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New Exercise Study Brings Both Illumination and Questions
Simon McGrath looks at new objective evidence of abnormal response to exercise in ME/CFS patients, and the questions that researchers are still trying to answer ...
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Sept 10: CDC 'conference call' including Unger and Lipkin

Discussion in 'General ME/CFS News' started by Sasha, Aug 14, 2013.

  1. Ember

    Ember Senior Member

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    The Stevens Protocol involves a test-retest CPET regimen: “Our group subsequently developed a testing regimen (Stevens Protocol), requiring patients to perform a second test 24 hours after the first test to assess physical function in the post-exertional state.” Here's the evidence that the 2013 study confirms the diagnostic utility of the Stevens Protocol:
  2. Bob

    Bob

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    Ember, the abstract wording is inexplicable to me, and has been discussed here:
    http://forums.phoenixrising.me/inde...-paper-on-exercise-and-cfs.24050/#post-368228

    The wording of the abstract does not appear to be supported by the data, unless I'm misinterpreting the data.
    Nor does it seem consistent with the wording elsewhere in the paper:
  3. Ember

    Ember Senior Member

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    Not being a statistician, I won't engage in your debate over whether or not “significantly lower values” should have reached statistical significance, through univariate analyses, at the Bonferroni-adjusted alpha level. Dr. Snell explains in layman's language how his 2013 study confirms the diagnostic utility of the Stevens Protocol:
  4. Bob

    Bob

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    Ember, repeating something doesn't make it correct, especially if no supporting evidence is provided. I think I've provided enough evidence now to show that repeat VO2 peak CPET testing was not shown to be helpful in the 2013 study. And that workload, or Watts output, at ventilatory/anaerobic threshold was shown to be very useful in the 2013 paper. (Incidentally, ATWL was not tested in the 2005 or 2007 Snell papers, as far as I understand them, so I doubt if the Steven's Protocol was originally based on ATWL.)

    I think it's important for us all to be aware that the VO2 peak test was not shown to be as useful as it was in past studies, and that the 2013 study has superseded the earlier studies. I'm sure that the Stevens Protocol, whatever it is exactly, will be adjusted based on the latest research evidence.

    In any case, as always, further research is needed to test and replicate past research results, which is where Unger could play an essential role.

    Here's a handy graph from Dr Snell to demonstrate the difference between the VO2(AT) test (oxygen consumption at anaerobic threshold) and the ATWL/VTWL test (workload at anaerobic threshold).
    It demonstrates that there is very little difference for the ATVO2 test between CFS patients and controls but, with ATWL, there is a huge difference between CFS patients and controls in the second test:
    [​IMG]

    And here's a graph with the results from the 2013 paper:

    [​IMG]

    The graphs are taken from Dr Snell's FDA presentation, @83:25 and @83:08:
    http://www.tvworldwide.com/events/f..._archive.cfm?gsid=2251&type=flv&test=0&live=0
    Sea and SOC like this.
  5. Ember

    Ember Senior Member

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    I find no disagreement here, Bob, if we define our terms. The Stevens Protocol is defined (above) as "a testing regimen...requiring patients to perform a second test 24 hours after the first test to assess physical function in the post-exertional state." Notice its usage in the July 22 letter to Dr. Unger: “The two-day CPET regimen known as the Stevens Protocol provides gas exchange and other measurable results 'which can't be faked.'”

    Dr. Snell uses the slides that you've shown to illustrate what he calls "slightly different results" following the Stevens Protocol in 2013: "We didn't get such a dramatic drop-off in oxygen consumption, but one of the measures we did look at was workload. We get that on a bike; it's exclusive really to a bike. And we saw a big drop-off on second test workload at ventilatory or anaerobic threshold in the CFS population...." Dr. Snell's presentation provides supporting evidence and is entirely correct. His 2013 study confirms the diagnostic utility of the Stevens Protocol.
  6. Bob

    Bob

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    The link that you've provided, to define the Stevens Protocol, goes onto say "The two most important measures are peak oxygen use or aerobic capacity (known as VO2peak) and oxygen use at the anaerobic threshold (VO2AT)."

    Based on the latest research, that is no longer the case. Why don't we just agree that research is fluid, and that we should not ignore the latest research findings? And leave our discussion there?
  7. SOC

    SOC Moderator and Senior Member

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    Thanks for bringing this up, Bob. It had slipped my mind that the VO2AT and the ATWL, not the VO2 and work load at peak performance, showed major decline in the two day test. Rotten memory. :rolleyes: This would suggest that the less damaging AT test could demonstrate significant decline in functionality in ME/CFS without the major crash of a maximal exercise test. This may not be "industry standard", but might be the standard for ME/CFS patients.

