Review Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials 2024 Park et al

Abstract

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients.

Methods
We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively.

Results
Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigue severity of the whole 7,088 patients was 77.9 (95% CI 74.7–81.0), showing 77.7 (95% CI 74.3–81.0) from 54 RCTs in 6,706 adults and 79.6 (95% CI 69.8–89.3) from 6 RCTs in 382 adolescents. Regarding the domain of fatigue, ‘cognitive’ (74.2, 95% CI 65.4–83.0) and ‘physical’ fatigue (74.3, 95% CI 68.3–80.3) were a little higher than ‘mental’ fatigue (70.1, 95% CI 64.4–75.8). The ME/CFS participants for non-pharmacological intervention (79.1, 95% CI 75.2–83.0) showed a higher fatigue level than those for pharmacological intervention (75.5, 95% CI 70.0–81.0). The fatigue levels of ME/CFS patients varied according to diagnostic criteria and assessment tools adapted in RCTs, likely from 54.2 by ICC (International Consensus Criteria) to 83.6 by Canadian criteria and 54.2 by MFS (Mental Fatigue Scale) to 88.6 by CIS (Checklist Individual Strength), respectively.

Conclusions
This systematic review firstly produced comprehensive features of fatigue severity in patients with ME/CFS. Our data will provide insights for clinicians in diagnosis, therapeutic assessment, and patient management, as well as for researchers in fatigue-related investigations.

Open access, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05349-7

 

Lovely, they're measuring a clinically unquantifiable factor (fatigue) to .1% accuracy. That's leaving out the rather important issue of ME's "fatigue-like symptom" not being the same thing as physical fatigue or lack-of-sleep fatigue or probably toxin-induced-fatigue.

For their next trick, they might measure the size of a happy thought to 5 digit accuracy.

 

Also ignores the issue that most trials will not include the most severely affected.

 

GIGO

 

Is there a big ME or ME/CFS issue in South Korea?

 

Can't speak to the prevalence of ME/CFS in South Korea. Publications about ME/CFS from there crop up fairly often but nothing compared to those from the researchers based in the EU, UK and USA. Two of the authors of this paper are listed as being affiliated with the "Research Center for CFS/ME, Daejeon Oriental Hospital of Daejeon University".

 

Short summary:

They searched for RCT, removed those that were high risk of bias according to the Cochrane Risk of Bias tool 2 (RoB2) and converted all baseline fatigue scores of ME/CFS patients into a scale of 0 to 100 point.

60 RCTs with 7088 patients with ME/CFS were included in their meta-analysis. 21 RCTs evaluated the efficacy of pharmacological interventions, while 39 RCTs were conducted to evaluate non-pharmacological interventions.

Among the 60 RCTs, the overall fatigue severity in the total 7,088 participants with ME/CFS was 77.9.

There was no major difference in physical fatigue (74.3), mental fatigue (74.2) or cognitive fatigue (74.2) score. Diagnostic criteria also showed no significant difference probably because there were only 2 RCT that used the Canadian criteria and only one that used the ICC. There was a different for the fatigue questionnaires used. The Dutch CIS questionnaire showed the highest scores.

 

7-8 in a scale out of 10
That's probably expected right?

"I have this symptom, it's bad but it's not the worst I've ever felt right now, 7-8 out of 10"

 

Yes, and further fatigue is variable in ME. On the extreme end I have experienced fatigue so bad I could not move, that is extreme functional impairment. But is this even fatigue? Fatigue is the sensation that goes with that, but it is probably not the same thing. On the flip side I can have periods with no fatigue at all, though I did not experience that with ME until about 12 years ago, prior to that it was all fatigue all the time aside from brief remissions. Yet even without fatigue sensations so many other symptoms remain. Why have we not moved past the fatigue issue to incorporate the broad suite of issues?

 

I think because it's most common along with PEM but PEM is harder to measure. The FUNCAP is probably a welcome step forward in that it's measuring perceived functional capacity. I think most RCTs will now use a combination of FUNCAP and activity tracker to monitor perceived functional capacity and level of actual activity.

 

I think activity measuring should be mandatory in ME treatment RCTs, and desirable in other kinds of ME studies. Perceived fatigue is an interim till we have something objective.