Collecting papers on Evidence Based Practice for ME (plus distinction from FND)

[JemPD]

Hear hear!

I wanted to add a quick clarification to what I said about getting an instinct for your activity limits, given that others have described repeatedly pushing themselves into PEM because their radar's not working.

At first sight it might look like two different opinions about the same thing, but I don't think it is.

People are right to say that, mid-activity, you often get no feedback about where your limit is or whether you've already breached it. It's a real problem.

What I meant was more general, for instance people getting to know what impact an activity like attending a medical appointment will have on them. For some it will mean not scheduling anything else the same day; for others it will mean days of pre-emptive resting followed by a recovery period during which they'll struggle to meet their basic needs.

So it's not the specific or immediate, it's getting a grasp of your overall severity level. What's usually possible if you manage it carefully, and what's out of the question. How often you can do it, for how long.

It isn't a skill that needs to be taught by a therapist, either. Someone recovering from knee surgery quickly learns that some activities leave them shattered and sore, and if they try to do them again the next day they'll really regret it. This is no different.

completely agree with this

 

[ElephantNerd]

This is all so helpful, and I can't possibly respond to everything properly. I'm asking questions about things I'd like further clarification on, but I am reading ALL your excellent comments and responses and they will inform my decisions and how (and when) I talk about MECFS etc. You all are stellar!

And re: disputing my ideas. I came to this forum with this topic specifically to have my ideas critiqued. There's no use in me overstating unproven conclusions, and you all know the data much better than I do. I wasn't aware about the lack of evidence for some of those statements above, so you are helping me to avoid the pitfall i would have fallen into. That's really important to me. So really honestly THANK YOU for helping me learn!

I mean it 100% when I say that hearing your inputs (including correctional inputs) helps me feel less alone and worried. I am afraid of saying something wrong/unhelpful to the editors, and I'm much less likely to do that with your helpful critiques to my letter outline! It's such a relief to hear your thoughts instead of going it alone.

Re: pacing/energy conservation evidence. I was hoping you guys could help point me to some evidence? I think the CDC recommends pacing, and anecdotally I can attest that pacing is really important for me to avoid PEM. I thought I read a study once about how some MECFS patients who remain below their adjusted anaerobic threshold and stay within their "energy envelope" have less PEM and more physical ability a year later, but I can't find it so I may be remembering wrong. If such a paper exists, y'all seem sure to know about it!

I like the idea to use the CDC and NICE resources!

Tangentially, the daylight thing is SO relatable and I'd like to ask questions in a different thread about it later.

Re: OI evidence. This is what I've got but I'm far outside my scope of practice here, so I appreciate any input you can give.

I've seen a few smatterings of studies on pharmaceuticals like these:
https://pmc.ncbi.nlm.nih.gov/articles/PMC7255540/
https://pmc.ncbi.nlm.nih.gov/articles/PMC7660715/
But I have NO idea how good these studies are. (Hence me asking y'all's opinions of what evidence there is)

And I thought I had read at least a single cohort study about the effect of abdominal binder and compression stockings on post orthostatic tachycardia in ME CFS and Long COVID patients (authors' words, not mine), but I can't find it now. Have you guys heard of such a study?

When I FINALLY got diagnosed last year (after a sixteen year journey of gradual onset MECFS), I started reading studies and articles about management strategies etc, but I wasn't good at keeping a record of what I read at first. Hence my fuzzy memories.

Re: no solid evidence for physical Illness/disease process. Is that really true? Help me understand. There isn't solid evidence for energy production issues, orthostatic issues, autonomic system involvement, immune involvement, etc in people with ME CFS? What about the 2 day exercise test results? Are those based on some kind of evidence? Even if we don't know what causes it, is there not evidence of physical illness with replicated results?

I trust y'all's judgment over mine since this is waaaaaay outside my scope. Am I not distinguishing the terms "disease, illness, and syndrome" correctly? Be brutal -- I don't want to say untrue things.

Re: terminology. What about the term "dysautonomia"? From my limited understanding, what that means is the autonomic nervous system doesn't do its job well. That sounds like a "diagnosis" that just describes what isn't working without claiming to know why. But I am new to the term, so please help!

Re: PEM. Do y'all prefer the term PEM or PESE (post exertional symptom exacerbation)? I've heard PEM more, but I also like PESE. Thoughts?

Thank you so much! Usually I keep my writing away from medical diagnoses since I am not educated about giving them--but as a patient, I wish someone had educated my providers for me about FND vs MECFS, etc. So I wonder if I can be that voice in this case. Maybe not, but it can't hurt to become educated myself about my own chronic illness (syndrome?).

Again, thank you all for your excellent critiques and inputs! This is really helpful as I figure out whether to write to the editors of that magazine and if so, how/when. And also for generally understanding how to accurately communicate about MECFS etc.

