GETSET (white) in Lancet 22/06/17

[Barry53]

Our trial has limitations. ... All outcomes were self-rated, which might lead to bias by expectation, although the effects of such self-rating are uncertain because of the mixed perception of GET.30 We did not measure any objective outcomes, such as actigraphy, which might have tested the validity of our self-rated measures of physical activity.

Is the above not a blatant acknowledgement their trial was worthless, in the very paper reporting it? Seeming themselves to effectively suggest their findings too unreliable to influence clinical treatments involving physical function?

It's as if they think that by stating an absurd limitation of their trial methodology, that makes the issue go away so it must still be OK. Cloud cuckoo land.

If real scientists had to publish a self-crucifying limitation such as this ... wouldn't they conclude it was better not to publish at all? Or is it just publish and be damned with the outcome (yes I know there is a slight play on words )

 

[Barry53]

Interpretation
GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation ...

So it is self-acknowledged to be an interpretation that needs confirmation. Has the authors' interpretation been confirmed independently and by peer review? If not then should it even remotely be used to influence clinical treatments?

 

[slysaint]

Duration of illness at baseline in the GETSET trial is reported as 46 months for the GES group (that's a median rather than a mean), with an interquartile range of 23-114 months (aka most fell within that range) and 42 months for the control group, with an interquartile range of 75-570 months. This is in table 1, p.6 of the paper. So GETSET participants were generally sick for 3-4 years at the start of the trial, but some for shorter and some for longer.

For comparison, duration of illness in PACE was reported as 32 months with an interquartile range of 16-68 months.

This information tends to be included in papers in a table of baseline characteristics.

Thanks for this; have amended my previous post accordingly.

 

[Barry53]

[my highlighting]

Patients were excluded if they were younger than 18 years, had current suicidal thoughts or comorbid psychiatric conditions requiring exclusion, had read the GES guide previously, had already received GET at one of the trial clinics, were unable to speak or read English adequately, or had physical contraindications to exercise.12 Participants provided written informed consent before entry into the trial.

[my bold]

So a current major depressive disorder did not constitute a "comorbid psychiatric conditions requiring exclusion". So of those whose subjective impressions of fatigue and physical function improved, do we know the distribution within each group? Whether the people with depression at baseline were the same or less depressed later? Was there a stronger bias within this sub-group toward self-reporting of less fatigue and better physical function?

The trial excluded people who "had physical contraindications to exercise", which must surely have excluded an unspecified number of people with genuine ME/CFS. Yet they conclude ...

GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome

Edit: Or am I misunderstanding this bit? Is it saying people with broken legs, other physically evident limitations on exercising?

Edit 2: Is there anything in the published information that clarifies what they mean by "had physical contraindications to exercise"?

Edit 3: Only just twigged the MEA review of this, and that asks the very same question in point 19.

Note: I've not delved through it all, and not all of it is comprehensible to me, so if the answers to the above are actually in the paper it would be good if someone enlighten me.

 

[Molly98]

View attachment 22210
[my highlighting]

[my bold]

So a current major depressive disorder did not constitute a "comorbid psychiatric conditions requiring exclusion". So of those whose subjective impressions of fatigue and physical function improved, do we know the distribution within each group? Whether the people with depression at baseline were the same or less depressed later? Was there a stronger bias within this sub-group toward self-reporting of less fatigue and better physical function?

The trial excluded people who "had physical contraindications to exercise", which must surely have excluded an unspecified number of people with genuine ME/CFS. Yet they conclude ...

Edit: Or am I misunderstanding this bit? Is it saying people with broken legs, other physically evident limitations on exercising?

Note: I've not delved through it all, and not all of it is comprehensible to me, so if the answers to the above are actually in the paper it would be good if someone enlighten me.

Yes I am confused by this, out of all psychiatric conditions, major depressive disorder must be the one where fatigue is a major issue, so most likely confused with ME, and most likely to respond to exercise.
Am I reading this wrongly or are they saying almost 10% of GET group had major depressive disorder and if so doesn't this cancel out most of their improvement findings?

 

[Barry53]

Am I reading this wrongly or are they saying almost 10% of GET group had major depressive disorder and if so doesn't this cancel out most of their improvement findings?

Yes 10% approx. Whether it cancels out presumably depends on the outcome distribution ... if most of the fatigue improvements were heavily biased towards the depression sub-group, then I would guess yes, but I'm not an expert on this by any means. Others much better qualified here in PR. Presumably we have no access to the raw data that holds the answers to any of this.

 

[dangermouse]

So, with the recruiting criteria, do we think it likely that any of these patients actually had ME?

 

[Molly98]

So, with the recruiting criteria, do we think it likely that any of these patients actually had ME?

I wonder if GETSET JULIE was one of these

 

[Molly98]

The thing with Depressive disorders is that Like ME people can go undiagnosed for years and years, society helps keep people in denial, so many do not get help, so in reality, it is very difficult to tell how many of these participants could have been suffering depression and wrongly diagnosed as ME CFS. For some, a diagnosis of depression can be more unwanted than a diagnosis of ME-CFS.

