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

[adambeyoncelowe]

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.”

That reads like garbled nonsense.

 

[JemPD]

From Prof John Martin

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.”

Yes, it would be good to check against MDD & anxiety as well, because we don't know whether this is an as-yet-unknown effect of emotional distress on cells.

ETA just to clarify - i dont think ME is in any way a result of 'emotional distress', i'm just saying that it needs ruling out in the same way that deconditioning does, as a reason for the test result... if we are ever going to squash the BPS juggernaut

 

[Sean]

SW is clearly backpedaling...ready to throw his BPS colleagues under the bus at the right time,...

In. A. Heartbeat.

 

[beverlyhills]

Looks like the statistician already said what I said, much better than how I said it. Oops.

In a CFS research context, the sample blinding was even more critical. You need a group with

• the technical expertise to replicate this study
• the actual equipment to complete it
• another research entity with any desire to do so.

If you add the blinded samples, and/or sedentary controls, diseased controls, or even actual controls (they were not matched) it creates a better indicia for other groups to replicate.

That is the last I will critique though. OMF only has a budget of like 2 million dollars.

 

[ladycatlover]

I think that maybe more has been added to the "expert" responses on the SMC website. Went to the web archive link, and got a message that the content was being downloaded - I've never had that happen before, though must admit I don't visit the web archive much unless it's links from here, so maybe I'm wrong. Prof Kevin McConway's response seems rather longer than that quoted in early posts in this thread. But here's the bit I wanted to quote:

“An important question to ask about any potential diagnostic test, that finds a difference between people with a disease and those who do not have it, is whether there’s some other difference between the two groups of people apart from whether they have the disease or not. If there is, perhaps that’s what the test is picking up, and not the disease at all. I’m not sure that this has been yet considered carefully enough in this case. We’re told that five of the healthy people were matched to five of the people with ME/CFS for age and gender, but the remaining 15 health people seem not to have been matched in this way. Perhaps there’s a difference between the two groups in age, gender, or indeed something else, that is contributing to the observed differences at least in part. Also, the researchers report that they handled the samples from the ME/CFS patients and the controls in exactly the same way, but they do not say whether the people handling the samples and recording the results knew whether each sample was from a patient or a control at the time the samples were being prepared and the measurements made. Ideally they should not know, in order to eliminate the possibility that the researchers unintentionally do things in a slightly different way for the two groups. I’m certainly not accusing the researchers of any kind of deliberate cheating here, but with such sensitive equipment, perhaps some tiny, entirely unintentional and unnoticeable change in what the experimenters do might conceivable have an effect on the results. Again, this can be dealt with in further research.

(my bolding above)

Prof Kevin McConway: “I am a trustee of the Science Media Centre, but I am writing these comments in my capacity as a professional statistician.”

 

[adambeyoncelowe]

I think that maybe more has been added to the "expert" responses on the SMC website. Went to the web archive link, and got a message that the content was being downloaded - I've never had that happen before, though must admit I don't visit the web archive much unless it's links from here, so maybe I'm wrong. Prof Kevin McConway's response seems rather longer than that quoted in early posts in this thread. But here's the bit I wanted to quote:



(my bolding above)

Prof Kevin McConway: “I am a trustee of the Science Media Centre, but I am writing these comments in my capacity as a professional statistician.”

One wonders where this rigour was when the SMC bigged up the Lightning Process.

 

[JemPD]

Prof McConway

“An important question to ask about any potential diagnostic test, that finds a difference between people with a disease and those who do not have it, is whether there’s some other difference between the two groups of people apart from whether they have the disease or not. If there is, perhaps that’s what the test is picking up, and not the disease at all. I’m not sure that this has been yet considered carefully enough in this case. We’re told that five of the healthy people were matched to five of the people with ME/CFS for age and gender, but the remaining 15 health people seem not to have been matched in this way. Perhaps there’s a difference between the two groups in age, gender, or indeed something else, that is contributing to the observed differences at least in part. Also, the researchers report that they handled the samples from the ME/CFS patients and the controls in exactly the same way, but they do not say whether the people handling the samples and recording the results knew whether each sample was from a patient or a control at the time the samples were being prepared and the measurements made. Ideally they should not know, in order to eliminate the possibility that the researchers unintentionally do things in a slightly different way for the two groups. I’m certainly not accusing the researchers of any kind of deliberate cheating here, but with such sensitive equipment, perhaps some tiny, entirely unintentional and unnoticeable change in what the experimenters do might conceivable have an effect on the results. Again, this can be dealt with in further research.

