A nanoelectronics-blood-based diagnostic biomarker for ME/CFS (2019) Esfandyarpour, Davis et al

[Barry]

At the risk of getting no likes, am I alone in thinking that SW comments were surprisingly sensible and even quite helpful?

As stand alone comments I think they were. But of course none of his comments are ever really stand alone. e.g. Yes, he is right to say that the test results could be due to either the cause or consequence of whatever ME/CFS turns out to be, and that it is important we know. Well yes ... and no ... to the importance aspect. From the perspective of finding a diagnostic marker, it may not be so important, even though it will become important to know when seeking a cure. It's classic SW smoke and mirrors. I imagine medical history must have many examples where reliable diagnostic markers were discovered well before cause and effect relationships were unravelled.

 

[Forbin]

I must admit I don't understand why a small pilot study should warrant such a massive media blitz. It seems to me a bit of an own goal. It leaves it wide open for the likes of Wessely to dismiss it as too early to say whether it will prove to be clinically helpful as a diagnostic test. The researchers themselves say there's a lot more steps to go through before it is proven. It could fall at any of those steps.

I suspect that the "media blitz" is probably the result of the paper being published in PNAS. It's the second most cited journal in the world (after Nature) and health & science reporters no doubt search each issue closely looking for something of general interest to write about. ME/CFS, with its history of controversy and its human interest angle, just makes it a better story. Stanford University itself is probably promoting the story more than it would otherwise simply because it's in PNAS - although you'd think they'd be long used to their research landing in top journals. Had it landed in the Journal of Electrical Bioimpedance, it probably wouldn't have made quite so large a splash.

 

[Londinium]

IMHO: Don't tweet this at anyone. If it turns out to have less specificity than hoped (and it hasn't been tested on any other non-ME/CFS condition) then it'll look bad. And if it turns out to be "the" biomarker then the BPS paradigm will continue to unravel anyway.

Just remember, one intemperate tweet can be quoted at will and used to make all of us look unhinged. You could literally be harming every other ME/CFS sufferer by doing so.

 

[Inara]

It is also regrettable that it is claimed that such a test would give “scientific proof” of the existence of the condition, and prove it is “not imaginary”. You don’t need a blood test to prove that an illness exists, and nor does the absence of such a test mean that it is “all in the mind”. Any sub who runs a headline that says ‘new test proves CFS is real and not psychiatric’ should be ashamed of themselves.”

This from someone who may be called THE reason why in Germany (and elswhere), politicians, doctors and everyone else believes and propagates ME/CFS does not exist.

 

[Londinium]

In the discussion, the authors say


"According to our experimental results, ME/CFS blood cells display a unique characteristic in the impedance pattern…"

TBF, they also say "Although all of the above are possible contributing mechanisms, further experiments are required to understand the precise contributing mechanisms behind the observed differences, and whether they are specific to ME/CFS or whether the response might be found among other similar diseases"

What they could've said is that they have achieved clear blue water between healthy controls and patients, with the pilot results achieving 100% specificity and 100% sensitivity. This is a remarkable result and does give hope of finding differences with other illnesses.


So the most important step now is to demonstrate its ability to discriminate from other illnesses — at least it is the priority if this is ever to become a biomarker. There I am hardly the first person to say that.

I realise this is only an N=20 sample but I find the 100% sensitivity and specificity result almost too good to be true.

 

[lansbergen]

Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:

But suppose that the debilitating symptoms of ME/CFS turn out not to be caused by the sort of stress response in blood cells that is being picked up by the new method, but that instead the symptoms and the effect in blood cells are both caused independently by some other problem in the body. Then a drug that deals with the response in the blood cells might turn out have no effect on the symptoms. Likewise a drug that seems not to affect the stress response in the blood cells might turn out to be effective against whatever is causing the symptoms. So the use of the new method for screening potential drugs might turn out to be very useful, or it might not.

 

[Keebird]

Interesting quote from Ron Davis in the Medscape article:

"It's a potential diagnostic test.... Most of the time, patients hear, 'There's nothing wrong with you.' Our major focus is to say that these patients have something wrong with them," Davis continued. "At this point, whether this tests positive in other illnesses is irrelevant. The point is, they're not healthy. Let's figure out what's wrong with them.... That's number one. The second thing would be to look at lots of other patients and see what they show."

https://www.medscape.com/viewarticle/912336#vp_1 (account might be required to access, but it’s free and easy to sign up)

 

[Keebird]

Plus, why only CFS, not ME/CFS in the headline?

and I wish that bio researchers would stop using 'chronic fatigue'
Ron Davis

Frustratingly, the CFS label continues to be used in the US. Many drs here still don’t use or even recognize ME as a diagnosis. Trying to get a diagnosis changed from CFS to ME or ME/CFS can be like climbing Everest. Even my ME/CFS specialist coded my diagnosis as CFS last year even though I meet ME criteria, although I think he’s now updated it. I’m surprised that Ron Davis isn’t more sensitive to that issue, but I’m just happy that he’s focused on helping us in other ways.

