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What this discussion however seems to illustrate to me is that short trials for POTS populations, that inevitiably aren't well characterised, with fast acting drugs can often not tell you whether your drugs work even if your trial is a perfectly triple-blinded placebo-controlled trial. Since no...

It's the definition we all have in our head (edit: I just saw that your definition was something along the lines of "effective blinding is when people only guess the allocation arm correctly as often one would expect by chance", this is definitely not the definition I had in mind and I don't...

No. Your blinding could be working perfectly if people are more likely to guess they are receiving active treatment whenever it works. That doesn't necessarily mean the blinding didn't work. I think what then matters is what the reasons for your guessing are, at what point those questions came...

As far as I'm aware assessing blinding via asking participants about guessing their allocation arms is not standard. Possibly because it doesn't tell you anything in situations where people guess they are on the treatment because they are getting better, rather than the blinding not working, or...

I think the easy and straightforward thing to have done first would have been to assess blinding directly as @Hutan already pointed out by asking participants whether they could guess their allocation arm. Then subsequent discussions could have been useful. Otherwise one is left discussing...

Who says this applies to patients in the trial? I'm not too sure. If you simply have patients that have POTS in your trial it can be quite hard to make out what their problem is. Some might have brainfog combined with an increase on a HUTT for others it might dyspnoea during activity (+HUTT...

I think you're right. Looks like they listed the study more than once and I didn't do enough reading. I edit my comment above.

I think some of the reasons for concern have not been well founded as already discussed by others (both the blinding argument and the seemingly circular argument on objective measures). However, I think the following looks like a rather genuine reason for concern: Apparently there was a...

These issues were also addressed in the following editorial: https://www.jacc.org/doi/10.1016/j.jacc.2020.12.028. I would also point towards the following press release: https://ma1.mdedge.com/content/ivabradine-knocks-down-heart-rate-symptoms-pots and the ACC summary...

Good. Yes, but I don't think we've even seen evidence for that or and good evidence to suggest how large the increase is. You should not forget how low the standards in this field are. You will struggle finding well controlled studies. They hardly exist! ME/CFS might have no impact when studies...

A high score in LDSC simply means that 2 groups on average look more similar thoughout their whole genome than one might expect via a flip of a die. That is the case here for ME/CFS and whole range of other things, but it is also the case for IBD and a whole range of things, Schizophrenia and a...

Thanks for this piece. Really great! I will definitely come back to this more than once, whenever I've forgotten what had been talked about. What I didn't quite catch in the text is why some of your dots in the graphs are grey and why some are black? I might have missed it in the piece, but if...

I cannot comment on POTS in general and I find it possible that there may be instances where it has its use (for example there might be a different "group" of doctors outside of the Lyme/ME/CFS/Long-Covid "communities" where POTS is used in a different context even though the article at the...

No information on controls?

My layman understanding: One allele, HLA-DQA1*05:01, was significantly associated with ME/CFS. Its frequency was lower in cases (21.7%) compared to controls (23.2%) (the finding held even when they restricted analysis to a genetically more uniform group). The association was very statistically...

I think you're gonna get a lot more value for money for other things than forcefully trying to speed things up, that from all we know, are already very quick and where we have no idea about current processes. I think we've seen some renewed interest in studying B-cell markers here on S4ME. One...

I think there's probably already someone doing that for them (I doubt they'll be spending their time with R, Python or whatever). But I agree, these are the type of things were some extra money could probably be helpful.

I agree. Recruitment within a year is fast for ME/CFS standards, probably for any illness without a predefined cohort. I think faster than most things we've seen elsewhere. It's the same speed as their previous trial, for which they already had a cohort and only needed half the size. Cutting...

Yes, I'm suprised to see that getting everybody enrolled within a year is somehow seen as slow, especially under this aspect. I don't really see how things could be faster in a sense that it would make any meaningful difference, but I think @Sasha very reasonably asks if there is something...