CBT combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a feasibility study, 2020, Wyller et al

I've also found a statistical analysis plan (see attachment) and previous versions of their paper and the peer-review history (haven't read any of these yet).

There was also a protocol, written in 2015 which I can't seem to locate (the links no longer work). Anyone who can help out?

 

So, if this is the case, why do we feel ill during activities we look forward to and enjoy? Or where we can do an enjoyable activity experience delayed PEM?

As a youngster I had several flare ups of an ongoing condition which caused me to be bedbound for a month or so at a time. When it was over I would be too weak to stand, yet within a few weeks I was racing around the place with my pals? So, having already experienced being bedbound & significantly weakened and know what it feels like to bounce back from that, I can confidently say this doesn't feel.like that.

 

Yes, this seems to be what he actually means (although he talks about Pavlov's rats). Here are some notes from a lecture by him from Nov. 2019:
https://www.s4me.info/threads/psych...ogy-wyller-among-lecturers.10647/#post-214986

 

I believe it is this one? Shared by the blogger Toto NeuroImmunologisk Kurativ Behandling.
It's in Norwegian, but here's link to google translation

 

That's some serious weapons-grade nonsense. If only we had a process by which we can tell whether something "can arise" or not. If only. That would be so useful. I have no idea how someone can actually convince themselves of such nonsense.

I find that one particularly insulting because losing the ability to listen to and play music has been particularly hard for me. It's unfortunately exhausting despite being highly pleasurable. I technically can but it hurts the whole time and leaves me exhausted. No matter how much I like it, which is A LOT.

I can't remember the exact term but there are people who experience music in a way that is almost orgasmic. I'm one of those people. That has not changed. I enjoy listening and playing every bit I ever did. Still hurts, still causes PEM.

Quacks. So many quacks. So much quackery.

 

Again, I couldn't see any mention of the 'recovery' criteria they make so much of in the abstract and paper in their statistical analysis plan.

Sorry for being an idiot, but can anyone link to the supplementary material? I just can't see it.

edit: @Michiel Tack found this in the protocol - thanks Michiel!:

https://www.ahus.no/seksjon/forskni...n/Paedia/Forskningsprotokoll - behandling.pdf

 

Thanks Kalliope!

However, I suspect that this is something else than the protocol, like the application they had to write to get funding. I think the protocol is divided into two parts: one about the longitudinal study and one about the subsequent clinical trial.

 

Nina E. Steinkopf has written a thorough walkthrough of the study in this blog post

In a Norwegian study, young people with chronic fatigue were treated with music therapy. The result is an article full of contradictions and illogical conclusions, which essentially disproves the researchers' own hypotheses and conclusions - without the researchers themselves seeming to have discovered them.

Kurere ME med musikk?
google translation: Curing ME with music?

 

Great thorough analysis. This incompetent experiment is an embarrassment to both the letter and spirit of science.

This is interesting:

Always remain in a safe space, never put themselves in a situation where difficult questions can be asked by people who haven't bought in on the belief system. The circle jerk must remain unperturbed.

 

https://twitter.com/user/status/1258803911701475330

 

Changes through peer review process from submitted manuscript to published paper
- and everything actually happened inside the Journal BMJ Paediatrics Open


-> Cognitive behavior therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: An exploratory randomized trial

Manuscript ID bmjpo-2019-000620
Date Submitted by theAuthor December 3, 2019

"Power calculation and statistical analyses​

In a previous research project from our institution, the mean (standard deviation, SD) steps/day count (primary endpoint) for CFS adolescents was approximately 4500 (2400) [29]. In the present study, a total of 50 participants were assumed to be available for endpoint evaluation; that given, the power to detect a difference of 2000 steps/day is about 80 % (α=0.05). This effect size is rather large; however, as CBT alone is documented to have a moderate effect in CFS, only a substantial effect size is of direct clinical interest."

Abstract
Background
Cognitive behaviour therapy (CBT) is effective in chronic fatigue syndrome. However, CBT has not been investigated in post-infective chronic fatigue (CF), nor is it known whether addition of therapeutic elements from other disciplines might increase effectiveness and feasibility. The present study explored the combination of CBT and music therapy for CF following Epstein-Barr virus (EBV) infection in adolescents.

