@eskabadu Thanks for this interesting question and set of observations. I appreciate you sharing them, as I also appreciate the chance to share. In the first part of the thread, you asked whether I think CPET measures PEM or the energy deficit associated with it. I think it is the latter. @eskabadu My expertise involves two-day CPETs. In this methodology, a first CPET is used as a physical stressor (more on stressors in a minute) to *induce* PEM. A second CPET 24 hours after the first one is then used to measure the physiology of the post-exertional state.

Look, I’m always perfectly happy to accept interventions like talk therapy and brain retraining might be effective for any range of conditions. My only requirement is for sufficient data supporting the claim. Anecdotes, positive though they may be, need not apply. I’ll never take away a person’s narrative about what they believe worked for them. In fact, more power to them. But I will always dispute that an individual’s personal narrative should generalize to others in the absence of adequate evidence suggesting that should be the case.

Here are some things PEM reliably is that post-exertional fatigue in other conditions reliably is not:
* delayed
* prolonged recovery time
* response to multiple types of exertion, not just physical
* meaningfully impairs function
* involves unusual symptoms that aren’t fatigue

https://twitter.com/SockFoam/status/1764993496002314486

If the module is talking about “scientific facts,” I hope some of the studies comparing and contrasting post-exertional signs and symptoms with deconditioning is getting included. That work is just a short Pubmed search away and it adds some important context to this discussion.

Well, since everyone's choosing their little part of the NIH Intramural Study to focus on, let's have a little "phun with physiology." Here's an interesting little factoid related to moderate physical activity as measured by actigraphy.

Dang. So much disuse!

Or is it? I mean after all moderate activity is moderate activity, it isn't a big deal, and maybe people with PI-ME/CFS couldn't do it because they haven't done it. With their effort preference toward low value activities, maybe they didn't want to anyway.

Right? Not so fast, my friends.

Declines in submaximal CPET measures corresponding with PEM symptoms and signs on the second day of a two day CPET have nothing to do with effort preference in people meeting accepted physiological criteria for maximal exertion. You can’t choose or fake your anaerobic threshold. Of course, you need to do a two-day CPET to see these trends, one CPET isn’t the right thing to do, this is not just my “idea” because there are systematic review/meta-analyses of two-day CPET data now, and it’s *checks calendar* 2024 and I can’t believe I still have to say this.

nature.com/articles/s4146…
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 jury is still out✌🏻 seems like a deeply unserious response to a deeply serious issue when there’s more than enough evidence already for a jury to have decided and gone home to rest easy with their choice.

It’s all here. No wonder the good prof still has me blocked. 🤷🏻‍♂️ Graded exercise has been studied for years in POTS, and the people who treat it with exercise rely on a largely flimsy literature to suggesting efficacy, including in this case, direct evidence from *checks reference section again* an unpublished abstract for people with PASC.

Hi, @ChrisCuomo. I know you’re committed to getting this right and
@mjsportspt is a friend. But as a physio working with (commonly) infection associated complex chronic disease, I hope you’ll take this video down. It’s riddled with inaccuracies and may wind up hurting people. I’ve watched this video three times already and it’s making my head hurt.

LinkedIn saw it first, but I’m proud to announce that, as of yesterday, I’ve finished a PhD (Publication) at @portsmouthuni @UoPSportScience. It was a winding and unorthodox route to develop content expertise and demonstrate the relevant scholarly skills, but worth every second. The title of my thesis is “From Function to Physiology and Back in Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” It consolidated findings from 11 publications over the last decade of work in this area to tell the story of post-exertional symptoms and signs.

Dr. Putrino is outstanding in so many ways, but even regular people with a standard commitment to solid science and humane clinical practice quickly find themselves in the position of remediating deep and long-standing injustices in infection-associated chronic complex diseases.

https://twitter.com/PutrinoLab/status/1747246020893843817

It doesn't have to be a motivation to enter and stay in the field, but once you're here, it's hard to miss. Some folks just want to do the science and practice and avoid the rest of it, but that's not how it works. Just a presence as a scholar and clinician makes you an advocate.

I’m a small account @EricTopol but I just want to underline the importance of including post exertional malaise in any analysis of exercise in PASC. This latest article you reviewed didn’t and should’ve. We know too much about exertional intolerance to be able to claim ignorance. Any article published in 2024 citing the PACE Trial as evidence of safety and efficacy of graded exercise should not be taken seriously. It’s one citation, so maybe that seems unfair. But to neglect that level of scientific misconduct calls into question the authors’ judgement.

