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Typing myalgic encephalomyelitis by infection at onset: A DecodeME study, 2023, Bretherick et al

Discussion in 'ME/CFS research' started by Andy, Apr 24, 2023.

  1. Andy

    Andy Committee Member

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    Abstract

    Background: People with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) daily experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment or brain fog. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding their pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age.

    Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Their detailed questionnaire responses provided an unparalleled opportunity to investigate illness severity, onset, course and duration.

    Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females’ comorbidities and symptoms tend to be more numerous than males’. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an identified infectious onset; and, (v) where the occurrence of an infection at or preceding onset is not known.

    Conclusions: This revealed that people with a ME/CFS diagnosis are not a homogeneous group, as clear differences exist in symptomatology and comorbidity.

    https://openresearch.nihr.ac.uk/articles/3-20/v1

    [As the DecodeME team are waiting until peer review has been passed before we promote this or make any official comment, I won't be joining in the conversation below until then but will definitely follow it with interest.]

    Edit to add: Final, peer reviewed version can be found here, https://openresearch.nihr.ac.uk/articles/3-20/v4
     
    Last edited: Aug 24, 2023
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  2. Tom Kindlon

    Tom Kindlon Senior Member (Voting Rights)

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    This study has funding to analyse the DNA of 5000 people with ME/#CFS following Covid. At the time of this analysis, only 380 had completed the questionnaire. Hopefully more people with #LongCovid can be reached to take part in this important research.

     
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  3. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    @Andy Can you say where this is submitted, or not? I do hope you're going for a leading / high-impact journal.
     
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  4. rvallee

    rvallee Senior Member (Voting Rights)

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    Damn, that's so disappointing. Such an easy goal to meet, all it would have taken is the tiniest bit of support and messaging. The LC clinics alone could have easily met that goal. The continued forced separation is really screwing everyone over.
     
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  5. Kitty

    Kitty Senior Member (Voting Rights)

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    I didn't realise there were so few questionnaires from people diagnosed after Covid. I wonder whether they're getting diagnosed with long Covid rather than ME, regardless of their symptom profile? The number of online support groups would suggest that at least some of these folk are proactive, engaged, and networked, and it'd be surprising if they aren't taking part simply because they don't want to.
     
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  6. Aimossy

    Aimossy Established Member (Voting Rights)

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    Woah.
    I have waited so long to see work like this and it's starting. I actually cried I was so relieved to see this pre-print paper and genuinely surprised by some of the findings. Well written and important. The beginnings of fundamental work that is so badly needed.

    Thank you DecodeME team.

    ...and hello and welcome to the nice dose of Epidemiology
     
    Last edited: Apr 24, 2023
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  7. NelliePledge

    NelliePledge Moderator Staff Member

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    Interesting as a person almost 60 the findings about severity being higher in older women. I think it’s really important that information about people with severe and particularly very severe ME gets into the public domain. But the only stories I’ve seen highlighted are people in 20s and 30s. Clearly there’s a gap in representation and research needs to be done to find out more about older people with severe ME .
     
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  8. Sid

    Sid Senior Member (Voting Rights)

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    The team are wasting no time putting valuable work out there. Impressed.
     
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  9. Trish

    Trish Moderator Staff Member

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    Interesting analysis. Well done to the team.

    I have a concern about some conditions, particularly IBS and FM, being described as comorbidities, especially if they started concurrently with the ME/CFS symptoms. Rather than separate comorbid conditions, they may be part of the clinical presentation of ME/CFS for many of those individuals, as muscle pain and bowel symptoms commonly occur as part of ME/CFS and are included in symptom lists. I don't know how that can be dealt with in situations like this. Perhaps by asking specifically whether the onset of the FM or IBS was before, at the same time or after the onset of ME symptoms.
     
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  10. Wyva

    Wyva Senior Member (Voting Rights)

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    @rvallee @Kitty

    The other moderator I have in my ME/CFS FB group is a covid long hauler who lives in the UK. She really wanted to participate but she said only long haulers with a diagnosis of ME/CFS can, which she doesn't have. Not everyone gets this diagnosis even if their symptoms are similar to ours (I mean she wouldn't be my moderator in an ME/CFS group if she had some totally different presentation of the post-covid sequelae but these are the rules).

