BMJ editorial: GET and CBT advised for ME

[alex3619]

I absolutely agree. But the other explanation given when people can't find a cause is 'a virus'. Everything has to be challenged on an equal basis.

Which is why when something isn't known the answer is "I don't know". For example, I believe in UFOs = unidentified flying objects. There is lots of stuff we don't know, or can't know without extensive and expensive medical testing ... and I don't mean the usual testing available to doctors.

Medicine is bad at this, but I think economics is worse. Most of the laws of economics are at best weak heuristics, and economics make predictions all over the place ... looks a bit like a bell curve. They are making informed guesses, but they are still guesses, and based upon hypotheses that in some cases have been disproven, and sometimes disproven more than half a century ago.

I would be interested in seeing an accuracy comparison between weather forcasting, medical forecasting, and economic forecasting.

Not all doctors make the psychosomatic or virus jump though. Some are honest. Even when a doctor cannot help me I can respect an honest "I don't know".

Psychiatry in particular has the notion of the Noble lie, in which patients are told what the psychiatrist thinks is in their best interest and not the truth. Again not all psychiatrists do this.

 

[alex3619]

It wouldn't surprise me if there were a lot of patients who had recovered while doing CBT/GET, especially teenagers/those not ill for long who have high recovery rates for natural course. There are lots of people claiming all-sorts helped them to recovery from CFS.

This is how quackery becomes accepted. However what happens when quackery becomes mainstream and protected by the medical profession?

 

[alex3619]

Just a note that "lots" can be derived by just a few recovering out of a large number of people who came down with the illness...

I think the biggest issue is with post viral fatigue. Its very very very common. People recover. This gets confused with CFS, which gets confused with ME.

 

[Countrygirl]

Here is Dr Kerr's response to which Dolphin provided the link:

Editorials
The long wait for a breakthrough in chronic fatigue syndrome
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2087 (Published 05 May 2015)Cite this as: BMJ 2015;350:h2087

The biological pathogenesis of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis
This editorial (1) comes from authors from two of three CFS/ME centres whose prolific academic production in CFS/ME provides almost the sole support for a supposed psychiatric basis for the disease; these centres are Kings College London, Nijmegen Medical Centre in the Netherlands, and the University of New South Wales, Sydney, Australia. However, the scientific basis on which the treatments, Cognitive Behavioural Therapy (CBT) and Graded Exercise Therapy (GET), are offered is critically flawed. The original PACE trial conducted by Kings College London, enrolled patients using the 1991 Oxford criteria (2), which allows inclusion of patients with affective disorders. This is in direct conflict with the internationally accepted 1994 CDC criteria which specifically excludes patients with affective disorders. This means that this study was performed using patients whose exact diagnoses are unknown. However, despite this flaw, global insurance companies do not pay sickness benefit to CFS/ME patients on the basis that effective treatments are available. Yet these interventions are not effective in CFS/ME.

CBT helps only a fraction of patients and GET has been shown to exacerbate the symptoms of patients with CFS/ME, which is logical as one of the cardinal symptoms of CFS/ME is post-exertional malaise, and so GET should not be used for CFS/ME patients. Furthermore, the Institute of Medicine in the USA has recently recommended that the name, CFS/ME, should be changed to Systemic Exercise Intolerance Disease (SEID) (3), which again reinforces the truth that exercise therapy should not be used for CFS/ME.

We know that CFS/ME can be triggered by a variety of infections, vaccines, exposure to organophosphate chemicals, and that the pathogenesis involves prolonged immune activation, which results in a flu-like illness that persists for months to years, and we all know how we feel during a flu-like illness, and there is no dispute that flu-like illnesses are caused by viruses. Several infection models have been presented which illustrate very well this progression in patients followed from the time of acute infection to development of CFS/ME. Parvovirus B19 triggers CFS/ME and this is predisposed to by carriage of HLA-DRB1*01, *04 and *07 alleles, is characterised by raised levels of circulating TNF-α and IFN-γ, and CFS/ME triggered by B19 has been cured with intravenous immunoglobulin (IVIG) which is the specific treatment for B19 infection (4). Coxiella burneti also triggers CFS/ME and this is predisposed to by carriage of HLA-DRB1*11 and certain IFN-γ polymorphisms, is associated with chronic immune activation and Q fever-associated CFS/ME is treated successfully with tetracyclines which are the specific treatment for Q fever (5). Epstein-Barr virus triggers CFS/ME, and patients with EBV-triggered CFS/ME have been successfully treated with valacyclovir (6), which is a specific treatment for EBV infection. In all of these models, the infectious agent persists long-term with chronic genomic persistence and antigen presentation, which appears to be important. The diversity of infectious triggers and individual responses likely account for the heterogeneity observed in CFS/ME, and the existence of subtypes, which are recognised to be important for the optimal management of patients.

