Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: a prospective cohort study,2018,Pedersen et al

Andy

Andy

Retired committee member
I've put this in Research Unrelated to ME/CFS for the time being as the authors seem to do lot of flip-flopping between Chronic Fatigue and Chronic Fatigue Syndrome, it could be that it should be in Psychosocial Research.

Abstract
Introduction
Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection.

Materials and methods
A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents).

Results
In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09 to 1.6]), pain severity (0.2[0.02 to 0.3]), functional impairment (1000 steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2 to 0.6]), verbal memory (correct word recognition) (1.7[0.1 to 3.3]), plasma C-reactive protein (2.8[1.1 to 4.4] for CRP values >0.86) and plasma Vitamin B12 (-0.005[-0.01 to -0.001]).

Conclusions
Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes.
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Open access at https://www.sciencedirect.com/science/article/pii/S0889159118306251?via=ihub
 
Prof. Wyller as principal investigator with his BPS approach is usually a red flag. He is currently doing a trial on music therapy as treatment for CFS and wants to research Lightning Process as treatment as well. But he is highly respected within the establishment and has a lot of influence, particularly when it comes to children/adolescents and ME.
 
A couple of interesting bits
leaving 195 individuals for the final analyses. A total of 91 was classified as chronic fatigue cases (a total score of 4 or more at the Chalder Fatigue Questionnaire, each item scored dichotomously), whereas 27 and 20 individuals, respectively, fulfilled the Fukuda-definition and Canada-definition of CFS
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Of note, the final multiple regression models only explained about one third of the variance in six months fatigue, suggesting that non-charted variables – ranging from genetic markers to family dynamics – might have important impact, and calling for cautious interpretation of the results.
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I think this study is worth us having a careful look at. As a semi-prospective study (measurements 1 month and 6 (7?) months after EBV infection) with a wide range of measurements, it has some good points. Unfortunately, these good points just help to make their conclusion that the study confirms the BPS theory of dysfunctional beliefs seem a lot more credible.

At six months follow-up in the EBV infected group, a total of five did not attend the scheduled visit (Figure 1), leaving 195 individuals for the final analyses. A total of 91 was classified as chronic fatigue cases (a total score of 4 or more at the Chalder Fatigue Questionnaire, each item scored dichotomously), whereas 27 and 20 individuals, respectively, fulfilled the Fukuda-definition and Canada-definition of CFS.
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It's important to note that a large number of adolescents were classified as having chronic fatigue at followup (91/195), but much smaller numbers met criteria for CFS (20 for CCC). The authors believe that their findings for chronic fatigue and chronic fatigue syndrome cohorts are similar (although they give us no data to support that). So they say that chronic fatigue and chronic fatigue syndrome are not different things - and that they didn't have enough people with CFS to draw any statistically valid conclusions separate from the chronic fatigue cohort.

I can't spend more time on it now, but I will try to come back to this study. I'd like to see others have a good look at it. As well as working out how the researchers' bias has affected their conclusions, I think there may be some useful information in it,

(e.g. people infected with EBV had, on average, lower CRP than healthy controls at one month. But those who went on to still be fatigued at followup had, on average, higher CRP than healthy controls at one month. It would be so good to see a scatter chart, with people meeting CFS criteria differentiated.)
 
Hutan said:
The authors believe that their findings for chronic fatigue and chronic fatigue syndrome cohorts are similar (although they give us no data to support that).
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Yeah, they give the impression throughout the study that their results also apply to ME/CFS, because results for this subgroup were similar. Only at the end is it noted that:

"As relatively few individuals in the EBV infected group adhered to case definitions of CFS at 6 months follow-up, a multiple logistic regression analysis featuring CFS caseness as dependent variable was not statistically feasible." ​

Also important to take into account:

"the final multiple regression models only explained about one third of the variance in six months fatigue, suggesting that non-charted variables – ranging from genetic markers to family dynamics – might have important impact, and calling for cautious interpretation of the results."
​
 
A big newspaper, Aftenposten, has an article today about this study.

