“Dr. Ken Friedman and Dr. David Maughan – ME/CFS and Long Haul Covid Similarities and Ramifications” podcast

[EzzieD]

Wessely's interest emerges at the time the biological work declines, yes, but I don't see how we can know what caused what. Durval Costa's work on brain blood flow actually came out in 1992-4, although there were never any really definitive findings.

I lost touch with what was going on in ME research after 1990, because I had recovered, thought recovery was permanent, and wanted to just forget all about that horrible episode of my life. Am glad to hear that a brain blood flow study did finally get published, although it's unfortunate no definitive findings had been achieved.

Wessely's comment on T cells, to be fair, was after he had tried studying T cells himself and got nowhere. Studying T cells is generally a waste of time and in 1988 I was going around saying a bit more physiology and a bit less T cells might help for rheumatoid arthritis. Forty years later none of the T cell research has told us anything but I realised in 1996 that the B cells, which everyone was ignoring, held the key.

I think if you have a junior psychiatrist who is not very conversant with scientific method studying T-cells, it goes without saying that he is unlikely to find anything - especially as he was so invested in ME being a mental illness for his own ends.

Ah, yes, along with T-cells, B-cells were indeed also being studied in relation to ME back in those days by real researchers. I don't know how that panned out, as, again, I had recovered and wanted to forget the whole thing. I guess if that did go anywhere, it got buried under all the loud psych noise.

 

[duncan]

The concept of ME/CFS is a concept of a state of ill health, without reference to cause because that is unclear.

It's how that concept is qualified that I am trying to call attention to. Most of us really knows the descriptions of ME/CFS are at best anemic. Pretty much the only good thing that has happened definitionally over the past 20 or so years is the recent inclusion of PEM as a salient feature - but even that has a name that illicits ambivalence.

without reference to cause because that is unclear.

Other diseases make such references without certitude. It's actually quite common in cases with possible autoimmune agents. Psoriasis, MS, Excema, PTLD. There are others. I think there is an argument that possible causes be included definitionally, so as to convey the overt biological nature of the disease. "Scientists believe ME/CFS could be brought about by persistent pathogens, or dysfunctional immune responses, or genetic factors, or a combination of the three." Period.

The predominant view is that even if there is an infective trigger there is no evidence that infection is present long term or that treatment directed at infection is relevant. That might prove wrong but I actually doubt it. So defining the illness of PWME/CFS in terms of infection has no particular motivation. And for those without such a history it makes no sense.

Well, that's not quite true. There is evidence. Chia thinks so, Petersen thinks so. That's another long list. A possible problem here is that multiple pathogens may be involved in manifesting what we call ME/CFS, so if you're looking for one, and you've a cohort of 50 patients, you are not likely to find any significant success. Or, the diagnostics simply don't pick up the pathogen in serum - that's another long list. (Anybody remember "Don't look at tissue?") So I repeat, to say there is no evidence of infection, although technically sorta correct, is misleading. Worse, it's a disincentive for a new generation of researchers to want to parse down and find the culprit. Find what it is and where it is, i.e, in possibly privileged sites like brain tissue. As for motivation, is fending off psychologizing motivation, or incenting a new generation of researchers? Or giving patients hope instead of dashing them with claims like there is no evidence infections is involved - which they've been saying about MS for 20 years until recently they reversed position?

As for those without such a history, or even those who do, but where no pathogen still persists, that's why we include possible dysfunctional immune/autoimmune responses as well as possible genetic causes.

We exclude any woowoo psych nonsense.

Right now we are sitting targets. We need to rethink wording and flaunt the descriptors that have been foisted on us, that we have inherited from often bad faith actors, and that our advocates have struggled to work with and fashion into some medically feasible contrivance that won't solicit confusion and disdain and, far too often, abuse. Yes we got PEM added. After 40 years. We still carry the other wording like yokes.

I think we have to be realistic. If we don't have a biomarker, what are we left with? Lists of symptoms.

Yes. Whose phrasing predates most of us, and most of us are unhappy with it. Not the symptoms per se, but how they are presented. That IS a fact. Most of us lament the presentation.

