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Is CDC Out to Bury PEM?

Discussion in 'Action Alerts and Advocacy' started by Mindy Kitei, Jul 8, 2014.

  1. Firestormm

    Firestormm Guest

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    But that wasn't what Cindy was on about - was it? She was talking about your CPET tests being buried. Unger was talking about the practicalities of getting such testing - IF it can be proven to be a realistic indicator of the disease (and not functional ability) - into the clinic.

    If I did not display and relate my experiences of PEM I would not have been diagnosed with ME. And it was certainly one of the main things asked of me again even more recently by the - yes indeedy - NHS CFS/ME Specialist Clinic and my GP is most certainly aware it is a symptom to be included within a diagnosis and before a diagnosis is made.

    But - to be the devil's lawyer once again - asking a patient is not the same as confirming it as being key to a disease mechanism. And I hate to do it but referring to the 'meme' discussion... well pretty much anyone who is unwell will feel worse after they have 'done too much' and could report it as PEM.

    I just don't think we are there yet - maybe wont ever be - and perhaps PEM will not emerge as the de facto requirement. I still refer back to conversations I have had with RR MS friends and even with my Mum who has RA. They will similarly 'flare' after over exertion.

    Maybe this test can be shown to demonstrate something 'different' about people like you and me with this diagnosis: but establishing cause and a mechanism is more likely to - in my opinion - be the thing to eventually make it into the clinic and be part of any diagnostic testing.
     
  2. Valentijn

    Valentijn Activity Level: 3

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    Oh noes, people might try to fraud by claiming they have PEM! How is that any different than claiming "fatigue" to get the diagnosis currently? At least it would be a relevant symptom used for diagnosis, for a change.

    And someone would have to be a complete moron to falsely claim to have ME/CFS if looking for support or sympathy :meh:
     
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  3. Firestormm

    Firestormm Guest

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    Not fraud. Doctor says to patient: 'how do you feel when after you have been for a walk/had a shower/tried to get to the bathroom/whatever. Immediately after? The next day?' Patient says: 'Not too good. I feel worse.'

    I am merely saying that for 'PEM' to be the key symptom of ME we do need more and I don't believe this test to be 'it'. PEM encompasses a raft of symptoms flaring and worsening ability to do what could be done previously.

    Personally, I despair at the PEM I feel most associated with overdoing it mentally: from reading 'too much', from engaging in conversation/socialising to the extent that I can, I dare say my trip to the garden centre shortly with Mum will be more overpowering for me mentally, than physically etc.

    I don't 'look for' or 'expect' PEM and sometimes it doesn't happen (which I tend to put down to my ability now to better manage my activities and plan and a level of acceptance and accommodation of this shite life I have): but the 'trigger' the ones that really kicks off a flare is often the one I don't expect - and it isn't always the same one.

    Are there different 'mechanisms' associated with different aspects of what we collectively term PEM? I don't know. But getting on a bike can only test physical aspects of 'something' that might have a bearing for some/all on that part of PEM.

    This is all in the context of Mindy's blog. The claim that the 'CDC is burying PEM'. Which all began really - if you ask me - which some patients not liking the fact she wasn't doing a two-day test in the multi-site study...
     
  4. Sean

    Sean Senior Member

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    Anybody who opposes PEM being a diagnostic requirement due to it being difficult to quantify in the clinic, has to accept the same argument about fatigue.
     
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  5. anciendaze

    anciendaze Senior Member

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    One thing everyone high up in an hierarchical organization must be good at is playing internal politics. This is simply a sine qua non for such positions. Solving research puzzles is very far from being a requirement, and I can even argue that this has negative correlation, because you never know which faction will benefit from new discoveries. Preserving the status quo is far more important.

    Medical organizations already have a strong motivation to preserve the status quo, which primarily means making the gulf between doctors and patients unbridgeable to protect the power and perquisites of doctors. In my reading of the history of medicine, I've found no cases in which the profession ever forgot a tactic or strategy which could delay change.

    One strategy for solving research problems is to break off a piece of the problem you can deal with and tackle that, in the hope you will learn something to make approach to the remainder possible. Patients with objectively measurable PEM are such a subset. Find out what is wrong with them, and you may crack the problem for other subsets.

