As the evidence supporting ivermectin as COVID treatment collapses, you might expect *less* certainty from the drug’s evangelists.

Instead they’ve doubled down on ivermectin.

It’s worth reading this passage from Festinger’s Theory of Cognitive Dissonance to understand:
1/
For context, Festinger & colleagues joined a cult (“The Seekers”) who believed the world would end on December 21, 1954 & that true believers would be rescued by a UFO

The researchers wondered how the Seekers would react to “disconfirmation” when this didn’t happen.
2/
As the date approached, the researchers watched many “Seekers” take irrevocable steps because of their belief: they quit their jobs, severed ties to loved ones, & disposed of possessions.

What would happen when their beliefs were discredited?
3/
When 12/21/54 came and went without the promised apocalypse, they observed that rather than abandoning their discredited beliefs, the “Seekers” adhered to them even *more strongly* & began to proselytize *more fervently*.

4/
Examining the Seekers & other examples, Festinger & colleagues theorized that in order to resolve the dissonance between belief & reality, believers sometimes become more fervent in their belief (discounting reality).

They observed 5 conditions that make this more likely:
5/
Now consider the experience of ivermectin believers:
- many of the initial studies supporting IVM have been discredited as fraudulent (Surgisphere, Elegazzar, Cadegiani)
- several large RCTs have found no benefit to IVM (EPIC, TOGETHER, IVERCORCOVID)
6/
nature.com/articles/d4158…
- a reputable meta-analysis by Cochrane (the gold standard) concluded “the reliable evidence available does not support the use of ivermectin for treatment or prevention of COVID‐19”

7/
cochranelibrary.com/content?templa…
- multiple state & federal agencies (FDA, CDC, NIH, etc) have warned people explicitly NOT to take ivermectin
- the rampant use of veterinary ivermectin has led to a surge in poisonings. (Last week >70% of calls to poison control center in MS were about ivermectin)
8/
- And finally, the rapid development of safe, highly effective, & widely available vaccines has eliminated the raison d'être of IVM as a “bridge to vaccines”

In light of all this evidence “disconfirming” IVM, why do its proponents cling to it all the more fervently?
9/
If we look at Festinger’s 5 conditions, we can see that all are met:
1. The core believers (FLCCC, BIRD, etc) are deeply & publicly committed to this belief. One has testified before Congress that IVM is a “wonder drug” & “miracle cure.” Others have built a brand on IVM.

10/
2. Believers in IVM have invested all of their reputation in the belief. Most have lost the respect of colleagues. At least one has stopped practicing medicine to focus exclusively on promoting IVM as a cure.
For many it would be hard, or impossible, to undo these effects.
11/
3&4. At least a dozen large high quality RCTs of IVM are ongoing. Each is explicitly testing whether IVM can prevent or treat COVID.

Each can potentially falsify the belief that IVM prevents/cures COVID (and several already have).
12/
5. Although some people, confronted by the overwhelmingly negative evidence, have stopped believing in IVM, most have stayed committed to the core belief and the group.

Having invested so much time & reputation, many find it is hard to just walk away.
13/
The core IVM believers have taken on increasingly anti-vaxx conspiracy theorist beliefs:
- Not only do they discount the mounting negative studies of IVM but they allege a massive global cabal of governments, big tech, & pharma to encourage vaccination and “suppress the cure”
14/
What will happen?

Faced with “disconfirmation” & increasing cognitive dissonance most cults eventually collapse.

After the world didn’t end on 12/21/54, the “Seekers” rescheduled the apocalypse to Christmas Eve. When 12/25 came & went, most members returned to their lives.
15/
I suspect the same will occur with the #CultOfIvermectin

Recall that a founder of FLCCC claimed to have “cured sepsis” a few yrs ago. In light of negative RCTs that cult/belief also collapsed

The question is how many will be harmed along the way?
16/16
pulmccm.org/critical-care-…

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More from @nickmmark

4 Sep
The last few weeks have been tough. For those in need of a light hearted thread, here’s a brand new 3rd #tweetorial in my extremes of #physiology series. What can the animal kingdom teach us about our physiology?

Buckle up for some fun animal pulmonary facts 🫁!
1/
CASE 1:
You are performing a bronchoscopy. Upon reaching the main carina instead of the usual TWO airways (right & left mainstem bronchi) you see THREE.

