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Can ME/CFS patients in the UK choose who they go to see on the NHS?

Discussion in 'General ME/CFS Discussion' started by charles shepherd, Aug 2, 2014.

  1. Marco

    Marco Old blackguard

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    I fully agree that there are currently no alternative (apart from CBT/GET) with sufficient evidence to warrant inclusion in any guidance for ME/CFS treatment or even to be considered at the discretion of individual physicians? So called 'ME experts' really need to get their act together if they expect anything to change.

    I also agree that, in the absence of knowing the heterogeneity of the population or what the various pathologies might be, that any blanket prescription (of CBT/GET) is unwarranted especially given that subjective symptom change doesn't appear to lead to objective functional improvement.

    I also agree with the sentiment that the limiting of further investigation post a ME/CFS diagnosis is unwarranted/reckless.

    I'll give one example. Fibromyalgia is a closely related and frequently 'co-morbid' condition to ME/CFS which some would argue is another example of 'medically unexplained symptoms' or a psychosomatic disorder. Recent studies (5 possibly 6 from various labs) have now shown objective evidence of small fibre peripheral neuropathy in around 50% of fibro patients which could very well be driving their central pain. Whether this represents misdiagnosis, co-morbidity or is a central driver of fibro is up to the scientists.

    The point being is that it can be objectively measured, has known causes and can be treated.
     
    Last edited: Aug 17, 2014
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  2. Leopardtail

    Leopardtail Senior Member

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    I also saw research some years ago showing a phenomenon in Fibro patients in which 'cross talk' appeared to be going on between nerves in the spinal cord. Not sure how relevant that is to drug treatment, but the idea of CBT/GET does bugger belief in light of such abnormalities.
     
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  3. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    But it is actually true to say that there is currently any evidence for CBT/GET? Many would query this, in which case the above statement might be improved by excluding any reference to CBT/GET, to read that "there is currently no treatment with sufficient evidence to warrant inclusion in any guidance for ME/CFS treatment or even to be considered at the discretion of individual physicians."
     
  4. Sasha

    Sasha Fine, thank you

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    Thank you! I really appreciate you discussing this.

    One of my constant sources of surprise is how unjoined-up things are in terms of research and clinical practice, when there's such unmet clinical need. If consultants don't have it as part of their remit to do research, I can't understand why consultants (and, indeed, GPs) who see a lot of ME patients haven't for years been banding together and demanding that the MRC fund biomedical research on a large scale and as a matter of urgency so that the clinicians can do their jobs and treat these patients. Maybe it's something that's not in their professional culture and it doesn't occur to them. There are a lot of doctors who are in no doubt that this is an organic immune disease and yet they stay silent. I find that baffling. That's a whole new thread, though!

    Agreed.

    I take your point about study quality and reporting but I think we're back to the distinction between what the researcher/clinician proposing the treatment can expect, and what a severely and chronically ill patient who has been untreated for 30 years can expect.

    Others on this thread have made the point that there are investigations that would make sense to do for us (tilt-table testing as standard, for example) to reveal conditions that could at least partly be treated, but my focus here has been on trying to address the core pathology in some way. And in the absence of a well-understood mechanism, that's going to involve risk.

    I've been wondering what happens to patients who don't have a diagnosis - any diagnosis, let alone an ME one - who are extremely sick and who their clinicians firmly believe have an organic disease. Do clinicians try treatments on them? Are clinicians not trying things on us because we have an ME diagnosis and trying things out on PWME is somehow psychologically or institutionally off-limits? Perhaps because they're thinking, "this is ME and everyone knows that we don't know how to treat it" rather than, "this is an unknown disease and there are no guidelines so I'm going to have to feel my way in the dark and try things out"?

    I agree that things are moving on, and much faster now than ever before. But I wonder how many more years before any treatment comes down the pipe and we can start using it. I can see potentially rapid payoff from the Lipkin microbiome study, for example, which can be done in less than a year once funded (one reason why I support it) but I don't know if there's anything currently ongoing that could be expected to get into clinical practice straight away if the results look good. And NICE is insisting on not reviewing its ME clinical guidelines (though I hope if new evidence turned up they'd change that pronto).
     
  5. Marco

    Marco Old blackguard

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    First up - sorry for the mangled sentence.

    I wasn't stating my view as much as what I suspect would be the view of NICE, commissioning bodies or your average GP (assuming they're interested). These people are not immersed/pre-occupied with the ins and outs of or politicking around ME/CFS or PACE and taken at face value they see a large apparently well conducted trial using a 'gold standard' methodology that reports moderate success and few adverse impacts. Often that's all they need to read.

    Most other ME/CFS studies don't come anywhere near having that 'gold standard' stamp of approval regardless of how meaningless it may be in terms of the actual validity of the model or the findings.