Methods
A total of 200 adolescents (12-20 years old) with acute EBV infection were followed prospectively and classified as CF cases or non-CF cases at 6 months. The CF-cases were eligible for a randomized controlled trial comparing combined CBT and music therapy (10 therapy sessions and related homework) against treatment as usual (regular visits to the general practitioner). Endpoint evaluation was concealed for therapists and participants. Primary endpoint was physical activity (steps/day) at 3 months follow-up; secondary endpoints included symptom scores, recovery rate and possible harmful effects. Total followup time was 15 months.

Results
A total of 91 CF cases were eligible, and a total of 43 were included; 21 were allocated to the intervention group and 22 to the control group. In intention-to-treat analyses, there was no statistically significant difference in number of steps/day (difference [95 % confidence interval]=-1158 [-2642 to 325], p=0.122), but a trend towards improvement of post exertional malaise in the intervention group at 3 months. At 15 months follow-up, there was a trend towards higher recovery rate in the intervention group. No harmful effects were recorded, and compliance was 99 % among the participants that completed the mental training program.

Conclusion
Combined CBT and music therapy tended to improve recovery and symptoms of postexertional malaise, did not cause harm, and appeared feasible in adolescents suffering from CF after Epstein-Barr virus infection. These preliminary findings should be addressed in further research.


**
-> Cognitive behavior therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: A feasibility study
Journal: BMJ Paediatrics Open

Manuscript ID bmjpo-2019-000620.R1
Date Submitted by the Author 9feb2020

"Power considerations and statistical analyses​

In CFS, the effect of CBT alone is often reported to be moderate [5]. In a previous research
project from our institution, CFS adolescents had a mean (SD) steps/day count of approximately 4500 (2400), and a mean (SD) CFQ total score of 19.1 (6.3) [34]. This given, more than 120 participants would be needed in order to detect a moderate effect size (Cohen’s d≈0.5), such as an increase in steps/day of 1200 or a reduction in CFQ total score of 3 (α=0.05, β=0.2). In the present study, the total number of eligible individuals were 91 (defined as CF cases 6 months after acute EBV infection), and only 43 consented to inclusion. Hence, the study was strongly underpowered regarding efficacy, and the results should be interpreted accordingly."

Abstract
Background
Cognitive behaviour therapy (CBT) is effective in chronic fatigue syndrome. However, CBT has not been investigated in post-infectious chronic fatigue (CF), nor is it known whether addition of therapeutic elements from other disciplines might be feasible. We studied the feasibility of a combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents.

Methods
Adolescents (12-20 years old) participating in a post-infectious cohort study who developed CF six months after an acute EBV-infection were eligible for the present feasibility study. A combined CBT and music therapy program (10 therapy sessions and related homework) was compared to care as usual in a randomized controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects. Total follow-up time was 15 months.

Results
A total of 43 individuals with post-infectious CF were included; 21 were allocated to the intervention group and 22 to the control group. Seven individuals left the study during the first three months, leaving 15 in the intervention group and 21 in the control group at three months follow-up. In intention-to-treat analyses, number of steps/day tended to decrease (difference [95 % confidence interval]=-1158 [-2642 to 325]), whereas post exertional malaise tended to improve (difference [95 % confidence interval]=-0.4 [-0.9 to 0.1]) in the intervention group at three months. At 15 months follow-up, there was a trend towards higher recovery rate in the intervention group (62 % vs 37 %). No harmful effects were recorded, and compliance was high among the participants that completed the mental training program.

Conclusion
An intervention study of combined CBT and music therapy in post-infectious CF is feasible,
and appears acceptable to the participants. The tendencies towards positive effects on
patients’ symptoms and recovery might justify a full-scale clinical trial.

**
-> Cognitive behavior therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: A feasibility study

Manuscript ID bmjpo-2019-000620.R2
Date Submitted by the Author 10mars2020

"Power considerations and statistical analyses​

As this was a feasibility study, a formal power calculation was not considered necessary. It should be noted, though, that in a previous research project from our institution, CFS adolescents had a mean (SD) steps/day count of approximately 4500 (2400), and a mean (SD) CFQ total score of 19.1 (6.3) [34]. This given, more than 120 participants would be needed in order to detect a moderate effect size (Cohen’s d≈0.5), such as an increase in steps/day of 1200 or a reduction in CFQ total score of 3 (α=0.05, β=0.2). In the present study, the total number of eligible individuals were 91 (defined as CF cases 6 months after acute EBV infection), and only 43 consented to inclusion. Hence, the study was strongly underpowered regarding efficacy."

