I expect this in mild patients, but less likely in the severe. It might be more about how bad the other symptoms are. Not only PEM can be very intense.
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A Comprehensive Examination of Severely Ill ME/CFS Patients, 2021, Chang et al
I expect to see a series of papers over time, this is just the first. Maybe someone who knows more about their thinking can comment?
I suspect the measures are done, and its in analysis and publication phases.
Simon M
Senior Member (Voting Rights)
Comments on the Severely Ill ME/CFS Patients Study (SIPS)
In a nutshell: SIPS looks at patients who are much more severely affected than any other study I know of. The impact of their quality of life is more than most other illnesses.
1 – Background and 'how severely affected?'
The idea of this study was that by looking at severely ill patients there would be a greater chance of finding real differences in the patient cohort. They also used family controls as they likely to be better matched on genetics and other factors such as diet, environment during upbringing et cetera. Better matched controls reduces random variation, making it easier to find a true positive result.
The study took a "small but deep" approach. There are only 20 patients and 10 healthy controls but the researchers are looking at them in great detail. As well as self-report and activity levels, they ran cognitive tests (with EEG), sleep profiles and a whole bunch of blood, urine and saliva lab tests.
It's worth noting that patients were visited in their own homes for the physical examination (required for definite diagnosis) and blood, urine and saliva samples were taken at the visit.
The results of multiple omics studies [metabolomics, genomics, proteomics and microbiome] and cytokines are being conducted on the biological samples of these patients to identify molecular signatures of severe ME/CFS, and the results will be reported elsewhere.
How severely affected?
All participants met the International Consensus Criteria (ICC), and were homebound – spending more than 14 hours a day sedentary and in a reclined position as reported by the patient or caregiver. This report was checked later by Fitbit data.
The average (median) number of daily steps was 912.
— The average SF 36 physical function score was 13/100, much lower than seen in most general surveys of any CFS patients. (Pace trial participant average was about 35).
— The average social functioning score was 4/100, compared with 92.5 the controls.
— on the Karnofsky scale, 35% were classed as disabled, requiring special care and assistance (hospital admission was indicated 5for one patient with this). 50% of patients (the most able group) require occasional assistance but are able to care for most personal needs.
SIPS patients stood out as far more disabled and affected by the illness then a whole bunch of other illnesses. Compared to other major diseases, these severely ill any CFS patients have lower scores in six of the eight scales. The exceptions were Role Emotion and Mental Health.
Quality of life scores were most positively correlated with Congestive Heart Failure. And most negatively correlated with clinical depression.
The graph below shows SF 36 scores for these patients versus a representative group of illnesses (the less-severe comparison illnesses were removed from the image for clarity).
Note that the comparison is with a general selection of patients while the ME/CFS group were selected because they were all housebound.
Sleep quality was pretty poor, with an average score out of 21 of 11.9 compared with 2.3 for controls.
2. Symptoms and statistics
Statistics and interpreting results
There is a statistical issue baked into the study because they are looking at everything, the study inevitably involves a huge number of comparisons. This means that P <0.05 is much too high to use as the threshold. Excluding the clinical tests (which did apply some statistical correction), I counted well over 40 different comparisons. As a result of this, there will almost inevitably be some false positives reported.
To compound this problem, the study is small so that comparisons are between 20 patients and 10 controls. As a result, differences have to be very large to meet even <0.05. This increases the chance of false negatives (missing true findings).
In other words, treat the results with a degree caution.
Symptoms
The study assessed an enormous number of symptoms using a range of different questionnaires. To simplify things, the researchers pooled these into the five symptoms required by the Institute of Medicine (IOM): fatigue, PEM, sleep disturbance, cognitive impairment and orthostatic intolerance. As well as seven additional common symptoms relevant to ICC, such as pain and flulike symptoms.
Because different questionnaires were used, the researchers standardised scores for all questions, so that a pain score from one questionnaire could be directly compared with physical function from another.
The researchers also asked patients to list their first, second and third most troubling symptoms.
Results
100% of patients had PEM, fatigue, sleep and cognitive symptoms; 80% also had orthostatic intolerance – and every patient met the IOM criteria as well as the ICC.
Figure 2B from the paper shows the top three symptoms reported by patients, ranked as first, second and third most troubling.
Although post-exertional malaise doesn't feature strongly, as @Trish pointed out, PEM is defined as a symptom flare so its constituent symptoms might show highly instead. PEM was also ranked second, behind fatigue, for the "first most troublesome symptom".
To be continued, if there is interest.
Andy
Retired committee member
I think this highlights an issue with how PEM is defined, and even how it is understood by all parties involved. As we have often discussed here, the most severely ill ME patients could very well be in a continuous state of PEM, so if the definition of PEM is given as exclusively a flare of symptoms then it may not be capturing what exactly is happening. The problem obviously is how could that be proved? Until we have an actual test for PEM I can't see how it can be.
Sly Saint
Senior Member (Voting Rights)
This article belongs to the Special Issue ME/CFS – the Severely and Very Severely Affected
https://www.mdpi.com/journal/healthcare/special_issues/me_cfs_issue