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I think because it's most common along with PEM but PEM is harder to measure. The FUNCAP is probably a welcome step forward in that it's measuring perceived functional capacity. I think most RCTs will now use a combination of FUNCAP and activity tracker to monitor perceived functional capacity...

I think some of the same physiology described here is used to try understand the vascular abnormalities.

7-8 in a scale out of 10 That's probably expected right? "I have this symptom, it's bad but it's not the worst I've ever felt right now, 7-8 out of 10"

Sham will be a reduced volume infusion yes. It's not perfect I agree but by giving each patient 4 infusions we expect that each may feel a little different. If it is shown that saline is useful we would absolutely do long-term trials on salt and water and other forms of ORS. What do you think...

I think clinicians provide the first layer of evidence this is how trialling Rituximab and Ampligen came about. Then it comes down to a design placebo-controlled trial to test the treatment. We all remember what a disaster the PACE trial was. As you say, we want objective evidence.of treatment...

Yes the sham part is difficult, we will be providing some saline. We are also providing 4 different interactions per individual and expect all will feel a little different. But I agree it's something to consider as a limitation when we publish

So the infusions are all used in patients already they aren't hypotonic or hypertonic tona degree that would be abnormal. It's dextrose, saline and Hartmann's. It could be an impressive placebo and this is why we want to test it once and for all. The placebo in the Rituximab trial was saline...

They had a mouse for every sample. Makes me think they planned to do one person per mouse but then realised they forgot to account for inter-mouse variability and would've struggled to get it published. So they decided to pool IgG. But yeah the right thing to do would have been 5 times the mice...

If it is effective then it could be doing many things. We will have a better understanding after the study based on the design. If we wanted to just test saline then it would be saline vs placebo. But we want to test whether the variations in salts makes a difference and if repeated volume...

You would get much wilder variation in the groups if you did it that way and little chance of statistical significance. Though technically you are right, at the end of the day you couldn't point at 1 mouse with 1 person IgG and know if it was the IgG or the mouse that made it behave that way. So...

Not convincing data in ME yet we hope to provide the answers to this question by testing sham, saline, hypotonic saline and hypertonic saline. Some evidence in POTS though and it may very well be that those with POTS are who we see improve. Generally though saline is the most commonly...

Mice vary a lot like people, especially in behavior. So if you are going to use behavioral measurements then you really need 10 or so per IgG sample. As you can see in their data for the behaviour (each dot on the boxplot is a mouse). If they wanted to see each person's IgG impact then they...

@butter. This is actually all you need as a summary. I didn't actually add much more. Just that an acute infection control would have been helpful.

The hot plate test shows a difference between Long COVID and acute COVID. Heat intolerance is a sign of dysautonomia. Perhaps anti-M3. Interesting to know if they also pooled, I'm guessing they probably did based on sample size.

That's cool, where is that from? Oh I just saw the embedded link. :thumbsdown:

The controls aren't really there.. would have been nice to see what IgG from healthy with an infection does. Plus the pooling really lowers the power. Kind of just suggests that elevated inflammation is not good for you. But maybe this is a good model for future work where they get enough IgG...

To be clear, I'm not a fan of mouse work but it can be necessary for answering certain questions on a system level. Ethics is very strict for animal work in Australia. Most concern is for suffering. They would rather you kill more mice if it means the average of those mice suffer less. Average...

More could be done but it wasn't because it has been very difficult to get funding for animal work in ME. I know people that tried years ago and never got up. I applied with a group last year but didn't get funded, that was more mechanistic to look at how EBV and RRV might go from acute to...

Well I think characterising 500-1000 ME/CFS would give a great overview of the heterogeneity and it would be a target for developing severity markers. Obviously decode targeted 20k+ people, this wouldn't be to that level but could be a start. Need more of these large-scale data projects.

What differentiates malaise from fatigue to you?