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A Major Flaw in the IOM's Definition of ME/CFS

Discussion in 'Institute of Medicine (IOM) Government Contract' started by Advocate, Feb 18, 2015.

  1. Advocate

    Advocate Senior Member

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    In a public Facebook note, Danny Ze-dog addresses the flaw from many angles, and then explains how the IOM committee could easily fix the problem. The essay begins:
    "There is a serious flaw in the premise and design of the Institute of Medicine's new ME/CFS definition. In a nutshell, the new definition lacks any exclusion criteria or even differential diagnostic suggestions to guide clinicians in making accurate diagnoses. This is a surprising omission that could render it, in practice, highly non-specific, and thus ultimately detrimental to patients both with and especially without ME or CFS who appear to meet its criteria. In this post I'll discuss some of the real world implications of this flaw, and how it might (easily) be corrected."

    https://www.facebook.com/notes/849911435058362/?pnref=story
     
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  2. eafw

    eafw Senior Member

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    There is some guidance already in the report about assessing patients (Tables 7.1 and 7.2)

    Additionally there is a clinicians guide, yet to be released. Referenced under "Report at a Glance" here:

    www.iom.edu/Reports/2015/ME-CFS.aspx

    We will have to wait and see how much detail that goes into regarding exclusion or whether they consider the tools, criteria and operationalisation already given as sufficiently exclusive.
     
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  3. Valentijn

    Valentijn WE ARE KINA

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    PEM is a unique symptom. By making it mandatory, there's no need to exclude anything.
     
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  4. Ember

    Ember Senior Member

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    PENE is more strictly defined than PEM. And PENE is required in the ICC which excludes primary psychiatric disorders, somatoform disorder, substance abuse & paediatric 'primary' school phobia.

    The CCC also requires PEM; it excludes:
     
    Last edited: Feb 18, 2015
  5. alex3619

    alex3619 Senior Member

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    If and only if it can be reliably assessed by primary care providers. That is the real issue, the sticking point. A failure to adequately assess PEM could lead to low specificity for SEID, or in other words they will diagnose lots of patients with SEID who should not be diagnosed.
     
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  6. alex3619

    alex3619 Senior Member

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    Aside from the name I like PENE. However the ICC and CCC do not stop psychs from redefining patient diagnoses. This is much more than about definitions, its about prevailing medical failures.
     
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  7. alex3619

    alex3619 Senior Member

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    Some things we have to keep in mind about a new definition include issues relating to sensitivity and specificity. Sensitivity is about correctly identifying patients, and specificity is about avoiding wrongly diagnosing other patients.

    We need to be able to adequately determine the presence of the subcriteria, plus adequately determine the overall validity of the definition. Inability for most doctors to adequately identify PEM is going to be a major issue. Cognitive issues can also be a problem, and while most of us have sleep issues there is high variation there.

    This definition needs a study to determine how reliable or unreliable it is before its adopted. I would suggest that should be a priority.

    Only then could it be considered evidence based.
     
    Last edited: Feb 18, 2015
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  8. Sean

    Sean Senior Member

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    IIRC it goes something like: Sensitivity reduces false negatives, specificity reduces false positives. You need both.
     
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  9. anciendaze

    anciendaze Senior Member

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    Here's the rub, alex, what do you use as a standard to test that study? This definition hasn't been implemented to the level of clinical use, and the IOM has not set separate standards for research.

    We've already seen research groups making a complete hash of diagnosis of PEM, just like fatigue, exertional intolerance, sleep disorders and cognitive impairment. Orthostatic intolerance might offer another route, but the literature on POTS and NMH also reflects a wide range of medical opinions.

    The 2-day CPET shows a pretty unmistakeable signature, but that is a provocative test with risks. Don't expect government agencies to encourage use of this. They will mention danger to patients, but will also be thinking about lawsuits aimed at them. Behind everything is the thought that every patient with illness validated by such a test is in position to claim disability benefits. The thought of hundreds of patients suddenly qualifying for disability based on a test in a government-funded research program is as frightening to them as a substantial lawsuit. Small-scale studies will not qualify as high-quality.

