The Concept of ME/CFS, 2024, Edwards

[Jonathan Edwards]

However, I think there is still evidence connecting ME with infection (even if most post-infectious cases are not ME/CFS).

I agree, but I am wary of lumping MECFS in with other 'post-infective' states.

One thing that strikes me is that if you have a moderately severe case of glandular fever, as I did (I required steroids in order to maintain fluid input through my pharynx) then you go through a period of two or three weeks when all normal life events cease other than going to the toilet and drinking some water. If ME/CFS involves an error in signalling circuits involving central nervous system and peripheral cytokines/hormones then EBV infection could trip the switch simply by rubbing out all normal signal traffic. It might have nothing to do with adaptive immunity, although I think it may be significant that ME/CFS seems to follow intracellular infections (viruses, rickettsia etc.) and not so much bacterial sepsis or things like head injury.

 

[Sasha]

although I think it may be significant that ME/CFS seems to follow intracellular infections (viruses, rickettsia etc.) and not so much bacterial sepsis or things like head injury.

We've heard for years about cases of ME/CFS after head injuries, though (but bearing in mind what you said about coincidence). I wonder if there are any stats on what percentage of people who have a head injury develop ME/CFS, and how that would compare to the 11% (?) or so of people getting EBV who developed ME/CFS in the Dubbo study.

 

[Jonathan Edwards]

We've heard for years about cases of ME/CFS after head injuries, though

I wasn't aware of that. Maybe it often gets called something else.

 

[Haveyoutriedyoga]

I wasn't aware of that. Maybe it often gets called something else.

There is talk of post concussion syndrome with exercise intolerance

 

[Haveyoutriedyoga]

https://pn.bmj.com/content/15/3/172

 

[Sasha]

I wasn't aware of that. Maybe it often gets called something else.

I hadn't thought so. I first heard about it decades ago, when I think the ME charities were pointing out that head injury was one of the ways that you could get ME/CFS. I remember being (misguidedly, obviously!) annoyed that they seemed to be watering down the definition of what I thought was a post-viral illness. But my impression was that patients were being diagnosed with ME/CFS following head injury.

Does anyone else remember this or have any references? This is probably from 30 years ago and my memory of it is fuzzy. I may have got it all wrong.

 

[Robert 1973]

Jonathan has now responded to each of the reviews that have been left under his Qeios article. If you click on “comments” under each review you can read the responses: https://www.qeios.com/read/NXCXM1#XcXle3Bhh3wO

Jo’s response to Dr Raijmakers’s comment on bias is particularly relevant to members of this forum:

My view on bias is that patients are less likely to introduce bias than academics. Patients have a single interest – finding out the mechanism of their illness and how to treat it – not a conflict of interest. In contrast, academics have conflicting interests in personal advancement through publications, grants, fees from insurance companies, promotion with salary enhancements, honours from royalty and goodness knows what! Patients may make unwise decisions about backing research through ignorance of biology but that is a different issue (and academics do that too).

Moreover, we now have an international community of hundreds of patients and researchers talking together on the Science for ME website with many patients being highly skilled in biological disciplines and in creative sceptical scientific thinking. Personal interests can intrude in any context and do sometimes they emerge. I am aware of patients obtaining financial benefits from promoting certain types of treatment. But across the board I see no new risk of bias in patient-led research. Moreover, the bias in academic led research has been hard to compete with. When I first took an interest in ME/CFS I was horrified not only by the poor quality of methodology in studies but also by the vilification of critical patients by the academics producing studies that deserved that criticism. Coming from a different branch of medicine it came as a shock, and over the last ten years I have come to see things were even worse than I thought. Dismissal of patients’ contribution to the science in the past has been disgracefully disingenuous.

Re Ref 17: I understand the value of citing the White et al Anomalies paper as evidence of “their lack of understanding of either the illness or research methodology needed to identify effective treatment” but I think you may be overestimating the average reader of your article if you think they will understand all the problems with the Anomalies paper just by reading it. (Indeed, some of reviewers’ comments on your article could be cited in evidence of that!) I would therefore suggest adding Barry et al’s response as an extra reference – particularly as there is no link to it from the White et al paper on the JNNP website as far as I can see.

 

[Jonathan Edwards]

I think you may be overestimating the average reader of your article if you think they will understand all the problems with the Anomalies paper just by reading it.

I am reminded of that quote from Bertrand Russell 'If the gentleman at the back has not understood what I have been saying it is not necessarily my responsibility'.

Anyone adequately trained in modern medicine, which includes a basic knowledge of the problems of bias in trials, and hence the reason why we spend billions on blinded controlled trials, should immediately follow my argument. I have pointed out that all the trials are unblinded with subjective outcomes. That is all that needs to be said. If the reader then looks at ref 17 they should see the absurdity of the claims there immediately. It is blatantly obvious, in the said context, that this is a group of people with a conflict of interest trying to extricate themselves from a pit of ignominy.

