ME är inte “trötthet”, del 3

Laura Hillenbrand, citat

“This illness is to fatigue what a nuclear bomb is to a match. It’s an absurd mischaracterization” ~ Laura Hillenbrand

Detta är mitt tredje inlägg med anledning av den desinformation kring “kroniskt trötthetssyndrom” som spriddes av media förra veckan. Läs gärna även de två tidigare inläggen: ME är inte “trötthet”: Att försöka gömma en atombomb i en tändsticksask och ME är inte “trötthet”, del 2.

Skribenten Miriam E Tucker skrev för inte så länge sedan en fenomenal artikel som publicerades i Medscape: “Chronic Fatigue Syndrome: Wrong Name, Real Illness”. I sin senaste artikel fokuserar hon på de vilseledande påståenden som låg till grund för förra veckans “nyhets”rapporteringar i svensk media, och lyfter fram de vetenskapliga fakta som motsäger dem. Tucker citerar bl a flera av de världsledande experterna i ämnet. Utdrag:

Andreas M. Kogelnik, MD, PhD, founder and director of the Open Medicine Institute, told Medscape Medical News, “While physical deconditioning is a factor in ME/CFS patients, time and again we’ve seen clear evidence in practical community settings that CBT and GET can be extremely detrimental to a patient’s well-being and treatment course. The PACE trial did little to address the heterogeneity of the ME/CFS population, nor did it account well for severity of illness and fragility of many of these patients. CBT and GET need to be used very cautiously.” [...]

Leonard Jason, PhD, professor of psychology and director of the Center for Community Research at DePaul University in Chicago, Illinois, told Medscape Medical News, “despite the application of a few case definitions, it’s still possible that the sample included individuals who have chronic fatigue due to psychiatric reasons. Overall, I think that the sample would need to be more well-characterized in order to draw any conclusions about CFS or ME from this mediation model.”

Dr Jason, whose article on adaptive pacing in ME/CFS was among those cited in the current study ( J Human Behav Soc Environ. 2000;3:59-77), added, “The differences found might be due to response biases, the therapies causing people to answer questions about their health differently. However, a more generous interpretation might be that small improvements were obtained for some individuals. But CFS is a very heterogeneous condition, and just because some therapies can help some people a little doesn’t mean they’re suitable for all or should be seen as sufficient or curative therapies.”

Kenneth J. Friedman, PhD, a coauthor of an ME/CFS “primer” for clinicians and a former associate professor of pharmacology and physiology, New Jersey Medical School, Newark, pointed out another problem that the PACE trial shares with nearly every study done on ME/CFS: All have been conducted on ambulatory patients, leaving out the most severely affected, who are too sick to participate in studies.

“The extent to which the ambulatory population represents the spectrum of CFS patients is really not known,” he told Medscape Medical News. “If you’re lying in bed and you can’t move your head and you have to speak in whispers, GET therapy is not going to help you, and were you to attempt it, it would most likely kill you.

With regard to the PACE trial, Dr Friedman said, “It does not represent all CFS patients…. Because CFS is so variable, the management must be individualized. Any mandate that this is what you do for all patients, I would be leery of and would oppose. I think that really is the take-home message.”

Läs artikeln i sin helhet här: Adressing Fear of Exercise Cuts Chronic Fatigue… Perhaps (kräver inloggning, är kostnadsfritt).

Även Dr Byron Hyde har skrivit en kommentar med anledning av artikeln i The Lancet:

Regarding the Lancet paper, you have to understand who these people are.
It is my understanding that they are primarily in-hospital or in-University psychiatrists, physicians and allied specialists, who to the best of my knowledge have opinions, which will get them or their departments national grants. To the best of my knowledge they toe the financial line for political rather than medical grounds, which is very smart if you wish funding.

Their views to my opinion are dangerous in so much as the mere diagnosis of CFS or M.E. in the UK is sufficient to get patients hospitalized in psychiatric hospitals and the keys thrown away. Unfortunately I have seen this among UK patients who I have examined, tested or had tested and even brought to Canada for intensive testing. Among these UK patients, one was a lad with an MA in chemistry, who presently is in a psychiatric hospital; none of my confirmed physical diagnoses were treated. They simply gave him antipsychotics and locked him up.