Aerobic exercise particularly involving scheduled benchmarks of volume to be achieved regardless of symptoms is contraindicated in people living with ME. Certain types of exercise may be beneficial depending on severity and whether PENE/PEM is/can be effectively self-managed. Turns out there’s a lot of gray area after we dismiss the kind of exercise that is consistently harmful based on what we know about post-exertional metabolism in PENE/PEM from ME, actually.

This might be unpopular but here's a connection I think a lot of people still haven't made: PEM isn't deconditioning, but that doesn't mean that people with PEM can't have deconditioning, too. You just can't address the deconditioning in the normal way (i.e., exercise) with PEM. So when I see "PEM isn't deconditioning," it gets a vigorous head nod. Then when I see studies in ME/Long Covid using single CPET and histology that have findings suspicious for changes associated with deconditioning, no biggie, there's space in the thought process for that too.

@EnyaDaynesPT Thanks for the chance to contribute here. I'll highlight five papers here and give honorable mention to several others. This might be a long-ish thread, so please bear with me. @EnyaDaynesPT In many ways, the first paper describing the prevalence of PEM in Post Covid Condition is still the best. Cross sectional work from the early days on an international cohort of about 3,750 people with lab confirmed and suspected wild type COVID-19 infection. Patient led research.

As a researcher and clinician who has worked for awhile to build an evidence base (“acceptability”) to what some consider the “margins” of clinical practice, all I can think is this paternalistic nonsense is what makes preventable suffering such an engrained part of human life. Meanwhile, if these folks were just listen to the people whose labels they denigrate, apparently in their “best interests,” it would represent a quantum leap in medical care.

Changes in mitochondrial function are related to how viruses hijack their processes to ensure viral replication. Viral proteins keep cells from killing themselves (i.e., apoptosis) in the process. Pretty clever process. So, when these changes are passed down to subsequent generations of mitochondria, in which theoretically the dysfunction can persist even in the absence of viral particles, is that “infection associated” or “post infectious?”

Probably neither. At that point, it seems like an acquired mitochondrial genetic disorder.

This. 💯

Clinicians, the key question is “Does this person have PEM?” If the answer isn’t convincing “No,” then a graded/progressive exercise program is not the place to start. Activity recovery responses are abnormal, so typical adaptations to exercise shouldn’t be expected.

https://twitter.com/angryhacademic/status/1710314105897173419

If I had a nickel for every time someone asked me "What about deconditioning?" then I would have a lot of nickels--which I'd immediately put back into ME/CFS and Long Covid research, of course.

So what about it?

Fauci was a counterbalance against the most criminal parts of (in)actions by the prior administration, but this is exactly the kind of response I would expect from a bureaucrat who has slow-walked and underfunded research and researchers in post-infectious illnesses for years.

https://twitter.com/mehdirhasan/status/1704970139341402532

The simple fact is that chronic effects of infectious diseases historically have not been a focus for researchers entering this area who have the kinds of pedigrees and resources to attract and spend big research money--and in interviews like this, it shows.

The key to understanding PEM/PESE is to recognize the body no longer "plays by the rules" we thought we knew about how it should respond to exertion. Short and long term physiological responses to exertion are abnormal. We should not design treatments expecting they should be. Adding load on top of dysfunction is the dumbest possible thing you can do even in a system that has the capacity to adapt. Now imagine thinking it's somehow a good idea to do that in a system that demonstrably can't.

Fun fact for folks keeping track of their lactates at home: 8 mmol/L is a criterion for maximal exertion on a cardiopulmonary exercise test. Judging from some of your measurements, you’re already exerting at that level just getting out of bed to take your first test. #TheAcidTest But, sure. I bet someone will hop on here to remind me again how throwing a progressive exercise program on top of an abnormally high lactate level indicative of inappropriately pervasive anaerobiosis at rest, or as close to rest as we often can get, is supposed to help. 🤔

The NIH RECOVER fiasco has a lot of people with in #LongCovid (and #MECFS) patient communities justifiably on edge, so this tweet got a good run today. If you'd shown it to me three months ago, I would have gleefully joined the pile-on.

Here's why I didn't. And won't. Yet.

https://twitter.com/IpLongCovid/status/1688176667359956993

First, it's important to know that this website is a repository for trials large and small, funded and unfunded. This particular study will enroll 21 people to measure symptoms within a 2-4 week timeframe. Doesn't seem to be funded by big money that takes away from other work.