    (Opinions about exactly what determines AHRQ assessments vary. I propose this simple rule of thumb: the quality of a study is proportional to the money government agencies put into it. Anything else would be tantamount to infighting between different agencies.)

    The present situation, where individual patients undergo testing at their own expense, absolves government agencies for liability if the result is permanent injury. The cumulative results of such tests can be rejected as "unscientific" because they are not under the control of "impartial investigators" with uniform standards, even if the individual evidence is convincing enough to eventually satisfy requirements for disability claims.

    Don't expect anyone from HHS to break this logjam.
     
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  10. WillowJ

    WillowJ คภภเє ɠรค๓թєl

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    The report says to diagnose "if diagnostic criteria are met following an appropriate history, physical examination, and medical work-up."

    This implies differential diagnosis and excluding other conditions.

    However, as has been mentioned, physicians are not familiar with PEM and might even think they have an idea what it is. The success of this will depend on the education which goes with it, which we haven't seen yet.

    @alex3619 said the same thing I had been thinking: we won't know how accurate or inaccurate this is until we study it.

    Although it is a fair point that we don't have a gold standard to compare it to, it should be possible to see how many misdiagnoses we are getting in clinical settings (we have some data using current clinical methods, and it's not fantastic).
     
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  11. alex3619

    alex3619 Senior Member

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    Study design is critical. I know there will be issues. There are many ways such a study could go.

    The doctor's guide might change things.

    I know the CPET cannot be mandatory, but is an optional possibility for some. We need a better test for PEM. Yet at a research level it shows that in principle its possible to distinguish between exercise intolerance and post exertional malaise.

    The big worry here is false positives on the PEM subcriteria. You could have a cohort of doctors diagnose existing patients, and then have experts rediagnose them. Compare the two. Until we have decent tests then any definition will be improperly tested. Biomarkers are so very overdue.

    I wonder if a post exercise blood tests like the Lights use might be where we go with this in time.

    So one thing we might do is find out how a cohort of depressed patients go. Could any be diagnosed with SEID?

    One possibility, without involving actual patients though you might need permission, is to randomize case data for patients and find out how, for example, a hundred primary care doctors would diagnose them. Can they separate depression from SEID?

    The pros and cons of various designs would have to be investigated by potential researchers.
     
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  12. Ecoclimber

    Ecoclimber Senior Member

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    What is needed is research funding so that a replication study can be conducted in sufficient sample size for verification for the below reports.

    Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls
    Thus, the pathology of CFS may include a susceptibility to disproportionate fatigue in response to exercise stress that is uniquely expressed in this patient group. The pattern of gene expression may have potential for use as a biomarker for diagnosis and treatment responses. Abnormal increases in adrenergic receptors following exercise in both MS and CFS patients suggest that dysregulation in sympathetic pathways contributes to the exaggerated fatigue in both conditions

    Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome
    Post-exercise increases for 4 genes meet published criteria as an objective biomarker for CFS, and could be useful in guiding treatment selection for different subgroups.

    Discriminative Validity of Metabolic and Workload Measurements to Identify Individuals With Chronic Fatigue Syndrome
    VO2 Max test


     
    Last edited: Feb 19, 2015
  13. alex3619

    alex3619 Senior Member

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    @Ecoclimber, not just replication though that is necessary too. We need to know the findings are unique, at least for PEM. So at least some cases of other disorders that resemble what we have need to be investigated for each potential diagnostic test.

    So far as I am concerned we have considerable validity testing so far on the 2 day CPET, including independent replication. We do not have that for the Light's studies though.

    What is very clear though is that static testing is very limited in us, we need some kind of stress testing to invoke the problems, though to be fair if you are very sick, and have to exert yourself to get tested, this might be enough. Further the evidence is that delayed testing is a good idea. Our maximal response is not anything like immediate.

    We know that a great many disorders do not appear to show the delayed crash in energy on repeat CPET, though I would like to see a formal publication stating that. So many look alike disorders do not appear to have this. The same cannot be said, yet, for the blood testing. I think in time we will focus on one or several blood markers, get it replicated and tested multiple ways, and we will have a diagnostic test. When though?