    That's the way it is I'm afraid.
     
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  6. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    As Prof Edwards has stated in another thread (his original rituximab one, I think) it takes a long time for research findings to be translated into clinical practice. I think it's typically about 10 years - if it actually happens. First treatments have to be tested. Unfortunately Lipkin has hinted that he may start with animal 'models' which will be a waste of time, money and lives. Then the treatment evidence has to be assessed by bodies such as NICE. Then they may deem that it is approved. Then it has to become part of clinical practice. It's clear from Physician's First Watch that many doctors are still not following correct clinical practice for things that became part of their guidance years - or even decades - ago (look at the number of antibiotics still being prescribed inappropriately, for example).

    So don't expect anything to happen quickly as a result of new research.
     
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  7. Sasha

    Sasha Fine, thank you

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    An animal model is one possibility that he's mentioned but I think the next step will depend on the outcome of the study. Some outcomes I can see as having fairly rapid translation to treatment. If the problem is clearly located in the gut, that puts a focus on dysbiosis and it may be possible to focus diagnostic effort on that (an area currently totally ignored for PWME in the NHS) and treat it (depending on the nature of the dysbiosis) with existing, accepted treatments.

    But yes, I agree that translation from research to clinical practice is usually very slow. I hope that some of the US initiatives around our "orphan disease" status might get some stuff fast-tracked.
     
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  8. Leopardtail

    Leopardtail Senior Member

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    With the current 'model of science' we can't really hope for much better than that.
    There is work being done at the University of Chester to address the issue of the 'hierarchy of evidence' since it suffers a number of inherent flaws. Firstly it completely disenfranchises the most ill patients. Most especially those who have multiple diseases since it is impossible to test for every permutation of illness combination. Most of use when we get access to tests report not just one but multiple lesions. If you have two lesions that affect the same 'vital function' then research on one lesion at once will produce misleading and useless data.

    E.g. ATP synthase requires NADH and FADH and CoQ10 along with B1 to function correctly. Delivery of subtrates to it also requires forms of B1, B2, B3 (NAD+), Acetyl-Choline, Carnitine.

    This gives more than five possible and partial lesions that can affect the function of a single aspect of metabolism. It's no co-incidence that NADH helps 30% of patients, it's equally predictable whey people might have energy problems that it does not resolve.

    The expectation that one solution should fit all, that it should be possible to research a comprehensively suitable solution for most patients before we can identify the subgroups is just naeive. If we were very naive and assumed there were only eight dysfunctions that cause ME and therefore eight groups of patients. If we further assume also that the distribution of those dysfunctions is even and that each group is mutually exclusive. To achieve N=5 requires that we test 40 patients and means that an 80% success rate in each group would mean 4 successes. Since each investigation would involve one treatment (usual practice in science) that would mean a 'statistically insignificant result of 10% improving and more than likely at least that number getting worse.

    It comes back to the point many have made earlier, there needs to be a rush to test, rather than a rush to treat. Action is then needed based upon pathology. Put simply out diagnosis means "an unknown set of dysfunctions causing an only semi-predictable symptom pattern". We need science to focus on gathering comprehensive data sets of metabolites rather than data on single metabolites at once. We need statisticians to be utilising those shared data sets to identify symptom clusters, we further need the same action on metabolite clusters. Those clusters then need to be correlated with each other.

    This however requires a much more 'grown up' model of science in which each individual is working as part of the 'global team' data is recorded in a manner that can be correlated and reporting is standardised. In that particular issue my criticism is levelled squarely at the panels handing out funding, this kind of steering is their responsibility. Individual researchers cannot achieve this.

    What most concerns me about the science around ME is the 'rush to treatment' - the science around the relationship between our variable symptoms and variable biochemistry does not give (me for example) the raw material to form a good working hypothesis, or work out one which groups of patients I should run a trial.

    The reporting systems are an even bigger failure of science, giving little rigour to how the effects of treatments affect full symptom profiles. The efforts we have been making in another thread to construct an adequate scalable database are in large part to resolve some of these issues. My most obvious comment is that 'science' should already have done this to some adequate and consistent standard.

    Further comments on treatment as opposed to science, but probably better in a different post.
     
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  9. Leopardtail

    Leopardtail Senior Member

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    I suspect most of us are ware that for any specific treatment for ME long time scales will be involved. It's important however not to forget the issues that annoy us most: we should still be getting sensible testing for causes of our illness; if there is a treatment for the identified illness then we should get it.

    If for example I compare what happens with my diabetes: if the treatment works any co-morbidity (e.g. I get a treatable infection) then its applied as long as diabetes in not a known contra-indication. The same needs to happen with ME. ME + orthostatic intolerance = treatment for the later unless there is a known issue with the treatment and ME.

