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BMJ editorial: GET and CBT advised for ME

anciendaze

Senior Member
Messages
1,841
There are objective indicators of maximal effort built into the CPET. One of those is the Respiratory Quotient (or Respiratory Exchange Rate), which is the ratio of CO2 exhaled to O2 inhaled. This cannot be controlled or faked by the patient. If the RQ gets to 1.1 or higher, the patient has exerted maximal effort, and accusations of slacking off are completely absurd at that point...
There's an even simpler way to falsify any hypothesis based on volition which I noticed in looking at some individual results patients supplied us before these publications when they were tested for disability claims: the peak power output was the same on day-1 and day-2. If you can detect a patient holding his/her breath there does not appear to be any other way to voluntarily control the transition from aerobic to anaerobic metabolism.

There are disputes within the research community, unrelated to ME/CFS, about exactly what constitutes the threshold for this switch, which we would do well to avoid, where possible.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
My sense is that Prof Lloyd started out enthusiastic, without judgement of people with post-infective fatigue and keen to find the answer to the problem. Then, years of doing experiments and finding nothing has ground him down. He has watched lots of possible theories on cause and treatment be proven wrong and he has grown very sceptical. He probably burned his professional reputation a bit by being associated with CFS and has been criticised by those grumpy frustrated people with CFS too.

He seems to have decided that, for post-infective fatigue, all the problems are a result of the brain getting stuck in the ‘acute sickness response’ (sickness behaviour) mode. And I think he has lost interest and isn’t keeping up with recent advances. In the video, he isn't aware of recent research advances.

So, what compelled him to be a co-author of this paper, I still have no idea.

I agree that there is something puzzling here. Having listened to Lloyd speak I am fairly sure that he is a first rate scientist. His description of his methods and interpretation of his results seem to me to be way ahead, in quality, of virtually all of the 'positive' studies we discuss. I agree that, like Simon Wesseley, he seems to have started out with a genuine desire to find a biological mechanism. He has come to the conclusion that in long standing ME/CFS the problem resides in a brain cell loop. He may well be right. I am pretty sceptical of any metabolic abnormality in muscle and his electrical stimulation studies do sound to me sensible.

However, having looked and not found is not a reason not to encourage others to keep looking. A brain cell loop has biology just as much as muscle failure. Why write an article, as first author, saying, oh well all we can do is try to find out who benefits most from CBT, given that across the board it isn't that good so we need to find the few people it really helps.

That brings me back to the fact that this was an invited editorial, not peer reviewed. When I was asked to do something like this there was usually something in the news that prompted the journal making 'an informed response'. I thought it was probably the Chalder paper, but I wonder if it was the IOM report. If it is the latter then my reading might be that Lloyd is basically saying that people like him and Wesseley have seen all this before and the studies quoted in the IOM are still not replicated and convincing. And I would agree with that. Lloyd may not have wanted to say this explicitly enough to upset IOM members. As a result he produces a comment that does not seem to be a response to anything in particular and ends up saying 'well the news today is that there is nothing new'.

Then there is the question of why he teamed up with vdM. An editorial would normally be requested from a single individual.

Maybe fatigue clinic doctors are getting stressed out by patients saying that there is evidence for mechanisms and therapies when we do not yet in fact have good evidence. Maybe there are political issues in Australia about this.

I remain puzzled.
 

justy

Donate Advocate Demonstrate
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5,524
Location
U.K
If it is the latter then my reading might be that Lloyd is basically saying that people like him and Wesseley have seen all this before and the studies quoted in the IOM are still not replicated and convincing. And I would agree with that.

Really? Not one?
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Really? Not one?

I fear not. A number of studies are interesting and worth following up, but I have yet to see something consistently replicable in the way one needs before being confident it will prove reliable. And that was the consensus from the researchers attending the IiME worksop last year.
 
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13,774
re Lloyd: Also, people aren't very good at recognising that they've spent decades with patients and not found a way of helping them. Maybe a bit cognitive bias, a bit corrupt self-interest... maybe one or two patients genuinely helped by CBT/GET.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
So, what compelled him to be a co-author of this paper, I still have no idea.


.

You need to go further back and see why Andrew Lloyd was not considered a friend to the 80's and 90's ME and CFS patients. Have a read of Osler's Web.

Also have a read about his earlier colleague Ian Hickie and who else he collaborated with.

Also take a look at his influence on the Australian CFS work such as definitions and guidelines which patients strongly resisted and rejected but were ignored.

Factor in that he has never offered treatment to patients with antiviral drugs or immune modulators or supported the work of the doctors who do. Also not ever offered much in the way of treatment or investigations for any of his Australian patients.