Maybe the big breakthrough in CFS/ME comes when we are free to apply our significant existing knowledge of CFS/ME towards the best investigation and treatment of INDIVIDUAL patients, whom we know have different pathogenetic processes which account for the existence of disease subtypes. Disease subtypes are a feature of multiple chronic inflammatory autoimmune diseases and are taken into account in their management, and therefore CFS/ME is typical of such a biological disease.

References
1. Lloyd AR, Meer JW. The long wait for a breakthrough in chronic fatigue syndrome. BMJ. 2015;350:h2087. doi: 10.1136/bmj.h2087.
2. Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al. A report--chronic fatigue syndrome: guidelines for research. J R Soc Med.1991 Feb;84(2):118-21.
3. Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC: National Academies Pr; 2015
4. Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN. Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis.
2003;36(9):e100-6.
5. Sukocheva OA, Marmion BP, Storm PA, Lockhart M, Turra M, Graves S. Long-term persistence after acute Q fever of non-infective Coxiella burnetii cell components, including antigens. QJM. 2010;103(11):847-63.
6. Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. In Vivo. 2007;21(5):707-13.

Competing interests: No competing interests

07 May 2015
Jonathan R Kerr
Professor of Epidemiology

Universidad del Rosario
Quinta de Mutis, Bogota, Colombia

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[Snow Leopard]

Big thanks to Dr Kerr, if he ever reads this!

 

[anciendaze]

I'm afraid that in terms of the British medical research establishment Dr. Kerr has been discredited by the simple standard of losing his funding and position, forcing a move to another country.

 

[chipmunk1]

This is how quackery becomes accepted. However what happens when quackery becomes mainstream and protected by the medical profession?

it gets an acronym

 

[Hutan]

I think the biggest issue is with post viral fatigue. Its very very very common. People recover. This gets confused with CFS, which gets confused with ME.

Hi Alex, can you explain this for me please? I see others make these distinctions too.

Two and a half years ago, my two children and I all developed classic CFS symptoms, definitely following what seemed to be a gastroflu that had my daughter in hospital for several nights, initially with suspected appendicitis. My guess is what we have could be called post-viral fatigue. Yes, from the Dubbo studies etc , that is very common.

So two and a half years later, my daughter has mostly recovered and has started university.

My son was desperate to go back to school this year after two years off, but is only getting to school two days a week - and that is a struggle that I'm not sure can continue. He sleeps or rests in bed most of the time.

I have given up work, which was central to my identity, as I can not manage sustained complex thinking, and have fatigue (along with all the other usual symptoms). Now, I'm pleased when I can cross off 'have a shower' from my 'to do' list. So, my son and I are still greatly affected by this illness.

But, whatever we have, my daughter had it too and she has essentially recovered. And so, whatever we have, some people get better and others either take longer - or don't. What would you call what we have?

 

[alex3619]

@Hutan, this is a grey area in the science. Its most likely a post viral fatigue state, but CFS and ME both include those symptoms as well. I cannot tell from what you said if its CFS, or under which definition its CFS. Gastroflu makes it likely to be enterovirus related, a known trigger for CFS and ME.

There is a qualitative difference between CFS and post viral fatigue, probably symptomatic as well. CFS is so much more than fatigue, and ME has specific problems that do not always manifest in fatigue states and patients may even have ME without chronic fatigue.

What has been reported is that recovery from post viral fatigue appears to be less than six months in most cases, to up to five years. We also know that some with ME and CFS will be diagnosed with post viral fatigue in the first six months, and that at least some with CFS and ME recover in the first year and for up to five years. Most who recover from ME appear to do so in the first year. CFS is currently often considered long term if it lasts more than five years, with a very low natural recovery rate at that point.

