Risk factors for severe ME/CFS, 2009, Pheby and Saffron

[Hutan]

https://bnu.repository.guildhe.ac.uk/id/eprint/9823/1/Pheby, Derek Risk factors for severe ME & CFS.pdf
2009 paper
Derek Pheby and Lisa Saffron

Abstract

ME/CFS is a serious illness affecting several hundred thousand British people. Some 25% of people with ME/CFS may be severely ill (housebound or bedbound), sometimes for decades. This observational, questionnaire-based study was designed to identify risk factors for severe disease. Exposure to potential risk factors, including familial risks, personality, and early management of the illness, was compared in 124 people with severe disease and 619 mildly ill controls. Severity was determined by self-report and the Barthel (activities of daily living) Index. Premorbid personality was assessed using the Neuroticism and Conscientiousness domains of the IPIP scale. Analysis was by tests of association and logistic regression. Early management of the illness appeared the most important determinant of severity. Having a mother with ME/CFS was also important. Smoking and personality were not risk factors, neurotic traits being more frequent among the less severely ill. Conscientiousness overall was not related to severity.

 

[Hutan]

I've put this 2009 paper in a the 'psychosomatic research' subforum as it investigates whether personality is a risk factor in the severity of ME/CFS. It seems to conclude that it is not.

This paper has been cited as evidence of the need for early management in order to manage the risk of developing severe ME/CFS. Neither the information resource nor the abstract here suggests what 'early management' is associated with lower risk, so I thought it was worth having a look.

 

[Hutan]

On personality type:

Personality type did not appear to constitute a risk factor for severe disease. There was an inverse association between neuroticism and severity, but none overall between conscientiousness and severity. Mean scores for neuroticism were consistently higher among mildly ill subjects than among the severely ill, which may indicate either that severely ill people may develop a degree of stoicism that affects their responses to personality questionnaires, or that the mild category included some people whose illnesses were not ME/CFS at all, but other fatiguing conditions which may have been related to personality.

There was no association overall of conscientiousness with severity, but, among the sub-domains of conscientiousness, self-efficacy and self- discipline were more marked among the severe cases, which may indicate that only the most motivated of severely ill people persevered to the end of the questionnaire.

I liked that the authors recognised that their investigation approach created a bias, with determination, stoicism and aspects of conscientiousness like to have been prevalent in those people with severe ME/CFS who chose to participate and actually finish the questionnaire.

In fact, they were remarkably frank about the feedback they got from participants, who criticised the fact that they were contemplating the possibility that the illness was driven by personality and also the cognitively demanding nature of the survey.

Personality tests are designed for well people and are meant to be completed rapidly. Instructions to score 135 statements in 15 minutes elicited useful feedback on the inappropriateness of these instructions for people with ME/CFS. “Do you seriously expect brain fogged people to do the personality questions in 15 minutes or less, to cope with things like the double negatives involved and to remember accurately what they were like pre ME?” Multiple questions for each sub- domain were included for greater accuracy, but the cognitive dysfunction associated with ME/CFS, together with fatigue, may have contributed to inaccuracy.

The existence of a personality test in the questionnaire angered some people and may have contributed to the low response rate. Some of the comments made by respondents illustrate the strength of feeling about the role of personality in ME/CFS, e.g.: “I hope no one answers this totally biased questionnaire. I have a physical illness!!!” and “I had hoped this old chestnut had been buried long since about perfectionist personality being a factor in severe ME. If any substance to it, then there would be a veritable epidemic of ME among chief executives and the driven personalities of the city.”

This was no great surprise. There is widespread and deep-seated sensitivity among people with ME/CFS regarding suggestions that ME/CFS is primarily psychological in nature, to the extent that even to ask questions of this nature elicits antipathy, even though it is necessary to undertake research in this area if the hypotheses considered objectionable by people with ME/CFS are to be rejected.

