Investigating the relationship between physical activity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Franklin, 2021

Dolphin

Dolphin

Senior Member (Voting Rights)
From: Dr. Marc-Alexander Fluks

Source: Teesside University
Date: February 19, 2021 (version august 2020)
URL:
https://research.tees.ac.uk/ws/portalfiles/portal/25523843/John_Franklin_PhD_Thesis.pdf
Ref:
https://research.tees.ac.uk/en/stud...lationship-between-physical-activity-and-myal


Investigating the relationship between physical activity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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John Derek Franklin
- School of Health and Life Sciences, Teesside University, U.K.


Abstract

Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a
debilitating illness characterised by severe fatigue which causes a
significant reduction in levels of activity. Post exertional malaise
(PEM), unrefreshing sleep, cognitive impairment, and/ or orthostatic
intolerance are all key symptoms of the illness. PEM is described as a
unique attribute of ME/CFS which results in significant worsening of
symptoms following a physiological, cognitive, or emotional stressor.
Due to this, those with ME/CFS are required to manage their activity
levels to control PEM symptoms. Nevertheless, there is some evidence
that graded exercise interventions could improve symptoms in ME/CFS
although this is contested with some arguing that graded exercise
programmes cause a worsening of symptoms. The aim of this thesis is to
explore the relationship between ME/CFS and physical activity.

Methods and Findings
The first objective was to assess if people with ME/CFS had a reduced
peak oxygen uptake (VO2peak) compared to apparently healthy controls as
this may increase their risk of all-cause mortality. A meta-analysis of
32 cross-sectional studies demonstrated that pooled mean VO2peak was 5.2
(95%CI 3.8 to 6.6) ml.kg−1min−1 lower in people ME/CFS vs. healthy
controls. This study provided evidence that ME/CFS patients have a
substantially reduced VO2peak compared to controls which could increase
their risk of all-cause mortality. However, there was insufficient data
to ascertain the impact of peak exercise testing on ME/CFS symptoms in
the days following testing.

A meta-analysis was conducted on studies which conducted repeat maximal
exercise tests separated by 24h. The difference in work rate (WR) at
anaerobic threshold (AT) (n=4) was -20.64 (95%CI -40.95 to -0.33)W in
favour of controls, demonstrating that people with ME/CFS had a reduced
power output at AT in the second of the two tests compared to apparently
healthy controls. The effect size for this difference was large (d =
-0.95) providing evidence that WR at AT effectively discriminates
between ME/CFS and controls. These findings provide evidence of an
objective and measurable response to repeat high intensity exercise
which provides some evidence of a possible physiological element of the
illness and may provide a potential objective marker in future studies.

In light of this evidence it was important to assess the effectiveness
of exercise interventions in managing symptoms of fatigue in ME/CFS.
Meta-analysis of studies assessing the effectiveness of graded exercise
demonstrated that the pooled percentage difference for the overall
effect (n=10) was -13.4% (95%CI -24.2 to -2.6) in favour of
intervention. This indicates that exercise results in a clinically
relevant reduction in fatigue. However, when studies using the Oxford
Criteria case definition were removed from the analysis (n=5) the
percentage difference reduced to -9% (95%CI -21.8 to -3.7). The findings
indicate a degree of uncertainty around the effectiveness of exercise
programmes in ME/CFS which would support evidence from survey data that
graded exercise programmes may only be effective for a limited number of
people with ME/CFS.

To explore this in more detail, in-depth interviews were conducted with
six people with ME/CFS using an interpretive phenomenological analysis.
Participants described feeling as though they are losing themselves and
feel a lack of legitimacy about the hidden nature of the illness. Those
with ME/CFS described 'battling' their illness which is not commonly
cited in other chronic health conditions. Those with ME/CFS described
wanting to be more active although this is contrasted with the
unpredictability of the illness. People with ME/CFS described a desire
for others to empathise and demonstrate understanding of their illness.
Nevertheless, there was some evidence that when people with ME/CFS were
able to engage in activities which had personal meaning this resulted in
improvement in mood. Evidence indicated the potential for an activity
management strategy in ME/CFS.

A new form a graduated physical activity was considered for people with
ME/CFS. The proposed intervention is designed to be flexible in
intensity and duration depending on the symptom profile of the
individual and allow individuals to choose from a number of possible
activities.

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(c) 2021 Teesside University
 
Dolphin said:
A new form a graduated physical activity was considered for people with ME/CFS. The proposed intervention is designed to be flexible in intensity and duration depending on the symptom profile of the individual and allow individuals to choose from a number of possible activities.
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"New"
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It just never ends, does it? Why do people think superficial understanding of an issue and giving it a few minutes' attention is good enough to deliver something useful?
 
