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Discussion in 'General ME/CFS Discussion' started by charles shepherd, Jul 10, 2015.

  1. charles shepherd

    charles shepherd Senior Member

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  2. charles shepherd

    charles shepherd Senior Member

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    Two comments so far - from Peter White et al and Tom Kindlon and myself:

    PD White, MD,1 DJ Clauw, MD,2 JWM van der Meer, MD,3 R Moss-Morris, PhD,4 RR Taylor, PhD,5
    1. Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University, London, UK 2. Department of Anesthesiology, Medicine and Psychiatry, University of Michigan
    Conflict of Interest: PDW, JWMvdM and RMM were principal investigators or co-investigators in some of the trials reviewed. PDW does consultancy work for the UK government and a re-insurance company.

    In their systematic review, Smith and colleagues concluded that “trials of … counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for …. harms is insufficient.”(1)

    While we support the general conclusion of benefit with these treatments, we suggest that some aspects of this review may be misinterpreted. Firstly, the most frequently tested behavioural intervention has been cognitive behaviour therapy (CBT), which aims to reduce symptoms and improve functioning, and it would be unusual to consider this as “counseling”, which has different objectives and content. One would not combine different types of medicines in a review; why do this with therapies? A review that combines counselling and CBT simply dilutes the efficacy of CBT, which has been amply demonstrated in several previous meta-analyses (2).

    Secondly, there is little evidence of harm caused by graded exercise therapy (GET); a Cochrane systematic review of eight trials of exercise therapy for chronic fatigue syndrome (CFS), published this year, concluded that “..no evidence suggests that exercise therapy may worsen outcomes.” (3) Suggesting evidence of harm by stating that “one trial reported significantly more serious adverse events ….and more nonserious adverse events … in the GET versus comparison groups,…” without mentioning that serious adverse events were independently judged to be unrelated to the intervention, and that the differences between non-serious adverse events was not statistically significant, is a potentially misleading representation of the evidence. Adding that “..in a trial of GET, 20% of patients declined to repeat exercise testing because of perceived harm of testing” encourages further misunderstanding by failing to mention that the exercise testing was not part of the therapy and that the proportion of patients in the control intervention who also declined exercise testing was 50% (4). (Incidentally the proportion declining testing in the GET arm was 44%, not 20%.4) There is a world of difference between the effects of maximum exercise testing and graded exercise therapy. It is important not to overemphasise the harms associated with an effective treatment when there are so few others available.

    Finally, the authors concluded that we need trials with analyses of patients meeting different case definitions; we agree and this has already happened. White and colleagues found no statistically significant differences in the efficacy of CBT and GET in sub-groups of those patients meeting Oxford criteria for CFS who also met either CDC defined CFS or myalgic encephalomyelitis (ME)(5).

    Note: Seven other CFS clinical scientists supported and approved this letter.

    References
    1. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a national Institutes of Health pathways to prevention workshop. Ann Intern Med 2015; 162: 841-50.
    2. Castell BD, Kazantzis N, Moss-Morris RE. Cognitive behavioral therapy and graded exercise for chronic fatigue syndrome: A meta-analysis Clin Psychol Sci Prac 2011; 18: 311–24.
    3. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD003200.
    4. Moss-Morris R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. J Health Psychol 2005; 10: 245–59.
    5. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet 2011;377:823-36.
    Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
    Posted on July 9, 2015

    Tom Kindlon1, Charles Shepherd2
    1. Irish ME/CFS Association, Ireland. 2. ME Association, United Kingdom

    Conflict of Interest:
    TK is Information Officer and a committee member of the Irish ME/CFS Association. All his work for the Association is unpaid.
    CS is medical adviser to a charity (the ME Association) that collects and publishes patient evidence relating to safety and efficacy of graded exercise therapy and pacing.

    We concur with Smith and colleagues that evidence regarding harms for therapies such as graded exercise therapy (GET) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is insufficient.(1,2)

    The focus in GET trials for ME/CFS has been on efficacy measures which do not provide good information on whether adverse events occurred.(2)

    A recently published systematic review included an assessment of the reporting of "treatment side effects" in 16 randomized controlled trials (RCTs).(3) Eleven were allocated the lowest mark with only one, the PACE Trial, awarded the top mark.(3,4)

    One RCT is generally seen as insufficient to make firm recommendations.