(my bolding above)

Prof Kevin McConway: “I am a trustee of the Science Media Centre, but I am writing these comments in my capacity as a professional statistician.”

All very valid points. But i do hope he will apply them in exactly the same way to the next BPS study that the SMC want to promote - MAGENTA perhaps. If this type of rigour had been applied to PACE et al we wouldnt be in the mess we are now in would we. So yes I'm glad he is pointing out these things but he'd better point them out in an unbiased way to every study he reviews rather than only the biomedical ones..

ETA lol @adambeyoncelowe ... we cross posted & you said it in a much more succinct manner I needent have bothered

 

[Hoopoe]

That reads like garbled nonsense.

It shows why we need this test .

 

[Sly Saint]

One wonders where this rigour was when the SMC bigged up the Lightning Process.

yes, I was just thinking the same about the interferon alpha research (only involvement of ME/CFS patients was as controls, not sure if they were matched up there either).

From what I read somewhere(it might have been on one of his videos, interview with Ben(?)), I think Ron Davis was putting this 'out there' as a carrot for funding; there might be other applications for the technology and if they can get the money to fund it then it should secure more regular financing (hopefully from the NIH).

 

[Mithriel]

At the risk of getting no likes, am I alone in thinking that SW comments were surprisingly sensible and even quite helpful? I sincerely hope that this test may be able to differentiate between ME or CFS patients and patients with other sorts of fatiguing illnesses or incapacities but, as far as I can see, we have no evidence to suggest that it can – and it feels appropriate and necessary to make that point loud and clear, lest people start to get carried away.

I also thought his other points were valid and relevant. I wonder to what extent this may be a sign of his changing perceptions of ME/CFS amid the shifting landscape, and whether it may be part and an attempt to try to row back from some of his flawed and unethical ideas and actions. Sadly, I doubt that he has the humility to ever admit that his was wrong or to apologise, but I would love to proved wrong.

Over the years, the likes of SW and PW have been quick to respond to biomedical research with justified cautions of correlation against causation, the dangers inherent in small preliminary studies and other perfectly valid things that cannot be argued against. However they do not apply these standards to their own research which have all these problems in spades.

Means that it is not ignorance driving their awful research methodologies but deliberate manipulation.

I wonder if the newspaper hype is actually being run by the SMC so that they can get their attacks in quickly.

 

[chrisb]

Perhaps a literature review would indicate the nature of the papers to which such, perfectly proper, rigour is shown.

 

[Simon M]

where is the signal for MDD major depression disorder ?

compare it with mecfs.

this would include mild/moderate ME/CFS patients, autoimmune conditions, POTS, fibromyalgia, plus anxiety and depression disorders - and sedentary controls. At this stage it's hard to know whether the result diagnoses ME/CFS or just general illness.

This is the key issue, particularly given the frequent claim that this shows ME/CFS is not "all in the mind" (I really dislike that phrase because it denigrates mental health problems).


Depression probably has a stronger immune signal than ME/CFS. Michael VanElzakker has pointed out that you get stronger signal of microglial activation in the brain for depression than for this illness.


So it is very important to show that there isn't a comparable signal from the Nanoneedle set up in illnesses such as depression and anxiety.

 

[MeSci]

Simon Wessely, a psychiatrist at King’s College London’s Institute of Psychiatry,
said
"The (first) issue is, can any biomarker distinguish CFS patients from those with other fatiguing illnesses? And second, is it measuring the cause, and not the consequence, of illness?”

First of all. British psychiatrists should keep their nose out of CFS they've done enough damage.

Second. We test the consequence of 100s of diseases without knowing the cause. Crohns, Alzheimers, cancer, MS. etc

I agree with their first point though, does it identity CFS only.

Either way, it's pretty conclusive that the psychiatrists are wrong. No surprise their backs are up.

Not sure if this comes from here, a message I've just received:

(edited)

"URL:
https://www.nbcnews.com/health/heal...r-possible-blood-test-chronic-fatigue-n999766

Ref: https://www.pnas.org/content/early/2019/04/24/1901274116

Scientists say they're closer to possible blood test for chronic fatigue
----------------------------------------------------------
Simon Wessely, chair of psychiatry at King's College London's Institute of Psychiatry Psychology & Neuroscience, who has worked with CFS patients for many years, said the study was the latest of many attempts to find a biomarker for CFS, but had not been able to solve two key issues: 'The (first) issue is, can any biomarker distinguish CFSpatients from those with other fatiguing illnesses? And second, is it measuring the cause, and not the consequence, of illness?' he said in an emailed comment. 'This study does not provide any evidence that either has finally been achieved.'

