Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test, 2019, Morten, Newton et al

It would be nice and easy if we could assume Tomas et al are the gold standard by which to judge Myhill et al but as I see it, its not the case because the Myhill et al response said Thomas et al may have the protocol wrong and did not take up the offer to learn it from JMH which is a critical issue. So it cannot be considered a reliable replication and the null result does not disprove that there are problems with detection in the replication, more the reverse.

Also, likewise, I believe the Myhill et al response indicates that they consider its not accurate to characterise neutrophils as the "wrong" cell type and suggests they are a perfectly good cell type, simply more difficult to use in the lab because they are liable to morph over short timescales. I know of no argument to contradict this. Would be grateful to know if there is one.

As you mentioned in your previous the Thomas Newton Morten grouping have indicated a competitive interest regarding the provision of testing services/patents. So they do not appear to be completely free of interest which ideally a replicating lab should be due to the unconscious biases which have been mentioned elsewhere in the thread.

So while I absolutely agree the mito test should be given proper scrutiny by the highest authorities, NIH would be ideal, because of the potential it or something like it could have, by that same token it must be subjected to rigorous replication testing by disinterested parties and IMHO this disagreement between two interested parties is the starting point for that, rather than the conclusion. So I will be interested to see how this pans out!

 

Surely Myhill has the same conflict of interest?

I'm just sceptical that there's some mystical process that only her team can do to get the 'right' results. If it wasn't described in the protocol, what could it be? And could it be some process that biases the results?

I think if Myhill wants to continue to use this test, the onus is on her to replicate it and show exactly how it can be replicated by others so they can follow the same process.

 

Both labs should process samples from the same patients at the same time.
Had this been done ( as suggested) then the picture may be clearer.
Get them in the same place doing the same thing with the same samples. No arguments after that.

 

I have a feeling that the dysfunction is not in immune cells, but in the brain cells.

 

Without wishing to be alarmist here there are reasons why laboratories are regulated e.g.
Industrial Bio-Test Laboratories [https://en.wikipedia.org/wiki/Industrial_Bio-Test_Laboratories]. Things "go wrong" for various reasons --- we need regulators.

If you wish to see a model test then check out the results from Ron Davis's nano-needle test. All of the controls are clearly separated from the people with ME -- ideal situation for a diagnostic test.

In this case you suggest that neutrophils are an appropriate sample type --- where is the data? I.e. the method used to prepare and analyse the samples; plus results which show a clear separation between controls and people with ME? Also, if neutrophils are the basis for a valid method then why change to PBMCs? Where you have a reference method (neutrophils?) and you switch to a new method (PBMCs) then its customary to have the comparison data showing that in fact the new method gives the same result --- is this available?

The data published by Tomas, Newton and others clearly shows that the samples are not sufficiently stable to be sent through the post (72 hours) and then analysed:
"It is possible that differences between patients and controls reflect differences generated during prolonged storage and do not reflect differences at the time of sampling".

I'm wondering if this laboratory is regulated and if so will this be investigated by the regulator - if it is not regulated then why not? We shouldn't have to rely on reviews such as Tomas, Newton and others - however welcome they are.

In my previous post I referred to a method validated by the NIH -- I'm in the UK so I should have written NHS -- although I'd be content with either (NHS/NIH) or (preferably) both.

Might I inquire where our government is i.e. regulators/regulation? Fine speeches in Westminster about ME are one thing but this needs to be investigated and resolved. @EspeMor @Andy

 

https://www.meassociation.org.uk/20...n-in-me-cfs-by-dr-karl-morten-21-august-2019/

 

With any commercial test, I think the onus is on those are are charging for it to prove its reliability. Independent researchers have concluded that the test is unreliable and should not be used in the assessment of people with ME/CFS. If Dr Myhill and her colleagues are still convinced that the test is useful and intend to continue charging patients for it, the onus is on them to prove that it is valid. I don’t know what it would cost to receive and test 20 blinded samples from the ME biobank, but it would surely be a small fraction of the commercial value of the test if they were able to prove that it can accurately distinguish people with ME from healthy controls.

The same applies to any private companies or individuals who are charging for any other tests which have not been independently validated. As Jonathan pointed out in the thread on the German Lyme disease test, “the company has had ample time to do this obvious study and has not. Which to me is a fairly clear indication that they are not interested in any scientific validity for their test, just selling it.” (https://www.s4me.info/threads/lyme-disease-on-bbc-today-programme.10707/#post-191935)

It is surprising to me that we do not have better regulation to prevent the sale of tests and treatments before they have been scientifically validated. As I seem recall @Tom Kindlon has pointed out in the past, if patients were to spend a little bit more on donating to charities funding scientific research instead of paying for dubious private tests and treatments for which there is little or no scientific evidence of efficacy, we might all be better off.