    We are constantly hit with statements equivalent to "the science isn't there". What goes unsaid is that the science isn't going to be there without research. Official research on exercise intolerance is long overdue. There are definite reasons why this has not happened.

    We've been constantly whipsawed between clinical and disability requirements and requirements for research, which need not be the same. Anything which makes disability claims harder to reject has immediate budgetary consequences, which leads to political problems. HHS knows that doctors who have run thorough tests to document such claims have a high rate of success in these claims. If a patient hits anaerobic threshold at 40 watts output nobody in their right mind is going to push them to exercise heavily. Research on overtraining syndrome in healthy athletes has shown that exercise beyond that threshold is destructive.

    The political reality is that HHS isn't going to help anyone develop means of pushing through disability claims. They are under pressure right now to reduce long-term disability costs, and an incurable disease with a controversial diagnosis is exactly the kind of thing that looks vulnerable. Before you argue that addressing this disease is vital to reduce costs in the long term, you need to realize that most economic thinking is in terms of the next quarter or next fiscal year. Long term concerns the next election.

    By conflating clinical and research problems, a person in Unger's position is sure to benefit from the general medical tendency to say "this is how we've always done things, so it must be right (look where we are today)". When it comes to introducing new diagnostic tools she is on safe ground in thinking this is fiscally impossible. Here's a kind of syllogism: A & B => C.

    A: introducing new diagnostic tools, and getting regulatory approval, costs at least a billion dollars.
    B: we haven't been handed a billion dollars.
    C: therefore change is impossible.

    There are any number of variations which produce C. A skilled player can keep producing these long enough to retire.
     
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  6. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Some of us will have had tests done before becoming ill that may show interesting contrasts with how we are now. For example, in the year I became ill I took part in a test at the summer school for my biology course, in which volunteers performed a step exercise while wearing a mask to collect exhaled gas, and IIRC they measured VO2 (max?) and maybe some other things. I have my results somewhere. I think that @peggy-sue did something similar.

    I wonder how many people have test results of this kind that could be usefully compared with our performance now? (My metabolic rate came out as extremely efficient and seemed to indicate that I was super-fit!)
     
  7. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    We also appear to have excessive sympathetic nervous system activity which might account for the 'stiff blood vessels/stiff veins' which I have heard reference to. The excessive sympathetic neural activity would cause excessive contraction of muscles in the walls of blood vessels, would it not. I think that some scientists put this down to excessive nitrosative/oxidative stress.

    But would this not be expected to cause hypertension (which incidentally I have)? Perhaps if the sympathetic nervous system were just excessively reactive this could account for OI/dramatic fluctuations in BP?

    I may have misremembered some of this but don't have time to look it all up! Hope I'm not talking complete rubbish. :D
     
  8. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I think that the unpredictability of how much - if at all - a particular activity will affect us is common to most - maybe all - of us.

    I suspect that such outcomes depend partly on the physiological state we are in when undertaking the activity, which may be hard to perceive subjectively, but which may be measurable using devices such as those which have been discussed.

    I think that being able to predict such outcomes would make our lives a lot easier. We would be better able to know our limitations on a particular occasion.

    Heart rate monitors seem to be useful in this respect. If heart rate starts shooting up as soon as we start something, it means that we need to stop. But it would be even better to ascertain our capabilities before planning and starting activities.
     
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  9. Nielk

    Nielk

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    I was just in middle of watching this video from Dr. Enlander's at the Mt. Sinai conference in November 2013. AT about 24:10, he is talking about the use of fitbit to show PEM in patients as compared to controls.

     
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  10. anciendaze

    anciendaze Senior Member

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    @MeSci,

    I do not think you are talking rubbish. What is going on in a great deal of medical controversy is that people who have little experience with the concept of feedback keep trying to force a subject into their own Procrustean bed of misconceptions based on thresholds which may bear about as much relationship to the manifest outcomes of a pathology as low oil levels in an automobile to performance. If the engine seizes up, you have something corresponding to mortality. Until that happens you have nothing more than evidence like the spot on the concrete, that the machine requires maintenance it is not getting.

    Physiology is chock full of feedback loops, and most are strongly nonlinear. For people who still have nightmares about being back in calculus class, this kind of thinking is likely to be strongly rejected in favor of "extensive clinical experience" which mostly (about 90%) deals with patients who will get better, as one professor put it "no matter what you do".