Your assistant says “Whoa! That’s weird”

You say no it’s totally normal because the patient is a:
2/
Answer: 🐖
In pigs, the RUL lobe bronchus originates from the supra-carinal trachea (e.g. before the R & L mainstream branches). The view from the trachea looks like this (see the tracheal bronchus on the right).

image source: casereports.bmj.com/content/12/5/e…
3/
Read 26 tweets
1 Sep
The #COVBARRIER RCT now published @LancetRespirMed & it looks like we have a new COVID tx: Baricitinib
-n=1525 hospitalized COVID pts not on IMV
-lower mortality w/ Bari compared to placebo (10% vs 15%) (NNT = 20) & larger benefit in sicker pts!
-bit.ly/3yDmJ9r
1/
COV-BARRIER was a 101 site, double blind RCT performed in 11 countries.

It enrolled hospitalized COVID patients who were hypoxemic (but not on IMV) and had evidence of inflammation.

It had many exclusion criteria including monoclonals, immunesuppression. This is a🔑 point.
2/
The intervention was 4mg of baricitinib, an orally available JAK1/2 inhibitor, dosed once daily for 14 days or until hospital d/c. (It can be crushed and given by FT).

Bari is an FDA approved treatment for RA. It costs ~$50-75 per pill (thus a 14 day course is ~$700-1000).
3/
Read 12 tweets
20 Aug
.@PierreKory

First off, I’m sorry that you got COVID and I’m glad you recovered. I respect that you have the integrity to admit that ivermectin wasn’t able to prevent your illness.
1/
I’ve read the same studies & I disagree with your assessment of IVM; A few small methodologically flawed studies are just not compelling in light of negative results from large high quality RCTs.
@cochranecollab & many experts have likewise concluded that IVM is ineffective
2/
What I find alarming is your failure to use your platform to advocate for vaccination. You claim to follow the evidence. Do you really think there is more evidence for daily mouthwash use than for vaccination to prevent COVID?

3/
Read 9 tweets
9 Aug
A few weeks ago I tweeted about the rising cases due to #DeltaVariant. I was surprised by the number of people who replied saying essentially “they did this to themselves.”

A short 🧵about why we ought to look at this situation differently
1/
Seeing the #DeltaSurge among the un-vaccinated, I'm reminded of an adage I learned in my residency: “The trauma ICU is filled by man’s cruelty to man & the medical ICU by man’s cruelty to himself.”
2/
It’s true.

Without tobacco, alcohol, & opioids, there would be less COPD, cirrhosis, & endocarditis.

Without dietary indiscretions & "noncompliance”, we would not see fewer complications of DM or exacerbations of chronic illness.

But it's also not so simple.
3/
Read 16 tweets
1 Aug
Soo NEJM has an educational COVID critical care “game.” Obviously I had to play on expert.

First off let’s talk about the name: Bagel Mage?!?

I’m not one to criticize - my name is just two synonymous verbs - but Bagel Mage 🥯 🧙‍♀️ sounds like the lamest D&D character ever.

1/
Bagel’s hypotensive with sats in the mid 80s, better do a quick assessment & start someO2.

“May I ask about your goals in the event of a cardiac or respiratory arrest?”
- maybe the worst possible way to ask this but here it goes…

…Ok I guess he’s an everything bagel.
2/
No POCUS - guess I’ll do an exam & order some tests: ABG, basic labs, procalcitonin, CXR, some cultures, & a COVID test (you know “trust but verify”)

While I’m waiting I’ll order APAP, HFNC

Ugh oh. I guess im trouble for not coding enough. Damn this simulation is realistic!
3/
Read 24 tweets
25 Jul
Pre-print of the #COVIDSTEROID2 RCT comparing dexamethasone 6mg vs 12mg in hospitalized patients on high flow O2 or MV:
- no difference in survival or days free of MV with higher dose dex but…
- interesting “trend towards benefit” w/ higher dose dex
📄medrxiv.org/content/10.110…
1/ ImageImageImageImage
🔑 Question: we know from #RECOVERY that steroids are beneficial in severe COVID, but what’s the ideal dose?

#COVIDSTEROID2 was a large DB multi center RCT to answer this. It randomized patients on high flow O2 or MV to either 6mg or 12mg of dexamethasone for up to 10 days.
2/ ImageImageImageImage
The 1° endpoint was days alive free of lifesupport (MV, ECMO, RRT). 2° endpoints included 28 day mortality.

Based on prior studies, they powered for a 15% relative mortality reduction (ARR ~4.5%) combined w/ a 10% reduction in life support duration.

This is pretty ambitious.
3/ ImageImage
Read 13 tweets

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