    Moreover, questions remain about the level of compliance with GET in the PACE Trial: the only reported measure of treatment adequacy was the number of appointments attended, not the type, intensity, or duration of activity/exercise performed each week. If participants dutifully complied with the exercise program one would not expect no improvement in fitness in the GET cohort as has recently been reported.(4)

    If participants do not take their medication in a trial, reliable information on safety will not be provided; similarly if participants do not adhere to an exercise regime, good information will not be obtained about the safety or otherwise of complying with the intervention.

    An earlier review of three trials of graded activity-oriented interventions for CFS found that following treatment participants had not actually increased their activity levels (objectively measured using actometers) compared to the controls.(5)

    Data from outside of RCTs can be useful to assess the safety or otherwise of interventions.(2)

    A clinical trial can represent a somewhat artificial environment and so outcomes may not correspond directly to those in routine practice.(2)

    One of us (TK) previously reviewed the data from eight ME/CFS patient surveys from four countries.(2) Fifty-one percent of survey respondents (range 28-82%, n=4338) reported that GET worsened their health.

    Such findings, along with the aforementioned poor reporting of harms in trials of GET for ME/CFS and the lack of evidence regarding adherence to the intervention in the trial with better harms reporting, mean we should not rush to accept any claims that GET has been found to be safe for ME/CFS.

    References

    1. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a national Institutes of Health pathways to prevention workshop. Ann Intern Med. 2015;162:841-50.

    2. Kindlon T. Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Bull IACFS ME.
    2011;19:59-111.

    3. Marques MM, De Gucht V, Gouveia MJ, Leal I, Maes S. Differential effects of behavioral interventions with a graded physical activity component in patients suffering from Chronic Fatigue (Syndrome): An updated systematic review and meta-analysis. Clin Psychol Rev.
    2015;40:123-137.

    4. Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. Lancet Psychiatry.
    2015;2:141–152.

    5. Kindlon T. Harms of cognitive behaviour therapy designed to increase activity levels in chronic fatigue syndrome: questions remain. Psychother Psychosom. 2011;80:110-1.
     
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  3. Scarecrow

    Scarecrow Revolting Peasant

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    I thought White et al. always denied that PACE studied patients with ME. Wasn't the international criteria they used Empirical? Call me confused.
     
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  4. Dolphin

    Dolphin Senior Member

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    No, they denied studying "CFS/ME" patients (in relation to a question on the Canadian criteria I think). Some activists jumped on this quote to say they were saying they never studied ME patients but if one looks at the Lancet 2011 paper, they have figures on the subgroup satisfying ME criteria so I never felt one should say they said they weren't studying ME patients.

    No, not the empirical criteria (which uses odd thresholds for the SF-36 and MFI).
    They asked about the CDC symptoms in this way:
    while the Fukuda asks about symptoms over the last six months so not a perfect way of using the Fukuda criteria.
     
  5. Scarecrow

    Scarecrow Revolting Peasant

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    Thank you for the clarification. I see that they used the London criteria for ME: 329 of the 641 participants met those criteria.
     
    Last edited: Jul 10, 2015
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  6. jimells

    jimells Senior Member

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    Thank you Tom and Charles for your reply to White et al. It definitely helps my morale to see dedicated folks such as yourselves calling out the psychobabbler's nonsense.
     
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  7. Dolphin

    Dolphin Senior Member

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    https://listserv.nodak.edu/cgi-bin/...P=R2764&I=-3&d=No Match;Match;Matches&m=21522
     
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  8. Scarecrow

    Scarecrow Revolting Peasant

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    Strangely enough, I've been pondering something similar, based on the figures here:

    http://forums.phoenixrising.me/index.php?threads/help-me-find-some-facts.38626/#post-616771

    If a minimum prevalence of 0.10% for CCC and 0.19% for 1994 CDC is accurate, it did make me wonder what the figure for Oxford might be. Very interesting. Thank you.
     