On other studies:

A recent study (Le Bon et al., 2007) suggested that personality does not play a major role in CFS. This is consistent with our findings, which are also in line with those of the Dubbo study, in which persistence of post-infective CFS was largely related to the severity of the acute illness, rather than to demographic, psychological or microbiological factors. In particular, neuroticism was unrelated to the development of prolonged illness (Hickie et al., 2006).

(Note that years later Hickie and others wrote a very bad paper where they tortured the Dubbo data trying desperately to show that actually neuroticism was related to prolonged CFS.)

 

[Hutan]

On depression:

A review of studies published from 1982 to 1992 (Manu et al., 1992) concluded that the majority of patients with CFS have a high prevalence of current major depression and abnormal personality traits. It is likely though that studies showing a positive association between ME/CFS and depression are reporting a consequence of the way in which ME/CFS patients are treated rather than an association with pre-morbid personality or pre-existing mental illness.

 

[Hutan]

On factors associated with severity:

Major risk factors for severe disease included being female, and having a family history of ME/CFS. Early management of ME/CFS appeared also to be a major determinant of severity. The logistic regression model was refined without loss of precision to a final model comprising just six variables, viz. occupation, problems with social security, interval between falling ill and diagnosis, perceived value of initial treatment, relationship with GP before and after diagnosis, and involvement of a psychiatrist in initial treatment, all but one of which, it will be noted, pertain to the management of the condition in its early stages.

Familial factors

37.9% of severe cases reported a family history of ME/CFS, compared with only 17.1% of mild cases. This was statistically highly significant

There was a strong association between having a mother with ME/CFS and developing severe disease, less strong associations with having a sibling or child with ME/CFS, and no association at all with having a father with the illness (table 4).

Pre-illness exposures

There was no association between smoking habits and development of severe ME/CFS (table 8) (chi sq. (Current smokers v. Non- smokers) = 2.45; p = 0.118). Severely ill subjects were more likely than mild cases to have reported exercising six or more hours per week prior to falling ill (chi sq. = 6.4; p = 0.009) (table 9). As regards last occupation before
developing ME/CFS, homemakers and students were over-represented in the severe category, while teachers and academics were under-represented (table 10). Working night shifts before falling ill was not a risk factor for severity.

 

[Hutan]

Management in the early stages of the illness

Two-thirds of the respondents received treatment in the early stages of the illness (66.6% of mild cases, and 67.7% of severe cases). Among those subjects who did receive treatment in the early stages of the illness, 32.7% of mild cases (98 out of 300) found treatment in the early stages of the illness to be useful, compared with only 11.5% of severe cases (6 out of 52) (chi sq. = 8.52; p = 0.0035). By contrast, 73.1% of severe cases found it damaging, compared with only 30.0% of mild cases (chi sq. = 44.7; p <0.00001).

Table 17 summarises the extent to which respondents found the attitudes of professionals involved in their initial care after diagnosis helpful or unhelpful. It will be noted that severe cases were significantly less likely than mild cases to have found helpful the involvement or clinical psychologists, and significantly more likely to have unhelpful the involvement of social workers.

Conclusion
I really don't think we can make much of the findings about management in the early stages. People who have severe ME/CFS or are naturally getting worse can be expected to have a poorer relationship with their doctors, versus others who aren't so affected or are improving. They are also more likely to get treated by psychologists. They are more likely to be dissatisfied with the treatments they are given.

There isn't evidence here for people who are given activating therapies becoming worse - the right questions for that are not asked.

Similarly, we would expect people with more severe illness to have more social problems including problems with social security - because their need is greatest, and they have the least capacity to jump through the hoops, and because the degree of skepticism about their illness is likely to be greatest. I think the direction of causality is 1. severe illness>>> 2. problems with medical and welfare staff and a longer diagnostic odyssey.