Yes, there will be readers who conveniently 'forget' how simple the matter is, but that is not my responsibility.

It might be nice to quote Barry's response but in a sense that would be invoking a perceived authority - implying that the matter is not already as plain as day. Barry produces cogent responses to each complaint but he actually misses out the real argument (the zero reliability of all the studies) - because GRADE doesn't allow the real argument to show through. So actually no, it would weaken the case.

 

[rvallee]

I am reminded of that quote from Bertrand Russell 'If the gentleman at the back has not understood what I have been saying it is not necessarily my responsibility'.

Anyone adequately trained in modern medicine, which includes a basic knowledge of the problems of bias in trials, and hence the reason why we spend billions on blinded controlled trials, should immediately follow my argument. I have pointed out that all the trials are unblinded with subjective outcomes. That is all that needs to be said. If the reader then looks at ref 17 they should see the absurdity of the claims there immediately. It is blatantly obvious, in the said context, that this is a group of people with a conflict of interest trying to extricate themselves from a pit of ignominy.

Yes, there will be readers who conveniently 'forget' how simple the matter is, but that is not my responsibility.

It might be nice to quote Barry's response but in a sense that would be invoking a perceived authority - implying that the matter is not already as plain as day. Barry produces cogent responses to each complaint but he actually misses out the real argument (the zero reliability of all the studies) - because GRADE doesn't allow the real argument to show through. So actually no, it would weaken the case.

Sadly, it's clear you are in a tiny minority who understand that those problems matter here. Your colleagues mostly seem to understand those problems, they just don't think they apply in the case of psychosomatic concepts, because those concepts can't survive without those exemptions, and since the concept of psychosomatic illness is untouchable, far more than even the Aristotelian geocentric model was when Galileo challenged them with scientific observations, then it must be that the exemptions are necessary and good.

Which is still the same problem, but it remains that however adequately most physicians may have been trained, applying that training is a whole secondary set of training and reasoning that has been turned off here, where pseudoscience is considered fine for pseudoillnesses, and bias is actually perceived as good and benevolent.

Because I mostly see praise, even demands for more bias, coming from the profession when it comes to those trials. The root cause problem of biases is that you can't point out biases to biased people, they never see them. This here has been a historic lesson of how important this problem is, that a profession dealing with matters of life and death and understands those biases still falls for them them hook, line, sinker, fisher and boat.

 

[Grigor]

Ruud Raijmakers en Jos van der Meer in the Dutch journal of Medicine:

"The IOM also retired the term ‘chronic fatigue syndrome’ (CFS), replacing it with the suggestive name ‘systemic exertion intolerance disease’ (SEID)."

"prognostic factors (recovery is limited when complaints are attributed to a somatic cause and in the case of psychiatric comorbidity)."

No mention of their own problematic CBT/GET work or promotion.

https://docs.google.com/document/d/1dULvQ-HvQ2BCN-5m1bBivkSbcQHsxl3hGsLfymyy7M4/edit?usp=drivesdk

And of course Ruud Raijmakers is the author of the QFS CBT long term follow-up and he collaborates with tie COFFI consortium which he now also introduced in the Dutch biomedical research program. Highly problematic!! I'm curious what he thinks about your comment of psych interventions.

https://www.mdpi.com/2227-9032/8/4/552

 

[Grigor]

I do wonder if he might be a bit more open to biological causes of post-infection fatiguing illnesses than some. His engagement with the Concept paper therefore is possibly a win for the relatively neutral stance taken by Jonathan.

He's BPS so he does a little of everything. I'm not too excited about it. Especially since he collaborates with COFFI for the Dutch biomedical research program. It's a loss lol.

 

[Nightsong]

Yet another peer review, from someone whose MEPedia page says he was a former chair of the US CFS Advisory Committee:

Link | PDF

 

[Jonathan Edwards]

Can anyone help me grasp exactly what points Chris Snell is trying to make?

Is the suggestion that we should invent a 'disease' even if we don't know what it is, in order to satisfy the injustice of insurance based health care systems?

I don't know about 'knowing the history' but judging by what I see in Guidelines, scientific papers, YouTube presentations and so on my analysis seems significantly different from that made by many people in the ME/CFS world who would regard themselves as 'knowing the history'. I have known the history for a good while too but some of my thoughts in the paper are quite new for me.

 

[Hoopoe]

"prognostic factors (recovery is limited when complaints are attributed to a somatic cause and in the case of psychiatric comorbidity)."

Isn't this just a less blunt way of saying that disability is caused by attitude to the problem, not the problem itself?

Can anyone help me grasp exactly what points Chris Snell is trying to make?

Is the suggestion that we should invent a 'disease' even if we don't know what it is, in order to satisfy the injustice of insurance based health care systems?

I think he's just expressing frustration that ME/CFS isn't treated as disease.

I agree. Whether someone is taken seriously should not depend on being able to prove that there is something wrong.

