UK Genome Wide Association Study (GWAS) project - draft website goes live, feedback sought on recruitment plan, and updates

[Saz94]

Sorry, I'd forgotten all about that! Not having a great day today.

No worries at all, I wouldn't expect anyone to remember. Frankly it's a miracle that I even remember it myself

 

[JemPD]

Would this involve signing up or committing to using their app? Some ME patients don't use smartphones. Others (like me) will not agree to downloading an app on their smartphones.

Edit- also re the app - I found keeping a diary for symptoms and activities a huge additional burden in the past. I also found it to be a wholly negative experience as it just focused my mind on ME all the time.

Me too, I cant bear doing those symptom diaries!

I don't have a smart phone because I cant use it to send texts the lack of keys makes it impossible, & it really irritates me that everyone on the planet is assumed to use one.

But am happy to download an app onto my windows laptop if required.

Did see your post about making things as easy as possible @Andy & that's great much appreciated

This needs to be made very clear in how the questions are asked, because a lot of people don't understand the difference between PEM and PEF and will say they have PEM when they don't really. (Especially since a lot of people in the UK have been diagnosed with ME/CFS purely because they have fatigue and the doctor didn't investigate much further.)

Couldn't agree more.

 

[JemPD]

Don't know whether this has been picked up on but someone on MEAfb said they cant provide saliva for DNA (tried & failed) because of dry mouth. I know that's a side effect of many medications & a symptom of sjorgens too.... So some of those who might want to participate (& qualify) may not be able to produce a sample.

I don't know if there are ways to stimulate saliva but perhaps this should be investigated? & if there are ways they should be made clear on the website - we don't want people like the person I mentioned not signing up because they think they cant produce a sample if there are ways around it... that could be a significant number of people?

 

[Jonathan Edwards]

My guess would be that a mouth rinse with plain water in someone with a dry mouth would probably do but needs checking.

 

[Ravn]

So I will be looking for us to use the fewest questionnaires required for the GWAS to be successful but with the above action we will be making it easier for anybody who wishes to follow-on with any future study, whether that be questionnaire based or not.

The FAQ said:
When people sign up to this study, we will ask them if they are willing to be contacted about taking part (directly, or by agreeing to share samples and data from this study) in new studies, either related to this one or unrelated. This will make it much easier for researchers to recruit participants for studies, speeding up the pace of research.

That sounds like a good plan.
If there are suitable extra questionnaires - and I don't know if that's the case or not - they could be presented as an optional, totally no commitment, entirely voluntary opportunity to participate in additional research. That way they wouldn't put off anybody but could maybe attract people who are keen to contribute to research but who don't otherwise have the possibility to do so because of location and houseboundness.

This needs to be made very clear in how the questions are asked, because a lot of people don't understand the difference between PEM and PEF and will say they have PEM when they don't really.

I agree the PEM vs PEF question is a major confounding issue and needs to be phrased better than is usually seen. I have 3 neighbours with, respectively, heart failure, post-stroke, and post-traumatic brain injury. All 3 would endorse PEF with prolonged recovery time, the latter two also as a result of mental and social exertion, not just physical. So PEF is clearly not unique to ME.

However, their experience differs from mine in 2 main ways:
1) They are fatigued and I'm ill & fatigued.
2) The timing of peak symptom load: their symptoms peak around the end of their exertion, stay high for hours and then slowly improve with rest; my symptoms sometimes start during exertion but always peak the day after, stay high for days and then slowly improve with rest.

Since some members here say they only get fatigue without any additional symptom exacerbation, then maybe any PEM question needs to be very clear about the peculiar timing of PEM?

Is there a chance here to drill down into the whole PEM definition thing? Maybe by subdividing the PEM question, which is undoubtedly part of the basic questionnaire already, into several sub-questions that ask about types and timing of symptoms separately?

When I did the biobank questionnaire last year, there was a question like "do you have fatigue that is not relieved by rest?" I think this is not a good question

I agree, the question "do you have fatigue that is not relieved by rest?" is misleading. One, there would be no point in pacing if the rest breaks didn't reduce symptoms including fatigue at least somewhat. And two, that question, too, could drag in people with other conditions, e.g. un- or misdiagnosed depression or burnout.