Dolphin said:
No, this was just a post by a patient to an ME/CFS list. Marc goes to a lot of trouble searching for news so I like to acknowledge him.
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Sorry @Dolphin if it seemed I was criticising the creation of this thread, it was not my intention. It is important we share such information. Indeed thank you for posting this.

I was initially confused by what I was reading in terms of the origin of the abstract itself, and trying to psych myself up to looking at the full 400+ pages of the thesis itself so it took me a moment to recognise that you were sharing what Dr Fluks had shared which was originally released through Teesside University. Presumably this will/has resulted in research article(s) (a very cursory search for Dr Franklin, did not alert me to any articles, but I need to look again when I am more with it.)

Finding a way to distinguish between those that recover from post viral conditions and those that do not would be valuable, and be able to say if for those that do recover if exercise helps or if the anecdotal reports of this are a fortuitous coincidence would be good. Presumably this would also provide confirmation of whether or not PEM itself is a sufficient predictor of those who will not recover and for whom inappropriate exercise will be harmful or if there are other factors involved.

However from the abstract I worry that we will not see an answer to these questions rather just an attempt at individualised GET or GET-lite, but this is unfairly prejudging something I have not yet read.
 
PEM is described as a unique attribute of ME/CFS which results in significant worsening of
symptoms following a physiological, cognitive, or emotional stressor.
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This is a description of post exertional fatigue which is common to many illnesses. It annoys me because it makes it sound as if we are whiny by claiming to be unique when we are not.

The uniqueness of ME is that activity (only stressors in a very particular meaning of the word) causes worsening of symptoms which often don't appear for days and there is an unusually prolonged recovery. Exertion also causes immune symptoms such as sore throats and enlarged glands which are not common with other diseases.

He did not take into account the methodological problems with GET studies, though it is good that the Oxford definition was seen as a problem.

The findings indicate a degree of uncertainty around the effectiveness of exercise programmes in ME/CFS which would support evidence from survey data that graded exercise programmes may only be effective for a limited number of people with ME/CFS.
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This is seriously dodgy. If he is familiar with the surveys he surely knows that the problem is the number of people who claim to be harmed by GET, not the limited number who say it is effective. You cannot put forward any form of graduated exercise treatment until the problem of the massive number of people who claim to have been harmed by such a treatment has been resolved.

The answer to thalidomide was not to give a lower dose to pregnant women. Because of these surveys, all exercise treatments for ME, and, in my opinion, for any post viral disease, must be embargoed until it is discovered why some people are harmed.
 
More information on Dr John Franklin

Teeside University Website
https://research.tees.ac.uk/en/persons/john-franklin-2

Publication

Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis
DOI:10.1055/a-0802-9175

https://www.researchgate.net/public...romeMyalgic_Encephalomyelitis_A_Meta-Analysis

Abstract

To evaluate the magnitude of the difference in VO2peak between patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) and apparently healthy controls, 7 databases (Cochrane, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus, Medline) were searched for articles published up to March 2018. Search terms included “chronic fatigue syndrom*”AND (“peak” OR “maxim*” OR “max”) AND (“oxygen uptake” OR “oxygen consumption” OR “VO2peak” or “VO2max”. Eligibility criteria were adults>18 y with clinically diagnosed CFS/ME, with VO2peak measured in a maximal test and compared against an apparently healthy control group. The methodological quality of included studies was assessed using a modified Systematic Appraisal of Quality for Observational Research critical appraisal framework. A random effects meta-analysis was conducted on 32 cross-sectional studies (effects). Pooled mean VO2peak was 5.2 (95% CI: 3.8–6.6) ml.kg−1min−1 lower in CFS/ME patients vs. healthy controls. Between-study variability (Tau) was 3.4 (1.5–4.5) ml.kg−1min−1 indicating substantial heterogeneity. The 95% prediction interval was −1.9 to 12.2 ml.kg−1min−1. The probability that the effect in a future study would be>the minimum clinically important difference of 1.1 ml.kg−1min−1 (in favour of controls) was 0.88 – likely to be clinically relevant. Synthesis of the available evidence indicates that CFS/ME patients have a substantially reduced VO2peak compared to controls.
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Which presumably arose from the literature review stage of his PhD thesis.
 
 
Nevertheless, there was some evidence that when people with ME/CFS were able to engage in activities which had personal meaning this resulted in improvement in mood.
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People feel better when doing things they enjoy doing. Who knew?

A new form a graduated physical activity was considered for people with ME/CFS. The proposed intervention is designed to be flexible in intensity and duration depending on the symptom profile of the individual and allow individuals to choose from a number of possible activities.
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The project to confabulate pacing with GET continues.

And still obsessed with the exercise is always good trope.
 
Concerning concept: still hanging onto GET, "let's just make it custom, or GET Lite."