As a physician, it is important to physically examine in a knowledgeable fashion, both with a hands on classical examination (and re-examination) along with a technical examination of every major system and organ. This does not mean a few routine blood and urine tests. It is totally important to take a good history, to listen to the patient: not with this 5-10 minute history, examination pill and out the door or into a psychiatry diagnosis because that is convenient.

To be clear about this, prior to the advent of widely available MRI brain examination availability from 1984 onwards, many if not the majority of female patients with Multiple Sclerosis were diagnosed as hysteria or psychiatric illness. Less so among men, and more so among younger females, younger than 30.

You will recall that Sharpe was amongst the original writers of the failed Oxford Definition of CFS, which has never been used, but was concocted in the hope of obtaining major financial grants from NIH in Bethesda. (I believe they didn’t receive any grants.) White is also a psychiatrist and I don’t know the occupations of the others but I assume they are all either psychiatrists or allied in some way to that curious profession, or in for the grants. This is not a criticism of psychiatrists, they are a needed and useful profession, but psychiatrists must not forget, that they are first and above all, physicians and are not a waste basket for non-psychiatric physicians who do not wish to take the time to properly examine chronically disabled physically ill patients. So once again we have PhDs and MDs who do not examine patients physically and technologically and are working on the basis of a theory. Theory is simply not good enough when you are dealing with the lives of patients. It is my understanding that real M.E. and CFS patients were excluded in the PACE trial, and those who got into the trial by accident and then became ill were then excluded.

Their magical theory of medicine was fine for the period prior to 1800 when anything and everything goes in medicine was acceptable but certainly not since 1900 and certainly not post 1984.

Is it possible that support of this PACE action is part of a criminal action? Remember, the PACE program is essentially about (a) cognitive behavior therapy, (b) graded exercise therapy and (c) cost effectiveness comparisons. There is a statement among crime investigators of white-collar crime: If you wish to understand what is going on, “Follow the money”. Who is to benefit financially from the magical theories developed by the PACE enquiry? Certainly (a) the insurance industry shares a major part in the profit. Those patients who drop out of the PACE program are “resisting treatment,” so no insurance disability payments need to be made. Also the UK National Health system doesn’t have to pay for any tests of these chronically disabled patients. National Health can thus continue their non-investigation and non-scientific treatment, but rather their continued abandonment policy of a significant portion of their younger population with smug indifference.

In the near 30 years I have been following these M.E. and CFS patients, and they are not the same, the vast majority of these patients have been (a) teaching professionals, (b) health care workers including (physicians and nurses), and (c) students. Is this not curious, the professions most in contact with infectious disease are the most represented? Is it not curious that the two professional groups, health care workers and teachers, due to the strenuous academic streaming, which weeds out the physically and psychological prone individuals, are those most effected.

If you wish to know what medicine is about, take one of their names of the Lancet paper and look up Pickles, not the same Pickles, but Will Pickles (1885-1969) of Yorkshire. In his book, Epidemiology in Country Practice (1939), he described one of the first epidemics of Myalgia, CNS dysfunction and dysautonomia, a patient with normal lungs free of infection yet with a respiratory rate of 60/minute. This was in 1883. We have not come very far. Has the UK, the source of some of medicines greatest physicians, stopped seriously examining the disabled?

In the 1990s, I went to the island of Bornholm to see Dr. Sylvest who was still alive to obtain his experiences on the Coxsackie B epidemic on that Island in the 1930s and simply to see if there were chronic patients from that epidemic which had not been written up. There were, and although most had died by then, many had not recovered. Dr. Sylvest was a physician who examined and cared for his patients.

So what do I think about physicians who (1) do not examine patients, (2) do not use the available and less available scientific and technological tools, (3) rely on myth and magic to examine chronically ill patients? Not very much. Nor do I think much of the imaginative papers they write to obtain grants and what terrible things that happen to patients due to their dangerous folly.