 

[Jonathan Edwards]

Isn't this just a less blunt way of saying that disability is caused by attitude to the problem, not the problem itself?

Yes.

 

[Hoopoe]

Something similar to learned helplessness, then.

That is how it must look to the outside to people unaware that others can have bodies that don't behave like theirs.

They wonder why don't we just get up and return to a normal life. We tell them it's not possible but they interpret our words as evidence of thinking that keeps us locked in a state of passivity and negative expectations. Because they have always been able to overcome their problems in that way, and therefore in their mind, we must be able to as well.

 

[Sean]

I am very uncertain about that.
It used to be said that rheumatoid arthritis was often triggered by infection or trauma but it probably isn't. When I asked people about lag between infection and ME/CFS onset the results were pretty variable. It may well be that infection is often the straw on the camel's back so to speak but I am not convinced that chasing viruses will tell us much about the illness.

There is currently a big push to include ME/CFS in 'post-infective syndromes' and I worry that that is mostly driven by very naive immunology bound up with 'cross-reactivity' and such-like.

I have similar concerns. The reports of association between onset and an apparent infectious event, could be just biased reporting, or the causation could even be the other way around – the immediate onset process (briefly) rendering the patients more susceptible to incidental opportunistic infection that exists around and within us all the time.

Your colleagues mostly seem to understand those problems, they just don't think they apply in the case of psychosomatic concepts, because those concepts can't survive without those exemptions, and since the concept of psychosomatic illness is untouchable, far more than even the Aristotelian geocentric model was when Galileo challenged them with scientific observations, then it must be that the exemptions are necessary and good.

+1

For some bizarre reason psychosomatics is given a free pass on the standards that every other branch of medicine and science is expected to meet, and which the psychosomatic fans demand they do. They are very quick to point out limitations in biomedical studies, thus proving they know full well what robust methodology looks like. But consistently turn a firm blind eye to far worse shortcomings in their own studies, and come up with the most ludicrous excuses for it. See PACE. And almost any FND paper ever.

Patients have a single interest – finding out the mechanism of their illness and how to treat it – not a conflict of interest.​

Patients clearly have the least bias in motive of all players. Personally I have never had any preference what the real explanation is. I just want to know what it is, and hence how to fix the damn problem.

 

[Kitty]

Is the suggestion that we should invent a 'disease' even if we don't know what it is, in order to satisfy the injustice of insurance based health care systems?

Yes, I think so.

I don't know about 'knowing the history' but judging by what I see in Guidelines, scientific papers, YouTube presentations and so on my analysis seems significantly different from that made by many people in the ME/CFS world who would regard themselves as 'knowing the history'.

Maybe he's just missed the point a bit?

He says he understood as far back as 2010 that the term ME/CFS is a placeholder for something we're not yet able to name, which is part of what you're suggesting.

But not everyone understood that. Worse still, some neither understand nor accept that we know almost nothing, or that pretending we know things we don't is a barrier to progress. That part of the history, and your call for less confusion and more honesty in order to move forward, might be part of what he's missed or is frustrated about.

 

[Robert 1973]

Patients clearly have the least bias in motive of all players.

BPS advocates would argue that the nature of ME/CFS (ie that it is “perpetuated by unhelpful beliefs”) causes patients to have a bias for biomedical explanations over psycho-behavioural explanations. Just as @rvallee points out that BPS authors appear to understand the flaws in biomedical research but fail to apply the same standards to scrutiny of BPS studies, there appear to be some patients who are less willing to accept valid criticisms of biomedical research than BPS research.

I don’t think that bias applies to most of the patients who are actively involved in analysis of research on this forum, but there is evidence of it elsewhere.

However, bias is not the same as a conflict of interest, and Jo is right to say that patients’ only interest is in understanding the mechanism of our illness and how to treat it, which is not a conflict. (Writing this makes me wonder whether a bias for truth could be considered a bias.)

I also think it is worth noting that, whatever patients’ preconceptions about their illness, as a population we have repeatedly demonstrated a willingness to suspend our beliefs in order to cooperate with BPS therapies in the hope of improvement or recovery. In other words, in most cases, patients’ desperation for improvement appears to supersede their beliefs and fears. Ironically, and tragically, it may be those who are most desperate and most determined who are most willing to suspend their beliefs and keep pushing through worsening symptoms, which may result in the greatest harm.

It should also be noted that dismissing valid criticism of research on the basis of perceived biases due to health status is both unscientific and unethical.

On the subject of bias, it’s a pity we don’t have more medics/scientists without COIs trying to understand ME/CFS. I can only think of one. How could we get more emeritus professors involved?

[Edit: typos for clarity]

 

[Kitty]

On the subject of bias, it’s a pity we don’t have more medics/scientists without COIs trying to understand ME/CFS. I can only think of one

Maybe there are physicians who're interested, but their involvement is less public?

There are good scientists, but I imagine they're doing full time+ jobs. That'd mean they're less able to engage online.