 

[JemPD]

Interesting quote from Ron Davis in the Medscape article:

"It's a potential diagnostic test.... Most of the time, patients hear, 'There's nothing wrong with you.' Our major focus is to say that these patients have something wrong with them," Davis continued. "At this point, whether this tests positive in other illnesses is irrelevant. The point is, they're not healthy. Let's figure out what's wrong with them.... That's number one. The second thing would be to look at lots of other patients and see what they show."

https://www.medscape.com/viewarticle/912336#vp_1 (account might be required to access, but it’s free and easy to sign up)

My bolding

I can see that even if, for example they tested the blood of several different illnesses - eg MS, RA, Liver disease & found the same results, then it doesn't matter so much - because as Ron Davis says - it's showing that pwME are not healthy.

So surely the crucial thing is to compare with sedentary controls & major depressive disorder as well? or even before moving on to other conditions. Because this could be some way that the cells start responding when the body is deconditioned/circadian rhythms go awry? Proving it's more than deconditioning is the only way to knock the BPS/CBT/GET theories out of the game for good. IMHO that should be more of a priority than comparing with other illnesses.

 

[Suffolkres]

Ahhhhhhhhh,.... as predicted Kate Kelland, Reuters and S Weasel, all doing their bit to reinstate themselves as 'experts'.....

 

[MSEsperanza]

I made the mistake to search a SW quote I remember I found most telling -- stating that it's irrelvant to distinguish whether people actually have ME or have the belief of having ME.*) Couldn't find it. (@chrisb ?)

Instead I faced the abundance of SW's inconsistent quotes (not all of them unreasonable, but every time I checked a paper for the conetxt, it got muddled again...),

With respect to SW's expert opinion on the Stanford nanoneedle paper, for now only these two:

Wessely, Simon. (1990). Old wine in new bottles: Neurasthenia and 'ME'. Psychological medicine. 20. 35-53. 10.1017/S0033291700013210, https://www.researchgate.net/publication/20973575_Old_wine_in_new_bottles_Neurasthenia_and_'ME'

I shall conclude with a description of the Section on Practice of Medicine held at the 94th
Annual Session of the American Medical As-
sociation in Chicago on 14 June 1944 (Allan,
(1988). Allan began by presenting a series of 300
fatigued patients (Allan, 1944) of whom the majority had
minor psychiatric conditions, and emphasized
the poor yield of further detailed investigations.

Whereas Alvarez had
spoken in psychological, and Sieve in organic
terms, [Dr Freeman] linked the two. The answer was
hyperventilation: ' If you want to demonstrate
to the patient how these symptoms develop just have him stand by your desk, open his mouth
and breath for...three minutes and he will be
ready for collapse'.

And this from 2006:

Huibers M, Wessely S. The act of diagnosis: pros and cons of labelling chronic fatigue syndrome. Psychological Medicine 2006: 36 , http://www.simonwessely.com/Downloads/Publications/CFS/179.pdf

Diagnosed CFS patients have a worse prognosis than fatigue syndrome patients without such a label. The ways in which CFS patients perceive themselves, label their symptoms and appraise stressors may perpetuate or exacerbate their symptoms, a process that involves psychological, psychosocial and cultural factors,

The answer to the question of ‘to label or not to label’ may turn out to depend not on the label, but on what that label implies. It is acceptable and often beneficial to make diagnoses such as CFS, provided that this is the beginning, and not the end, of the therapeutic encounter

More quotes collected in this thread: https://www.s4me.info/threads/simon-wessely-research-related-quotes.1304/#post-22178

*) Edit: Thanks to @chrisb I found not exactly what I recalled, but this:
"I will argue that ME is simply a belief, the belief that one has an illness called ME."
(Wessely, Simon (1994), "Microbes, Mental illness, the Media and ME: The Construction of Disease", Eliot Slater lecture (draft, 8.6.1994), p.1
www.margaretwilliams.me/2003/prof-wessely-lecture-notes_12may1994.pdf (p.2)

Will comment on this in a seperate post.

 

[beverlyhills]

I realise this is only an N=20 sample but I find the 100% sensitivity and specificity result almost too good to be true.

They should have paid an independent third-party to blind the samples. Did they not do this? It costs like $1000.

If you have to know the disease state a priori then it is not a diagnostic test, it is a clinical observation and it will not pass device approval.