Aftenposten: 22 unge med kyssesyke er fulgt tett: De som er sårbare, får oftere ME
(200 adolescents with mononucleosis have been followed closely: Those who are vulnerable, more often develop ME

The article is paywalled, so here's a translation of parts of the article.

After the researchers had followed 200 patients over 6 months, they found that nearly half, 91 of the adolescents, were particularly tired.
27 fulfilled the formal criteria for ME/CFS (Fukuda and Canadian criteria)
De other 67 were suffering from fatigue and other symptoms, but did not fulfil the formal criteria for a diagnosis

The participants were tested for over 140 factors for vulnerability. They were asked about biological, psychological and social circumstances which might explain why some develop long term fatigue or ME.

- We found that symptoms of anxiety were twice as strong with those patients that developed most fatigue six months later, compared with those who were least fatigued. Those who were most fatigued, reported twice as much pain at the start of the infection, compared with those least fatigued, according to Wyller.

When it comes to vulnerability, Wyller means anything from how the immune system and hormone system reacts, to the patient's thoughts and feelings.

- Genetic dispositions and sad or harrowing experiences earlier in life are also possible factors of vulnerability. There are reasons to believe that also genes play a role for who develops fatigue/ME after mononucleosis.

Professor Kristian Sommerfelt says the study is thorough, but an explorative study. It doesn't prove in itself reasons for different degrees of fatigue after mononucleosis. He has some objections to the study, amongst other that everything that got registered happened after the patients had gotten sick.

- An important finding is that the degree of the infection, the mononucleosis, seems to have very little to say regarding who later develops fatigue or gets ME. What's important, is how bothered you feel. Worrying and how much worried you are, may play a role. Long term fatigue and ME is not only about the body, or only about "the soul", but a union where both thoughts, feelings and the immune system - and probably also several other factors we still don't know about - play a role, Wyller concludes. He strongly oppose the categorisation of ME as either psychiatric or bodily. - This kind of separation is old fashioned and should not be used. ME is a complex condition - both psychiatric and bodily. Our study confirms this, Wyller says.

Professor Kristian Sommerfelt says - There are a lot we don't understand here. A measurement of worry at illness debut had connection with fatigue six months later. The authors of the study interpreted this as worrying can increase fatigue later. Another and just as reasonable explanation is that those with more explicit illness were more worried because they were more ill, and thus more fatigued. He emphasises that the study discusses levels of fatigue after mononucleosis, not prevalence of ME, who were only 27 of the 91 with fatigue.
 
The article also tells the story of a young man who got mononucleosis when he was 18, was diagnosed with ME and recovered after a year of illness with Lightning Process. He believes one of the reasons he got fatigued after the illness, is that he is particularly sensitive. He believes a lot who gets severe fatigue are Highly Sensitive Persons.
 
Kalliope said:
The article also tells the story of a young man who got mononucleosis when he was 18, was diagnosed with ME and recovered after a year of illness with Lightning Process. He believes one of the reasons he got fatigued after the illness, is that he is particularly sensitive. He believes a lot who gets severe fatigue are Highly Sensitive Persons.
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What bullsh*t. Thank you for reporting @Kalliope
 
Kalliope quoted Aftenposten who said:
Another and just as reasonable explanation is that those with more explicit illness were more worried because they were more ill, and thus more fatigued.
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So the authors have recognized this possiblity but prefer to emphasise
Kalliope quoted Aftenposten said:
What's important, is how bothered you feel. Worrying and how much worried you are, may play a role.
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If pain severity, functional impairment and negative emotions (anxiety) are all correlated with poorer outcome then it seems plausible that it is severity of the acute phase that is the predictor and anxiety just correlates with being more severe, which sounds like a natural response.
 