    Actually, this is also what the DecodeME FAQ says:

    I have Long Covid, can I take part?
    We think many people with Long Covid will meet the criteria for ME/CFS, but not everyone. If a health professional has given you an ME/CFS diagnosis, then you can take part.​
     
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  11. Aimossy

    Aimossy Established Member (Voting Rights)

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    One of the things that surprised me was the percentage that said they had IBS being as low as it was. I was personally actually ok about that separations at this time @Trish because more in-depth work on the cohort can happen with questionnaires. They can look further into the things your talking about which are really good questions and information that is needed which I also agree with.
     
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  12. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I think most data of this sort coming from an online patient trawl will be affected by various biases and problematic interpretations. But as long as everyone knows this, and the team clearly will, it is likely that internal comparisons will throw up genuinely useful information. I think it is creditable that the team are getting this out now. As @Kitty, @NelliePledge and @Aimossy point out, the mix of expected and unexpected is intriguing.

    It is interesting that longer duration is associated with severity. One obvious possibility is that this is skewed because those who have stabilised or improved a bit may have decided to 'put their ME behind them' as a way of coping and if I remember rightly people who have got better enough to feel they are no longer ill cannot take part. I do slightly wonder, if numbers are below target, whether it would be legitimate to ask for 'people who once diagnosed with ME' samples. I can think of one or two. It would have to be a separate cohort but it might be an interesting comparator, looking both for common features and differences.
     
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  13. Kitty

    Kitty Senior Member (Voting Rights)

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    Yes, that's what I wondered. In some respects I can understand why some GPs wouldn't take the diagnosis further than long Covid. They might think it's unlikely to help the patient or their doctors to call it by another name if there's a strong link to a Covid infection and the symptoms haven't changed.
     
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  14. Hutan

    Hutan Moderator Staff Member

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    So many good things about this paper including the inclusion of people with ME/CFS in the writing team (including a number of our members), the open peer review that is underway, and the plain English summary for improved accessibility.

    Very minor points that maybe are worth mentioning given the preprint stage
    People with ME/CFS don't necessarily experience the core symptom of PEM "daily". I think "daily" could be removed from that sentence. In the second sentence, the subject is "people with ME/CFS" - there is reference to their diagnosis, their treatment. "Their pathogenesis" is therefore a bit odd, with "pathogenesis" defined as "the process by which a disease develops", it reads a bit as though people with ME/CFS are the disease. It could be fixed by saying "and no scientific breakthrough regarding the pathogenesis of the illness has been made".


    The reference given for that is the IOM 2015 report. However, that report identified just three core symptoms, and none of those, or the two optional symptoms include pain. The IOM report emphasised decreased daily function, but that isn't mentioned in the DecodeME sentence.
    Therefore, I don't think that sentence accurately represents the disease description as set out in the IOM, although I don't disagree that pain is part of ME/CFS. I'd like to see the decreased capacity for function added to the core symptoms. Perhaps if another one or two ME/CFS criteria were added to the references, pain could also be listed as a main symptom.


    Personally, I think it is important to note the requirement for symptom persistence over a number of months, as the IOM did:
    This is particularly so, when the paper goes on to talk about diagnosis rates after EBV, Ross River fever and Q-fever. I think it's important for readers not familiar with ME/CFS to understand that chronicity.


    Long COVID is an umbrella term for heterogenous conditions arising after a COVID-19 infection, but a substantial proportion of people with symptoms following Covid-19 labelled as Long COVID do qualify for a diagnosis of ME/CFS. I think "Long COVID" is actually occurring at a substantially higher rate than around 10%, and is probably a term often best avoided in research papers aiming for precision, especially given that hopeless WHO definition.
    I think it would be better to focus in on post-Covid-19 ME/CFS e.g.
    "Many people with ME/CFS report an infectious episode prior to their initial symptoms. Up to 10% of people with glandular fever (also known as infectious mononucleosis) are eventually diagnosed with ME/CFS4,5, with similar fractions of people with Ross River virus or Coxiella burnetii infections also developing ME/CFS4. There seems to be a similar incidence of ME/CFS after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)."
     