To complicate matters many with CFS (and I am unsure if this applies to ME but suspect it does) can recover and then relapse.

The exact relationship between people diagnosed under these different definitions is uncertain.


Here are just some of the things that may differentiate ME from post viral fatigue:

Excessive fatiguability with delayed onset and delayed recovery, and exacerbation of other symptoms.

Cognitive disturbance, which may include poor sleep or poor cognition, orthostatic intolerance, or a disruption of circadian sleep cycles.

SPECT scans also often show brain abnormalities in ME patients. Most appear to have non-cytopathic enteroviral infection. Most appear to have mycotoxins and poor NK cell function (function, not necessarily numbers).

One thing that appears to be the case with current research is strictly defined CFS and ME patients have very poor aerobic metabolism response, with a crash in aerobic capacity after exercise that is not seen in other diseases.


With CFS all this is less clear, and I think it needs to be kept in mind that CFS is most likely at least several different diseases plus a host of misdiagnoses. Its less a disease than a collection of diseases with similar symptoms. However we don't yet know if this is the same with ME, several different diseases with similar symptoms.

Until we have biomarkers all we really have is labels. Those labels are probably not very accurate. Misdiagnosis rates vary but claims of 40-90% misdiagnosis rates are in the literature. Without biomarkers though we cannot be sure. For example, under most CFS definitions some patients would be excluded due to comorbidities, resulting in failure to diagnose. Similarly using chronic fatigue as the only diagnostic criteria seems to produce misdiagnosis of about 70% (I can write more about how I get that figure). Under stricter application of the more stringent CFS and ME definitions the misdiagnosis rate appears to be low however, perhaps only 5% or so. All these figures I am citing are rubbery as there is no definitive science, though there are published papers.

All of these people are sick. Some are sick with different symptoms and severity than others. Yet "CFS", "post viral fatigue" and "ME" are just labels until the science is done, and the pathophysiology determined.

The name is much less important than whether or not someone can get good medical care.

 

[duncan]

Unless you live in the United States where, for all intents and purposes, ME does not exist; it is folded into CFS (or at least has been for the better part of 35 years).

 

[SOC]

Just a note that "lots" can be derived by just a few recovering out of a large number of people who came down with the illness...

Or a substantial number of misdiagnosed people recovering for any number of reasons related or unrelated to being subjected to CBT/GET.

If those patients had pure POTS and no ME/CFS, for example, GET might actually help. People with post viral fatigue could recover spontaneously in the time frame of the CBT/GET treatment totally unrelated to the treatment, but the CBT/GET practitioners happily claim these misdiagnosed, spontaneously recovering patients as success stories for their treatment. And so on, and so on, and annoyingly so on...

 

[alex3619]

If those patients had pure POTS and no ME/CFS, for example, GET might actually help.

Traiing the leg muscles to be stronger is a standard treatment for orthostatic intolerance.

PS If even careful exercise makes you worse you probably have ME rather than post viral fatigue. The rules of exercise for ME patients appear to be different and involve energy expenditure and heart rate.

 

[Hutan]

Thanks @alex3619 for your quick and comprehensive reply.

I think the biggest issue is with post viral fatigue. Its very very very common. People recover. This gets confused with CFS, which gets confused with ME.

From my reading of symptom lists, we qualify for all three labels. We have PEM, we have POTS, we have migraines and vision and hearing disturbances, my son certainly has circadian rhythm disruptions (it's nearly midday and he's still asleep). Yesterday after standing doing the dishes for five minutes, my pulse pressure was 22%. But we haven't had brain scans or our NK cell function tested.

I've known people with clearcut post viral fatigue after glandular fever who were sick for less than a year, but they had full CFS symptoms, not just fatigue. So I don't think we or researchers should write off post-viral fatigue as something that isn't related to at least some subsets of CFS or even ME.

I agree with your comments below - I could not have put it better myself:

Until we have biomarkers all we really have is labels.

All of these people are sick. Some are sick with different symptoms and severity than others. Yet "CFS", "post viral fatigue" and "ME" are just labels until the science is done, and the pathophysiology determined.

The name is much less important than whether or not someone can get good medical care.