 

[Milo]

I agree the PEM vs PEF question is a major confounding issue and needs to be phrased better than is usually seen. I have 3 neighbours with, respectively, heart failure, post-stroke, and post-traumatic brain injury. All 3 would endorse PEF with prolonged recovery time, the latter two also as a result of mental and social exertion, not just physical. So PEF is clearly not unique to ME.

However, their experience differs from mine in 2 main ways:
1) They are fatigued and I'm ill & fatigued.
2) The timing of peak symptom load: their symptoms peak around the end of their exertion, stay high for hours and then slowly improve with rest; my symptoms sometimes start during exertion but always peak the day after, stay high for days and then slowly improve with rest.

It would be interesting to compare diseases and their related post exertional symptoms, markers of inflammation and gene expression, just to name a few.

in general, heart failure and strokes would be an exclusion to get a ME diagnosis. Post concussion present some interesting dynamics that can be messy in untangling considering that some may develop fibromyalgia which is somehow related to ME.

Certainly the more co-morbidities means it gets more complex in determining exactly what Is the cause of Me and what is the pure mechanism of illness. Are there pathways that are shared with other diseases? There are no doubts in my mind. There is value in comparing ME to other diseases, including MS for instance, and post-Ebola also comes to my mind.

Then there is the case of depression, which can be so very common in the general population. Do we exclude all patients with depression? What about Asperger’s and Autism? What about all the overweight patients? What about all patients who have been slapped on the butt as a child?

 

[Saz94]

That sounds like a good plan.
If there are suitable extra questionnaires - and I don't know if that's the case or not - they could be presented as an optional, totally no commitment, entirely voluntary opportunity to participate in additional research. That way they wouldn't put off anybody but could maybe attract people who are keen to contribute to research but who don't otherwise have the possibility to do so because of location and houseboundness.

I agree the PEM vs PEF question is a major confounding issue and needs to be phrased better than is usually seen. I have 3 neighbours with, respectively, heart failure, post-stroke, and post-traumatic brain injury. All 3 would endorse PEF with prolonged recovery time, the latter two also as a result of mental and social exertion, not just physical. So PEF is clearly not unique to ME.

However, their experience differs from mine in 2 main ways:
1) They are fatigued and I'm ill & fatigued.
2) The timing of peak symptom load: their symptoms peak around the end of their exertion, stay high for hours and then slowly improve with rest; my symptoms sometimes start during exertion but always peak the day after, stay high for days and then slowly improve with rest.

Since some members here say they only get fatigue without any additional symptom exacerbation, then maybe any PEM question needs to be very clear about the peculiar timing of PEM?

Is there a chance here to drill down into the whole PEM definition thing? Maybe by subdividing the PEM question, which is undoubtedly part of the basic questionnaire already, into several sub-questions that ask about types and timing of symptoms separately?

I agree, the question "do you have fatigue that is not relieved by rest?" is misleading. One, there would be no point in pacing if the rest breaks didn't reduce symptoms including fatigue at least somewhat. And two, that question, too, could drag in people with other conditions, e.g. un- or misdiagnosed depression or burnout.

Yes that's a really good point, I think the peak of post exertional fatigue is probably a good way to differentiate PEM vs PEF? PEF I'd think the peak ("worst point") would usually be immediately or soon after the exertion, whereas with PEM the peak is between hours to days afterwards.

 

[wastwater]

Will those with named genetic disorders be excluded

 

[Saz94]

Another thing... Some people will think "well nobody else in my family has ME, so it can't be genetic, so this is pointless research". So it would be good to emphasise that that's not exactly what is meant by genetic research.

 

[Robert 1973]

Thanks. What other optional questionnaires would you like to see? SF-36, for example? Yes, we need to ensure that the questionnaire load for a person with ME/CFS is not too great.

I’m not particularly knowledgeable about all the different questionnaires, but I have filled in quite a few over the years. One thing I would like to see included, whichever questionnaires are used, is the opportunity for participants to add, as succinctly as possible, any significant symptoms which they do not feel have been covered by the questionnaire.