Andrew Lloyd, an infectious disease doctor professor at the School of Medical Sciences, University of New South Wales, Sydney, Australia said that it's premature to make broad conclusions about the study results.

'It is very premature to suggest this may represent a 'diagnostic biomarker for ME/CFS' as the sample size of patients was only 20 patients (and 20 healthy control subjects). This is very small for validation of a new diagnostic test,' Lloyd said.

Wessely also noted that doctors and patients should not be disillusioned by the study's results. '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'."

 

[Sasha]

@Ben H - it looks as though several of us are wondering why there were no control patients from other disease groups (e.g. MS, depression). I'm not able to read much at the moment but is it the case that the controls used were just healthy people, not deconditioned ones? If so, why were there no deconditioned controls?

My impression is that participation is easy from a subject's point of view (you just donate a bit of blood) and from the researcher's (you just stick the blood on the nanoneedle). So the research seems easy and cheap. Surely there are biobank blood samples for disease controls, at least, that would be easy to access?

As a patient I'd love to think that this is the 'holy grail' test for us but without comparison to deconditioned healthies and to other disease groups, the findings are far weaker than they might have been if what seems like easy steps had been taken.

So do you know why those steps weren't taken? Am I underestimating the difficulty of using such additional control groups? I'd really like to know. Are you able to feed that question back to Dr Davis?

Sorry if this has already been answered somewhere - as I said, I'm having trouble reading much.

 

[roller*]

most interesting may be indeed the "psychology" behind this odd publication.

surely, they wouldnt do anything that sheds a bad light on "stanford".

 

[Jonathan Edwards]

SW said: "is it measuring the cause, and not the consequence, of illness?"

If it really proved to be a unique biomarker, would SW's comment matter?

Absolutely not. It would still be a biomarker. Wessely has put a foot wrong there.

 

[Jonathan Edwards]

Hope that helps.

Not really because I cannot work out the geometric relation between probe and a cell? several cells? - how do we know what the impedance is being measured across?

I would also like to see the raw renormalised impedances to see how variable they were.

 

[Londinium]

This is the key issue, particularly given the frequent claim that this shows ME/CFS is not "all in the mind" (I really dislike that phrase because it denigrates mental health problems).

Agree 100%. Indeed, I'd go further and say if this disease was one day to be shown by faulty brain wiring or whatever I wouldn't necessarily have a problem with that: but even if that were to be true it would remain the case that CBT and GET are ineffective, as are denial of medical tests and welfare/benefits (an approach I believe has been attributed to a certain scientist who's been popping up in the media to downplay this paper).

In my view, the biggest harm to ME/CFS patients hasn't been the suggestion this is a mental illness - though that remains entirely unproven. The biggest harm to patients has been that this is an illness that can be cured easily by the patient thinking his or herself better, that the patient can effectively 'snap out of it' and should ignore what their bodies are telling them, that failure to improve is the fault of the patient, and that any complaints around the efficacy of this treatment approach are a symptom of the patient's delusion rather than an indication of the treatment being entirely ineffective.

 

[Jonathan Edwards]

“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.

Perhaps I should take John up on that. The quote sounds like twaddle to me.

Diabetes is a syndrome rather than a disease and a blood sugar test is quite good. A rheumatoid factor test picks out people with swollen joints and it took fifty years to work out why the two are linked - after the diagnostic test had become standard worldwide.

 

[Sasha]

@Ben H - it looks as though several of us are wondering why there were no control patients from other disease groups (e.g. MS, depression). I'm not able to read much at the moment but is it the case that the controls used were just healthy people, not deconditioned ones? If so, why were there no deconditioned controls?

My impression is that participation is easy from a subject's point of view (you just donate a bit of blood) and from the researcher's (you just stick the blood on the nanoneedle). So the research seems easy and cheap. Surely there are biobank blood samples for disease controls, at least, that would be easy to access?

As a patient I'd love to think that this is the 'holy grail' test for us but without comparison to deconditioned healthies and to other disease groups, the findings are far weaker than they might have been if what seems like easy steps had been taken.

So do you know why those steps weren't taken? Am I underestimating the difficulty of using such additional control groups? I'd really like to know. Are you able to feed that question back to Dr Davis?

Sorry if this has already been answered somewhere - as I said, I'm having trouble reading much.

Actually, I see @Ben H isn't often on the forum - @JaimeS, is this something you can help with, please, in terms of passing on a message?