Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank, 2024, Huang et al

[DMissa]

Can @melb and/or @DMissa comment a bit more on how the findings of Huang et al. 2024 link in with those of Missailidis, Armstrong et al. 2026 in simple terms please? (I'm aware team members overlap!)

I see these mentions of Huang 2024 in Missailidis 2026:


I'd like to hear more, in layman's words, of what you think of the Huang 2024 findings in light of Missailidis 2026?

The broad strokes that align are mentioned briefly in the paper but are left there. Didn't want to harp on about it too much because it would just be supposition. Can't make any confident or specific comment without more data. If we have primary cell data linked with biofluid data, collected together from the same people, it may be more possible to draw meaningful relationships between the studies. As it stands, what we have in one study is biofluid data, and in the other study transformed cell lines from a different cohort of people. Much too hard to dig into relationships between them in detail.

We have a couple of collaborative projects that may shed light here. Including a component of Chris's recent big grant

 

[Kitty]

We absolutely don't want fast track to false positives. But I'd probably prefer an err on side of the earlier recommendation of pacing management. Yes you may get some people being told to pace that don't need to.

Do you think that is a problematic point of view?

I don't find that problematic, I think it's eminently sensible when ME/CFS is suspected.

Thing is, people who're finding activity makes them feel ill will already (consciously or not) have started pacing to some extent. To have a physician endorse that as a reasonable course of action, at least whilst we see what's going on, would be really valuable.

What I'm not sure about is whether we need a test to endorse it as a reasonable course of action for physicians. If a patient's feeling ill and exhausted, advice to avoid overdoing it is just common sense.

Interesting debate, though!

 

[Evergreen]

Why do you find Supplementary Figure 7 reassuring?

What was dimly visible yesterday is obscured today - brain bunched. So I can't answer, sorry!

 

[Evergreen]

The broad strokes that align are mentioned briefly in the paper but are left there. Didn't want to harp on about it too much because it would just be supposition. Can't make any confident or specific comment without more data. If we have primary cell data linked with biofluid data, collected together from the same people, it may be more possible to draw meaningful relationships between the studies. As it stands, what we have in one study is biofluid data, and in the other study transformed cell lines from a different cohort of people. Much too hard to dig into relationships between them in detail.

We have a couple of collaborative projects that may shed light here. Including a component of Chris's recent big grant

Well that's good news!

Thank you for not speculating, and for explaining what data you would need to comment.

 

[Utsikt]

We absolutely don't want fast track to false positives.

But you’re literally saying you want to make the diagnosis faster and more accurate by using the test, and that doctors will learn to trust it because outcome is what matters.

Fatigue is one of the most common complaints at GPs. If the GPs with poor knowledge of ME/CFS (that you said could be helped by this) use your test for all those cases, you’d get an enormous amount of false positives.

Lets say Norwegian GPs perform 100,000 tests a year. That’s <0.6 % of the GP consultations (17.8M in 2024, with 1.2M excess compared to pre-covid expectations, so many will be LC related - study). For comparison, there are ~250,000 vitamin D tests a year for women aged 20-50 alone (source).

If just 1 % of the tests give a false positive for ME/CFS, you’d get 1000 false positives a year. That would make ~1/3 of all ME/CFS diagnoses a year definitive false positives (study on prevalence).

And if the doctors trust the test, the diagnosis might stick for a long time. Especially when most doctors don’t know what ME/CFS looks like, and they haven’t been taught because it isn’t needed because we have a diagnostic test for it..

But I'd probably prefer an err on side of the earlier recommendation of pacing management. Yes you may get some people being told to pace that don't need to.

Do you think that is a problematic point of view?

I don’t mind people being told to pace. But I do mind people being told they have ME/CFS when they don’t, and they might have something treatable instead that will be missed because your test that everyone trusts said so.

 

[MelbME]

But you’re literally saying you want to make the diagnosis faster and more accurate by using the test, and that doctors will learn to trust it because outcome is what matters.

Fatigue is one of the most common complaints at GPs. If the GPs with poor knowledge of ME/CFS (that you said could be helped by this) use your test for all those cases, you’d get an enormous amount of false positives.

Lets say Norwegian GPs perform 100,000 tests a year. That’s <0.6 % of the GP consultations (17.8M in 2024, with 1.2M excess compared to pre-covid expectations, so many will be LC related - study). For comparison, there are ~250,000 vitamin D tests a year for women aged 20-50 alone (source).

If just 1 % of the tests give a false positive for ME/CFS, you’d get 1000 false positives a year. That would make ~1/3 of all ME/CFS diagnoses a year definitive false positives (study on prevalence).

And if the doctors trust the test, the diagnosis might stick for a long time. Especially when most doctors don’t know what ME/CFS looks like, and they haven’t been taught because it isn’t needed because we have a diagnostic test for it..

I don’t mind people being told to pace. But I do mind people being told they have ME/CFS when they don’t, and they might have something treatable instead that will be missed because your test that everyone trusts said so.

Understand the concerns, important to consider.

False positives happen with just about every diagnostic tool. I believe there are certain standards to adhere to. Even the current diagnosis path has false positives. As an example, early MS can be misdiagnosed as ME/CFS, a good clinician will still look for follow up tests. The question for us is if the tool generates a net positive in patient care/outcome.

Typically specialists will still look for other explanations. Given that there is no treatment for ME/CFS beyond management, it would be far easier for a clinician to identify another reason for the patient experience.

I suspect a lot of patients, that would have been ME, now get diagnosed with Long COVID unless they are sure the trigger wasn't COVID. Do you see that as a problem?