Lipkin's Monster ME/CFS Study: Microbes, Immunity & Big Data
The Microbe Discovery Project outlines an ambitious new study by top researchers that has collected patient samples, but needs desperately funds to complete the work.
Discuss the article on the Forums.

Patients diagnosed with ME/CFS also fit systemic exertion intolerance disease criteria

Discussion in 'Latest ME/CFS Research' started by Dolphin, Mar 16, 2017.

  1. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
     
  2. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
    I didn't understand what they had done when I read the abstract initially. It is interesting that so many people can be missed.

    I know myself that I only got some symptoms when I became more severely affected. And some of the ones that I did have initially were not that prominent (after I gave up sports).
     
    Last edited: Mar 16, 2017
    mango, Webdog, BurnA and 3 others like this.
  3. hixxy

    hixxy Senior Member

    Messages:
    1,019
    Likes:
    875
    Australia
  4. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
     
    Webdog and Valentijn like this.
  5. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
    It is interesting that the criteria can be operationalised in different ways.

    If use the 2/2 threshold, the figures drop to 56% for the Canadian clinical criteria and 45% for the international consensus criteria. They are 72% when Fukuda requires 2/2 for fatigue, the same percentage as SEID. (Table 2)
     
    Last edited: Mar 16, 2017
    Valentijn likes this.
  6. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
    I had missed that 2/2 not required for Orthostatic Intolerance in SEID as did Leonard Jason.
     
    Webdog and Valentijn like this.
  7. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
     
    Keela Too likes this.
  8. Dolphin

    Dolphin Senior Member

    Messages:
    9,533
    Likes:
    22,943
     
    Webdog and Valentijn like this.
  9. joshualevy

    joshualevy Senior Member

    Messages:
    101
    Likes:
    130
    I think this is another in a long line of studies which show that all the commonly used case definitions of ME/CFS or whatever, are pretty much the same. My belief has always been that this CCC vs. ICC vs. Fukuda vs. Oxford vs. SEID vs. whatever was just an excuse to ignore studies that came to results that people didn't like. At a minimum, this study provides evidence that CCC, ICC, and Fukuda are pretty much the same, and (for example) research done with Fukuda is not any worse than research done with ICC or CCC. Another way to view it, is that to understand ME/CFS, we should look at all the studies done with all the case definitions,and not exclude those done with some of these definitions.
     
  10. Sean

    Sean Senior Member

    Messages:
    2,691
    Likes:
    13,360
    CCC vs. ICC vs. Fukuda vs. Oxford vs. SEID vs. whatever...

    At a minimum, this study provides evidence that CCC, ICC, and Fukuda are pretty much the same...


    Drop Oxford from that list, because it almost certainly picks up too many false positives, and I agree with you. The diagnostic differences between the rest of them probably isn't enough to give one preference over the others. Mostly just comes down to which is the most practical to use in the clinic.
     
    valentinelynx, Diwi9, Jan and 3 others like this.
  11. A.B.

    A.B. Senior Member

    Messages:
    2,867
    Likes:
    15,669
    Agrees with my personal experience. My illness did start suddenly, but at first it was so mild that I didn't meet any case definitions. It was confusing. I could feel that something was wrong and that I was often exhausted from activity that had not been an issue before, and it had negative impact on my life but I couldn't put my finger on what the problem actually was. Only much later, when the illness had become more severe, I read about ME/CFS and realised that what I had been experiencing was PEM. And I may have made myself more ill by trying to push through the exhaustion and maintain normal activity levels.

    It is much harder for patients with gradual onset to be correctly diagnosed because it may take years before they fully meet case definitions. In the meantime they're likely to be given some other diagnosis such as depression, and when more symptoms appear later, these are just seen as somatisation of depression, or comorbid IBS or whatever.

    PS: an experienced doctor asking the right questions could have correctly recognised PEM even very early on because there clearly was a rest -> feel better -> increase activity -> crash cycle repeating over and over again.
     
    Last edited: Mar 17, 2017 at 3:08 AM
    Laelia, Diwi9, Keela Too and 7 others like this.
  12. Valentijn

    Valentijn Activity Level: 3

    Messages:
    12,427
    Likes:
    32,804
    My problem with Fukuda is that it provides an opportunity for the unscrupulous researchers to select a cohort which primarily features some symptoms but not others. Eg, they could effectively exclude patients with PEM, and still call it Fukuda based on some of the less specific symptoms. It also makes it difficult to compare studies, even if they all use Fukuda, when Fukuda can mean so many different things.

    A similar problem could occur in a clinical setting, though wouldn't have the same impact on how the disease is treated. But it would still result in the absurd marathon-running, pole-dancing, and world record paddle-boarding cure stories, and also doesn't help the people being mislabeled as having a disease where they lack the core symptoms. Hence I think the SEID criteria are far superior for clinical diagnosis.
     
  13. joshualevy

    joshualevy Senior Member

    Messages:
    101
    Likes:
    130
    Do you have any evidence that Oxford picks up too many false positives?

    As a counter example, the PACE study got the same result for Fukuda and Oxford patients. Now even if you hate PACE, the fact that they got the same answers for Fududa and Oxford suggests that these two definitions are not that different.