After completing research questionnaires about my condition, I have often felt that I haven’t been given the opportunity to record some of my specific symptoms which could help to differentiate my condition from that of someone with the same diagnosis but a different condition or phenotype.

I appreciate that recording and interpreting this type of data could be labour intensive, and possibly impractical with the numbers we are talking about, but there may be innovative ways around that and I think it would be useful to have that data. Better to have the data and not be able to use it than to not have it and wish you did.

[Edited to add: I’ve not managed to keep up with all of this thread so apologies if I’m repeating something that’s already been said.]

 

[JemPD]

Another thing... Some people will think "well nobody else in my family has ME, so it can't be genetic, so this is pointless research". So it would be good to emphasise that that's not exactly what is meant by genetic research.

Yes that was my initial understanding of 'genetic' … I wouldn't know that it meant anything else unless I was an active member here. So i'd say that was a very important point. Perhaps it could be added to the FAQ? @Andy ?

 

[MerryB]

Does everyone get immune symptoms with PEM? I've always had this, but I don't know whether it's universal. If I've only exceeded my energy envelope by a bit, it's nothing more than slightly raised neck glands on waking, which go down again within half an hour.

Once you recognise it – rather than dismissing it as dehydration from mouth breathing, or something like that – it's unmistakable as an immune response. If it is universal, then questions would need to be carefully framed to describe it, as I'm sure some people with mild ME won't recognise it as a PEM symptom.

Do you mean that 'fluey' feeling that happens when you start getting tired?

Yes that's a really good point, I think the peak of post exertional fatigue is probably a good way to differentiate PEM vs PEF? PEF I'd think the peak ("worst point") would usually be immediately or soon after the exertion, whereas with PEM the peak is between hours to days afterwards.

I think this issue is confounded by how the condition can change over time. When I was mild I didn't get clearly delayed PEM. At first I felt ill (fluey, not tired) on exertion without PEM. Then I improved for a while and felt fatigued but not ill on exertion, still without delayed PEM. Then I got worse and felt both fatigued and ill on exertion and took several days to recover. Then got even worse and had clear delayed PEM which was really intense - felt like I was dying and took weeks or months to recover from exertion. Then I started some new medications and now I get the intense symptoms of PEM but in short, intense crashes which last hours rather than days, and which happen immediately after exertion.

So I think it's quite complicated!

 

[Kitty]

Do you mean that 'fluey' feeling that happens when you start getting tired?

For me it happens around 36 hours after I've exceeded my energy envelope – but yes, it is 'flu symptoms.

For me, the pattern's been pretty stable since I became ill in 1976, though of course I didn't know what it was before I was diagnosed. I just thought I got a lot of viruses!

 

[Saz94]

Do you mean that 'fluey' feeling that happens when you start getting tired?


I think this issue is confounded by how the condition can change over time. When I was mild I didn't get clearly delayed PEM. At first I felt ill (fluey, not tired) on exertion without PEM. Then I improved for a while and felt fatigued but not ill on exertion, still without delayed PEM. Then I got worse and felt both fatigued and ill on exertion and took several days to recover. Then got even worse and had clear delayed PEM which was really intense - felt like I was dying and took weeks or months to recover from exertion. Then I started some new medications and now I get the intense symptoms of PEM but in short, intense crashes which last hours rather than days, and which happen immediately after exertion.

So I think it's quite complicated!

What medications are those that have changed your experience of PEM?

Honestly, what you've described suggests that it's worth investigating whether you may have something else rather than ME, because I don't think that's typical. I don't think I had PEM when I was mild either, then I eventually developed a pattern of PEM, and since starting a med recently I seem to have, just in the last few weeks, stopped having PEM (although I still feel shit all the time)... I am wondering whether I really have/had ME after all. (I will write properly about what's happening for me, on the forum in due course. Waiting til things are clearer before doing so.)

 

[MerryB]

Tha

What medications are those that have changed your experience of PEM?