I could write more, but I want to make certain this did not occur.

 

[Sean]

Any sub who runs a headline that says ‘new test proves CFS is real and not psychiatric’ should be ashamed of themselves.”

I wouldn't be lecturing others on being ashamed of themselves for playing games with words, if I was you.

Not to mention that I don't recall Sir Simon ever correcting or commenting similarly on the decades of headlines that misrepresented his work and claims in ways favourable to him.

In fact, I am fairly sure there would be a quote from him somewhere to the effect that he is not responsible for how the media presents his work.

A quarter century after first becoming acquainted with this man's views and work his hypocrisy and arrogance remain just as breathtaking. He has clearly learned nothing.

Better stop there.

 

[beverlyhills]

So surely the crucial thing is to compare with sedentary controls & major depressive disorder as well?

Multiple Sclerosis would be better.

This was a methodological aberration in the last paper, they did not mention that RBC deformability is a common pathological result of any illness, and of sedentary individuals.

 

[Peter]

Interesting, but how many times have we had “great news” that is prematurely blown out of proportion? Not saying that this is, but with history just trying to be cautious.

It is obviously both tempting and reasonable to throw this at the BPS-brigade, but maybe wise just to let science do the work and the talking?

Not much for quotes in general, but like the “when they go low we go high”. A good principle. As an example of the opposite, we see the BPS’ers trying to take advantage of the rituxme-study with a very narrow and dogmatic angle. It is obviously a “null”-result, but from there to arguments that rituxme is strengthening they’re hypothesis, is nonsense. Like the world is isolated in only to things, a CBT-model and rituxme and nothing else?

We all hope for a big breakthroughs and biomarkers. It would be vital. Great work by Davis and many others trying to solve the puzzle. But it is kind of sad, that people still have to use “scientific proof”, “not in your head” and so on after all these years. Really says all of the power and influence of pseudoscience. Guess those things have to be said, it is understandable given the history, but in my naive world I wish we could put such rhetorics aside once and for all.

And the aaargh use of CF and CFS. Understand that it is even trickier getting this right in the US, but mind the language. It matters.

 

[lansbergen]

They should have paid an independent third-party to blind the samples. Did they not do this? It costs like $1000.

I think they did not, They were in a hurry.

 

[chrisb]

I made the mistake to search a SW quote I remember I found most telling -- stating that it's irrelvant to distinguish wether people actually have ME or have the belief of having ME. Couldn't find it. (@chrisb ?)

The only quote I can think of which comes close to that would be from the Eliot Slater lecture
www.margaretwilliams.me/2003/prof-wessely-lecture-notes_12may1994.pdf

On looking at that again it is perhaps surprising that he has not reprised a variation of that all that all time favourite from there:

"What's a little up or down regulation among friends?"

 

[Daisymay]

http://www.sciencemediacentre.org/e...al-biomarker-for-chronic-fatigue-syndrome-me/

Prof John Martin, Professor of Cardiovascular Medicine, UCL, said:

“If a test is to have meaning it has to be able to be applied to a population of patients who can be defined clinically. The patients described had a variety of symptoms that could have arisen from a variety of causes. The population was not clinically defined in a way that could be related to a test. Further the authors do not relate the cellular finding in the test to a possible cause of the disease. CFS/ME is probably not a disease but a syndrome.

“It is interesting that all the patients tested had the same response in the test even though they had different severities of complaints. Could the test be picking up something in the 20 patients not present in the controls such as anxiety? The biological mechanistic meaning of the test needs exploring and the clinical description of CFS/ME needs specific definition. The authors should consider whether their test is related to an affect of symptoms and not related to the cause.”

 

[Daisymay]

Multiple Sclerosis would be better.

This was a methodological aberration in the last paper, they did not mention that RBC deformability is a common pathological result of any illness, and of sedentary individuals.

In the recent video, Ron Davis said they are going to do the nanoneedle test on MS and other diseases.

 

[JemPD]

Multiple Sclerosis would be better.

This was a methodological aberration in the last paper, they did not mention that RBC deformability is a common pathological result of any illness, and of sedentary individuals.

Yes i said MS... i was saying to test sedentary & MDD as well as other illnesses like MS.

I can see that even if, for example they tested the blood of several different illnesses - eg MS, RA, Liver disease & found the same results, then it doesn't matter so much - because as Ron Davis says - it's showing that pwME are not healthy.

I wasnt meaning not to test MS etc, just that even if it does turn out that people with other conditions have this same result, then it still indicates that pwME do actually have something biologically wrong... as long as sedentary controls do not have the same result. Therefore, it seems to me that testing against SC is just as, if not more important than testing against other illnesses.