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  15. rvallee

    rvallee Senior Member (Voting Rights)

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    Yeah, makes sense. How was it mentioned recently, "we don't like to give ME/CFS diagnoses"? They still don't. To work out would have required the system to fix itself beforehand. So we have studies on ME hindered by the refusal to acknowledge it, which makes it far more difficult to do because the system is too obstructionist and invested in the tradition.

    A kind of "we'll give you the right to vote if you can pass a law for it, and you can't vote on laws, or the people who vote on laws, and we'll fight you the whole way". Good old Catch-22 disease. It's the only catch we got.
     
    Last edited: Apr 24, 2023
  16. rvallee

    rvallee Senior Member (Voting Rights)

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    Problem with that is that there is no actual term for the feeling sick every day that most of us have, no matter what you do. Fatigue ain't it. There is no term for this other than "malaise" which is also awful because it can be used to mean anything. To me it's a sort of mix between being typically ill, though not as bad as full-on flu with fever, and some sort of TBI/concussion "poisoned" feeling. And then some, because ME is rarely ever just ME, there are so many less typical symptoms.

    So the lack of that term kind of forces to use PEM, since it's not actually possible to exist without exertion. Only coma meets that. So there is some baseline sickness feeling, but medicine is unable to work with the concept of feeling ill without a cause they accept. That's how we got fatigue, and it's caused so much problems.

    And it's still causing problems, with us and LC, because everything is made about some magical level of exertion that people can somehow find and continue indefinitely, then grow like magical beans.

    So I don't see an alternative term that could be used here. Even a better term would need years of spreading the word around, since it would be impossible to get any consensus from the medical community, they categorically reject the very notion that there can be illness when they dispute any disease at all. And even worse, now the standard is that it's happening even with respected diseases. It's not about to get any better, at least until AI medicine gets under way. This is a people problem, a problem of empathy, of being unable to understand other people's subjective experience.

    I've actually seen some dudebros psychosomatizers discuss Selma Blair's denunciation of how long it took for her MS to be taken seriously, and asserting that most of the symptoms look more like conversion disorder. We are still in the golden age of medical pseudoscience, it's growing in every nook and cranny of the profession, spreading like a cancer, or maybe more appropriately like a zombifying fungus.
     
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  17. Hutan

    Hutan Moderator Staff Member

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    The PPI aspects of DecodeME are truly impressive. I'm not entirely sure that all of the information about PPI belongs in this paper, especially given a separate paper largely covers that ground. I'm genuinely not sure, as perhaps the high PPI involvement is such a step forward, it should be shouted about whenever possible.

    That could use a comma e.g. Before the launch of the study, public awareness...

    Figure 2. I think the use of open circles to indicate both the most and least frequently reported symptoms in each question group is confusing, especially as some question groups don't seem to have a least frequently reported symptom in the figure.
    Given that the least frequently reported symptoms in a question group are likely to be less important than e.g. the second more frequently reported symptom, why not delete the labels for the least frequently reported symptoms?


    The questions were, I think, specifically about diagnoses by a medical practitioner. I think it is worth strictly reporting that, as it makes a considerable difference to the interpretation. Also, the label of 'co-occurring' is a bit circular - someone had to decide that these conditions co-occur in ME/CFS and how many to include in the set. So, I don't think the 50.6% of participants having two or more of a set of disease labels tells us much. I think that section would be better as
    "Conditions that participants most often reported having been diagnosed were irritable bowel syndrome (IBS; 41.3%), clinical depression (32.4%...."


    On the "clinical depression" - were participants asked specifically about that, or did they report clinical depression, as opposed to just 'depression'? As far as I can see, clinical depression is severe e.g. this from the Mayo clinic:
    So, is the 32.4% for people who reported either clinical depression or major depressive disorder, rather than just depression? If the 32.4% is for anyone reporting having been diagnosed with 'depression', then I don't think it's accurate to report that as clinical depression. I'm no expert in how UK doctors diagnose depression though.
    Edit - I see that the questionnaire did ask specifically about "Clinical depression". I'd be interested to know of UK people see this as synonymous with Major depressive disorder.
     
