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

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.

Thank you for the opportunity to share this proof-of-concept work, @CPTJournal. @wearlumia @4Workwell 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

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.

If exercise makes symptoms worse…you know that exercise makes symptoms worse.

You do not know if it’s PEM from that observation alone. For example, I work with people who have low back pain. Sometimes the treatments I provide overload things enough they feel a little worse temporarily. There’s a school of thought that says exercising into a little pain might even be helpful because it gets even better over time.

Today’s unpopular opinion is evidence based practice isn’t just following a cookbook established by scientific research or the lack of it but it also involves a meaningful synthesis of lived experience and clinical judgement as co-equal sources of evidence. Three legs of a stool. This means that, to practice in an evidence-based manner, we are *obligated* to meaningfully elicit the patient’s perspectives on what’s happening to them and why, including information they obtained from Internet searches, AI ramblings, social media, and patient support groups.

I’ve now been able to read the new iCPET paper a few times (I’m slow). As you know, I do love a CPET paper. My first thought is: good that a second group is using this methodology for replication purposes. Adds credibility to the findings if more than one group are finding them. My second thought is: they didn’t seem to have any requirement for max tests. They mentioned respiratory quotient for their healthy controls, but not for their patients. Why is this important? The potential to compare apples with oranges: results of maximal and submaximal tests.

We still know precious little about PEM, but one thing's for certain--it represents an impaired recovery response to exertion. How do we know this? We had data from systems to molecules, replicated across myalgic encephalomyelitis cohorts originating regardless of patho-etiology. Who cares? Because a foundational aspect of being human is being able to count on physiological adaptations to exerting ourselves. Walk a little more so you can walk a little more. Read a little more so you can read a little more. Do some more to do more later. It's fundamental.

Maybe it’s just another day ending in “y” around here but I’ll volunteer we can never do enough to educate health care practitioners about PEM—the thing that breaks all the rules. We simply can never have enough caution and clarity surrounding PEM, particularly how to do no harm. In trying to understand this confusing phenomenon, I’ve spent more times wrong than right. After all, as a researcher all your best ideas are still just hypotheses and as a clinician the best you’ll ever do is still considered practicing. The greater pursuit isn’t to be right…

The sooner we can move away from this still-pervasive idea that PEM is a feature of multiple conditions, the better. We’re still not seeing the forest for the trees. It’s hurting our ability to subgroup patients with different kinds of triggers that share common pathophysiology. Here’s some data from a recent study we did with patients reporting PEM/PENE. Notice the overlap between Lyme, SARS-COV-2, Gulf War Illness and other conditions. Not all people with them have PEM/PENE and meet criteria for ME, but the ones who do…have ME. journals.sagepub.com/doi/10.3233/WO…

@twoShaws Some interesting notes while waiting for a flight: 🧵

The exercise cohort was not pre-screened for PEM because they did not fill out the DSQ-PEM. It's no secret that I'm not a huge fan of how investigators use this questionnaire, but they did not use the most common survey. @twoShaws Instead, they used a visual analog scale survey and focused on a symptom cluster they found to be prevalent after CPET in a prior study. Maybe this is fine but using a different survey tool may compare apples with oranges. Seems odd to not screen for PEM using a common approach.

I totally acknowledge the role of poor mental health in people with ME and ME-like/ME-subtypes of conditions. But to say there’s a reciprocal relationship between mental and physical health, and to leave it there, only tells part of the story and leaves out the *important* part. Let me explain. If you stop at saying there’s a bidirectional relationship between mental and physical health, you might be tempted to assume, as a clinician, that you can intervene on both ends and those interventions should have exactly the same effect. After all, why bother…

Yet another trial that doesn't appear to track PEM properly through using the DSQ as designed and validated. They say DSQ Short Form but it appears from the supplemental tables they mean DSQ-PEM. DSQ was only assessed in a subset of participants at follow-up and not at baseline.

https://twitter.com/atranscendedman/status/1906719213751771511

It is so unhelpful how investigators use validated measurements however they want because vibes. The prevalence of PEM in this study sample may be overestimated. The incomplete follow-up prevents our ability to determine the influence of PEM on the primary and secondary outcomes.