    (It should go without saying that most diagnoses are made without much in the way of solid evidence. I'm adding this note because of a common misconception among doctors that most of the time they know what is going on.)

    I don't understand the high-blood-pressure variant of this illness because my personal experience has been with the low-blood-pressure form. I have no trouble with the idea that damaged organ systems attempting to maintain homeostasis will sometimes operate in the regime where bp goes too high. Another aspect, which I can't rule out, is that chronic disease usually involves more than one defect if allowed to persist for long. I simply don't know what is going on.

    I strongly suspect that even the concept of homeostasis is wrong. There is considerable evidence that living systems actually prefer to maintain variability, not stay near mean values -- even in the absence of variations in external conditions.
     
    Last edited: Jul 11, 2014
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  11. Scarecrow

    Scarecrow Senior Member

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    You're not alone. After first being horrified, I was surprised to find that I did, too
     
  12. Bob

    Bob

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    Clearly, it is (superficially at least) possible to determine via a questionnaire if a patient experiences PEM. But perhaps, in the eyes of the CDC, it would have limited value to determine PEM via a questionnaire. The CDC would be asking themselves what it would achieve in a clinical setting.

    Unger's remit is for chronic fatigue. (Nearly all chronically fatigued patients satisfy the Fukuda CFS criteria.) Her remit is not for ME. So she has got to cater for all fatigued patients. If she were to introduce PEM as a diagnostic criteria in clinical settings, then this would exclude some patients, which would be problematic from her point of view, unless she can see a very good reason to do so. (She would still need to serve those patients who don't experience PEM.)

    The CDC wouldn't know how to cater for the patients who don't have PEM or the patients who do have PEM, so it would probably be an unnecessary complication to separate the different patients in clinical settings, in the eyes of the CDC. (Perhaps they might see it differently if there was some easy way to make a biomedical determination for PEM in a clinical setting.)

    So my (charitable) feeling is that the CDC doesn't want to use PEM as a clinical marker until PEM can be more easily determined by a blood test etc. Because they can't see any benefit from it.

    I think Firestormm makes some valid points: In reality, asking a patient if they experience PEM would have very little practical value in a standard (general practitioner) clinical setting because PEM means different things to different people, and it's difficult for people (including clinicians) to understand the concept of PEM in ME if they've never experienced it. As Firestormm says, if asked, many people without ME would say that they experience PEM. So a questionnaire would not be a great method of creating well-defined subgroups. (Also, PEM is not a clear-cut or obvious phenomenon in many ME/CFS patients, even if they do experience it.)

    And once a doctor has determined whether a patient has PEM, or not, then what? There are still no treatments on offer for the average patient.

    So, determining PEM via a questionnaire would have some value, but limited value, in a clinical setting, in my opinion. Its biggest value would be to start to move the field forwards, by having the symptoms of ME properly recognised. So it may make a long-term difference. A step in the right direction. (We might be able to better fight the cognitive-behavioural model of illness if PEM was recognised as a prominent symptom.) However, in the UK, PEM is a requirement (via NICE - although the NICE criteria are worded ambiguously, in my opinion) and it hasn't made the slightest difference for us.

    I am a strong advocate of subsetting though, and of diagnosing ME using PEM, esp in research settings.
    I'm just pointing out the various flaws in the current system.
    Determining PEM in a clinical setting would not be a panacea. It's made little difference, if any, in the UK. But perhaps it was a baby step forwards.

    In the video that I linked to earlier, Beth Unger did emphasise the importance of subsetting (but it's never clear if she's talking about clinical or research settings), but she didn't specify that PEM should be one such subset. Perhaps, if we give her the benefit of the doubt, for the sake of discussion, she recognises the difficulties of determining the precise nature of PEM via a questionnaire, and perhaps considers that it would make little difference. And perhaps if a simple and precise test were available for PEM, she would go with it?

    Anyway, she always says that she will follow her data, and she emphasises the importance of subsets. Who knows what she will conclude once she has finished her multi-site research. She says that roughly 80% of her cohort (I'm not sure if this is the multi-clinic data) experience or 'endorse' PEM. I don't agree with Mindy Katai that the other 20% are simply 'depressed', seeing as CFS is so complex and heterogeneous. Also, ME is very complex (not everyone with ME has clearly defined PEM) and ME is possibly heterogeneous.