    I'm going to have to reread the research to refresh my memory. There may be clear reasons why exercising only to AT would still be insufficient for research. Wish my brain retained all this better. **sigh**
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  8. Bob

    Bob

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    I think this might answer your question, SOC:

    Me too! :ill:
  9. Daffodil

    Daffodil Senior Member

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    lipkin is saying that the study points to changes in the microbiome. it looks to me like demeirleir is years ahead here, already having found the cells in the gut, which are harboring the active HERV's. why don't we raise money to support kdm's research? i say its time to donate to the WPI again, 110%.

    do we really want to wait around another 20 yrs until the powers that be, decide to do an antiretroviral trial, like in MS?

    give me a break
  10. Nielk

    Nielk

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    What would be great is if all these clinicians and researchers would get together and "talk" to each other and compare notes. They each might be holding a different piece of the puzzle which if put together would direct us to something greater.
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  11. Ember

    Ember Senior Member

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    Because you believe that the Stevens Protocol has been defined by its most important measures, Bob, you've called its diagnostic utility into question amid calls for its implementation. Previously, I've seen the term used to describe back-to-back CPET tests administered 24 hours apart.

    Our agreeing to disagree doesn't actually resolve the issue, so I wonder whether there's any way to get an accurate definition. We should be clear about what we're supporting or challenging.
    Bob likes this.
  12. Daffodil

    Daffodil Senior Member

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    nielk i totally agree. its a big competition and we end up losing
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  13. Bob

    Bob

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    I know nothing about the Stevens Protocol beyond what I read on the webpage that we've both referred to.
    I just wanted to bring to everyone's attention that VO2 peak results were not so useful in the latest study, but that the ATWL results were really impressive, and a potentially ground-breaking development.
    When pushing for repeat CPET tests, in the CDC study, I think we should keep the latest study in mind, and possibly reference it.


    In case anyone wants to reference it, these are the details for Dr Snell's 2013 paper:

    Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome
    Snell CR, Stevens SR, Davenport TE, Van Ness JM.
    Phys Ther. 2013 Jun 27. [Epub ahead of print]
    doi: 10.2522/​ptj.20110368
    http://ptjournal.apta.org/content/early/2013/09/04/ptj.20110368.abstract
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  14. Ember

    Ember Senior Member

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    This definition of the Stevens Protocol from the Workwell Foundation doesn't specify the objective measures used:
    From what you've quoted above, "the Workwell Foundation remains committed to the repeat-maximal approach."
  15. Bob

    Bob

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    But the protocol surely has to include well defined specific tests, and a detailed explanation of how the tests should be interpreted, if they are to use it as a diagnostic tool. Otherwise it isn't scientific. They can't just carry out undefined 'repeat tests'. They have to define those tests and interpret them. The published research enables them to validate the tests.
  16. SOC

    SOC Moderator and Senior Member

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    It's my impression that our clinicians and researchers do talk to each other. Don't they get together at conferences and such? I suspect the problem is in funding. When funding is extremely limited, and ours certainly is, researchers can only focus on the very small area that is their personal specialty. We don't even have enough money for adequate basic research much less cross-over research. We also don't have the money to get replication work done, so clinicians don't have definite information to work with in all the different areas. Which pieces of the puzzle does a clinician bet on when they don't have replicated, double-blinded placebo-controlled studies? They have to do the best they can with the knowledge they have.
  17. Ember

    Ember Senior Member

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    It's also possible that the Stevens Protocol is a more inclusive regimen than you've assumed.
  18. SOC

    SOC Moderator and Senior Member

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    My confusion here may stem from my lack of expert knowledge about exercise testing, so someone correct me if I'm wrong....

    I think the anaerobic threshold (AT) and the ventilatory threshold (VT) are essentially different names for the same point in exercise. There are some subtle differences, but they are generally used interchangeably. It is the point where the respiratory exchange ratio (RER) =1. In other words, VCO2/VO2 =1. This is easily, even routinely, measured in exercise testing. That's one of the reasons we wear that blasted mask. There's nothing difficult about measuring it on the fly as far as I can see, so Chris Snell must be talking about something else.

    Blood lactate threshold (LT) is (I think) a more accurate way to find a person's AT. I can see how that might be difficult to measure on the fly. But Dr Snell is speaking specifically about the VT which, as I understand it, is defined as a measure of respiratory gases, not blood or other measures.

    So I don't yet understand what Dr Snell is saying about the difficulty of measuring VT on the fly and knowing when to stop.

    I do understand his concern that some patients may show abnormalities at VT, while others show abnormalities on peak measures. This should definitely be taken into consideration, especially when trying to tease out different underlying pathologies.

    All that said, if the work load at VT (VTWL or ATWL) is the measure that plummeted severely on second day testing, wouldn't it work as an objective measure for treatment studies? Stopping at (or just past) VT should still show the second day exercise capability crash, but would be significantly less risky for patients.

    What am I missing here? :confused:
  19. Bob

    Bob

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    SOC
    Yes, my understanding is that VT and AT are the same.
    And they indicate the point at which not enough Oxygen is consumed to produce energy, so we start using anaerobic energy, and so produce lactic acid. (So I suppose your description is correct re the respiratory exchange ratio, but I can't remember having seen described in that way.) (I've got a bad memory!)

    Yes, it would.

    Perhaps it boils down to Dr Snell believing that peak exercise tests are useful, based on past research, and their experience in a clinical setting. But that's a guess, and I don't know that answer. I don't know why VT can't be measured on the fly.

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