    The science is of course vitally important, that's why I am involved in it. However science cannot replace common sense. It just isn't viable to give doctors a robotic instruction manual as NICE tries to do. Were that a viable system we would not need human beings (doctors) to apply their intelligence, and we clearly do.
     
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  10. Leopardtail

    Leopardtail Senior Member

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    Doctors have for the most part a 'technician mindset' that focusses on how we deal with an immediate problem. Scientists have for the most part a 'engineering mindset' focussing on how things work, why they work etc. The distinction for the most part works well with 'single illness medicine'. The separation also makes patients safe from science done in the name of medicine. I fully understand where you care coming from on that point. All medications however have side effects for some patients and a small handful that react badly - there would be no medicine in use if we tried to operate 'zero risk'. Every medicine taken by a patient is a 'low risk trial' backed up by earlier 'scientific trials'.

    In the case of the multiple illness presentation in the same patient however it becomes unworkable and as such we need a focus in health care on how such complex cases are dealt with. Industry and commerce deal much more successfully with such things and medicine really must put it's house in order in this area. A medical system that fails its most needy has a fundamental issue to address as some of your academic colleagues now recognise.
    Good point well made please elaborate.

    @Jonathan Edwards You raised a point earlier about the GP model being outdated, and I do recognise some of the issues with this model. The Warwick University CFS/ME service for example functions as a GP. But that GP has broad specialist knowledge of the disease. I suspect most of the other 'multi-system' diseases would benefit from a similar model given the large overlap between them. That 'mini debate' about the nature of the medical relationship and how services are accessed is a key point well made. This disease is overwhelming for a general practitioner, but the specialist service needs to act much more like one. It's impractical to have a purely endocrine, purely immune, purely psychiatric service.

    How would you see such a service functioning out there in real world medicine? How would you make it work to produce a better experience for the wide range of pathology you are experiencing in Phoenix?
     
    Last edited: Aug 24, 2014
  11. Jonathan Edwards

    Jonathan Edwards Board Member

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    I think we may overestimate what people thought was possible not so long ago. The sort of research that has been done in the last 20 years was completely 'unthinkable of' before that. Things have been slow for ME and part of that has been inappropriate sidelining as is evident to all of us. But it is genuinely very difficult to know where to start researching. We still do not have reliable biomarkers to use as a handhold.

    There are such people with no diagnosis and clinicians tend to want to try something if they can but for the symptoms of ME it is genuinely very difficult to know what to try. One can be pretty sure 99% of things one could try would do no good or have adverse effects. That is not a good place to start for just picking something at random. But I do think you are right that it has become acceptable to take inaction in ME as having some strange justification - essentially because nobody really believes there is any altered physiology.

    So I keep coming back to agreeing that you are getting a raw deal, but not feeling that I should be persuading colleagues to try anything specific at present.


    I think its hard to say. But what I do think is that if we can just get some consensus on one reproducible biomarker and get that published in a major journal the whole attitude to ME should change. And remember that almost all drugs in rheumatology are 'borrowed' from developments in other specialities. All we need is for the transplant people to come up with some new immune modulator and we suddenly find we have something that can be used on a compassionate basis for ME as well.
     
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  12. NK17

    NK17 Senior Member

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    @Jonathan Edwards how close are we to the one reproducible biomarker?
    Are the norwegian closer than anybody else to its discovery, thanks to their translational work which, if I'm not wrong, goes back to 2007?
    In my mind this ORB (one reproducible biomarker) resembles the Higgs boson ;).
    As a PWME I love theoretical speculation, but what I mostly need, are practical interventions.
     
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  13. Leopardtail

    Leopardtail Senior Member

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    This issue comes back to the old maxim of 'repetition repetition repetition' - Myhill, Booth and McClaren have shown reliable correlation between rate of ATP production and symptom severity. The issue is that it has not been repeated by another team. I have the impression (right or wrong) that the test is 'private property' and may only be performed by Acumen - that makes research for day to day use something funding bodies are unlikely to be happy about. It's use in research however seems more plausible until a 'free to air' test is developed.

    There is an obvious question that needs to be asked though: is ME/CFS a single function or the compound effect of a number of smaller dysfunctions. Is it in fact one disease or many smaller lesions? If it is indeed a Mitochondrial lesion that is common, they are very challenging to 'cure' or 'manage fully'. and we may still be left with the need to do what we can with the Mito issues and take multiple actions against other lesions that strain the Mitochondria.

    There is a large group of diseases similar to ME where medics are struggling to locate the issues and manage them. Perhaps the question that needs to be asked is how "what is the problem?" but "why haven't we found the problem and do we need to think differently?".
     