    Last edited: Apr 25, 2023
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  18. Lidia Thompson

    Lidia Thompson Senior Member (Voting Rights)

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    There's another thing they could do with taking into account: Those that have been ill for a long time and particularly those who were very sick throughout their childhood, often say they have recovered when they are adults. However, they do not actually realise how sick they actually still are. Their functional capacity is way below average for their age, they just don't know it. Pressumably, they do not actually remember or even know what it feels like to be well, so to them a substantial improvement feels like recovery.

    Here are some musings from Dr. David Bell on the topic:

    "My greatest concern is for the years from 35 to old age in persons who became ill as teens. In our first study of teens who became ill in 1985, we concentrated on risk factors and epidemiology rather than on the progression of symptoms5. At thirteen years after onset, we studied the same patients, now young adults, and we noticed a discrepancy between how they rated their overall health and their activity level6. Some of the young adults rated their health as “good,” while the amount of activity they could perform was minimal. They had become so used to their performance level, they accepted it as their new normal. Unfortunately, many of them, while they described their health as good, they were unable to work full time or carry on other duties.

    This same group of young adults was studied again at twenty five years after onset, and this pattern became more pronounced7. In this latter study, only five subjects said that they still carried the diagnosis of ME / CFS, despite their activity being limited and the symptom pattern persisting. All studies employed the Rand-36 (SF-36), a questionnaire is common use. The first question of this instrument is ’how would you rate your health?’ Many of the patients rated their health as ‘good’, while the rest of the questionnaire demonstrated how poorly they were actually functioning.

    ... Forty year old adults who had an acute onset during their teenage years have the activity of seventy year old adults."
    1. https://www.omf.ngo/prognosis-of-mecfs/
    2. https://www.massmecfs.org/more-reso...in-chronic-fatigue-syndrome-rising-incapacity
     
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  19. Hutan

    Hutan Moderator Staff Member

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    Interesting re recruitment:

    Again, I think better wording would be "Females with ME/CFS reported more comorbidity diagnoses..."
    I think it's likely that females with ME/CFS may be more likely than men with ME/CFS to be given diagnoses like depression and fibromyalgia by doctors.

    Figure 4 with an analysis of associations of reported symptoms with age and sex is very well presented and is worth a look. Sleep issues and mood issues seem to be more common in younger participants. Perhaps there is some interaction there, between sleep problems and mood. Perhaps too, younger people feel most disturbed about missing out on life. I imagine that older people are more likely to have had ME/CFS for longer, and may have developed a higher level of equanimity.

    I thought that was interesting.
     
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  20. Hubris

    Hubris Senior Member (Voting Rights)

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    From my experience, i have seen the exact opposite. The most severe patients tend to be young males, or just young in general. I am fairly confident that this is the case. As you say, an explanation might be that the severe young patients eventually get a lot better and put their past behind them. I have noticed this trend too, actually. It may be that the severe young patients who remain severe for their whole life are in fact very rare.

    This could also explain why doctors do not take ME seriously. For an old person complaining about fatigue and pain, and on the "moderate to severe" part of the scale, it could be very easy for doctors to erroneously assume those symptoms are simply a combination of burnout, old age and a sprinkle of depression and mid-life crysis - in the case of women, perhaps the stress of dealing with their kids. For a young mild patient, you can just say it's a psychological issue and that it doesn't concern you because the patient is still able to function at a decent level.

    On the other hand, severe young patients in their 20s or even teenage years are a lot harder to ignore.

    I have been severely ill since my teenage years and have not been able to finish my studies or work a single day in my life. It is hard for a doctor to ignore that. I have seen about 50 doctors and most of them told me they had never seen a patient like me - and that includes psychiatrists.

    I am concerned because i have been severely ill for so long and show zero signs of improving (i only get worse), which is clearly against the trend of young severe patients improving and disappearing from ME circles to carry on with their life. I had a suspicion that I am in fact a very rare patient, and the data seems to confirm that.
     
    Last edited: Apr 25, 2023
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