Sorry, rest time.

 

[Jonathan Edwards]

I think if you have a junior psychiatrist who is not very conversant with scientific method studying T-cells, it goes without saying that he is unlikely to find anything

I think he used the same methods as everyone else - and none of them have found anything in any other diseases much. The amount of money wasted on T cell research runs into many billions!

 

[Jonathan Edwards]

I think there is an argument that possible causes be included definitionally, so as to convey the overt biological nature of the disease.

Sorry but that makes no sense. In order to attribute a cause to some health condition you have to define the health condition you are wanting to explain first, and then consider whether to link it to a cause. If you don't know what the cause is there is no justification in making the link. You must already have a concept of the condition you were trying to explain so you are obliged to stick to that.

The whole point of science is to get away from slipping in ideas that people rather like but for which there is no reliable evidence.

 

[Jonathan Edwards]

Other diseases make such references without certitude. It's actually quite common in cases with possible autoimmune agents. Psoriasis, MS, Excema, PTLD.

Psoriasis, MS and eczema are entirely defined without reference to cause. Chapters on them may discuss causes but that is quite different. PTLD is defined in terms of cause so is unrelated.

Rheumatoid arthritis is still defined entirely without reference to cause even though we know have a pretty clear idea of causation. Rheumatoid arthritis did not become rheumatoid arthritis partly due to TNF and genetically linked to DR4. It remained rheumatoid arthritis and the clinical definition says nothing about TNF or DR4.

 

[Jonathan Edwards]

Chia thinks so, Petersen thinks so.

Yes, and I've looked at their evidence and it is meaningless. I mean real evidence, not artefacts on slides.

 

[Jonathan Edwards]

As for those without such a history, or even those who do, but where no pathogen still persists, that's why we include possible dysfunctional immune/autoimmune responses as well as possible genetic causes.

We exclude any woowoo psych nonsense.

And as long as patients insist on only allowing the ideas they like, to appear in definitions the medical profession can smile and shake their heads and carry on believing the patients are deluded.

If the patient community wants to convince anyone it wants to follow real evidence it needs to take the higher ground above the medics and forget about liking or not liking this or that idea. And the community here has already done that very successfully. But there are still people acting as patient community advocates in high places screwing up with insisting on things for which we have no evidence base.

 

[duncan]

Sorry but that makes no sense. In order to attribute a cause to some health condition you have to define the health condition you are wanting to explain first, and then consider whether to link it to a cause. If you don't know what the cause is there is no justification in making the link. You must already have a concept of the condition you were trying to explain so you are obliged to stick to that.

The whole point of science is to get away from slipping in ideas that people rather like but for which there is no reliable evidence.

Psoriasis, MS and eczema are entirely defined without reference to cause. Chapters on them may discuss causes but that is quite different. PTLD is defined in terms of cause so is unrelated.

Yes, and I've looked at their evidence and it is meaningless. I mean real evidence, not artefacts on slides.

And as long as patients insist on only allowing the ideas they like, to appear in definitions the medical profession can smile and shake their heads and carry on believing the patients are deluded.

If the patient community wants to convince anyone it wants to follow real evidence it needs to take the higher ground above the medics and forget about liking or not liking this or that idea. And the community here has already done that very successfully. But there are still people acting as patient community advocates in high places screwing up with insisting on things for which we have no evidence base.

And there's the loop.

I'm suggesting breaking out of the loop, simply with some rewording. All within the confines of Science. I wouldn't want it any other way. No one here would. But what I'm hearing smacks disturbingly similar to that EBM gimmick that ultimately sunk beneath cliche status, and was employed merely as a means to suppress differing opinions.

 

[JemPD]

And as long as patients insist on only allowing the ideas they like, to appear in definitions the medical profession can smile and shake their heads and carry on believing the patients are deluded.