Honestly, what you've described suggests that it's worth investigating whether you may have something else rather than ME, because I don't think that's typical. I don't think I had PEM when I was mild either, then I eventually developed a pattern of PEM, and since starting a med recently I seem to have, just in the last few weeks, stopped having PEM (although I still feel shit all the time)... I am wondering whether I really have/had ME after all. (I will write properly about what's happening for me, on the forum in due course. Waiting til things are clearer before doing so.)

Thank you for your reply, and it's interesting to hear that you have had a similar experience.

It has been ivabradine and low dose tricyclics that have changed my experience of PEM.

My ME was post-viral (mononucleosis, sudden onset) and I was diagnosed as a 'classic case'. All tests normal so far apart from platelets, neutrophils and active stand test.

It is possible I have post-viral autonomic dysfunction instead of ME as I have a lot of autonomic symptoms, but I haven't had autonomic testing.

I have many classic ME symptoms though, such as severe exercise intolerance, zero cognitive, physical or emotional stamina, flu-like symptoms on exertion, sound sensitivity, GI problems, brain fog, memory problems, rapid muscle fatigue, constant thirst, frequent urination, poor temperature regulation ,and horrendous 'crashes' if I over-do things.

Although I will stop there because I'm taking the thread off topic!

 

[MerryB]

For me it happens around 36 hours after I've exceeded my energy envelope – but yes, it is 'flu symptoms.

For me, the pattern's been pretty stable since I became ill in 1976, though of course I didn't know what it was before I was diagnosed. I just thought I got a lot of viruses!

Interesting. I get a fluey feeling immediately after minor exertion, as I am getting tired. But when I have a delayed PEM e.g. from a bigger exertion, I don't feel fluey, more like I have a terrible hangover, all my cells are raging, and I got run over by a truck. It feels like my whole body is having an inflammation attack and I feel extremely weak and woozy, but not like the flu.

 

[Saz94]

Tha

Thank you for your reply, and it's interesting to hear that you have had a similar experience.

It has been ivabradine and low dose tricyclics that have changed my experience of PEM.

My ME was post-viral (mononucleosis, sudden onset) and I was diagnosed as a 'classic case'. All tests normal so far apart from platelets, neutrophils and active stand test.

It is possible I have post-viral autonomic dysfunction instead of ME as I have a lot of autonomic symptoms, but I haven't had autonomic testing.

I have many classic ME symptoms though, such as severe exercise intolerance, zero cognitive, physical or emotional stamina, flu-like symptoms on exertion, sound sensitivity, GI problems, brain fog, memory problems, rapid muscle fatigue, constant thirst, frequent urination, poor temperature regulation ,and horrendous 'crashes' if I over-do things.

Although I will stop there because I'm taking the thread off topic!

Random question but are you on Twitter as @DrHomeslice? Because some of this sounds familiar.

 

[MSEsperanza]

In skimming-only mode so don't know whether this has been suggested:

Will participants be offered support with mailing the samples?

Could be relevant for pwME that have no carers or only tiny support.

Perhaps local support groups could organize collection of samples.

I think it could motivate people to participate in the study if it were announced that said support will be offered where possible.

ETA: This occured to me only after I had filled in the form where I suggested to involve any possible health care professionals who are likely to see pwME, also in collecting the samples for mailing.

 

[MSEsperanza]

If the SMC are involved in setting up press promotion then the prejudices of those at the SMC is likely to shape how reporters view it.

I think this is a worthwhile discussion.

If someone wants to play devil's advocate: Are there reasonable arguments to not fund the study?

(Except cost which is a bad argument for PACE defenders.)

In which way could the findings be misinterpreted?

Of course, the SMC's history shows how unreasonable arguments can be disguised as scientific and have very harmful long term impact.

But some institutions change for the better. Is this also possible for the SMC?

At least, Simon Wessely isn't on the SMC board of trustees anymore:

https://www.sciencemediacentre.org/about-us/governance/

 

[Hoopoe]

At least, Simon Wessely isn't on the SMC board of trustees anymore:

https://www.sciencemediacentre.org/about-us/governance/

Interesting.