Did you know that according to @NIH Common Data Elements Work Group on #MECFS, assessment for #PEM is a two-stage process involving the use of a questionnaire followed by a confirmation process? Most studies on PEM only use the symptom screening portion, but this is not specific. Did you know few exercise studies in Long Covid purporting to use the DSQ-PEM use both stages of the PEM scoring or the (unmodified) questionnaire as originally validated? Incomplete use and bootleg versions seriously compromise inferences about the effect exercise has on PEM.

A cross-post from 🦋 for my Twitter friends.

A 🧵. Back in early 2022, the editorial staff of the @CPTJournal approved a Special Issue on Long Covid. Against all better judgement, I was selected to be its Guest Editor. The Special Issue published today.

Here are the contents. @CPTJournal Leading off is a lived experience essay by Samantha Laswell PTA (USA). It appropriately centers this volume of work on the patient’s voice. We clinicians and researchers benefit from leadership from people living with Long Covid in all we do. journals.lww.com/cptj/fulltext/…

E. Coli is endemic, i.e. never going way. Given this, under what conditions will you advocate ever stopping washing your hands after using the restroom or coming into contact with contaminated material? Sexually transmitted infections are endemic, i.e. never going away. Given this, under what conditions will you advocate ever stopping the use of evidence based mitigation methods like condoms, vaccination, behavioral counseling, and prophylaxis?

@SteveFifield3 @KatyBruce108 @CaroleBruce17 @MEResearchUK @Invest_in_ME @OpenMedF @polybioRF @VirusesImmunity @mecfsbiobank @PhysiosForME @resiapretorius @dbkell @OxMEDiscovery @BhupeshPrusty I’d love to talk about how lack of funding and venues to share peer reviewed work have silenced ME research and researchers over time, and has limited progress. That’s influenced my whole career. It seems to be the censorship everyone’s complaining about, hiding in plain sight. @SteveFifield3 @KatyBruce108 @CaroleBruce17 @MEResearchUK @Invest_in_ME @OpenMedF @polybioRF @VirusesImmunity @mecfsbiobank @PhysiosForME @resiapretorius @dbkell @OxMEDiscovery @BhupeshPrusty It would be fantastic to talk about the reviewer comments I *still* get that dismiss infection associated chronic diseases as psychological, and now neurological, despite the physiological data we’ve cultivated *over many years* and *replicated by others* showing those are false.

I'm struggling with how cognitive dysfunction came to be considered part of deconditioning. We published data suggesting it isn't...11 years ago. If a patient or potential research participant reports cognitive dysfunction, they more likely have PEM/PENE. pubmed.ncbi.nlm.nih.gov/21208154/ We also published on this dataset indicating self-reported cognitive dysfunction was a robust symptom to differentiate between women with ME/CFS and matched sedentary women who are deconditioned. pubmed.ncbi.nlm.nih.gov/36938769/

For those of you who are thinking I don't understand the @theNASEM Long Covid definition, here's my thought. All of the things in the circle that aren't crossed out (and more!) can be PEM/PENE. It all depends on the timing with activity.

That's it. That's the tweet. Does that make other manifestations of Long Covid less valuable or worthy? Nope. But thinking about it as its own thing or an 'associated' condition is not helpful if half-ish or more of people with Long Covid identify that they have it.

Even having your hair washed by someone else involves at least 30% over baseline. For someone with severe #MECFS, characterized by correspondingly severe impairments in energy production and utilization, this kind of thing decidedly isn’t going to make them feel better.

https://twitter.com/ishbelfrazer/status/1816837819257479641

Source: pacompendium.com/self-care/

Eating requires a 50-100% increase in metabolic output over baseline. This doesn't cover meal prep, socializing, digestion nor effects of PEM/PENE. Saying that swallowing and digestion impairments in ME are 'functional' fundamentally (willfully?) misunderstands the problem. Source: pacompendium.com/self-care/