If the patient community wants to convince anyone it wants to follow real evidence it needs to take the higher ground above the medics and forget about liking or not liking this or that idea. And the community here has already done that very successfully. But there are still people acting as patient community advocates in high places screwing up with insisting on things for which we have no evidence base.

oh amen to that!! If anyone ever sees me doing it for goodness sake, please clobber me! Sooo glad we have you, and others repeatedly pointing it out Jonathan, its easy to fall into that trap if one isnt careful.

My intuition is that people with PVF feel 'when will I get rid of this feeling I have had since EBV?'. I suspect that people with PVFS or PVME/CFS much more often feel 'what is this new rollercoaster ride I find myself on since having EBV?'.

I think thats spot on.
FWIW, for me (with a non identified 'initial' virus), it started out as the former & morphed gradually into the latter. With PEM now being a return to the sensation/experience of the original virus, (even often with the cough/ painful sensitive trachea included), but then with the 'rollercoaster new symptoms' added in.
The morphing from one to the other came after i repeatedly tried to push through/ignore symptoms (with practices similar to those practiced in LP) because i thought if i believed i was well i would become well.

I highlighted the word 'after', because in my mind i see it as happening because/as a result of, pushing through/trying to ignore how crap i felt. But actually i have no way to know that it happened as a result of the pushing, only that it happened after, a period of doing so.
Any more than the person who at month 6 of PVF does a GET programme & recovers, can accurately attribute said recovery to the GET.

 

[EzzieD]

I think he used the same methods as everyone else - and none of them have found anything in any other diseases much. The amount of money wasted on T cell research runs into many billions!

Just remember, we're talking about the guy who calls the PACE Trial 'a thing of beauty', so his methods may not have been up to scratch with everyone else's... But yes, a shame the serious researchers didn't find anything either.

 

[Trish]

And there's the loop.

I'm suggesting breaking out of the loop, simply with some rewording. All within the confines of Science. I wouldn't want it any other way. No one here would. But what I'm hearing smacks disturbingly similar to that EBM gimmick that ultimately sunk beneath cliche status, and was employed merely as a means to suppress differing opinions.

Duncan I don't understand what you are talking about. What loop? What gimmick?

Perhaps it would help if you specified what in particular you think is wrong with current diagnostic criteria like IOM and NICE.

 

[duncan]

The loop I refer to is the loop of a vaguely defined/described disease that - when we try to get more specific and realistic about the symptoms (which today pretty much are how the disease is defined) and potential causes - we are referred back to those ill-chosen phrases that define us for most clinicians because there is no science yet to prove...anything. The "gimmick" I was referring to was EBM, which I've seen employed in many forums as a cudgel to beat back alternative albeit accurate manners of expressing our disease.

I cannot speak to NICE (although I read most of what is posted here). But I might suggest to you that in the US at least, most every GP, most every clinician, turns to the CDC for reference:
https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html

I'm saying that although clearly we have made progress thanks in great measure, maybe solely, to our many advocates, we remain shackled to lame descriptors and dogmatic restrictions. By restrictions, for instance, I repeat my earlier suggestion to add to the disease definition:

"Scientists believe ME/CFS could be brought about by persistent pathogens, or dysfunctional immune responses, or genetic factors, or a combination of the three."

This is factual. And because ours is a contested disease, and one held in contempt in some areas, this fact helps dispel the decades of misinformation our GPs have grown-up with. I've long ago lost my patience for orthodoxy. We need to be proactive in changing doctors' perceptions.

The principle manner we go about doing that is to reclaim our own narrative and discard words like fatigue and malaise for better choices. What GP's and internists and every other clinician reads about ME/CFS on sites like the CDCs is likely the only one they will care to see. Why? Because of time constraints and because they only care just so much, if at all. We have that one shot to convey how catastrophically sick we are.

Here's the CDC's diagositic references:
https://www.cdc.gov/me-cfs/symptoms-diagnosis/diagnosis.html

My same reservations hold true. They provide a link to the IOM. Bets on how many doctors will click on it? There are other CDC descriptions but I can't find them at the moment.

We need to rework how we are presented to doctors. The wording infrastructure. Yes, the wording is better than it was 10 years ago. Yes we have PEM. But it's still a kinda "eh" moment for most doctors who bother to even look this far.