Weirdly, given the comments about sex and familial relationships being predictive of severity, these are the items in the paper's model:

• Occupation
• Problems with social security
• Interval between falling ill and diagnosis
• Perceived value of initial treatment
• Relationship with GP before and after diagnosis
• Involvement of a psychiatrist in initial treatment

I think there may have been some correlations e.g. between sex and occupation there.


But yes, in summary, I don't think this paper should be cited as evidence that initial management makes a difference in disease outcomes. It doesn't track changes in severity from the first weeks until later.

 

[Utsikt]

But yes, in summary, I don't think this paper should be cited as evidence that initial management makes a difference in disease outcomes. It doesn't track changes in severity from the first weeks until later.

I suspect that the people that are happy received less GET and more pacing (not a treatment). I’m severe due to the treatment I received the first two years - exercise. I have no way of proving any of this.

 

[Midnattsol]

I suspect that the people that are happy received less GET and more pacing (not a treatment). I’m severe due to the treatment I received the first two years - exercise. I have no way of proving any of this.

I've never been more thankful for being lost in the system than I am for having dodged the bullet of exercise treatment for ME when I dropped out of high school and got no help. In stead I got two years of taking things at my own pace and eventually was able to complete school and go to university.

 

[Utsikt]

I've never been more thankful for being lost in the system than I am for having dodged the bullet of exercise treatment for ME when I dropped out of high school and got no help. In stead I got two years of taking things at my own pace and eventually was able to complete school and go to university.

It’s absurd situation when you would rather have your severe illness ignored than getting the standard treatments. I’m glad you dodged the bullet!

 

[Hutan]

I suspect that the people that are happy received less GET and more pacing (not a treatment). I’m severe due to the treatment I received the first two years - exercise. I have no way of proving any of this.

Before diagnosis, 2.9% of the people with mild severity got CBT while 6.5% of the people with severe severity got it. Also before diagnosis, 3.7% of the people with mild severity and 8.5% of the people with severe severity got GET. So, it's possible that these therapies made people get physically worse. It's certainly possible that these therapies contributed to poor relationships between the severe ME/CFS people and their health providers.

But, it's also possible that people who were already struggling with being very ill were prioritised for places on CBT and GET, and that's why they got the treatments.

I guess we need to track function and treatments in stratified Long Covid groups over time so that we can actually answer the question going forward.

 

[bobbler]

On factors associated with severity:




Familial factors



Pre-illness exposures

That first quote box is interesting. In the factors associated with severity there are six and one was ‘involvement of a psychiatrist’ but there isn’t detail whether this harmed (ie an indicator people got more severe because of being put through bad treatment due to errrant suggestions of psychosomatic cause) or was associated with less severity

I haven’t had the chance to look (and won’t fit a bit so might forget) whether the paper provides more detail on this

 

[Yann04]

There was a strong association between having a mother with ME/CFS and developing severe disease, less strong associations with having a sibling or child with ME/CFS, and no association at all with having a father with the illness (table 4).

My mother has suspected mild ME/CFS and I have very severe ME/CFS.

I was also a student exercising 6+ hours per week which the thing says are risk factors. It’s weird how much it mateches my n=1.

 

[Creekside]

I didn't do any conscious management of my ME for the first 10 or so years, since I didn't know I had ME. I didn't even recognize PEM as a reliable effect of some activities for maybe 8 years, and didn't make an effort to avoid those activities. So, I think sensitivity to exertion, for PEM and for long-term worsening, is another of those sub-group things. Until they can identify the factor involved in that, it's safest to recommend avoidance of exertion.

 

[Yann04]

If the mother having ME increases risk finding is replicated in a larger cohort, would that hint that something that makes ME more likely or worsens ME severity might be hiding in the X chromosome?

(Potentially also explaining the female bias)

 

[Midnattsol]

If the mother having ME increases risk finding is replicated in a larger cohort, would that hint that something that makes ME more likely or worsens ME severity might be hiding in the X chromosome?

(Potentially also explaining the female bias)

If somethings hides in the X chromosome, women are usually less at risk since we have a copy. But mitochondria DNA is from the mother's line too.