PS, I'm getting more and more eager to learn the Decodeme results. I didn't realize what a knowledge gap there was!

 

[Liie]

1. MECFS is a physical disease separate from FND.
...
3. There is evidence of physical disease process in MECFS.

It might have good rhetorical effect to refer to the findings of IoM and NICE when arguing that ME/CFS is a physiological decease towards your colleagues:

https://me-pedia.org/wiki/Institute_of_Medicine_report#Key_findings:

ME "is a medical-not a psychiatric or psychological — illness"

https://me-pedia.org/wiki/NICE_guidelines#Neurological_disease:

Be aware that ME/CFS... is a complex, chronic medical condition affecting multiple body systems and its pathophysiology is still being investigated

That is not evidence in it's self of course, but referring to trusted institutions might help convince your colleagues.

(Sorry if this duplicates some post, I have not read the whole thread, I have a fatigue syndrome which makes it hard for me. )

 

[Utsikt]

Re: terminology. What about the term "dysautonomia"? From my limited understanding, what that means is the autonomic nervous system doesn't do its job well. That sounds like a "diagnosis" that just describes what isn't working without claiming to know why. But I am new to the term, so please help!

What does «dysautonomia» mean? If you’re refering to feeling unwell when standing or sitting, I’d just use OI (orthostatic intolerance).

Re: PEM. Do y'all prefer the term PEM or PESE (post exertional symptom exacerbation)? I've heard PEM more, but I also like PESE. Thoughts?

PEM.

PESE means more symptoms after exertion. But that could technically also be DOMS, post-exertional fatigue, etc.

Our recent factsheet defined the concept of PEM as this:

Characteristics of PEM

People with ME/CFS experience episodes when they are much more ill and cannot do as much as usual following amounts of physical or mental exertion or sensory stimuli that they could easily tolerate before the illness. This is called post-exertional malaise, or PEM. PEM is the hallmark of ME/CFS and important for diagnosis.

The main features of an episode of PEM are:

• A person feels more ill. Their usual symptoms get much worse, and new symptoms may appear.

• They are much less able to function. They need to rest more, or even to lie still in silence and darkness, until it passes.

• The onset of PEM is typically delayed for hours or up to several days after it is triggered.

• The length and severity of an episode of PEM are out of proportion to the amount of exertion or stimulus that triggered it. An episode can last hours, but more often lasts days, weeks or longer.

https://www.s4me.info/threads/fact-sheet-2-post-exertional-malaise-pem-may-2025-discussion.44002/Fact sheet #2 Post-exertional malaise (PEM), May 2025 discussion | Science for ME

Edit: see also the section in the factsheet on effects of exertion that is not PEM.

 

[Utsikt]

And re: disputing my ideas. I came to this forum with this topic specifically to have my ideas critiqued. There's no use in me overstating unproven conclusions, and you all know the data much better than I do. I wasn't aware about the lack of evidence for some of those statements above, so you are helping me to avoid the pitfall i would have fallen into. That's really important to me. So really honestly THANK YOU for helping me learn!

I mean it 100% when I say that hearing your inputs (including correctional inputs) helps me feel less alone and worried. I am afraid of saying something wrong/unhelpful to the editors, and I'm much less likely to do that with your helpful critiques to my letter outline! It's such a relief to hear your thoughts instead of going it alone.

That is a great attitude! We need more people like this.

I also don’t like being wrong, so I try (with emphasis on trying) to avoid it by changing my opinions and beliefs when I am.

 

[Jonathan Edwards]

There isn't solid evidence for energy production issues, orthostatic issues, autonomic system involvement, immune involvement, etc in people with ME CFS? What about the 2 day exercise test results? Are those based on some kind of evidence? Even if we don't know what causes it, is there not evidence of physical illness with replicated results?

Basically none of this stuff adds up to anything tangible.
Most of the evidence on energy-dependent processes looks normal. When people try to replicate abnormal findings mostly they find something a bit different. There seems to be a shift in day 2 CPET and that does not seem to be due to deconditioning but it might reflect a whole lot of other spurious factors and it doesn't explain anything much.

The evidence for an orthostatic problem comes from the symptoms. We don't have any reliable evidence for what causes it. There is no evidence that the autonomic system is 'involved' rather than just mediates symptoms through normal mechanisms (driven by something unknown).
None of the immune findings provide a clear explanation for anything and most of them have not replicated.

The bottom line is that a medical scientist such as myself coming to the ME/CFS field doesn't find anything convincing in these areas. As mentioned before, all illness is 'physical' and there is no doubt people are ill. But if we want evidence of a cause (and all causes are physical) none of the stuff mentioned or anything else so far provides evidence for any specific cause.