    BTW, Unger is carrying out post-exertional research. She's carrying out cognitive tests up to 48 hours after the one-day CPET test. This should give us some interesting results, if they are the right kind of cognitive tests. (I can't remember if I know what tests she is using.)


    Anyway, just my two-pennies worth. Perhaps I'm being far too charitable towards the CDC. I'd certainly like to see them achieving much much more in a much shorter time frame, and I'd like to see them carrying out serious biomedical research. But I'm still hopeful that Unger is genuine about following her data, and her emphasis on the need to define subsets. I think that's what she is doing and working towards, albeit excruciatingly slowly, and without much meaningful biological data. (But I've always said that she's wiped the slate clean and is starting the CDC's program from scratch, which I think was the best approach to take. So she's got to start with clinical reports and questionnaires etc and epidemiology, rather than specific biomedical investigations.)

    In the mean time, I guess we've got to look towards other research for answers.

    I'd like to know where Unger stands with Lenny Jason's diagnostic criteria research. (i.e. the De-Paul symptom questionnaire whereby patients answer some simple yes/no questions for a diagnosis.)
     
    Last edited: Jul 12, 2014
  13. Hip

    Hip Senior Member

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    Forget the measurement issues for PEM; just from a scientific point of view, PEM has got to be the most fascinating, unusual and unique aspect of ME/CFS. It's one of the central phenomena in this disease.

    A scientist cannot just ignore a major phenomenon like PEM.
     
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  14. Gingergrrl

    Gingergrrl Community Support Volunteer

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    @Hip, I completely agree with you and still feel that PEM must be kept in any definition of true ME/CFS. I still feel that the CPET test measures it (but that many/most patients are too ill to perform this test.) But just b/c we do not have a current test that is safe or a biomarker, does not mean that we throw away one of the most core criteria of the disease. I'm sure there are unique features of other diseases that did not get thrown away prior to being measurable (even though I can't think of an example off the top of my head.)
     
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  15. Valentijn

    Valentijn Activity Level: 3

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    I agree with most of what you say, but I disagree with you somewhat on this point. If a patient has PEM, they are part of a subset who is harmed by exercise and likely to get really ticked off if offered CBT as treatment.

    PEM is an extremely important symptom in a clinical setting because it tells the doctor how the patient must not be treated.

    Additionally, if Unger is really interested in subsets, it's pretty obvious that there should be a PEM (ME) subset. And if you pull the PEM subset out of the CFS diagnosis, is anything substantial left? Or is it just psychological and physiological misdiagnosis that remains?

    Failure to have an officially recognized disease defined by PEM, whether under the label of "CFS" or under the label of "ME" is just too harmful to too many patients in too many ways. It's grossly negligent and unacceptable.

    It's not acceptable to throw ME patients with PEM into a "CFS" diagnosis where extremely inappropriate, harmful and unhelpful recommendations for treatment exist. Exactly what does that sort of grouping accomplish, aside from pretending a problem has been solved?
     
    Last edited: Jul 12, 2014
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  16. anciendaze

    anciendaze Senior Member

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    I've watched that segment, and I agree that he is talking about objective evidence from Fitbit. Unfortunately, this kind of evidence does not distinguish whether the reduced activity is simply a matter of choice for the patient. Had the data included reduced VO2 max it would be extremely hard to argue that this is under volitional control. Likewise, it would be much harder to argue with data showing systematic changes in heart rate following exercise. With the possible exception of yogis, people don't have that kind of voluntary control. The ultimate proof would be in measurements via MRS of increased lactate in the ventricles of the brain. Nobody has detailed control of brain chemistry.

    At this point we run into the problem of research vs. clinical utility. The more difficult or expensive tests are not likely to become common in clinical settings anytime soon. This is a standard problem in medical research. Limiting research to measures currently available in clinical practice is one way to avoid changing medical practice. If HHS is satisfied with current clinical outcomes this is exactly what they do, and ME/CFS is only one example where they have managed to delay coming to grips with the problem for decades.