 

[Tom Kindlon]

Do the letters have to be from medically savvy people? Or can they be from anyone who feels they have a slightly different but important take on a flaw/oversight in the paper?

As I mentioned, I have no degree and have had 18 letters published in the past including 2 in the Lancet. I can think of around 20 patients who have had letters published in recent years who have no medical or health care qualifications.

At the same time, it is probably best to include some references. One of course is the original paper you are applying to but best to include one or more others also as it does have to have the format of a publishable letter. On this occasion I only included one other reference but usually I have more as have most other letters that get published.

 

[Tom Kindlon]

Just seen this in The Lancet's correspondence information:-

All accepted letters are edited, and proofs will be sent out to authors before publication

How heavy handed is this likely to be I wonder. That of course is even if something is accepted.

My impression would be that it is not very heavy handed. Mainly to do with technicalities like grammar, syntax, etc. You should get the opportunity to see if you approve of any changes.

 

[dangermouse]

I wonder if GETSET JULIE was one of these

If she was she'd be the star performer for sure! She'd even outperform the therapists!!

 

[Barry53]

So, with the recruiting criteria, do we think it likely that any of these patients actually had ME?

I think one cautionary note would be if I was mistaken re exclusion due to "had physical contraindications to exercise". Would like to know very specifically what that means.

 

[BruceInOz]

Duration of illness at baseline in the GETSET trial is reported as 46 months for the GES group (that's a median rather than a mean), with an interquartile range of 23-114 months (aka most fell within that range) and 42 months for the control group, with an interquartile range of 75-570 months. This is in table 1, p.6 of the paper. So GETSET participants were generally sick for 3-4 years at the start of the trial, but some for shorter and some for longer.

@Karen Kirke, the interquartile range (IQR) you quoted for the control group (75-570) is actually from the next line in the table for Physical activity (min per week). The correct values for Duration of illness (months) are

GES group: median = 46, IQR = 23-114
Control group: median = 42, IQR = 25-99

I was alerted by the fact that the median did not lie inside the IQR.

Based on the differences between the interquartile ranges, doesn't it suggest that the mean duration was probably much longer in the control group? Maybe even by a factor of 3-4 times longer?

@Valentijn, I think this statement is based on the wrong numbers.

 

[Sean]

Patients were excluded if they... ...had physical contraindications to exercise.

Participants provided written informed consent before entry into the trial.

Somehow I doubt they were told the real story.

 

[Barry53]

The lancet 250 word limit is stated ...

Letters for publication in the print journal must reach us within 2 weeks of publication of the original item and should be no longer than 250 words

Does anyone know if salutations and references are included in the word count? Or is it just the body of the letter that must not exceed 250 words?

 

[JaimeS]

The lancet 250 word limit is stated ...

Does anyone know if salutations and references are included in the word count? Or is it just the body of the letter that must not exceed 250 words?

I'd err on the side of caution, there.

 

[Barry53]

I'd err on the side of caution, there.

Except some references are unavoidably very high word count!

 

[Tom Kindlon]

The lancet 250 word limit is stated ...

Letters for publication in the print journal must reach us within 2 weeks of publication of the original item and should be no longer than 250 words

Does anyone know if salutations and references are included in the word count? Or is it just the body of the letter that must not exceed 250 words?

References don't count (a few journals do count them but this is made explicit in my experience).

No need for any salutations.

Also have any reference numbers in the text tight to the previous full-stop/period so they don't get picked up as a word in a word count.

 

[Dolphin]

Manual followed by physiotherapists see http://www.wolfson.qmul.ac.uk/images/pdfs/getset/GETSET therapists
manual%20with%20appendices.pdf

The theoretical model within GET booklet

It is not fully understood why GET helps many people with CFS/ME. Several theories have been suggested and it is thought to be due to multiple factors which may vary from person to person.

One theory which can be used to explain GET, as outlined in the GET booklet is based on deconditioning which is the gradual decline in physical fitness and strength in the body as a consequence of a reduction in physical functioning. Another theory points to an altered perception of effort (this may be more significant than deconditioning). Researchers have noticed that some people with CFS/ME may experience changes in how they interpret the messages that the body gives them during physical activity.

These changes in both conditioning and perception of effort are thought to be reversible. Therefore, by gradually increasing physical activity, this may enable the body to gain fitness and strength as well as making changes to the perception of effort.

Preliminary research suggests that reduced symptoms (including fatigue) are related to simply participating in a GET programme, rather than necessarily getting fitter, whereas improved functioning is related to getting fitter and stronger. Participants are encouraged to see symptoms as temporary and reversible, as a result of their current relative physical inactivity, and not as signs of progressive pathology.

A mild and transient increase in symptoms is explained as a normal response to an increase in physical activity. Apart from the behavioural and perceptual effects of graded exposure to previously avoided physical activities, there may be other mechanisms involved in the success of GET such as reversing deconditioning, including elements of habituation, and positive effects of re-engagement with important activities. GET has also been shown to improve sleep, cognition, and mood; factors that are also likely to perpetuate the condition, although these are not directly addressed in the GET booklet or GES itself.