Most advocacy groups would love to believe the evidence is clearer but it isn't and to get the evidence needed we should recognise that.

HOWEVER, things are changing. For complicated reasons to do with a range of projects I think we can now say that we are as sure as we need to be that the cause is partly genetic. Moreover, I am personally confident that that will turn out to be mediated through genes involved in immune responses and genes involved with nerve function. But for the moment saying more than that in a simple fashion is pretty difficult. There are several other projects in the pipeline and once they are in I think it will be much easier. We don't yet know exactly what causes what and that is likely to take a little longer but we will be able to say what sort of processes are causing the problem. They probably have rather little to do with all the stuff the advocacy groups talk about but I think at least some of the research out there will be validated.

 

[Kitty]

Re: pacing/energy conservation evidence. I was hoping you guys could help point me to some evidence? I think the CDC recommends pacing, and anecdotally I can attest that pacing is really important for me to avoid PEM. I thought I read a study once about how some MECFS patients who remain below their adjusted anaerobic threshold and stay within their "energy envelope" have less PEM and more physical ability a year later, but I can't find it so I may be remembering wrong. If such a paper exists, y'all seem sure to know about it!

I don't think there's any replicated evidence, but I also don't think there needs to be.

First, every ME/CFS patient reports that doing too much activity makes them feel so ill it affects their ability to function. We can accept that much because it's one of the core symptoms.

Next, if doing something makes you feel so ill it affects your ability to function, it's best to stop. We can accept that because it's obvious. Whether it's eating dinner late when you have GERD, digging bean trenches when you have a hernia, or eating trigger foods when you get migraines, it doesn't need a clinical trial. Common sense will do.

 

[jnmaciuch]

Re: no solid evidence for physical Illness/disease process. Is that really true? Help me understand. There isn't solid evidence for energy production issues, orthostatic issues, autonomic system involvement, immune involvement, etc in people with ME CFS? What about the 2 day exercise test results? Are those based on some kind of evidence? Even if we don't know what causes it, is there not evidence of physical illness with replicated results?

At most you could probably say there are bits and pieces where details might be consistent with an overall story, but replication of the exact details has been sparse. I’m optimistic about the near future but don’t think we can say “X has been consistently found to be dysregulated in ME/CFS” yet.

The one exception would be 2 day CPET though, I’m fairly sure others have already written up somewhere on here that they show consistently reduced metrics on day 2 compared to controls. It’s just something that the BPS crowd has already tried to explain away with effort motivation or what have you. Like others have said, I think your best bet is to argue against the idea that we will all be cured with CBT rather than trying to explain ME/CFS as a physical illness with only shaky theorizing so far.

Some of Leonard Jason’s work might be helpful for estimating prevalence of various symptoms and comorbidities with ME/CFS—I have issues with his DePaul symptom questionnaire but I do think that’s one thing it is decent for.

 

[Hutan]

The one exception would be 2 day CPET though, I’m fairly sure others have already written up somewhere on here that they show consistently reduced metrics on day 2 compared to controls. It’s just something that the BPS crowd has already tried to explain away with effort motivation or what have you.

The argument about effort motivation doesn't hold, as, if people achieved and RER of 1.1, and they usually do, effort preference is irrelevant.

But, the CPET studies are less solid than is ideal. Most of the studies have problems - with the reporting of data, or biases such as having been done to provide paying customers evidence for insurance claims. The studies have tended to come from very few teams. Some studies found issues with VO2max, others only with the anaerobic threshold. If I'm remembering correctly, some studies found that healthy controls also had reductions in performance.

I say this as a person who has participated in a 2 x CPET study and was found to have the ME/CFS typical reduction in performance on the second day - I'm still not quite sure if the effect is an actual thing. Probably it is, but last time I looked, the evidence didn't seem completely solid. Which is very annoying.

 

[Utsikt]

I think your best bet is to argue against the idea that we will all be cured with CBT rather than trying to explain ME/CFS as a physical illness with only shaky theorizing so far.

This can be done by using studies like PACE and MAGENTA. They clearly showed that CBT/GET does not work.

 

[Kitty]

Am I not distinguishing the terms "disease, illness, and syndrome" correctly?

It's probably more about convention than strict correctness? So, as a complete non-expert(!), I think:

Illness just means not-wellness. It can describe a 24-hour head cold and fatal aspiration pneumonia.

Disease is usually used when the cause of an illness, or the effects of it, are known or can be found. So 'flu is a disease (infectious agent), as are breast cancer (uncontrolled cell proliferation) and MS (autoimmune tissue damage). But there are probably examples that don't strictly adhere to that.

Syndrome is usually used to mean a group of symptoms that occur together consistently enough to be recognised and given a label, but the cause may not be known.


