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1946 Birth Cohort. Etiology of CFS: Testing Popular Hypotheses (2008)

Discussion in 'Latest ME/CFS Research' started by oceanblue, Oct 15, 2011.

  1. oceanblue

    oceanblue Senior Member

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    One of two papers on sef-reported CFS in the 1946 Birth Cohort

    Etiology of Chronic Fatigue Syndrome: Testing Popular Hypotheses Using a National Birth Cohort Study
    Harvey, Wadsworth, Wessely & Hotopf 2008


    It concludes:
    but not for the first time these conclusions are not very robust.
     
  2. oceanblue

    oceanblue Senior Member

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    Commentary

    Method
    This survery is based on a random sample of 5,362 single births in one week of March, 1946. In 1999, at 53 years, the 3,035 remaining participants were asked if they had ever had a diagnosis of CFS/ME with 2,983 giving an answer. This makes it about 1/3 the size of the other 2 cohorts, which might explain the unreliable findings.

    CFS prevalence
    There were only 37 cases of CFS reported, and of these only 22 (65%) reported the diagnosis had been made by a doctor. Hospital records (primary care records were not checked) ruled out 3 of the 22 cases due to exlusionary medical conditions leaving 34 cases in total, giving a lifetime prevalence of 1.2% (ie people ever having CFS, no data was given for those with a current diagnosis). Age of onset was between 41 and 53 years ie the first case started in 1987, which ties in with the time CFS/ME was first being recognised. No doubt many particpants had CFS before this time but didn't know that's what it was. The same pattern of cases not begining until the 80s in seen in the other 2 birth cohorts too.

    Ruling out hypotheses
    This paper aimed to test a number of hypotheses, most of which were ruled out, including:
    • Atopy (allergy)
    • Specific childhood symptoms (persistent abdominal pain had been shown to be a risk factor for unexplained hospitalisations and the authors hoped it would be linked to CFS too; it wasn't)
    • Childhood Chronic Illness (age 0-15). This contradicts the finding of the much larger 1970 cohort. More to the point, this 1946 study lost a lot of those with childhood chronic illness making it an unrepresentative sample and so these findings are pretty meaningless:
    Frequent exercise a risk factor for CFS... ....or is it?
    The biggest finding of this study was that exercising frequently is a significant risk factor for CFS. A later and large study contradicts this finding but here are the results (full table):

    Extreme Energy levels reported by teacher (age 13) significant, p=0.006
    Sports more than weekly (age 31) NOT significant
    Self-rated as very fit (age 31) NOT significant
    Very active at age 36 NOT significant
    Sport weekly or more at 41 significant, p=0.006
    Vigorous activity at least weekly at 31 and 43 significant, p=0.01, OR=10.8 (2.7-43.8)

    Let's just look at that last finding - an odds ratio of 10.8? Woohoo! This must be the answer. But what the authors don't mention is that this figure is based on under half (43%) of all participants ie the data is missing for most of the participants (and the finding is based on just 4 energetic people with self-reported CFS), which makes it rather meaningless. This leaves me wondering if the reviewers of this paper were lazy, useless or biased, but this slightly harsh view may be coloured by Wales going out of the Rugby World Cup today ("it was never a red card, ref!").

    Other than that, it's a mixed bag of significant and non-signigicant findings. The extreme energy at age 13 only led to 5 excess cases and would only explain 17% of all CFS cases, suggesting it's a minor factor.

    More to the point, these findings were not replicated in the much bigger 1958 cohort, which found that high levels of activity were not a risk factor for CFS at any age.

    Main conclusions
    The findings on childhood illness are, according to the authors, questionable because some children with ill health were lost from the adult survey. The findings on exercise were mixed, based on small numbers and were not replicated in the larger 1958 cohort. It doesn't amount to much.
     
  3. justy

    justy Senior Member

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    Thanks Ocean blue for posting this ive been following it with interest.

    Why oh why didnt they just put him in the sin bin for 10 minutes - arrgggghhh!
    Wales played like heroes.
     
  4. Enid

    Enid Senior Member

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    Played far better than we did - off and on the field !
     