Abstract
Background
Cognitive–behavioural therapy (CBT) is effective in chronic fatigue syndrome. However, CBT has not been investigated in postinfectious chronic fatigue (CF), nor is it known whether addition of therapeutic elements from other disciplines might be feasible. We studied the feasibility of a combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents.

Methods
Adolescents (12–20 years old) participating in a postinfectious cohort study who developed CF 6 months after an acute EBV infection were eligible for the present feasibility study. A combined CBT and music therapy programme (10 therapy sessions and related homework) was compared with care as usual in a randomised controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects, but the study was underpowered regarding efficacy. Total follow-up time was 15 months.

Results
A total of 43 individuals with postinfectious CF were included (21 intervention group, 22 control group). Seven individuals left the study during the first 3 months, leaving 15 in the intervention group and 21 in the control group at 3 months’ follow-up. No harmful effects were recorded, and compliance with appointment was high. In intention-to-treat analyses, number of steps/day tended to decrease (difference=−1158, 95% CI −2642 to 325), whereas postexertional malaise tended to improve (difference=−0.4, 95% CI −0.9 to 0.1) in the intervention group at 3 months. At 15 months’ follow-up, there was a trend towards higher recovery rate in the intervention group (62% vs 37%).

Conclusion
An intervention study of combined CBT and music therapy in postinfectious CF is feasible, and appears acceptable to the participants. The tendencies towards positive effects on patients’ symptoms and recovery might justify a full-scale clinical trial.


**
published paper

Cognitive–behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a feasibility study

"Power considerations and statistical analyses​

As this was a feasibility study, a formal power calculation was not considered necessary. It should be noted, though, that in a previous research project from our institution, CFS adolescents had a mean (SD) steps/day count of approximately 4500 (2400), and a mean (SD) CFQ total score of 19.1 (6.3). This given, more than 120 participants would be needed in order to detect a moderate effect size (Cohen’s d≈0.5), such as an increase in steps/day of 1200 or a reduction in CFQ total score of 3 (α=0.05, β=0.2). In the present study, the total number of eligible individuals was 91 (defined as CF cases 6 months after acute EBV infection), and only 43 consented to inclusion. Hence, the study was strongly underpowered regarding efficacy."

Abstract
Background Cognitive–behavioural therapy (CBT) is effective in chronic fatigue syndrome. However, CBT has not been investigated in postinfectious chronic fatigue (CF), nor is it known whether addition of therapeutic elements from other disciplines might be feasible. We studied the feasibility of a combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents.

Methods Adolescents (12–20 years old) participating in a postinfectious cohort study who developed CF 6 months after an acute EBV infection were eligible for the present feasibility study. A combined CBT and music therapy programme (10 therapy sessions and related homework) was compared with care as usual in a randomised controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects, but the study was underpowered regarding efficacy. Total follow-up time was 15 months.

Results A total of 43 individuals with postinfectious CF were included (21 intervention group, 22 control group). Seven individuals left the study during the first 3 months, leaving 15 in the intervention group and 21 in the control group at 3 months’ follow-up. No harmful effects were recorded, and compliance with appointment was high. In intention-to-treat analyses, number of steps/day tended to decrease (difference=−1158, 95% CI −2642 to 325), whereas postexertional malaise tended to improve (difference=−0.4, 95% CI −0.9 to 0.1) in the intervention group at 3 months. At 15 months’ follow-up, there was a trend towards higher recovery rate in the intervention group (62% vs 37%).

Conclusion An intervention study of combined CBT and music therapy in postinfectious CF is feasible, and appears acceptable to the participants. The tendencies towards positive effects on patients’ symptoms and recovery might justify a full-scale clinical trial.

----------------------

 

And all of it based on the assumption -

I'd love to know how they define effective here. As far as I'm aware the numbers do not add up to value for money and if it was a drug NICE would probably refuse it on those grounds alone.

 

Nina E. Steinkopf has an opinion piece in a medical newspaper today about this study. She draws parallels to a Lightning Process-study that might take place which Wyller will be part of. She also calls for biomedical research being prioritised from now on.