 

[Sean]

Until we have biomarkers all we really have is labels.

Endlessly contested labels.

 

[anciendaze]

For medical research, the convenient choice is to assume that all infectious disease either proceeds to lethality or resolves completely. (Behind this there is an implicit assumption that infectious disease necessarily involves exponential replication.) The distinction between PVF and psychological problems labeled somatization following a real illness is based purely on the fact that PVF resolves without treatment. There is no need to study PVF because no treatment is required.

This fits the common observation passed on in medical schools that "85% of your patients will get better no matter what you do." (My own experience suggests this is overly optimistic about what doctors might do.)

Malpractice defense often involves the argument that the accused practitioner has helped large numbers of patients, and the ones harmed represent a tiny minority which no one could have predicted. The figure quoted above implies that you could make the same argument about actors wearing white coats without any real medical knowledge. The profession is far better at opposing innovation than policing itself w.r.t. incompetence.

We don't really know why post-viral fatigue states last so long. We don't know why this is characteristic of viral infections rather than bacterial ones. We don't really know why immune senescence progresses with age. These are processes which affect 100% of the population.

For the most part doctors aren't even curious about diseases which can make a healthy individual with a very active life suddenly behave like someone 20, 30 or 40 years older.

 

[duncan]

Perhaps because of all the recent media dust, researchers may consider throwing serious dollars at post-Ebola syndrome. I'd be interested in seeing where that leads.

Finding Ebola teeming in the eyes of patients - post-treatment - reminds me of finding Borrelia in the hearts of cardiomyapthy fatalities.

Regardless, with as many as half of surviving Ebola patients reporting ME/CFS-like symptoms following resolution of the disease, research efforts may command some $'s, and may produce results.

Assuming, of course, such efforts will be undertaken.

 

[Hutan]

Yes, @duncan, I was having exactly the same thought. Unless of course all those joint pains, headaches and so on are put down to post-traumatic stress - already I have seen a couple of comments to that effect. So many opportunities for CBT/GET trials....

My sympathies go to the Ebola survivors - to have gone through what they have, losing family and in many cases their houses burned down. And then to have these post-acute virus symptoms.

 

[jimells]

Endlessly contested labels.

Yes, the medical establishment is quite good at it. Apparently they have adopted the idea of

If you don't know what to do, do what you know

Sending emails, scheduling meetings, writing reports that say little, this is what bureaucrats excel at.

 

[anciendaze]

Incidentally, one subject raised in this thread still puzzles me, the question of "blinding" data going into the statistics. If this was actually effective, the dramatic changes from the initial proposal to the final report are inexplicable. If I assume researchers saw results they did not like, and changed the ground rules, the sequence of events becomes very easy to explain.

 

[Esther12]

A fair few new responses.

I didn't take them all in properly, but the Esmerelda Green one stood out for looking good to me - drew attention to their seeming recognition of spin in PACE reporting but failure to call for the release of protocol defined outcomes:

Lloyd and van der Meer talk of the PACE trial [6] testing CBT and GET; they clearly realise that the quoted recovery figures are misleading. I believe that when talking of PACE we should all be calling for the freeing of the results data from the confines of a database held under guard at QMUL. This should include pushing for the publication of the measures defined in the protocol [7] – some 5 years after the completion of the trial we should see their non-publication as unacceptable. Their lack of publication also makes the results the authors choose to publish uninterpretable.

The methodological elephant on the therapists couch needs to be addressed when suggesting theories as to why GET gave the modest quoted results from PACE. That is PACE was an unblinded trial where therapies addressed how patients perceived their symptoms yet primary outcomes were subjective patient judgements on their symptoms. Perhaps the surprise with PACE was their results were not better given therapies involved telling patients to ignore symptoms and they will get better and measurement looked at the change in how patients view their illness and disabilities.

A truly independent and transparent look at the data (including checking correlations in changes of fitness and walking measures and the subjective outcomes) may help illuminate the elephant but even then the enormity of the methodological issues should dominate any discussion. Unfortunately those who conducted the PACE trial see criticism and requests for clarity in their results as harassment [8] rather than an essential part of scientific endeavour driving us nearer to the truth.

http://www.bmj.com/content/350/bmj.h2087/rr-5