Liked your comparison to thalidomide, @Mithriel.

Will there never be an end to trying to force very ill people, people who become sicker with GET into this regimented control?

Well, I do know the answer...
 
GET was always sold as being individualized. Not true but they've been saying this for decades.

But it's not as if any of this matters, they can say something for decades, pretend otherwise and nobody cares. Which is why they can lie and fail for decades. Of all the failures, the simple inability to care, to basic professionalism, the so-called "duty" of care, will always be the worst flaw. It's just plain dereliction of duty, a simple pathetic "not my job, not my problem".
 
DokaGirl said:
Concerning concept: still hanging onto GET, "let's just make it custom, or GET Lite."

Liked your comparison to thalidomide, @Mithriel.

Will there never be an end to trying to force very ill people, people who become sicker with GET into this regimented control?

Well, I do know the answer...
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[added - in summary my understanding is Franklin is proposing an actual BPS model of ME involving all three components, where currently restricted activity undermines our sense of self worth which in turn limits what we are able to achieve, this should be managed by an activity programme focusing on self-validating activities which can then be gradually increased to a level considerably higher than the start point, but ultimately restricted by a ceiling dictated by the biological component. ]

I have not yet read the entire thesis cover to cover, but it seems the author is trying to develop a genuine BPS model of ME that does not just say it is only psychological, he does manage a reasonable critique of the previous CBT/GET research, and accepts there is a biomedical component which he discusses mainly in terms of peak oxygen uptake. However he seems to accept unquestioningly the research that identifies all sorts of psychological and behaviour issues in ME, such as depression or being risk averse, as contributing to limiting people’s daily activity levels.

Then drawing on research not directly relating to ME, but to other primarily psychological factors he presents all sorts of psycho-behavioural considerations which impact on people’s interest (or willingness) in exercising or undertaking activity.

My understanding so far is his own original research is based on in-depth interviews with six patients and for him the central problem of ME to be addressed is that restricted activity impinges on people’s self identity and sense of self worth, so he argues that the main focus of intervention should be enabling people to undertake activity that will validated them as people and improve their sense of self worth, he argues that this psychological boost will then enable people to do more than they can with just plain boring pacing and activity management.

He then seems to skim over the potential of treating the ‘biological’ component and produces a model of intervention that is a sort of activity management aimed at getting people to undertake activities they want to do and which will validate their self worth, and enable them in gradual steps increase the total activity. At this point I got confused and will need to reread the relevant sections, so I am not sure if he undertook a pilot study to investigate the possibility of evaluating such a self-validating activity management programme or if he just outlined the possible design of such a study. What confused me was I have failed so far to find the results of his pilot.

He did conclude that his self validating activity programme would enable patients to increase their daily activity significantly more than possible with just ordinary pacing, but that at some point there would be a ceiling related to the presumed biological component. So he was presenting a programme to make people happier and more productive though falling short of actually returning us to premorbid functioning. As I say I have struggled to integrate the full four hundred pages within my current cognitive constraints, even on several attempts, so I could still be doing the author a disservice.

My concern is despite the substantial effort put in by the author, he still does not understand the breadth of our symptoms and the very real problems relating to exertion and to PEM, that he unquestioning seeks to squeeze ME into a BPS model without understanding the range and restrictions of our biological issues, and that he has an unquestioning belief that we do less than we sustainably could because of our psychological issues.

Personally I would be happy to only undertake self validating and pleasurable activities if Dr Franklin could suggest a source of funding for a cook/house keeper, secretary/admin assistant and gardener/driver. I could perhaps get away with three domestic staff as long as they were willing to take on several roles and one could take on the admin/management of their fellow employees. Even then there is the problem on those days when the minimum functioning required for sustaining life, ie eating, going to the toilet and on a good day showering or (but not both) brushing my teeth are sufficient to trigger PEM.

My initial impression is that it is a strange mixture of both serious scientific enquiry and prejudiced speculation.

[corrected some typos]
 
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Peter Trewhitt said:
Personally I would be happy to only undertake self validating and pleasurable activities if Dr Franklin could suggest a source of funding for a cook/house keeper, secretary/admin assistant and gardener/driver. I could perhaps get away with three domestic staff as long as they were willing to take on several roles and one could take on the admin/management of their fellow employees. Even then there is the problem on those days when the minimum functioning required for sustaining life, ie eating, going to the toilet and on a good day showering or (but not both) brushing my teeth are sufficient to trigger PEM.
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Has anyone trialled a "give money to patients" study. Basically, whatever money they'd spend on therapists handed directly to patients? :D
 
Snow Leopard said:
Has anyone trialled a "give money to patients" study. Basically, whatever money they'd spend on therapists handed directly to patients? :D
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Yea when you look at the amount of money spent on maintaining healthy, useful people (OK not to people with ME but potentially others) to "treat" people with ME/CFS - for the interventions that don't work/are harmful you'd be better employed spending that on maintaining them in the community!
The other thing is that the money could be put into research.