 

I'd just like to point everyone to @Andy 's post above. The ME Association provided a link to Karl Mortens Feb 2017 report (that he supplied them over two years ago) on his work to replicate the Accumen test.

As it is a report it covers all their experiments and findings and provides more details than are in the paper. They went to a lot of effort in this work.
https://www.meassociation.org.uk/wp...al-Function-in-MECFS-Acumen-Test-21.08.19.pdf

I suspect following this work they engaged with the Newcastle team to see who was right, and that team replicated the Karl Morten team results and not the Accumen results. This would account for the two year delay i.e. it seems they did everything they could to make sure they did not make a mistake before publishing.

One difference I noticed is that this reports states that they had to use sodium azide for 2 hours, where the recent paper used 3 mins per the Accumen protocol. This is what Norman Booth had to say on PR about the use of sodium azide.

Source : https://forums.phoenixrising.me/threads/mitochondrial-and-energy-metabolism-dysfunction-in-me-cfs-—-myhill-booth-and-mclaren-howard-papers.47488/post-785000

 

I read the recent paper again.

On re-reading it is not clear to me how long the sodium azide was applied for - Norman Booth seemed to think this was important. In addition a NaCl solution is applied. We know from the nanoneedle tests that NaCl can alter PBMC's membrance impedance. Could it be this procedure with the time of sodium azide, or the NaCl addition, where something is different between Accumen and Oxford/Newcastle causing different results? It seems from the Oxford report they applied Sodium Azide for 2 hours!

Hopefully others can take a look and figure this out better than me.

 

Does anyone know where to obtain the Myhill 2016 protocol? Does it specify the time of Sodium Azide inhibition and the time of NaCl presence? Perhaps it is not included in the Tomas et al paper due to it being proprietary........

According to Norman Booth on PR (quoted above) the protocol changed on 1 Feb 2016 to measure mixed leukocytes containing monocytes as well as neutrophils. I wonder if they used this version?

 

This paper hasn't stopped the 'test' being sold.

https://twitter.com/user/status/1199332763683438593

 

#rolleyes...

 

This is not particularly useful for the GMC complaint, though correct on substance may be impacted by bad faith false equivalency and giving doubt to her credibility. Not that "no, u" is a valid defense but when "we prefer the results" for having cheated to get positive results and "those requirements are optional in this case" are accepted then anything can and will be accepted to defend interests and keep away inevitable litigation for as long as possible.

 

https://twitter.com/user/status/1204457819774312450


This is quite frustrating. If 100 people are planning to pay 300 pounds then in total 30.000 pounds are going to be spent on a clinical test that isn't properly validated.

The Tomas et al. study suggested that initial positive results might have been due to the longer processing of ME/CFS samples that were sent through the post. Until someone has clarified the differences between Tomas et al. and the Myhill studies it's inappropriate to use this test in clinical practice.

I'm concerned that many patients won't be aware of the recent Tomas et al. study, published in Scientific Reports. So I think it's worth trying to inform them and highlighting the issue on social media.

 

I've posted this on Facebook. Feel free to point out mistakes so I can adjust them:

 

Not a scientific observation, but I've just been listening to Myhill being interviewed by Gary Burgess and she talks in a hectoring tone, as if she was addressing a dog. The thrust of her approach seemed to be "it's diet, stop eating carbs and you'll be fine", which seems to me to highly simplistic. What's the consensus here?

 

I don't know about consensus but even if she was absolutely correct about diet it completely misses the point as to the social aspects of this illness. Many cannot afford a change in diet nor can they cook for themselves nor can some even think their way through how to apply a new diet. So what are they to do? Too bad for them.

It seems to me so typical for those people interested in sharing their opinions on our illness that they view things in isolation (because you don't need to spend time understanding) and they apply methods of wellness that (often) require more energy to apply than is available (this includes CBT too)

With this illness the most visible people are the least affected (not to say they are anything like well). And these are the people being considered as if they are the totality of those ill.

While I'm at it there are clinicians who will take credit for the more 'freshly' ill even though it's possible that some do recover without intervention early on.

 

I won’t go as far as to say they even mean well in all cases, even those have had, or claim to have had the illness. After all how can someone who is mild claim to have any real understanding of what it means to be severe? I had the recommendation of eating as much freshly prepared food as possible, which would be ideal anyway, but I am getting arthritis in addition to the ME. No way I’ll be preparing a whole load of salads. Most days it’s all I can do to open a can of soup, so unless it’s an actual fix I’m not entertaining that approach. So many of the approaches advocated, or at least the advocates themselves, radiate victim blaming to me

 

If ME was a dietary issue, we’d be all recovered and back to our lives. Give me a break! (Not you, @TheBassist )