 

[Cinders66]

I don't think anyone Who's been managed badly and become severe doubts that bad management & exertion is why they got severe. We know and warn people about the harms of repeated post-exertional malaise because there is correlation/ risks, so it's not just conjecture. It's like the correlation between eating a lot of cakes and noticing you're getting fat, if you've not got any other good reason as to why you've increased a lot in weight & you know that lots of calories is associated with weight gain.

& in m,e the association with exertion and decline ,occurs in lots of people
After thirty years of people with m.e accumulating moderate or severe or entrenched disability through not getting good early care *plus* the reported happier outcomes of those who did, or at least were not encouraged to push on or exert, . I think we can speak with some confidence on this and I wish we were brave enough to frame severe m.e more in exertion- injury terms. it seems incompatible to me that doctor Shepherd is confident to make chirpy statements about early diagnosis making m.e quite easily manageable but doesn't feel confident enough to directly link terrible NHS care, late diagnosis and pressure to inappropriately exert with the HIGH, Levels of disability, sometimes profound, We have an m.e in the UK..

I quoted that paper to an advocate early on in long covid, who had little grasp of the link between poor early stage management and bad outcomes and illness severity, risking PWLC long term harm that we have endured. She seemed to think the terrible severe ME cases we hear of were Just one of those unfortunate things (which i think is only in a minority of cases) or was related to initial illness severity etc, which probably reflects weak charities messaging around this. Another option to reference is the 2019 patient survey for NICE, where about 10% of people reported being severe pre get & CBT period of "treatment" & 40% after.

I would like to see more research on Post EX malaise in the m.e community to tease out difference in experience eg between male and female or just general presentations & see how diverse - some people seem to report a ceiling of 48 hours of feeling bad and other people can go on for weeks, pain and immune symptoms in response to exertion can vary. I think, even within an m.e diagnosis, there may be different experiences of what is called post-exertional malaise & so different risks associated with exertion.

 

[Yann04]

If somethings hides in the X chromosome, women are usually less at risk since we have a copy. But mitochondria DNA is from the mother's line too.

Doesn’t that depend the illness. Sometimes it defaults to the “healthy” copy (I think that’s called lyonisation), so males would be substantially more at risk, while in some illness just one of the two X chromosomes having a defect will be enough to trigger the disease, (I think that’s called X dominant).

Anyways we aren’t assuming a genetic illness, but perhaps a genetic factor increasing likelihood or severity of illness.

Interesting note about maternal inheritance of mitochondrial genes.

 

[Hutan]

That first quote box is interesting. In the factors associated with severity there are six and one was ‘involvement of a psychiatrist’ but there isn’t detail whether this harmed (ie an indicator people got more severe because of being put through bad treatment due to errrant suggestions of psychosomatic cause) or was associated with less severity

I haven’t had the chance to look (and won’t fit a bit so might forget) whether the paper provides more detail on this

Seeing a psychiatrist was associated with having severe ME/CFS (versus having mild ME/CFS). But, it's just an association; there are at least a couple of reasons why someone with severe ME/CFS might be more likely to be given a referral to a psychiatrist. It's not proof that seeing a psychiatrist worsened ME/CFS.

 

[Hutan]

Another option to reference is the 2019 patient survey for NICE, where about 10% of people reported being severe pre get & CBT period of "treatment" & 40% after.

Does anyone have a link to that readily to hand?

 

[Yann04]

Seeing a psychiatrist was associated with having severe ME/CFS (versus having mild ME/CFS). But, it's just an association; there are at least a couple of reasons why someone with severe ME/CFS might be more likely to be given a referral to a psychiatrist. It's not proof that seeing a psychiatrist worsened ME/CFS.

Wouldn’t you expect a bias the other way too. A lot of [very] severe people wouldn’t be able to make it to an appointment like that or hold a conversation like that.

(Though it’s likely those people were excluded from the study due to selection biases too).