[EDITED] Also, since those who might benefit from a physiotherapist can't access them (waiting lists for NHS in UK) why allocate them to diseases where there is no evidence they are beneficial - like ME/CFS?
 
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The thesis includes a review of exercise trials which has the following passage:
Each question on the RoB 2.0 tools was also considered and a consensus on what should be focused on to ensure consistency. For example, question 4 on the RoB 2.0 tool focused on the blinding of outcome assessors. Originally JF had assessed each paper as high risk, however following a discussion it was agreed that as the outcome was self-assessed by patients this could be assessed as ‘some concerns’ or ‘low risk’ depending on the specific information provided in each paper. It was agreed in this discussion that the ‘high risk’ rating is triggered on the study quality tool if there is an element of judgement from the observer on an outcome. However, as the outcome is a subjective scale which the participant scores themselves this would not result in a high risk of bias.
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So the PhD student believed that all trials were unblinded with subjective outcomes and should therefore be high risk of bias. But his colleagues convinced him that there was no high risk of bias because it were the patients themselves who filled in the questionnaires not an observer.

Sounds like a bad argument to me.
 
This was the result of the meta-analysis for the exercise trials review (page 171).
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The effect size is presented as percentage change from baseline with 10% used as the minimal clinically important difference. The overall effect and the one with the PACE trial removed was clinically significant but the one where trials who used the Oxford criteria were removed, was not.
 
The Wallman et al. 2004 trial was excluded because of discrepancy on how the data was reported in the original paper and in the Cochrane review.

On page 131 of the thesis (page 152 of the PDF):
7.9.1.3 Wallman et al. (2004) – excluded
A discrepancy was noted when extracting data from Wallman et al. (2004) and comparing against a previous meta-analysis (Larun et al., 2019). In Wallman et al. (2004), the total fatigue score for the exercise group and the relaxation/ flexibility was 12.6 and 14.4 respectively, resulting in a mean difference of - 1.8. In the paper by Larun et al., (2019), the post data for the exercise group and relaxation/ flexibility group was 11.06 and 15.34 respectively providing a mean difference of -4.28. This resulted in a larger effect in the meta-analysis by Larun et al., (2019) than was reported in the original paper (Wallman et al., 2004) (13% reduction in fatigue vs. 5.5%). Both research groups were contacted, however the Wallman research group no longer had the original data and this discrepancy was unable to be clarified with the Larun research group. Due to this inconsistency, the decision was made to exclude this paper from the analysis.
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ME/CFS Skeptic said:
The thesis includes a review of exercise trials which has the following passage:

So the PhD student believed that all trials were unblinded with subjective outcomes and should therefore be high risk of bias. But his colleagues convinced him that there was no high risk of bias because it were the patients themselves who filled in the questionnaires not an observer.

Sounds like a bad argument to me.
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One of the worst I have ever seen. Completely asinine excuse. This is a system in complete shambles.
 
Very interesting excerpts @ME/CFS Skeptic
ME/CFS Skeptic said:
So the PhD student believed that all trials were unblinded with subjective outcomes and should therefore be high risk of bias. But his colleagues convinced him that there was no high risk of bias because it were the patients themselves who filled in the questionnaires not an observer.

Sounds like a bad argument to me.
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Yes, certainly a very bad argument. I feel sorry for the PhD student. He drew a logical scientifically valid conclusion but it seems that he was led by his supervisors to exchange it for an unsupportable position. It is an argument we have seen before and goes to the core of the BPS view. If ME/CFS is just seen as a faulty interpretation or an over-reaction to normal sensations, someone reporting they are now better is taken to mean that the problem is solved. @Hilda Bastian was a big proponent of patient reported outcome measures when she engaged with us on the forum, and seemed to struggle to see the potential for bias.


ME/CFS Skeptic said:
The effect size is presented as percentage change from baseline with 10% used as the minimal clinically important difference. The overall effect and the one with the PACE trial removed was clinically significant but the one where trials who used the Oxford criteria were removed, was not.
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So, if the change is relative to baseline, am I right in assuming that that doesn't take into account the change reported from doing nothing for the same length of time as the treatment? Or was the difference after netting out results achieved by controls?

ME/CFS Skeptic said:
The Wallman et al. 2004 trial was excluded because of discrepancy on how the data was reported in the original paper and in the Cochrane review.
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That sounds quite a mess. So the 5.5% reduction reported by the Wallman et al study (versus the 13% reduction seemingly incorrectly reported by Larun et al) was for the GET treatment and was the change from baseline?
 
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