    (Borreliosis in another example. Once there was a clinical test that worked, in some cases, and doctors around Lyme Connecticut were told to use this, the problem was solved as far as the FDA and CDC were concerned. We now know Lyme disease is far more widespread, involves multiple species as well as strains, and that incidence is an order of magnitude higher than previously reported. This sequence of events makes no sense, unless you think in terms of solving political problems.)

    I've argued that HR recovery times offer a good way to demonstrate that at least some patients really do not benefit from exercise, and that the effort of simply staying alive may already push them up against thresholds of overtraining syndrome. This will not demonstrate PEM in the case of mental effort, or metabolic stress like a high-carbohydrate meal which leaves you wiped out the following day.

    (My experience with the latter comes from a time when doctors repeatedly ran glucose tolerance tests, GTT, on me, because they couldn't believe the results they were seeing. I was wiped out for three days after each one, until I quit cooperating with such tests.)

    It is not hard to find ways to measure negative effects of exercise on patients with severe ME, unless you start with the idée fixe that the patient has to be malingering.

    Even the recognition that some patients have very low thresholds for overtraining in official recommendations will run into predictable problems in practice. Having a doctor say you need to push yourself, but obviously you should not push yourself to the point of collapse, is useless to patients who have nerve damage which results in a constant perception of discomfort and considerable exertion in common situations -- like making a doctor's appointment. How are they expected to tell they are about to collapse before they wake up in the emergency department? (Been there, done that.)
     
  17. taniaaust1

    taniaaust1

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    It concerns me those tests as I have my doubts that they know the best cognitive test to do on us. I myself found when I was having cognitive testing for a ME/CFS research study being done in Adelaide Australia (it should be published in the future) that many of the cognitive tests didnt show my severe brain issues at all (which shocked me), while a couple of others certainly did (one did show up my issues very severely). So its a huge deal what test they are using to test this in us.
     
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  18. Hip

    Hip Senior Member

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    Cardiopulmonary exercise testing (CPET) may certainly be good for testing PEM precipitated by physical exertion, but many ME/CFS patients like myself only get PEM from mental exertion. In my case, I can relatively easily jog a mile; but if I spend say 3 or 4 hours socializing with people, that mental energy used in just talking to people gives me PEM for one or two ays after.

    I have often wondered why there are these two different types of PEM, one from physical exertion and the other from mental exertion. These might be considered as subtypes of ME/CFS. I have a hunch that in the physical exertion PEM subtype of ME/CFS, these patients may have something going on in their muscles, such as an enterovirus infection of the muscles (muscle tissue biopsies of ME/CFS patients have often found evidence of enterovirus infection — ref: here). But in those with only mental exertion PEM, perhaps their muscles are fine, and free of any enterovirus infection.
     
    Last edited: Jul 12, 2014
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  19. Valentijn

    Valentijn Activity Level: 3

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    I can get PEM from both, though the PEM from mental exertion seems less full-bodied than the PEM from physical exertion. I tend to just end up with a headache and difficulty thinking much after reading a novel, for example, whereas physical exertion will result in full-body pain + the cognitive problems and headache.

    Some enzymes are coded by nearly identical genes, yet one version is specifically for the brain, while another version is for the muscles. So perhaps there are some genetic components creating a vulnerability in just brain energy production or immune function for some, while others get the same problem just in the muscles, and some get the problem in both brain and muscles.
     
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  20. Hip

    Hip Senior Member

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    A very good candidate for explaining the biochemical mechanism of PEM is the release of the cytokine IL-6.

    A huge amount of IL-6 is released from exercise: IL-6 blood levels will increase 100-fold after exercise. Exercise also causes IL-6 to be released in the brain. High IL-6 levels are associated with cognitive dysfunction and cognitive decline. IL-6 release can also induce fever (high body temperature), and a few ME/CFS patients experience fever during PEM.

    So it might well be that the release of huge amounts of IL-6 from exercise is the cause of physical exertion PEM.

    IL-6 is also centrally involved in neuroinflammation. So if mental exertion somehow ramps up levels of neuroinflammation in ME/CFS patients, more IL-6 may be released in the brain, perhaps leading to mental exertion PEM.

    More info on IL-6 and PEM is found in this article: http://phoenixrising.me/archives/5217
     
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