Not sure, but I suspect it would be bigger because the standardized effect size was a Cohen's d of 0.56. That is usually larger than the minimal clinically important difference.
Think the biggest problems of this trial lie elsewhere: no control condition, no objective outcomes, no correction...
Anyone able to find the trial registration?
Don't see it either and they mention 5 primary outcomes. With correction none would be statistically significant.
Post-hoc usually means that it wasn't pre-specified and decided after seeing the results.
Don't think the ANCOVA versus MMRM...
In addition, the treatment effects were not clinically significant from what I can see.
They defined the minimally clinically important difference (MCID) for the primary outcome (the FAS) as a change of 3 points.
The FAS benefits compared to no treatment were :
-1.49 points [95% CI –2·92 to...
I suspect the daratumumab trial would be the quickest way to get a breakthrough, but it's very uncertain whether it will bring positive results. The underlying scientific evidence, in my (amateur) opinion, is not very strong.
The genetic data from DecodeME looks more robust, but it probably has...
One caveat here is that if you look at the raw numbers in supplementary table 2, the rate with infectious onset was almost identical. An infectious onset was reported by 61.1% in the high symptom burden group compared to 61.2% in the low symptom burden group. So this doesn't separate them at...
I think we also have to take into account that progress will likely not be linear. There are self-reinforcing trends, such as new researchers who bring in other researchers or provide helpful peer review in the grant decision process.
Especially when there will be a (small) breakthrough and a...
Isn't this what the results would look like if you don't find meaningful clusters or subgroups? Almost 50% split with only modest differences between the two groups.
The paper writes: "This large-scale cluster analysis of DecodeME symptom data reinforces that ME/CFS is a heterogeneous...
Thanks for sharing. One notable trend is how much is happening in Europe compared to the US.
Things used to be the exact opposite only a couple of year ago. It looked almost impossible to get Horizon Europe funding for ME/CFS. The number of respected research group across the continent could be...
There must also be an error in the effect size reported in table 3. With such low sample size a cohen d of 0.107 would never be statistically significant. They probably also misspelled the standard deviation for the patient group in the table (it should likely be 0.086 instead of 0.86).
Wrote more about this here:
The symptom signaling theory of ME/CFS involving neurons and their synapses | Science for ME
Don't see the issue with triggering versus maintaining the disease being two separate problems. Suppose the issue is overfiring of a neural network involved in fatigue and...
It uses tools like MAGMA that convert SNP associations with ME/CFS into gene associations with ME/CFS.
It doesn't only use the SNPs that reach significance but all the results for the millions of SNPs across the genome. It uses their p-value and combines them into a p-value for a gene. It does...
Dropviz
This is the mouse brain atlas with RNA data from 0.69 million cells.
The main publication is Saunders et al. 2018. but there's also a website with visualization and an option to download the data: http://dropviz.org/
The FUMA website has a pre-processed file that controls for the...
If I understand correctly layer 6A form a connection between the cortex and thalamus but perhaps also the claustrum and other inner structures.
Layer 6A Pyramidal Cell Subtypes Form Synaptic Microcircuits with Distinct Functional and Structural Properties - PMC
So one hypothesis for ME/CFS...
Using conditional analysis, three cell types remain as independent:
- the striatal inhibitory medium spiny neurons,
- the dentate principal cells in the hippocampus
- the layer 6a cells in the posterior cortex.
Here's some more info on these cell types by matching them to the annotation file:
ID
Brain Region
Common name
cell_cluster
GP.Neuron_Gad1Gad2-Th_Adora2a-Th.3_9
Globus Pallidus
Striatum, Th+ SPN
GABAergic
STR.Neuron_Gad1Gad2_Drd1-Cxcl14.10_5
Striatum
dSPN, lateral striatum
GABAergic...
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