    Last edited: Jul 10, 2015
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  9. Tom Kindlon

    Tom Kindlon Senior Member

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    Which part of the comment by Charles Shepherd and me is incorrect?
     
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  10. Valentijn

    Valentijn Senior Member

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    @Dr Speedy - Published comments have to be quite short and with only a few references. This means that it's impossible to address more than one or two simple points. But you can submit a comment as well if you like. Just keep in mind that it has to be 100% factual/unemotional and every statement must have a reference backing it up.
     
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  11. charles shepherd

    charles shepherd Senior Member

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    Yes, why not have a go yourself 'Dr Speedy' - whoever you are!
     
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  12. leela

    leela Slow But Hopeful

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    As a big fan of the Niceguidelines blog, I vote for @Dr Speedy to have a go as well!
     
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  13. Mark

    Mark Former CEO

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    Seriously?! o_O

    You're saying that this particular comment, which Charles Shepherd and Tom Kindlon managed to get published in the Annals of Internal Medicine, is "incorrect", not because there's anything wrong with what they said, but because they didn't happen to mention the MEA's own survey report on GET and because they didn't "mention how harmful graded exercise therapy is" - even though they did in fact reference Tom's paper on the evidence of harms associated with GET, and noted that "Fifty-one percent of survey respondents...reported that GET worsened their health".

    That's a creative use of the word "incorrect", especially since you say that in reference to a comment by the two people who have produced probably the best two papers in existence regarding the evidence of harms of GET. If you went to a lecture on black holes by Stephen Hawking, would you stand up to tell him he was wrong because he failed to cite his own paper on black hole radiation in his presentation?

    I agree that it would be a good exercise for you to try to get a post accepted by Annals on this subject. Perhaps it would be worth checking the guidelines for comments first though, to see whether the MEA's GET report actually qualifies as a paper that can be referenced in a comment, or whether one can only reference papers that were published in a recognised journal - conceivably that's the reason they referenced Tom's paper on the harms of GET and not the MEA survey.
     
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  14. Tom Kindlon

    Tom Kindlon Senior Member

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    Thanks Mark.
    One could likely be able to cite one unpublished survey as long as one gives a web link and ideally put "date accessed". The main reason we didn't mention it was because we ran out of references (one can only have five for comments that are considered for the print edition). One of the surveys covered in my paper is the ME Association one (published in 2010).

    Hopefully other people comment. A comment that has to use five references or fewer and be 400 words or fewer generally won't be able to make all possible points.
     
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  15. Bob

    Bob

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    More excellent rebuttals to White et al. have been published in the comments section... Unfortunately it's not possible to provide a direct link to the comments, so you have to click on the 'comments' section and scroll down...

    First, do no harm: graded exercise therapy and myalgic encephalomyelitis/ chronic fatigue syndrome
    Lily Chu, MD, MSHS (1), Lucinda Bateman, MD (2), Todd Davenport, PT, DPT, OCS (3), Eleanor Stein, MD, FRCP(C) (4), Staci Stevens, MA (5)

    Diagnostic sub-group analyses in the PACE trial may be unreliable
    Alem Matthees

    Response to White et al.
    SBM Kirby
     
    Last edited: Jul 14, 2015
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  16. charles shepherd

    charles shepherd Senior Member

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    ~New response from Lily Chu et al:


    First, do no harm: graded exercise therapy and myalgic encephalomyelitis/ chronic fatigue syndrome
    Posted on July 11, 2015

    Lily Chu, MD, MSHS (1), Lucinda Bateman, MD (2), Todd Davenport, PT, DPT, OCS (3), Eleanor Stein, MD, FRCP(C) (4), Staci Stevens, MA (5)
    (1) Independent Consultant, Burlingame, CA, USA; (2) Bateman Horne Center, Salt Lake City, UT, USA; (3) Department of Physical Therapy, Thomas J. Long School of Pharmacy and Health Sciences,
    Conflict of Interest: All authors are involved in ME/CFS research. LB, ES, TD, and SS are involved in the clinical care of ME/CFS patients. LB, SS, and TD were members of the International Association for Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis Primer Writing Committee. No funding was received in support of this work.
    We concur with Smith et al. (1) that graded exercise therapy (GET) can cause harm in some patients with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, we believe the benefits from GET would have been reduced and the harms assessed as even greater if the following points had been considered.