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  14. Jonathan Edwards

    Jonathan Edwards Board Member

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    You will understand that I am not suggesting that there is ONE reproducible biomarker to be found. There should be lots, some specific for individual subgroups and some more general perhaps. But to turn the tide of opinion all we need is to find one of these. It will, however, need to be something that hits people as being completely inconsistent with some secondary effect of 'deconditioning' or whatever. It may be that the 2 day CPET test is a valid biomarker and just needs repeating on other patient groups in other labs but it suffers from the worry that it is measuring an effect of a process rather than a possible upstream cause. So there is a lot of interesting work on muscle physiology and autonomic dysfunction that might be showing us the biological nature of MEs but I suspect it will not on its own shift the tide of opinion.

    Immunological markers are more likely to do the trick. It is hard to say that PWME have odd NK cells simply because they keep lying down. It is not bullet proof because lying down might well alter NK function a bit, but if labs could agree exactly what is wrong with the NK cells it might become clear that it cannot be just due to lying down (so to speak). I have seen a suggestion that the conflicting results may indicate that the NK cells themselves are normal but that they are affected by something in the plasma. If that could be shown to be the case then isolating the factor should be a relatively straightforward piece of science.

    So maybe the situation is a bit like the Higgs boson in that our problem is getting into the right position to measure the thing reliably - setting up the measurement apparatus right.

    The Norwegians are in a sense closest to giving us a precise biomarker that is far enough away from the 'efects of lying down' to be totally game changing. If their results hold up we have solid evidence for an autoantibody driven process in perhaps at least half of PWME. The work by Bansal on B cell populations and the recent PLOsONE paper on gene methylation give a hint that we might be able to tie that in to a B cell maturation marker that could be picked up just on a blood test, rather than having to test people by giving them rituximab. But there needs to be some test that can be readily reproduced in labs all over the globe - like a rheumatoid factor test.

    Another key factor is the need to get around the problem of biasing in population studies. If we are looking for something that turns up as a statistically increased frequency, which is likely, then it is no good studying populations of PWME that for some reason or other are unrepresentative of the problem as a whole. There is probably a need for a study like the Norfolk Arthritis Register which studied a whole population, unselected. That way there was no bias from the way doctors had already pre-labelled patients before the analysis.
     
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  15. Snow Leopard

    Snow Leopard Senior Member

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    I'm not JE, but I don't really think this is a question he or anyone else can answer at this point.

    @Jonathan Edwards
    My queston is not ME-specific, but what is your opinion on the current speculation of the role of these mysterious Bregs (mysterious because they have no specific cell makers differentiating them from other B Cells) and their role in autoimmunity?


    The following editorial as an example:
    http://onlinelibrary.wiley.com/doi/10.1002/art.38667/abstract
     
  16. Jonathan Edwards

    Jonathan Edwards Board Member

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    And of course if it turned out we could show the NK cells were affected by something produced by the shifted B cell population noted by Bansal which was taken away by rituximab and could also account for the muscle and autonomic disturbances... we would be home and dry. Not only that we could divide off the B cell subgroup and be able to find a marker for the next subgroup, not mixed up with the B cell one - if that's really the way things are!
     
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  17. Jonathan Edwards

    Jonathan Edwards Board Member

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    I don't think there are any cells worthy of the name B reg. I cannot see what they would have to do with human autoimmunity anyway. I think they are an artefact of mouse experiments. B cells go through all sorts of phases of different functions, as we have known for a long time. Inventing B regs just because we had T regs seems to me symptomatic of the way science nowadays is dominated by fashion.
     
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  18. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Could it not be useful to do a study of patients wearing actimeters and comparing their activity levels with their NK function? If, as you suggest, it might be possible for the psychs to argue that low NK function is due to inactivity, would something like this not disprove it?

    Or might the psychiatric argument be that prior inactivity caused the low NK function, and if so, how long ago and for how long could inactivity lower NK function (sorry about the muddled syntax - it's morning!)?

    Quite a lot of us are pretty active - me for example - but I probably have the typical low NK function as I have the typical symptoms of ME. The only lying down I do is in bed at night, like healthy people. I probably spend no more time lying down than the average person. Many of us also have proof of high activity levels prior to becoming ill, such as working long hours, athletic pursuits, family responsibilities, etc.
     
  19. Snow Leopard

    Snow Leopard Senior Member

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    I didn't think it was so much of a ban, but rather simply difficulties in obtaining funding. Eg the NIH aren't going to do it, most research organisations won't consider it (due to risks vs benefits) even if they could afford it on their own, leaving merely private benefactors and crowdfunding.

    A new Ampligen study would be brilliant, but I don't see it happening in the near future given the current attitude of Hemispherex.
     
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  20. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Recent Australian work looks at nk bright cells and nk dim cells. They are finding the bright cells are the ones functioning very low. Also another finding is low cd8 t cell function. So maybe a few biomarkers together could be used to help with a diagnosis.
     
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