Byron Hyde MD, The Nightingale Research Foundation


Fler relevanta kommentarer har kommit in i debatten på BMJ. Följande är säkert av intresse för den som vill granska studiens metodologiska brister i detalj.

Anna K Sheridan skriver:

The recent study in the Lancet Psychiatry [1] reported that fear of exercise was a mediating factor for fatigue and physical function in the case of both CBT and GET.

However the very presence of this fear on patients’ willingness to engage in physical activity is inadvertently called into question by one of the authors (Trudie Chalder) during a press interview [2], in which she states that: ‘On a day when they [patients] feel less symptomatic and very energetic they may do more than they are probably able to do and then of course suffer as a consequence’. It seems strange to me that a fear powerful enough to hinder the success of CBT and GET but which then abates on days when the patient is feeling less ill can actually exist, or indeed be a factor in the successful treatment of this condition.

What is perhaps particularly important to bear in mind is that the proposed ‘success’ of fear reduction is predicated on an increase in walking distance that is woefully small- after a year of therapy the patients receiving GET were able to increase the distance they walked on the six minute walking test (6mwt) by only 67m, (to 379m, 35m more than the SMC-only group) [3] but still far short of the 644m [4] average for a healthy adult. Even if such a fear were to exist, given these results, it seems unlikely that a change in beliefs will be enough to increase the walking distance by a further 265m.

Unfortunately we do not know what the mean 6mwt scores were for those who have low fear of exercise nor, despite a freedom of information request [5], for the 22% of patients receiving GET who have been labelled (controversially [6]) as ‘recovered’ [7]. I suggest that in order to avoid wasting any more tax payers’ money, these data should be made available as soon as possible, so that the true effect of overcoming fear of exercise may be properly evaluated.

What is clear is that treatments of this kind are only tinkering around the edges of an illness that is in urgent need of more rigorous indepth biomedical investigation. [...]


Alem Matthees skriver:

AllTrials supporters may be interested in the multiple major deviations/additions to the PACE Trial protocol, apparently occurring almost exclusively after the authors were already unblinded to the trial data and familiar with the distribution of various outcomes. This latest paper on mediators by Chalder et al. appears to continue this tradition.[1]

The protocol was published in BioMed Central on the basis that “the authors/investigators are unlikely to be able to make revisions to their protocol”. The editor(s) “strongly advise readers to contact the authors or compare with any published results article(s) to ensure that no deviations from the protocol occurred during the study.”[2] BioMed Central “believes that publishing study protocols will help to improve the standard of medical research by: [...] enabling readers to compare what was originally intended with what was actually done, thus preventing both ‘data dredging’ and post-hoc revisions of study aims.”[3] It is therefore concerning that the protocol underwent extensive, major, post-trial revisions, without adequate justification. All changes substantially decreased the stringency of the thresholds, made the tested therapies appear much more effective or less harmful than they otherwise would have, and lead to widespread media hype.

The primary endpoint was completely abandoned after the trial ended. For fatigue this had been either 50% improvement or a Chalder Fatigue Questionnaire (CFQ) bimodal score of ≤3/11 points. For physical function this had been either 50% improvement or a Short-Form-36 physical function (SF-36/PF) score of ≥75/100 points. The “clinically useful difference” for individual participants (≥2/33 points CFQ Likert score and/or ≥8/100 points SF-36/PF) was introduced post-hoc and was significantly less stringent than the “positive outcome”(s) as previously defined.[4][5]

The recovery criteria (a secondary analysis) underwent extensive, major, post-hoc changes, which made it much less stringent to the point of being highly doubtful whether anyone genuinely recovered.[6] It became possible to be classified as completely “recovered” without clinically significant improvements to either fatigue or physical function. None of these changes, described below, were included in the statistical analysis plan that was finalized shortly before data unblinding.[7]