    Are you familiar with any study that got statistically significant different results from Oxford patients as compared to CCC or ICC or Fukuda or SEID patients? That's the data you need. I only know about the one study, and I agree that one study does not settle a question. But one study beats zero studies.
     
  14. Valentijn

    Valentijn Activity Level: 3

    Messages:
    12,427
    Likes:
    32,804
    You mean basically null? Yes, it was impressive that CBT and GET don't work for anyone, even if they don't have PEM :thumbsup:
     
  15. Sean

    Sean Senior Member

    Messages:
    2,691
    Likes:
    13,360
    PACE modified their Fukuda criteria, in the direction of Oxford, which reduces the comparison value both within the study, and also to other studies that used a more standard version of Fukuda.

    When the most recent AHRQ review removed Oxford based studies from their list, the treatment effect for CBT/GET disappeared, which implies that Oxford is selecting a significantly different patient group.

    'False positives' may not be the best term. But there is clearly an issue with Oxford.
     
  16. joshualevy

    joshualevy Senior Member

    Messages:
    101
    Likes:
    130


    I'm not sure where you are getting your information, but it's wrong. I just looked at the PACE trial's main paper, and also the Recovery publication. Both just say that the Oxford criteria was used. No mention of modifications. For the Fukuda definition, the modification was to tighten it (not loosen it, as you seem to think). In the real Fukuda definition, various symptoms must be seen in a six month period, but they required those symptoms to be seen in a one week period, so that significantly tightened the definition.




    Wrong again. When the data based on Oxford is removed, in some cases the numbers remaining are too small to come to a conclusion (and the AHRQ reports that). However, in no cases did the Oxford based data come to a different conclusion than the non-Oxford based data. This is clearly shown on Table 7 of the Appendix (pages 12 and 13). Six different outcomes are compared (non-Oxford in column 5, Oxford in column 6). In each case, the results for non-Oxford match the results in Oxford. That's not likely to happen by accident, and is very strong evidence that non-Oxford and Oxford criteria are selecting a medically similar group of people.

    The AHRQ team said as much in their conclusion: "Our sensitivity analysis would result in a downgrading of our strength of evidence on several outcomes which can be attributed to the decrease in power, dominance of one large trial, or lack of trials using criteria other than the Oxford (Sharpe, 1991) case definition for inclusion."

    Note: "downgrading of our strength", but not change any of the results, and no differences between the results.

     
  17. trishrhymes

    trishrhymes trishrhymes.wordpress.com

    Messages:
    991
    Likes:
    6,685
    Dorset
    Since PACE was a null trial for recovery, a slight effect on subjective measures only for 'improvement', and a null trial at long term follow up, the stuff about which Fukuda definition may have been used for subgrouping seems to me irrelevant.

    For me, the important finding of both the PACE and FINE trials is that CBT and GET have no significant positive long term effect on anyone with any sort of chronic fatigue condition, whatever definition is used.

    Thus by broadening the definition to six months fatigue, the researchers inadvertently disproved the psychosocial theory for all fatigue related conditions.

    Ha ha ha!

    Now all we need to do is find a way to get that message across to doctors and politicians etc. That's the hard part.
     
  18. Valentijn

    Valentijn Activity Level: 3

    Messages:
    12,427
    Likes:
    32,804
    That's not tightening the criteria ... that's relaxing it. One week of symptoms is much more common and normal than 6 months of symptoms.

    When the Oxford data is removed, the effect of CBT and GET become insignificant. It doesn't matter if GET or CBT still look marginally better in Fukuda studies, if the math says it's not statistically significant.
     
  19. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,077
    Likes:
    9,186
    South Australia
    If you need very large numbers to prove an effect is statistically significant, it is because the effect is inherently weak.

    Efficacy should not require large sample sizes - even a 15/15 treatment/control trial is often sufficient to demonstrate efficacy. Larger trials are needed to demonstrate such treatments are safe because the incidence of side effects tends to be rarer (in drug trials for example), so the effect size is of course smaller and harder to measure without larger trials. The other use of larger trials (and replications) is to see if the treatment is generalisable over different diagnostic or entry criteria.

    The overall conclusion is that the effect is weak, not generalisable to stricter diagnostic criteria, the effect is short term only (disappears at 2+ year followups) and the effect is only found on subjective, but not objective measures of functioning. The latter observation is explained by the fact that the treatment (both CBT and this type of GET) is mediated only through cognitive factors, by that I mean how we think about our symptoms and report them to our doctor (or other people) or on questionnaires is changed, but not much else.
     
    Last edited: Mar 20, 2017 at 7:50 AM
  20. joshualevy

    joshualevy Senior Member

    Messages:
    101
    Likes:
    130
    The one week vs. six months is not duration of symptoms! It is window during which symptoms were reported. So PACE's use of Fukuda required 4 symptoms during the same week, while normal Fukuda allowed 4 symptoms spread out over 6 months. Clearly the PACE definition is a much more serious disease. Here is the quote from the PACE Recover paper:
    Nothing was said about the duration of symptoms. I'm sorry you misunderstood the paper in this way, but it is clear that the PACE team used a tightened version of Fukuda, not a loosened version.
     

See more popular forum discussions.

Share This Page