Everytime a doctor looks at a description of ME/CFS is a job interview for us. Right now we are going to that interview in a tattered old faded suite with a couple of bright shiny buttons that we've stitched on to help us look better. But those doctors will only see the old unkempt suite.

I am puzzled by how this hurts anyones feelings. To me it's an obvious Achilles heel to our collective efforts, one we've only made cosmetic progress in correcting.

 

[Trish]

"Scientists believe ME/CFS could be brought about by persistent pathogens, or dysfunctional immune responses, or genetic factors, or a combination of the three."

This is factual. And because ours is a contested disease, and one held in contempt in some areas, this fact helps dispel the decades of misinformation our GPs have grown-up with. We need to be proactive in changing doctors' perceptions.

I find this puzzling. Sure it's factual that some scientists believe some things. That doesn't make the things they believe facts. Science is not about beliefs, it's about evidence, and so far we don't have clear evidence that the illness suffered by people who fit any of the ME criteria can be explained by these beliefs, so we shouldn't claim that they do.

There are others who believe that ME/CFS is caused by deconditioning resulting from fear of exercise, and that CBT/GET will therefore cure ME/CFS.
That has been shown not to be true by the failure of any clinical trial of CBT/GET to lead to recovery or even to clinically significant improvement.

So as far as I can see, we can justifiably tell our clinicians that there is clear evidence that we will not recover by increasing activity, and the fear of activity theory is wrong. We can't tell them that there is evidence that ME/CFS is caused by any of the specific biomedical mechanisms you listed, much as we might like to, and we certainly can't justify asking for a specific biomedical cause to be written into diagnostic criteria.

Sure there are some parts of the IOM and NICE criteria I don't think are good enough, for example I think it would be better to include fatiguabilty rather than, or as well as, fatigue, and PEM needs to make it clear it's not just brief tiredness or aching after activity.

We have a lot we need to advocate for, including better research funding, complete removal of exercise and psychological treatments, better medical education, decent access to financial support and appropriate housing and accessible medical care.

I think continuing to advocate for changes to diagnostic criteria is a waste of time and energy.

 

[duncan]

Science is not about beliefs, it's about evidence

In theory. But far, far too often, not in the real world. In the real world Science is many times defined by who has the greater lobbying platform, the loudest voice, and yes, the better packaging.

If we continue to fail to impress upon the global medical community the dire nature of our disease and the sequelae that currently define it, we will continue to come up short in interest in us, and in research funding. No one is going to step up to the plate and remedy this for us. We will remain in that loop.

 

[FMMM1]

One biomarker for a large heterogeneous group of people would be great, but I suspect it will be difficult to achieve. Can only live in hope, though.

To state the obvious, this is where GWAS is intended to help. E.g. there's some discussion here* re a candidate gene (TPPP1), identified through a small GWAS study, which may increase risk. Chris Ponting (DecodeME) has stated that the drop in the cost, of running a GWAS study, prompted him to seize the opportunity/submit the funding application.

So opportunities may be available now, which were not in the past. But yes, I am concerned re when the breakthrough(s) will come - perhaps they have - TPPP1!

*https://www.s4me.info/threads/genet...ential-risk-loci-2022-hajdarevic-et-al.25070/

 

[Sean]

Almost as many people without viral histories came to see them and also people with different infective histories - EBV, Q fever etc.

That assumes that any infection was known about.

If they were asymptomatic, or no lab tests were run, or it is a hit-and-run agent, or a novel undescribed agent (possibly hitching a ride in via another known infectious agent), then that confounds what we can say about the role of infection.

Separately, there is also the possibility of a prodromal phase for some time between infection and clinical onset, that could explain the lack of consistent close temporal association in at least some cases.

I am not arguing for the above possibilities, or for infectious causation itself. Just saying I don't think we can safely rule too much in or out at this stage about it.

All we can say is that if there is infectious causation, then we have yet to describe it.