Kalliope said:
The article also tells the story of a young man who got mononucleosis when he was 18, was diagnosed with ME and recovered after a year of illness with Lightning Process. He believes one of the reasons he got fatigued after the illness, is that he is particularly sensitive. He believes a lot who gets severe fatigue are Highly Sensitive Persons.
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Looks like he's another of the Recovery Norge anecdotes Vogt has been collecting to try to manipulate media coverage with:



edit: I just googled his name and this came up - is this a coaching company?

https://www.purehelp.no/m/company/details/me-cfccoachingphilipgudimstroem/919542071
 
BruceInOz said:
If pain severity, functional impairment and negative emotions (anxiety) are all correlated with poorer outcome then it seems plausible that it is severity of the acute phase that is the predictor and anxiety just correlates with being more severe, which sounds like a natural response.
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It's also worth noting that Dr. Ramsay listed "emotional lability" (mood swings) as a feature of ME.
Emotional lability is often a feature in a person of previous stable personality, while sudden bouts of uncontrollable weeping may occur.
https://www.hfme.org/wramsay.htm
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Emotional lability is also a symptom listed in the Canadian Consensus Criteria.

The International Consensus Primer says:
Other Symptoms 1. Altered mood: Patients may become anxious or develop secondary depression due to coping with a poorly understood, chronic disease, and greatly reduced functionality.
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I'm somewhat embarrassed to say that this happened to me in my early 20's when I was hospitalized for tests about a month after onset. When the doctor arrived, I started to cry (which was totally out of character for me). When he asked why I was crying, I just put up my hands, indicating "I have no idea." The flip side was later feeling extraordinarily amused (practically "giddy") while watching comic monologues on late night talks shows. I was totally aware that my reaction was oddly intense and out of proportion, but I couldn't explain it.

I suspect that some kind of inflammation had affected my limbic system (my doctor suspected a kind of mild encephalitis from the severe infection that apparently triggered my onset). For me, this was only a feature of the first month or so following onset. The crying episode was a singular event.
 
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Esther12 said:
Sort of feels as if his desire to make money from other patients should have been reported.
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it doesn't seem that more has been done with the company besides registering it. but he seems to be part of the "patient" organisation Recovery Norge (for patients who has recovered from ME by their own efforts) and quite a few of the members have financial interests/spouses with financial interest in Lightning Process. Fishy.
 
Forbin said:
It's also worth noting that Dr. Ramsay listed "emotional lability" (mood swings) as a feature of ME.


Emotional lability is also a symptom listed in the Canadian Consensus Criteria.

The International Consensus Primer says:


I'm somewhat embarrassed to say that this happened to me when I was hospitalized for tests about a month after onset. When the doctor arrived, I started to cry (which was totally out of character for me). When he asked why I was crying, I just put up my hands, indicating "I have no idea." The flip side was later feeling inexplicably giddy while watching comic monologues on late night talks shows. I was totally aware that my reaction was oddly intense and out of proportion, but I couldn't explain it.

I suspect that some kind of inflammation had affected my limbic system (my doctor suspected a kind of mild encephalitis from the severe infection that apparently triggered my onset). For me, this was only a feature of the first month or so following onset. The crying episode was a singular event.
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Ditto. I had uncontrollable weeping episodes right at the beginning, but these quickly passed.
 
Kalliope said:
A big newspaper, Aftenposten, has an article today about this study.
An important finding is that the degree of the infection, the mononucleosis, seems to have very little to say regarding who later develops fatigue or gets ME.
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BruceInOz said:
Kalliope quoted Aftenposten who said: ↑
Another and just as reasonable explanation is that those with more explicit illness were more worried because they were more ill, and thus more fatigued.
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Do viral load and other blood work they did actually indicate the severity of infectous mononucleosis?

Did they document how long the patients suffered from acute IM?

I have no idea but I guess that documenting high temperature, measuring the number and size of swollen lymph nodes and the size of spleen and liver repeatedly over time would assess the severity of the acute illness and delay in recovering better than e.g. viral load?

(I remember that I still had a slightly enlarged spleen and liver a couple of months after my blood work showed no signs of an active infection anymore.)

(Edited to add second quote.)
 
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