The Dubbo study can be read to further the interests of different parties. It's not necessarily an entirely positive thing for people with ME and CFS. It can be spun.

He started with an idea and an agenda. He's been working to that ever since.
 
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Gijs

Senior Member
Messages
690
I fear not. A number of studies are interesting and worth following up, but I have yet to see something consistently replicable in the way one needs before being confident it will prove reliable. And that was the consensus from the researchers attending the IiME worksop last year.

Seriously? Not one? I think this study [1] could be the beginning if replicated in a large cohort. I would put my money on this. But i agree most publications are poor science but that doesn't mean scientists mustn't look any further like van der Meer proposed in the Netherlands.

1. Yasuhito Nakatomi, Kei Mizuno, Akira Ishii, Yasuhiro Wada, Masaaki Tanaka, Shusaku Tazawa, Kayo Onoe, Sanae Fukuda, Joji Kawabe, Kazuhiro Takahashi, Yosky Kataoka, Susumu Shiomi, Kouzi Yamaguti, Masaaki Inaba, Hirohiko Kuratsune, Yasuyoshi Watanabe, “Neuroinflammation in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a 11C-(R)-PK11195 positron emission tomography study”, The Journal of Nuclear Medicine, vol.55, No.6, 2014, DOI: 10.2967/jnumed.113.131045
 

Snow Leopard

Hibernating
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5,902
Location
South Australia
Coming up with fancy explanations for why CBT and GET might work when in fact they don't appear to work in terms of objective measures (subjective measures may simply represent response biases) doesn't impress or excite me. It's another way to continue prescribing ineffective therapies.

Exactly. Nothing much else needs to be said.

Maybe fatigue clinic doctors are getting stressed out by patients saying that there is evidence for mechanisms and therapies when we do not yet in fact have good evidence. Maybe there are political issues in Australia about this.

It could be political with respect to the Australian situation. There are no specific 'fatigue clinics' in Australia (just a few GPs with a direct interest) and CBT/GET is not routinely pushed by GPs, since in most places there are basically no specialised practitioners focusing on CBT/GET (or limited capacity where it is offered). So if a GP wishes to make a referral, it will usually be to a psych with no direct experience.
 
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anciendaze

Senior Member
Messages
1,841
...He has come to the conclusion that in long standing ME/CFS the problem resides in a brain cell loop. He may well be right...
With considerable evidence of autonomic dysfunction, and an implant outside the brain which reduces symptoms, I really have to wonder if medical schools have lost track of the location of most autonomic nerves.

In a previous conflict between the medical profession and patients the cause of peptic ulcers was said to involve a "brain cell loop". Not only did I know people treated for peptic ulcers during this period, I also knew one who went through vagotomy in an effort to break this loop. His autonomic nervous system went right on digesting food, etc. without input from the brain.

The lesson I learned from this is that the medical profession can espouse ineffective treatments for quite some time (18 years) when they believe a problem is psychological, even if effective treatments are available. Whether this behavior involves a "brain cell loop" or not is a question.

The puzzle of Dr. Lloyd has a simple solution: he has made the transition to "senior researcher", one who knows innovation is impossible.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Seriously? Not one? I think this study [1] could be the beginning if replicated in a large cohort. I would put my money on this. But i agree most publications are poor science but that doesn't mean scientists mustn't look any further like van der Meer proposed in the Netherlands.

1. Yasuhito Nakatomi, Kei Mizuno, Akira Ishii, Yasuhiro Wada, Masaaki Tanaka, Shusaku Tazawa, Kayo Onoe, Sanae Fukuda, Joji Kawabe, Kazuhiro Takahashi, Yosky Kataoka, Susumu Shiomi, Kouzi Yamaguti, Masaaki Inaba, Hirohiko Kuratsune, Yasuyoshi Watanabe, “Neuroinflammation in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a 11C-(R)-PK11195 positron emission tomography study”, The Journal of Nuclear Medicine, vol.55, No.6, 2014, DOI: 10.2967/jnumed.113.131045

The Nakatomi paper is certainly interesting but it needs replicating. What does seem odd is that Lloyd, to go by what he said in Bristol, thinks that maybe the brain problem is something like microglial activation. Now we have a paper that is at least in that direction and he makes no reference to it. But he may not have his mind on ME/CFS these days.
 

Gijs

Senior Member
Messages
690
The Nakatomi paper is certainly interesting but it needs replicating. What does seem odd is that Lloyd, to go by what he said in Bristol, thinks that maybe the brain problem is something like microglial activation. Now we have a paper that is at least in that direction and he makes no reference to it. But he may not have his mind on ME/CFS these days.