If the patient community wants to convince anyone it wants to follow real evidence it needs to take the higher ground above the medics and forget about liking or not liking this or that idea. And the community here has already done that very successfully. But there are still people acting as patient community advocates in high places screwing up with insisting on things for which we have no evidence base.

oh amen to that!! If anyone ever sees me doing it for goodness sake, please clobber me! Sooo glad we have you, and others repeatedly pointing it out Jonathan, its easy to fall into that trap if one isnt careful.

+1

There are times when I think we patients are our own worst enemy. And I include myself in that.

I understand why. Desperate situations tend to make people sloppy and desperately reach for something, anything that might work, as they watch their lives waste away, in a particularly cruel manner.

But false beliefs are no answer. We have to be as honest and rigorous as possible about our own claims and ideas. Better we weed out the dodgy ones before others do and make fools of us.

As it currently stands, there is simply no good insight into what is driving ME. Indeed, we are still grappling with how to even characterise it accurately at the diagnostic level, let alone at the explanatory level.

 

[Snow Leopard]

Also adolescents don't really have a concept of chronic illness. To me it was something that people over 60 had where they took a pill daily. All details were unknown. I didn't know how awful it is.

That was my experience too. There is little to no comprehension of never getting better from illness when you are young.

 

[alex3619]

In the real world Science is many times defined by who has the greater lobbying platform, the loudest voice, and yes, the better packaging.

Correct but its often bad, politicized or even corrupt science. Dominant or widespread does not mean good. In terms of what can be proved, not pushed as doctrine or dogma, evidence is key, but also what the circumstances of that evidence are. Studies have flaws. Evidence needs context so it can be properly evaluated.

Now the politics of science or medicine is something else. I often find academics, even good ones, have a poor grasp of it. Heck I am not sure my grasp is much better, but I recognize the issues. If political rhetoric gets a scientific claim adopted, rather than evidence, it will cause major issues down the track. Yet it happens so often its almost common-place. No wonder we have major issues in the world. We see that in the history of ME quite a lot.

Politics based on science is something else again. Politics takes into account economic, political, ideological and special interests, just for a few. Its why I am deeply suspicious of consensus arguments in science, even with ME. Its one thing to use consensus to develop public policy, its another to claim its good science.

Consensus in science is something else. It cannot be regarded as scientific fact, yet may form a basis for creating a better research agenda.

These are not simple topics.

Take ME. No, we don't have a reliable biomarker. We do not have a universal marker. We have few common markers that are unique, but instead share markers with things like sepsis. I stopped counting in about 2015 when we had over 2500 biomarkers. Not diagnostic biomarkers, there are many kinds of biomarkers. I am talking statistically significant differences in biological and measurable markers, and we have from from two to sixteen standard deviations from normal. Markers under two deviations are typically not listed. Its grossly inaccurate to say that ME patients have nothing wrong with them, or no markers, its just that we cannot be sure of outcome or diagnostic relevance, and its entirely fair to say we only have hypotheses about the big picture or reliable diagnostics.

Yet the lack of general medical awareness of these findings means we are a medico-political hard-place, and sometimes under a rock, and some are banging that rock down hard. It allows medical politics to take to the fore, not science, evidence or reason. You can spot it most easily when argument is almost entirely rhetoric without quality evidence, as we see from the BPS ideological brigades.

You can also follow the money. How much money is saved by denying ME patients care, insurance, medical treatment, medical research, social supports etc.? How is that playing out now with LC?

Now LC is running afoul of these issues as they are deeply entrenched. Even if LC patients have something else wrong with them they are still potentially valuable allies.

 

[alex3619]

That was my experience too. There is little to no comprehension of never getting better from illness when you are young.

I met an old university colleague some years back. When my status was obvious, even though he was maybe thirty, it was "You're still sick?" with almost no comprehension. This was from a university educated professional. Its not just teenagers and other young people.

 

[Milo]

I am talking statistically significant differences in biological and measurable markers, and we have from from two to sixteen standard deviations from normal.

I would like to know what study you believe has a cohort with patients greater than N=1 that has a 16 standard deviation from normal measurable marker.