1) The previously required CFQ bimodal score of ≤3/11 points was changed to a CFQ Likert score of ≤18/33. The change of scoring method obscures direct comparison, but a Likert score of 18 can be a bimodal score of between 4 to 9, which the protocol regarded as abnormal or excessive fatigue. About 1% of participants simultaneously met both definitions of ‘normal fatigue’ (CFQ Likert ≤18/33) and ‘severe fatigue’ (CFQ bimodal ≥6/11) at baseline.[8] Questions have therefore arisen over the method and normative population sample used to calculate this threshold.[9-12]

2) The previously required SF-36/PF score of ≥85/100 points was lowered to ≥60; worse than trial eligibility criteria for ‘significant disability’ (≤65).[6] About 13% of participants simultaneously met both definitions of ‘normal physical function’ (a criterion for complete recovery) and ‘significant disability’ at baseline.[8] The post-hoc revised threshold was derived from an inappropriate statistical calculation using a non-representative population sample which included the elderly and disabled.[13] CFS occurs at all ages but in this trial of adults, 97% were aged under 60 years at baseline, and a diagnosis of CFS requires that other chronic disabling conditions which explain the fatigue etc are excluded. The stated justification for this drastic change, erroneously asserted that about half the general working age population score under 85, but it is actually 17.6%. Note that 92.3% of the ‘healthy’ working age English population score 85 to 100, and 61.4% score 100.[13]

3) The required CGI score of 1 (“very much better”) was relaxed so that 2 (“much better”) also counted towards recovery. The next option 3 (“a little better”) was regarded as a non-improvement. A moderate improvement in CGI score is non-specific, could be a result of improvement to one complaint while multiple major symptoms remain, and on its own does not guarantee any clinically significant improvements to the primary efficacy measures of fatigue and physical function.[14-15]

4) No longer meeting Oxford CFS criteria did not guarantee real-world recovery, because participants who otherwise still met Oxford criteria as usually applied and still experienced either severe fatigue or significant disability, could be disqualified by failing ad hoc criteria for either, even if their CFQ and SF-36/PF scores remained abnormal or one remained unimproved.[16] (The optional requirements of not meeting CDC CFS criteria or London ME criteria were superfluous, not entry requirements, stricter than the Oxford CFS criteria, made no difference to the results, and were improperly applied.[6,17])

The technical details of the “planned” mediation analysis[1] are not adequately covered in the published protocol[4] or the statistical analysis plan.[7] It is unknown what methodological changes occurred during this exploratory analysis or whether it was influenced by ‘data dredging’ and ‘post-hoc revisions’. Earlier results were described in 2011 as: “There was modest mediation of CBT and GET effects (approximately 20% of the total effect).”[18] Now much higher figures are being reported, even for individual mediators, including, “fear avoidance beliefs, the strongest mediator, accounted for up to 60% of the overall effect.”[1] Interestingly, Chalder et al.[1] and the accompanying editorial by Knoop & Wiborg[19] conceded that the causal relationships between mediators and outcomes were unclear.

The 60% figure compared GET with a non-representative version of pacing (APT), but news articles have misrepresented this as strong evidence that patients recover by overcoming their fears and exercising. This is contradicted by “an almost complete absence of improvements in objectively measured outcomes”, including the fitness step-test which indicates that participants failed to exercise more, despite GET aiming to substantially increase activity/function e.g. 30 minutes of exercise at 60-75% maximum heartrate at least 5 times per week.[20] The exception (GET walking distances) was not clinically significant and was not due to improved fitness.[19] These results dispute the deconditioning model and instead reflect an activity ceiling determined by post-exertional symptoms and abnormal (pathophysiological) responses to exercise.[21,22]

This non-blinded trial tested therapies aimed to change participants’ beliefs about symptoms and impairments, so the discrepancy between subjective and objective outcomes raises plausible concerns about biases with self-reports.[23,24] [...]


UPPDATERING 25 jan: Nytt inlägg med ytterligare vetenskaplig fakta som motbevisar desinformationen, ME är inte “trötthet”, del 4.


Publicerat i: Osorterat