  5. oceanblue

    oceanblue Senior Member

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    Thanks, Justy and Enid. Yup, 10 minutes in the bin would have been fair, but I still think we should have sneaked a win even one man down; oh, those missed kicks... I don't fancy France's chances in the final next week.

    There is more commentary to come (on the paper, not the game) but I'm a tad tired at the moment.
     
  6. Esther12

    Esther12 Senior Member

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    I wonder if they've thought about the harm caused by earlier claims of CFS being the result of deconditioning on the psychosocial setting faced by patients?

    When I was still feeling exhausted after glandular fever I was told by my GP that it was deconditioning, and that, while it will feel like a lot of work, it's important that I push through to maintain a normal level of activity. At the time, my fatigue was taken as evidence of a lack of motivation, now it's being seen as evidence of a dysfunctional personality which pushes too hard. I really hate the psychosocial quacks that surround CFS.
     
  7. oceanblue

    oceanblue Senior Member

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    I've now updated my post #2 above.

    Esther12: yes, it does sometimes seem that psychosocial proponents start from the position that the patients cause their own problems and then come up with different -even contradictory - arguments to suit different situations. However, the findings of this paper that patients are pushing on regardless are - like the rest of the findings - not very robust:

    Evidence of prodromal fatigue
    Interestingly, this study provides some evidence of rising fatigue levels before the onset of CFS. The psychological questionnaires used at age 36 and 43 included questions related to energy levels and fatigue and the answers to these questionnaires suggested prodromal fatigue:
    Given all the problems with inaccuracy of diagnosis I'm not sure how much I trust this finding but it does tally with comments I've read on this forum from quite a few people.

    Evidence of continuing to exercise despite fatigue?
    The authors then noted that this group of 43-year olds who would go on to report CFS and were - as a group - showing significantly raised levels of fatigue were continuing to exercise at a high level:
    This is the basis for the authors claim that
    The problem with this conclusion is that it depends on those exercise levels findings (shown above) that were not replicated in the larger 1958 cohort. So maybe the fatigued pre-patients weren't really exercising this hard. Furthermore, Figure 1, which summarises this data, itself looks odd. At age 31, around 14% of non-CFS particpants were exercising at least weekly; 5 years later at age 36 this had mysteriously more than doubled to around 37% exercising weekly - so can we trust the data? Just as odd, the data shows that at age 53, the CFS cases were exercising weekly at the same rate as healthy controls (and I don't believe they were all doing GET in 1999...). And if the exercise data is dodgy then so too are the conclusions about over-exercising.

    The stuff about it being down to personality types not behaviour was plucked out of the air, and some of the studies that they cited re physical activity found no correlation with personality types.
     
  8. Esther12

    Esther12 Senior Member

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    Darn you OB - you've tamed my righteous recriminations. Nothing's more satisfying than a bit of indignation, and you've now made it quite clear that these findings have little to no bearing on my own experiences.

    Oh well. I still hate them, so at least I have that to enjoy.
     
  9. Enid

    Enid Senior Member

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    Apart from your marvellous analysis oceanblue - would one trust any of this lot - they are psychiatrists looking for psychiatric conclusions only - not real medicine.
     
  10. oceanblue

    oceanblue Senior Member

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    Esther12
    Keep on righteously recriminating - the authors made those very claims, I just suggested they were rather suspect (the claims, not the authors).

    Enid
    Thanks, and i can tell ou're going to love my forthcoming thread on a paper from the same authors looking at prior psychiatric disorder as a risk factor for CFS.
     
  11. eric_s

    eric_s Senior Member

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    I think we can be happy about this study. It seems to directly contradict what some of the same people said earlier. So it shows how credible their theories are. Also i like this conclusion better.

    22 subjects with a diagnosis made by a doctor. And when it comes to ME/CFS i don't especially trust UK doctors... Can you draw a valid conclusion from such a sample?
     
  12. oceanblue

    oceanblue Senior Member

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    I don't know how such speculation makes it into the abstract, especially as the authors offered no good evidence that personality factors were linked to the claimed excessive exercising. More to the point, the authors failed to point out evidence against their personality hypothesis: two months before submitting this paper, the same authors submitted another paper analysing the same cohort that concluded
     
    Dolphin likes this.
  13. Dolphin

    Dolphin Senior Member

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    Thanks for doing this, oceanblue. I read the studies at different times while it is interesting to consider them all in and around the same period to see how findings fit together.