[Minor edit to complete final sentence]

 

[Jonathan Edwards]

Re: terminology. What about the term "dysautonomia"? From my limited understanding, what that means is the autonomic nervous system doesn't do its job well. That sounds like a "diagnosis" that just describes what isn't working without claiming to know why.

That's right but it's worse than that. Dysautonomia is used for two very different situations. In one the autonomic system fails - no signals so no control (typified by Shy-Drager syndrome I think). In the other the autonomic system kicks in unexpectedly - as in 'POTS'. It is not clear whether it not regulating itself or whether it is doing its job normally in response to an unexpected failure elsewhere.

Without specifying what the situation is, 'dysautonomia' just reduces the information to lay gossip level.

 

[Cinders66]

This is all so helpful, and I can't possibly respond to everything properly. I'm asking questions about things I'd like further clarification on, but I am reading ALL your excellent comments and responses and they will inform my decisions and how (and when) I talk about MECFS etc. You all are stellar!

And re: disputing my ideas. I came to this forum with this topic specifically to have my ideas critiqued. There's no use in me overstating unproven conclusions, and you all know the data much better than I do. I wasn't aware about the lack of evidence for some of those statements above, so you are helping me to avoid the pitfall i would have fallen into. That's really important to me. So really honestly THANK YOU for helping me learn!

I mean it 100% when I say that hearing your inputs (including correctional inputs) helps me feel less alone and worried. I am afraid of saying something wrong/unhelpful to the editors, and I'm much less likely to do that with your helpful critiques to my letter outline! It's such a relief to hear your thoughts instead of going it alone.

Re: pacing/energy conservation evidence. I was hoping you guys could help point me to some evidence? I think the CDC recommends pacing, and anecdotally I can attest that pacing is really important for me to avoid PEM. I thought I read a study once about how some MECFS patients who remain below their adjusted anaerobic threshold and stay within their "energy envelope" have less PEM and more physical ability a year later, but I can't find it so I may be remembering wrong. If such a paper exists, y'all seem sure to know about it!

I like the idea to use the CDC and NICE resources!

Tangentially, the daylight thing is SO relatable and I'd like to ask questions in a different thread about it later.

Re: OI evidence. This is what I've got but I'm far outside my scope of practice here, so I appreciate any input you can give.

I've seen a few smatterings of studies on pharmaceuticals like these:
https://pmc.ncbi.nlm.nih.gov/articles/PMC7255540/
https://pmc.ncbi.nlm.nih.gov/articles/PMC7660715/
But I have NO idea how good these studies are. (Hence me asking y'all's opinions of what evidence there is)

And I thought I had read at least a single cohort study about the effect of abdominal binder and compression stockings on post orthostatic tachycardia in ME CFS and Long COVID patients (authors' words, not mine), but I can't find it now. Have you guys heard of such a study?

When I FINALLY got diagnosed last year (after a sixteen year journey of gradual onset MECFS), I started reading studies and articles about management strategies etc, but I wasn't good at keeping a record of what I read at first. Hence my fuzzy memories.

Re: no solid evidence for physical Illness/disease process. Is that really true? Help me understand. There isn't solid evidence for energy production issues, orthostatic issues, autonomic system involvement, immune involvement, etc in people with ME CFS? What about the 2 day exercise test results? Are those based on some kind of evidence? Even if we don't know what causes it, is there not evidence of physical illness with replicated results?

I trust y'all's judgment over mine since this is waaaaaay outside my scope. Am I not distinguishing the terms "disease, illness, and syndrome" correctly? Be brutal -- I don't want to say untrue things.

Re: terminology. What about the term "dysautonomia"? From my limited understanding, what that means is the autonomic nervous system doesn't do its job well. That sounds like a "diagnosis" that just describes what isn't working without claiming to know why. But I am new to the term, so please help!

Re: PEM. Do y'all prefer the term PEM or PESE (post exertional symptom exacerbation)? I've heard PEM more, but I also like PESE. Thoughts?

Thank you so much! Usually I keep my writing away from medical diagnoses since I am not educated about giving them--but as a patient, I wish someone had educated my providers for me about FND vs MECFS, etc. So I wonder if I can be that voice in this case. Maybe not, but it can't hurt to become educated myself about my own chronic illness (syndrome?).

Again, thank you all for your excellent critiques and inputs! This is really helpful as I figure out whether to write to the editors of that magazine and if so, how/when. And also for generally understanding how to accurately communicate about MECFS etc.

PS, I'm getting more and more eager to learn the Decodeme results. I didn't realize what a knowledge gap there was!

This is a forum, that IMO has a lot of expressed and educated views but is not the definitive truth on all things m.e & related illnesses. There is in the wider world variance in opinion on anything, from treatments, names, labels, criteria, definitions, appropriate framings, research evidence etc so any view/ comment may not be agreed on in other spaces and in wider circles.