it has been found to kill mosquitoes that drink your blood upto 10 days after you took ivm? Weird, I know, but small molecules are strange like that.

(3) The Biber et al. study was in israel, had a positive result, and is squeaky clean of worms. now what?

If you have found any particular errors in my piece, let me know.

There is very little if any evidence of people "taking megadoses and getting sick". There have been trials testing very large doses, far larger than those recommended by FLCCC, which are already much larger than standard antiparasitic doses, that have shown very little in terms of adverse effects, all of it transient. There is even a pre-pandemic case of a woman taking hundreds the time the recommended dose in an attempted suicide, and she walked out of the hospital 4 days later with no sign of lasting issues whatsoever. I'm not saying that people should go and take 100x doses. Only that ivermectin is one of the safest drugs we have, and even its most ardent opponents don't bother to make the case for a biologically-based downside anymore. I will steelman the opposing argument by saying that we don't know what its effects on the microbiome are, and I wouldn't feel comfortable taking large doses on an ongoing basis, but in terms of early treatment or post-exposure prophylaxis we have more than enough data to be incredibly comfortable with broad administration. Afterall, there's a reason it's available over the counter in many countries across the world. The potential for abuse is infinitesimal.

If you're interested in the deepest of deep dives on the topic, this is a good place to start: https://youtube.com/watch?v=ATiX0-2PEr4

As for the waters being muddied, one of the authors of an early and very influential meta-analysis has been caught on video admitting that he phrased his conclusions in a particularly cautious manner, recommending more studies needed to be performed, on the insistence of his funders, UNITAID. Of course, writing a conclusion you don't believe in because of the influence of third-party unnamed authors who control funding for the work is the definition of academic misconduct, but said academic is still respected and is now dedicating his time proving ivermectin results are explained by "fraud" (they're not).

Wow. I gotta say many of the comments here are quite something.

Look folks - I got word through a backchannel that a summary post might get the issues I raise actually addressed. I thought that was reasonable, so I wrote that post. I didn't even submit it anywhere other than post it on my twitter.

So I randomly open up theMotte website today, to see that people are losing their goddamn minds that I wrote something on my substack. And as /u/jimmy mentions, not a single person addressed any object-level argument. I believe the sum total is zero. And before someone jumps in and says "ah that's because you make it so personal" I will say that the sum total was pretty poor before anyone characterized my writing as "making it personal".

Like, seriously, what the flying fajitas?

Look, this may look like a lot of wasted words to you. That's totally fine by me. To me, this has been a course in learning about the absolute state that "evidence-based medicine" is in. I don't learn well from books, I learn from projects. So this was that project where I learned about all the things I wrote. Writing raises the bar and makes me dig deeper. And in the course of it I generated several novel findings, like correcting the Strongyloides hypothesis, finding that a Cochrane meta-analysis had violated its own inclusion criteria for most of the studies it included, putting together the Latin American hypothesis, as well as a few more things I've not published yet.

You don't have to understand how my brain works, and I sure as hell don't, but I've learned to trust it and follow it wherever it wanders, because there's usually something of value.

But for the life of me I struggle to conceptualize the ethical system that the people criticizing me here are implementing. In what world is it OK for Scott to call people "known fraudsters", "gullible rubes who were bamboozled by pseudoscience", attack many scientists who never did anything to him, and falsely so, and even attack me as a conspiracy theorist -- unprovoked, to a massive audience, but me responding by sticking my neck out and making concrete falsifiable claims is what attracts the outrage?

Now, I want to be extremely clear -- It is Scott's right to do all those things, a right which I will defend. And it is my right to call them out, and record the errors for posterity, so that nobody can say that they were not pointed out. And yes, as several people pointed out (thank you!) my extremely serious concern, moreso than it is with Scott, is with the rationalist community letting an argument that is this flawed go unchallenged. It follows that I don't want to be like the people I criticize, so I took it upon myself to do the analysis and explain the problems, in excruciating detail. And to do all this knowing that going after the most well-known and popular thought leader in the broader rationalist community will not get me any brownie points, even if I'm right.

I am acting in the only way I can see as morally consistent, and while obviously not everyone will agree with me on that, accusing me of being obsessed with demonstrating that the rationality community is failing at holding its own to account is a bit of a weird flex. If I'm right, then this is obviously extremely important for most people in this community. And if I'm wrong, then surely you can show me how. And if you're unsure, or can't be bothered to find out, that's totally cool also.

But weaponizing the lack of interest in finding out if I'm right into an attack that assumes I'm wrong is a better demonstration of my entire point than I could ever have hoped for. I can't claim to know what kind of rationalist discourse will help us address the various existential risks coming our way, but I am pretty sure this ain't it.

  1. This article has nothing to do with rehabilitating ivermectin. I myself am not sure how well it works today and if I had to guess, it worked a lot better for pre-Omicron variants. Naturally recent data is a mess, so it's hard to know, and I really should do some digging before I say much more because I could be very wrong. On whatever the "red tribe" is - I frequently tweet out about how I could never support a president who allowed Fauci to run the pandemic. As recent immigrant to the US, I have very little interest in whatever partisan bickering y'all are engaged in, other than that I'd prefer if the country my children were born in doesn't implode.

  2. Rehabilitating the rationalist community (the actual intent of the essay) would benefit everyone a great deal. Ivermectin is the perfect case-study of why the rehabilitation is needed.

  3. Once again, the article has nothing to do with defending ivermectin, and everything to do with defeating bad arguments. If you are interested in some material on mechanism of action, my friend Joomi has written a pretty good piece - https://joomi.substack.com/p/misconceptions-about-ivermectin-dosing

  4. There are many drugs we don't understand the mechanisms of, and I can personally confirm that some of these definitely work: https://en.wikipedia.org/wiki/Mechanism_of_action#Drugs_with_unknown_MOA . In fact, as you can read in Joomi's article, ivermectin's anti-parasitic action also is somewhat mysterious, but nobody doubts it works.