    PS Non-unique findings can still be used as confirmation of each SEID subcriteria. Its not an ideal situation though. There are, apparently, something like 30 confirmatory tests that many ME docs run. Many of those will be deemphasized under SEID.
     
    Last edited: Feb 18, 2015
  14. SOC

    SOC

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    None of those conditions includes PEM, so by definition all those conditions independent of PEM are excluded. No problem there.

    However, a patient could have both SEID and any of those other conditions. ME/SEID does not protect one from having a psychiatric disorder. Genuine patients should not be excluded only on the basis of having a psychiatric condition.

    Exclusionary conditions weaken a definition -- leading to it becoming a wastebasket diagnosis or missing patients with multiple conditions. An inclusionary diagnosis is more sound. By requiring PEM, the diagnosis should catch patients with the condition without unnecessarily eliminating patients with additional conditions.

    The main weakness I see at the moment is that most physicians don't know what PEM is and will confuse general fatigue or exercise intolerance with PEM and therefore misdiagnose many people. We will have to see how the diagnostic guidance plays out to see how much of a problem this is going to be.
     
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  15. Ember

    Ember Senior Member

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    Specificity concerns increase the need for exclusions.
     
  16. Ecoclimber

    Ecoclimber Senior Member

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    @alex3619
    The IOM report chronicles various stages of severity with this disease. Given the possible number of patients, doctors will be reluctant to conduct exercise tolerance tests especially among the more severe. Many symptoms do not show in severity until the later stages. Lipkin alluded to a fact that he notice a difference in patients after three years in his unpublished research paper. Perhaps during those three years, there is a possibility that the disease could mutate several genes resulting in subsets of patients with addional issues as outlined in CCC, ICC such light, noise, chemical sensitivity. A blood test would be a more feasible biomarker considering the estimated fact of over one million patients.

    I suggested a replication of the the Light study because they stated they found biomarkers in both tests that can be determined through blood tests. We are trying to find biomarkers that are easily distinguishable from other diseases and can be easily administered by doctors. That is why the Light study should be replicated with a larger sample size.

    I helped fund some of Bateman CFI work that can be verified by CBS. But, right know I'm focusing on MS.
     
    Last edited: Feb 25, 2015
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  17. alex3619

    alex3619 Senior Member

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    I think the Light research program is still going on. Every now and again we see a new paper. I look forward to a blood test.

    Its very likely the current multisite CDC study will have some surprises. I am still skeptical about this though. Still, we need to see their publications to make a judgement, and for that we have to wait. I would love them to dispel my skepticism.

    I know there are major limitations with CPET. Its really a research tool, and a tool for select cases, not a general clinical tool. There are too many problems with it.

    I suspect the three year change will have nothing to do with genetics as in mutations. It might however be epigenetic. It also might be that biochemical setpoints shift to a new stable state. This research could get even more interesting than it currently is.

    Mutation is unlikely. Alteration of gene expression via blocking and unblocking gene promotors and suppressors ... that is another matter. Its a process that goes on all the time, particularly in a body with serious stressors.
     
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  18. taniaaust1

    taniaaust1

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    PEM thou means different things to different people. Have they clearly defined what PEM actually is?

    I also dont know if PEM is a unique symptom. Those who have systemic mastocytosis also can get ill with exercise.
     
  19. Valentijn

    Valentijn WE ARE KINA

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    Yes. It's in the report. And when diagnostic guidelines are given to doctors, it should be in those guidelines too, though we'll have to make sure HHS goes through with it.
     
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  20. anciendaze

    anciendaze Senior Member

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    @Valentijn

    I certainly see words in the report which could be interpreted as defining the PEM we experience. I also see words which say other things. They mentioned a paper claiming 64% of patients with major depressive disorders had PEM, and expressed limited skepticism, but this is not the same as rejecting an overly broad definition. All the hard decisions have been deferred. I feel like an ancient Roman citizen hearing "Let the games begin!" (in this case meaning word games and bureaucratic games.)
     
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