In the Netherlands a Dutch group of scientists are doing replication. I know they have found the same 'Neuroinflammation' in CFS/ME patiënts. I think publication may take a while. If this data is correct then we have an objective diagnostic test.
 

Dolphin

Senior Member
Messages
17,567
The 5 million was for the FINE trial too. What makes me angry is that thanks to research like this, my GP says GET is the best evidence based treatment for ME.
Initially the two trials were going to cost in the region of £5 million. However, the PACE Trial got extra money as they didn't meet their recruitment target. So it alone cost £5 million (Sharpe had it in a RAE submission).

The FINE Trial cost £1.3/£1.4 million on top of this.

Incidentally, the PACE Trial investigators got their extra money so the trial was adequately powered for their dichotomous primary outcome measures. Then after the trial was finished they decided to change how they would assess the primary outcome measures. One could say in a region of £1 million was thus wasted on an overpowered study.
 

charles shepherd

Senior Member
Messages
2,239
Interesting that this was commissioned and not peer reviewed. Which is presumably why the article does not appear to have anything very specific to say. In view of events elsewhere it seems a bit of a damp squib.

Having invited Fiona Godlee, Editor in Chief at the BMJ, to chair the meeting on ME/CFS at the Royal Society of Medicine back in March - where there was discussion about controversies and uncertainties, including CBT, GET and the the PACE trial - I wonder if this involvement resulted in the editorial being commissioned

If so, it's a great shame that there wasn't (yet again) any reference to the fact that patient evidence relating to efficacy and safety of CBT and GET is not the same as reported from the 'Gold Standard' RCTs

The MEA will be publishing a summary of the largest ever report on the efficacy and safety of CBT, GET and Pacing next week to coincide with ME Awareness Week
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
If you can detect a patient holding his/her breath there does not appear to be any other way to voluntarily control the transition from aerobic to anaerobic metabolism.
Gas analysis is part of the measurement, and that includes volume. Someone trying this is likely to be detected very quickly. It would also take someone very practiced in controlling their breathing, and probably someone who is an exercise physiologist.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
but I have yet to see something consistently replicable in the way one needs before being confident it will prove reliable.
One of the issues here is that CFS, and possibly ME, is a heterogeneous cohort. It is likely there never will be a finding that is fully replicable and applies to almost everyone in broad cohorts.

Some findings have been replicated a number of times though, from independent researchers. The CPET findings, and NK cell function findings, for example.

It is interesting that double standards apply for CBT/GET advocates as the underlying theory used in this therapy is not ever tested. Its all outcomes based, and the outcomes are poor. I regard them as a failure of the theory tested at best, and are more like a failure to test in the first place.

There is so little funding, and funding approval, that replication of results almost never occurs in ME and CFS research. Its too soon to talk of SEID in this respect. However as the science advances then a big picture may emerge that could lead to targeted research, and eventually replication of that research. This first requires a big success though. Something to break through and grab attention, particularity from funding agencies, and focus subsequent research direction.

Rituximab has this potential.
 
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Snow Leopard

Hibernating
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South Australia
One could say in a region of £1 million was thus wasted on an overpowered study.

Too big to fail. ;)

If so, it's a great shame that there wasn't (yet again) any reference to the fact that patient evidence relating to efficacy and safety of CBT and GET is not the same as reported from the 'Gold Standard' RCTs.

Exactly.
 

Art Vandelay

Senior Member
Messages
470
Location
Australia
re Lloyd: Also, people aren't very good at recognising that they've spent decades with patients and not found a way of helping them. Maybe a bit cognitive bias, a bit corrupt self-interest... maybe one or two patients genuinely helped by CBT/GET.

I'd say it's self-interest. Lloyd has to defend PACE because if people became aware of the failings of GET and CBT, there be no rationale for any of the treatments used at his Clinic: http://www.fatiguecentre.com.au/#/treatment
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
There is a general railroading of medicine going on for the last few years in which so called evidence based medicine is used to modify or limit medical care, but the evidence is weak or poor. There is this absurd usually unstated notion that the RCTs are good just by virtue of them being an RCT. Any RCT has to be a quality study. PACE fails for example., but from what I am reading most psych studies are not high quality. Its for this reason that studies can be downgraded (or upgraded) in an EBM setting, but very rarely is this even looked at.

Anecdotal evidence, even in large quantities, is typically written off in this view. There is usually no suggestion that such evidence indicates the study design of the RCTs needs to be looked at very carefully.

EBM is not science. Its a way to do a rapid managerial review of the science.