Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue 2023, Palacios, Komaroff

Abstract


Fatigue is a common reason that patients seek medical care. Only a fraction of these patients meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To determine if ME/CFS is just a more extreme form of fatigue, or a qualitatively different condition, we assessed whether risk factors for ME/CFS and for Severe Fatigue were similar.

An email questionnaire that inquired about symptoms of Severe Fatigue and ME/CFS was completed by 41,802 US female nurses from whom detailed medical and lifestyle information had been collected since 1989: 102 met criteria for ME/CFS, 522 had Severe Fatigue, and 41,178 individuals were without significant chronic fatigue. We used Cox proportional hazards regression to estimate the Hazard Ratio (HR) of Severe Fatigue and of ME/CFS with each of several potential risk factors, according to the level of exposure to each risk factor.

The risk of Severe Fatigue was significantly increased among participants who were older, had a higher BMI in adulthood, used hormone therapy, had increased alcohol intake and decreased caffeine intake. In contrast, these risk factor associations were not seen in people with ME/CFS. A self-reported past history of acute infectious mononucleosis was associated with a non-significantly increased Hazard Ratio of later ME/CFS (HR 1.77, 0.87–3.61) and, to a lesser extent, of Severe Fatigue (HR 1.28, 0.98–1.66).

The different contribution of various risk factors to Severe Fatigue and ME/CFS suggests that ME/CFS has a qualitatively different underlying biology from the more common state of Severe Fatigue.

https://www.nature.com/articles/s41598-023-29329-x

 

Fukuda criteria, with no requirement of PEM.

 

Yet the prevalence of CFS is low in this cohort - 0.24% (102/41802), which is only slightly more than half than the UK Biobank’s 0.42% rate.

 

While the UK Biobank cohort is not typical of the general population, I think it would be fair to say that the cohort of this study is even less typical.

From the Nurses' Health Study website, https://nurseshealthstudy.org/about-nhs/history

"Establishing the cohort
The target population for NHS II was women between 25 and 42 years old in 1989; the upper age corresponded with the lowest age group in the Nurses' Health Study at that time. The NHS II enrollment strategy consisted of a single mailing. Only the potential participants who completed a questionnaire after one request were enrolled, thus identifying the most enthusiastic nurses who would be most likely to continue participating throughout the study.

Investigators contacted state nursing boards that were able to provide information on gender and date of birth or age, and that were in states with large populations. The states in the mailing included: California, Connecticut, Indiana, Iowa, Kentucky, Massachusetts, Michigan, Missouri, New York, North Carolina, Ohio, Pennsylvania, South Carolina, and Texas.

The original goal was to enroll 125,000 women. From the 517,000 baseline questionnaires mailed, the overall response rate was approximately 24% (123,000 of 517,000). After exclusions for incomplete forms and ineligibility, a total of 116,430 women remained in NHS II cohort.

Research focus
Every two years, cohort members receive a follow-up questionnaire with questions about diseases and health-related topics, including smoking, hormone use, pregnancy history, and menopausal status. Response rates to NHS II questionnaires are 85-90% for each two-year cycle.

In 1991, the first food-frequency questionnaire was collected, and continues to be administered at four-year intervals. Items on quality of life were first included on the 1993 questionnaire and continue to be administered every four years."

I'm not going to try to list the factors that might make this group more or less likely to experience ME, just highlighting that comparisons between the two groups might not be fair.

 

Given that this is not what the patients are reporting, there is really no need for that. It's not. Sadly lots of people are misguided and believe so, but I don't think they can be reached, they're not exactly bothered by accuracy, or evidence, or taking their job seriously.

This approach to medicine where they go with what they think, rather than what is actually happening to the patients, is pure garbage. I don't know where along the way medicine stopped caring about sick people and made everything about diseases in textbooks and limited diagnostic tests, but it's literally one of the worst things done by any profession in the entire history of our species. What a terrible, myopic approach.

 

As a member of that cohort, filling out the endless food-frequency questionnaires was a royal pain and those did not seem valid to me, as they relied on one's memory of what was eaten a month ago. I complained to the researchers about that and they assured that it was valid enough.

 

"It's valid enough to look good in our study." I don't consider my memory of what I ate yesterday to be reliable. What I ate a month ago is pure guesswork, and almost guaranteed to be wrong. It would be even worse for people who worry about what other people might think about their diet, so there would likely be false memories involved ("I'm sure it was bran muffins rather than cupcakes, and I only had chocolate once!").

I suppose their definition of 'fatigue' which encompasses both normal 'worked long hours' fatigue and ME's 'fatigue-like symptom' is also "valid enough" for their purposes; purposes which have nothing to do with helping patients or doing actual science.

 

Komaroff.

 

They compared patients who met the first criterium of the Fukuda criteria (severe unexplained fatigue) to patients who met the first and second criterium (4 out of 8 additional symptoms).The first group was labelled severe fatigue, the second ME/CFS. All diagnoses were based on retrospective questionnaires, so without clinical examinations.

The results are interesting thought in that increasing age, increased BMI, smoking, alcohol intake etc. were all significant predictors for severe fatigue but not for ME/CFS.