zosima

This is ridiculous.

Your meta review has like 80%-90% of the studies on semaglutide and liraglutide. When finding random effect per drug, they even say this:

> Hence, the drugs eligible for meta-regression were semaglutide (subcutaneous injection, once weekly) and liraglutide (subcutaneous injection, once daily), which both showed a dose-dependent treatment effect in terms of weight and BMI.

And the class-effect is much more modest than semaglutide by itself would have shown, exactly as I said. What is the point?

But has only weak/moderate effect on weight loss compared to semaglutide, tirzepatide and retatrutide.

Alzheimer is a lot more difficult to measure than weight and amyloid-beta in the brain obviously significantly harder to target than the GLP-1 receptor in the body.

Also, a review pooling together all GLP-1's (including those that failed in development) and concluding that they as a class have only moderate or weak effect on weight loss, would obviously be badly misleading.

Yes, the new anti-amyloids are not a revolutionary therapy. But they do have a small but definite effect on disease-progression. (something which in a highly noisy indication like Alzheimer's may actually mean a lot more to the patients than it seems by looking at the data. E.g. donepezil and memantine have very modest effects too, but patients and caregivers are still surprisingly positive about them).

And since these were developed using different methods and epitopes, it does not make sense to pool them together when doing a comparison. It's obvious that if you combine modestly beneficial compounds and compounds with zero beneficial effect then the mean effect will be worse than the modestly beneficial compounds.

And when you do so just because they were aimed at the same molecular target, not even considering if anyone claims that the old, unapproved antibody-therapies, with no positive studies to support them, have any effect, what you are doing is somewhere between extreme ignorance and deception.

I wonder. Because if that was the question, why would they include anti-amyloid treatments that were never approved and are not part of any current treatment regimen and dilute the real effect of the approved antibodies? (Not that the approved antibodies are a silver bullet, but clearly they have some positive effect.)

That systematic review is unfortunately severely flawed. They pooled the old anti-amyloid antibodies (which everybody agrees are inefficacious) and were never used outside clinical trials, with the new anti-amyloid antibodies, that does show modest efficacy in reducing the speed of progression.

While these two classes of drugs target the same molecule, they are developed to target amyloid-beta in very different forms. Pooling all those drugs together, and then showing very weak effect, makes absolutely zero sense, and I hope and expect this review to be pulled soon.

The genetic evidence that amyloid-beta is in some way causative of at least a subset of Alzheimer's disease is still extremely strong.

The fact that amyloid-beta binding drugs like Lecanemab and Donanemab decrease progression is also very strong evidence for the amyloid-beta hypothesis.

What seemed to be the hurdle was likely, that targeting amyloid-beta in its pathological form just wasn't easy and developers of pharmaceuticals instead focused (for unknown reasons) on the solid amyloid-beta grains in the brain.

The major reason things are moving so slowly is because of the long development times of pharmaceutical compounds. A new compound will at least have to spend 2-3 years in safety studies before being tested on its first real patient, and then for Alzheimer's, which is a slowly developing disorder, nothing short of a 2-year followup time will show efficacy unless it's truly a miracle compound.

What has closing a government agency to do with free speech?

Did you interpret the calls for the end of censoring and cancellations that all government agencies must continue to exist forever?

And if so is there any resemblance of logic behind that interpretation?

I wouldn't bother commenting if I were hallucinating figures. There is no figure 4a.

If you look at figure 4 in the supplemental material you also see, per your expertise, that covid vaccine protects against traumatic injury. However even adjusting for the protective effect against traumatic injury there is still quite a large protective effect against all-cause mortality. So the beneficial effect of the vaccine is not solely caused by its protective effect against traumatic injury.

Or it could be, bold proposition I know, that there is a difference between the groups that both protects against traumatic injury and protects against all-cause mortality, independently of the vaccine.

This is rather weird. Mortality in immediate connection with the vaccine (index time) would not have been captured here. I would hesitate to draw any conclusion from this paper.

> For all individuals, vaccinated or not, follow-up time zero began 6 months after the index date.

I am speaking about what the paper shows.

There are other sources of evidence for efficacy. This paper is not a very strong source of evidence for efficacy due to some obvious uncontrolled difference between groups.

The reduction in all-cause mortality was independent of covid deaths.

Which seems to suggest that there was big differences between the groups other than the vaccination.

This of course does not change that the vaccine seems mostly safe, but it definitely calls in to question whether the protection against covid death was vaccine-mediated or due to some other difference between the groups.

Therefore this paper is moderately strong evidence for the vaccine being safe, but quite weak evidence for the vaccine being efficacious.

Maybe those you call extremists are now the only sane people.

People who are poorer and have worse health are predisposed to live in cheaper dwellings, many of which are closer to roads and thus more noisy and with more air pollution.

People who are poorer and have worse health, also have an increased incidence of dementia, seemingly independently of the number of particles in their dwellings.

This is not "everyone".

I'd hope we'd fire anyone incompetent that's in a position to control the interest rate.