    (1) The authors recognized that the non-specific nature of the Oxford criteria might recruit subjects “with other fatiguing illnesses or illnesses that resolve spontaneously” (1) yet they analyzed studies using Oxford criteria with those using Fukuda criteria together. This is similar to lumping people who have congestive heart failure, chronic obstructive pulmonary disease, and pneumonia together because all three diagnoses share shortness of breath as a symptom. It would have been more informative had they assessed trials using Fukuda and Oxford separately and then compared those results to the combined results. Darbishire et al. found that the factor most predictive of a poor outcome when a GET or cognitive behavioral therapy (CBT) regimen was applied to a group of subjects suffering chronic fatigue was fitting Fukuda criteria (2).

    (2) Nunez et. al. is classified in Appendix Table 1 as not reporting any harms (1). However, this study found not just that the combined GET/ CBT intervention had no benefit but that these treatments caused a significant decline in physical function and increase in bodily pain scores as measured by the SF-36 at 12 months.

    (3) Smith et al. appropriately suggest that future research should strive to include the input of patients and advocates. Because their review was based on clinical trials, however, it did not include clinician and patient experiences outside of trials. On average, 50% of thousands of patients internationally have reported worsened health due to treatments involving exercise (3). Clinicians specializing in ME/CFS do not recommend GET and instead advise patients to balance their active periods with rest breaks (4). This cautious attitude is supported by studies (5) showing that patients with ME/CFS do not respond to or recover from physical activity in the same way as healthy people or people with other medical conditions.

    As with any medical condition, clinicians need to tailor treatments to the individual patient. If patients describe exacerbation of symptoms and no improvement with exercise-related therapies, rather than attributing those reports to low motivation, distorted thinking, or exaggeration, clinicians should consider that there is a problem and stop the treatment.

    (1) Smith MB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162:841-850. doi:10.7326/M15-0114

    (2) Darbishire L, Seed P, Risdale L. Predictors of outcome following treatment for chronic fatigue. Br J Psychiatry. 2005; 186 (4) 350-351.


    (3) Kindlon T. Reporting of harms associated with graded exercise therapy and cognitive behavioral therapy in myalgic encephalomyelitis/ chronic fatigue syndrome [Internet]. Chicago, Illinois: International Association for Chronic Fatigue Syndrome/ Myalgic Encepahlomyelitis; 2011 October [cited 2015 July 8]. Available from: http://iacfsme.org/PDFS/Reporting-of-Harms-Associated-with-GET-and-CBT-in.aspx

    (4) International Association for Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis Primer Writing Committee. ME/CFS: a primer for clinical practitioners [Internet]. Chicago, IL: International Association for Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis; 2014 July [cited 2015 July 8]. Available from: http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf

    (5) Institute of Medicine: Committee on the Diagnostic Criteria for myalgic encephalomyelitis/ chronic fatigue syndrome. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness [Internet]. Washington, DC: National Academies Press; 2015 Feb [cited 2015 July 8]. Available from: http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx
     
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  17. Kati

    Kati Patient in training

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    Great response. Thankful.
     
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  18. SOC

    SOC

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    This is beyond excellent. Clear, calm, and absolutely damning. Even a major idiot reading this would have a hard time missing the point. That's not easy to achieve in less than 400 words.
     
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  19. Valentijn

    Valentijn Senior Member

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    It's always cute when the psychobabblers trot out the line about how there's "controversy" regarding ME research, and make it sound like it's crazy patients and fringe quacks who are opposed to denial-based CBT and GET as treatments in this disease.

    But given the quality responses written by a long list of prominent names who are disagreeing with them outright via these comments (and elsewhere), I think it's now pretty clear that it's the psychobabblers who are part of the lunatic fringe.
     
    Last edited: Jul 15, 2015
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  20. leela

    leela Slow But Hopeful

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    Amen, and so well said!
     
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