The result of the study was that the participants in the intervention group received a significantly reduced level of function. They became more depressed, more exhausted and was in more pain. 38 percent withdrew along the way. Despite the findings, the researchers conclude that "the tendencies for positive effects on patients' symptoms and recovery can justify a full-scale clinical trial ." The result is a research article with contradictions and illogical conclusions, which essentially disproves own hypotheses and conclusions.

The study is likely to be referred to by the health authorities. It can be used in treatment recommendations and possibly be used in decisions made by the Norwegian Labour and Welfare Administration. This can cause patients to continue to be treated with inactive or harmful treatment methods.

This study is another example of research that causes patients to despair.

ME-pasienter skal ikke lide under forskningen
google translation: ME patients should not suffer due to research

 

"This would be a very very good high school science fair project."

Put me in, coach.

 

Steinkopf has written a lot of good pieces but I didn't think this was a great article. I can only go off the google translate version, but I thought it too readily classes things as pseudoscientific, without explaining to readers why. The results from the study were very weak, and I don't see what justified this claim of those who received the treatment (I feel as if I must be missing something here): "They became more depressed, more exhausted and more painful." I also thought that some of the examples of good research were not great. Given all the problems with this research that Nina had already written about I'm surprised that this article chose to focus on the claims it did.

I'm sorry for being a fool, but I still can't see the supplementary material - could anyone link me?

 

I can't work out how to link it here but in the full text of the article a bit under the subheading "Therapists, techniques and principles in the mental training programme" there is a link to the supplementary material.

 

Only skimmed the thread & the paper.

It's hidden in the full text: https://bmjpaedsopen.bmj.com/conten...ne-supplementary-material-1.pdf?download=true

Edit: cross-posted with @Theresa

Also found a related paper in a journal called 'Music and Medicine' :

Trondalen G, Mangersnes J,Bonde LO, et al (2020), Music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents. Music Med 2020
http://mmd.iammonline.com/index.php/musmed/article/view/679
(paywalled)

 

If you go to the article on the BMJ site and search the page for 'supplementary material' you'll find a link on the page. Here's a screenshot:


MSESperanza has linked to it directly in this post:

Marit also helped me find the protocol and other documents about the study here: https://www.ahus.no/fag-og-forsknin...esyke-hos-ungdom#relevant-sentral-informasjon

The interesting thing is that this study was only powered to detect large treatment effects. This wasn't due to a problem with recruitment because the protocol aimed for only 25 patients in each group. The authors justified this design by arguing that they expect to find large effects and that only large effects are relevant. Or more precisely they wrote:

When the intervention didn't produce a large treatment effect (it actually did worse than the control group who got nothing) everything about the study seemed to have changed. Now trends toward statistical significance are highlighted instead of saying that "only a substantial effect size is of direct clinical interest" and the study seemed to have morphed from a randomized trial assessing efficacy to a feasibility study.

I hope to write about this study when things get calmer after ME Awareness day, there seem to be quite a lot of problems...

 

Wyller has written a reply.

Nina Steinkopf's review of the study online in Dagens Medisin contains both falsehoods, omissions and inaccuracies. Thus, she unfortunately helps to confirm the suspicion that there are "ME activists" who are running a smearing campaign against research results they do not want. This is not in the patient's best interest.

...

All in all, this study is a small but important contribution in trying to improve the treatment options for patients with long-term fatigue. This, I believe, is welcomed by the vast majority of ME patients.

Svertekampanjer styrker ikke pasientenes interesser
google translation: Smearing campaigns doesn't strengthen the patients' interest

 

Which he knows to be false. "I believe", weasel words. What immoral hackery is this?

The fanaticism is simply stunning. Everyone hates it. We hate it because they are incompetent and recklessly indifferent to the impact they are imposing on us, because people are needlessly dying and suffering, much of this suffering on purpose. They hate it because we reject their incompetence and that makes them frustrated but they keep going even though it serves absolutely no purpose. It will all end up in the trash, these people will be hated as incompetent blundering monsters and saboteurs. Everything they will have done will be studied expressly for its incompetent cruelty, a study in failure.

So all this for what? They know they aren't helping us we are telling them so and they hate being told. They hate everything about it, never find any satisfaction because even when they push it into practice it fails completely, as it did at every step because it's complete delusional fantasy. So what is this all for? What are the motivations behind this coercive death cult and why is it still allowed to destroy millions of lives on the stupid altar of psychosomatic beliefs?