Todd Davenport Profile picture
Feb 21, 2024 11 tweets 2 min read Read on X
The conclusion of "alteration of effort preference" driving PEM from an underpowered study that blatantly misuses CPET in the face of all relevant research and clinical guidance for ME/CFS is what we get after years of developing the protocol and waiting for these results?
The sample size makes this study a glorified case series. In a heterogeneous condition like ME/CFS, there is no way 17 participants out of 217 screened is representative. But get this: not all the participants got all the endpoint measures. How can the authors infer causation?
For sure the CPET results are underpowered but there are some clear differences between groups. The authors interpret these differences as deconditioning, which is easy to do on the basis of a single CPET. That's why you need the second one completed in the post-exertional state.
One revealing thing from CPET was the fact the authors included obviously trained individuals in their analysis. Half of them performed at or above their age-predicted maximum heart rate. If you want to conclude PEM is deconditioning and altered effort preference, at least...
...make this comparison with sedentary people who are likely to be deconditioned instead of relatively fit individuals.
PEM is tricky because simply trying to measure it can induce it. The authors didn't grasp this important concept. The effort preference task is a lengthy complex choice reaction time task. This just sounds like the perfect way to induce cognitive PEM during a measurement.
So, there will be a lot more said about this study in the weeks and months to come, and most of it will be about how this study wasn't worth the resources, time, and waiting. For now I'll just contribute that Nature editorial staff were asleep at the wheel, ...
... there were plenty of people who had to do with this work who had reason to know better than what they put out both from basic scientific and content area perspectives, and this work is so poorly interpreted and so poorly reported that it should be retracted immediately.
This article reinforces every negative stereotype about PEM simply being a choice. It's so inconsistent with the findings of their own -omics analysis, to let alone the extant literature. And in light of that inconsistency, it's inhumane. People with ME deserve better than this.
There may be some useful details of this work stuck between the couch cushions, but they won't make the global headlines. What will make those headlines are people with ME are either lazy or crazy. Again.

What an utter and total waste of resources and good faith. I just can't.

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More from @sunsopeningband

Jan 22
Our latest work now posted as a pre-print on @researchsquare: "ME/CFS and Long COVID Demonstrate Similar Bioenergetic Impairment and Recovery Failure on Two-Day Cardiopulmonary Exercise Testing" @4Workwell researchsquare.com/article/rs-860…
Using two‑day cardiopulmonary exercise testing (CPET), we compared physiological responses in people living with #MECFS and #LongCovid with matched controls, stratifying by sex, to resolve the weaknesses of single tests in mixed-sex cohorts we've seen so far in CPET studies.
The primary studies comparing #MECFS and controls already have been published. You may recognize them from work often discussed here. The data is available from mapmecfs.org.
📌 Hansen et al 2024: pubmed.ncbi.nlm.nih.gov/38232699/
📌 Keller et al 2024: pubmed.ncbi.nlm.nih.gov/38965566/
Read 10 tweets
Dec 30, 2025
I was privileged to sign on to a recent op-ed appearing in Le Monde, arguing that medicine and science must finally move beyond the outdated mind–body divide. What follows is a quick summary and explainer for my English-speaking friends on here. @apresj20

🧵
While studying symptoms is important, treating a "science of symptoms” as separate from a “science of disease” risks perpetuating methodological dualism on top of inadvertently reinforcing the Cartesian dualism that terminology describing functional disorders aims to critique.
Of course, we know normal testing doesn’t mean nothing potentially detectable is wrong. Advanced neuro-imaging techniques and biological tools are increasingly revealing the structural and molecular changes behind diseases involving persistent but often hard-to-explain...
Read 7 tweets
Dec 21, 2025
Sometimes I talk with folks who don’t know much about myalgic encephalomyelitis and are researching it, such as for a media piece or class assignment, for the first time. The dogs are walking slow this morning, so here I’ll share a couple observations here about that experience.
First observation: it is impossible to portray the level of disability, suffering, expense, and marginalization characterizing the experience of ME/CFS in a short conversation with someone who has never thought about it before. Even if they’ve spoken with patients before speaking
with me, there’s a sense of magnitude that is impossible to grasp on the first pass. It all sounds too much to be believable. And, in fairness, maybe it’s a lot to take in and sit with and process if you’re well and have no lived context for it. I like to force the issue.
Read 8 tweets
Dec 19, 2025
Long COVID trials are struggling—not because of lack of effort or goodwill (mostly), but because of errors in trial design and poor endpoints. Our new paper, out today, lays out how to start fixing this. Now.

A short 🧵.
We recommend
* Thorough baseline disease characterization
* Longitudinal data collection
* Placebo arms to track natural history
* Measuring post-exertional malaise (PEM)
* Balancing severity and phenotypes across trial arms

These are challenges we can address. Together.
PEM eats Long COVID trials for breakfast. It’s the hallmark symptom of the Post COVID ME phenotype that can derail trial validity. We have tools to use! DSQ-PEM, FUNCAP, PAQ, 2-day CPET and others may be key. But we urgently need patient reported outcome measures and biomarkers.
Read 4 tweets
Oct 29, 2025
Thank you for the opportunity to share this proof-of-concept work, @CPTJournal. @wearlumia @4Workwell Image
We've known that post-exertional malaise is correlated with reduction in cerebral blood flow (CBF) for many years. We think cerebral hypo-perfusion may account for some of the signs and symptoms we observe.

However, measuring CBF takes expensive equipment. 1/n
Trying to measure CBF in any position or movement besides sitting or laying down is practically a non-starter. It is also not the kind of thing a person can do and interpret for themselves. Enter the Lumia™ in-ear device. It's a reliable measure of blood flow to the head, 2/n
Read 10 tweets
Sep 21, 2025
People on here like to discredit PEM symptoms as less credible or reliable, despite all evidence to the contrary. Assuming a trustworthy patient (we always should accept a trustworthy patient as a baseline clinical assumption until proven incorrect), this shouldn’t be a problem.
Besides, anyone making a bright line distinction between signs and symptoms is vastly oversimplifying clinical life. For example, what’s a “limp?” If you see it, a sign. If I say it, a symptom. The truth is never as clear as it initially seems. Too bad for deniers and minimizers.
Similarly, when I do consults with patients, I can usually tell when cognitive dysfunction has begun to set in about the same time or earlier than they do. I know if they’re having a crash day right from the jump. Symptom? Sign? No real difference to the astute clinical observer.
Read 5 tweets

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