    Is there any reason to believe the missing data would bias the findings one way or another rather than simply reduce the power? If it is simply reducing the power, if one looks at table 2 http://www.psychosomaticmedicine.org/content/70/4/488/T2.expansion.html , it doesn't look like it would make much difference.
     
  14. Esther12

    Esther12 Senior Member

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    lol. That's the sort of thing that makes me love those cheeky chaps.
     
  15. Dolphin

    Dolphin Senior Member

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    Could that be due to different questions being asked at 31 and 36 years? It looks to me that the list at 36 years is broader, or else why say what give the full list for the 31 years group, which comes earlier in the paragraph:

    To me, the findings of increased activity in the group that go on to develop CFS seem more trustworthy because of the lower BMIs at 36 and 43 years http://www.psychosomaticmedicine.org/content/70/4/488/T5.expansion.html.

    Interesting. (if you recorded the dodgy refs, feel free to post them).

    -------
    I imagine that doctors spend most of their lives incl. during medical school feel fatigued to some extent. I would think they might not like it seen as evidence of dysfunctional behaviour/personality type to exercise when fatigued, or they and lots of others could never exercise. Of course, it may be the case that people shouldn't; however, at this stage, people in society certainly don't get a clear message one shouldn't.
     
  16. oceanblue

    oceanblue Senior Member

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    If we're talking about those with childhood illness being lost from the study then - and we are looking at childhood illness as a risk factor - then yes, I think it could well bias the findings: those missing people could have gone on to develop CFS (if there really is a link between chronic illness and CFS) and the 'no risk' finding could have been changed to a finding of significant risk.

    Is that what you were talking about? I'm not sure I've definitely understood your point.

    In more general terms, there are presumably a lot of missed CFS cases in the study (as shown by no cases before the mid-80s in all 3 cohorts). I think these missed cases may well be missing at random and so would simply have the effect of reducing the power. Consequently, findings that appear marginally significant/non-significant could in fact be significant, eg a marginal finding of p=0.06 might change to a more convincing one of p=0.01 if the missing data could somehow be recovered.
     
  17. Dolphin

    Dolphin Senior Member

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    In fact, 0 of the subsequent CFS cases had it http://www.psychosomaticmedicine.org/content/70/4/488/T2.expansion.html (although it was relatively rare - only around 2% of non-CFS group had it also).
     
  18. Dolphin

    Dolphin Senior Member

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    It's unclear to me what you are saying in the first part - you seem to be saying a loss of power but actually what I was asking about was bias. What you say in your last paragraph is what I mean by loss of power.

    But I'm trying to get at is if there is a loss of power, but no biasing effect, the OR would still be in the same direction. If one looks at the data for childhood illness we have in Table 2, it isn't consistently showing that Childhood Illness Measures increase the risk. And the magnitude for the specific item "any chronic illness age 0-15" with an odds ratio of 1.20 isn't particularly interesting, even if it did become statistically significant with a bigger sample size.

    ----
    Here is info on where people were generally lost:
    If we are assuming people don't have CFS, and looking at pre-morbid factors, it is not clear to me why of people who have a chronic illness as a child, the ones who are likely to go on to develop CFS are less likely to return the form. But then I don't know what is the supposed mechanism of childhood illness subsequently causing CFS.

    There could be situations (outside the CFS) where I can see how bias could affect who of a particular group does and does not return a questionnaire.
     
  19. oceanblue

    oceanblue Senior Member

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    Ah, good point, I now see what you mean. The net result of loss of children with chronic illness should be on power, not on the size of the effect, and you're right, OR 1.2 is uninteresting whether statistically significant or not.

    Nonetheless, this 1946 cohort was only 1/3 the size of the 1970 cohort that did find chronic childhood illness was a risk factor - and crudely combining the data from the 2 cohorts still gives a sizeable and significant effect for childhood chronic illness.
     

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