Meta-analysis investigating post-exertional malaise between patients and controls, 2018, Jason and Brown

Sly Saint

Senior Member (Voting Rights)
Meta-analysis investigating post-exertional malaise between patients and controls

First Published
July 5, 2018

Abstract
Post-exertional malaise is either required or included in many previously proposed case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. A meta-analysis of odds ratios (ORs; association between patient status and post-exertional malaise status) and a number of potential moderators (i.e. study-level characteristics) of effect size were conducted. Post-exertional malaise was found to be 10.4 times more likely to be associated with a myalgic encephalomyelitis/chronic fatigue syndrome diagnosis than with control status. Significant moderators of effect size included patient recruitment strategy and control selection. These findings suggest that post-exertional malaise should be considered a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome.

http://journals.sagepub.com/doi/full/10.1177/1359105318784161
 
Those researchers and clinicians who endorse a more psychogenic explanation for the illness consider PEM the result of deconditioning or a learned fear of activity and encourage patients to treat their illness with exercise or cognitive behavioral therapy to learn strategies for re-evaluating certain illness cognitions and adopting recovery focused cognitions (Surawy et al., 1995; White et al., 2011).
 
Effect size

The weighted mean effect size (log(OR)) with a 95 percent confidence interval for all studies was found to be 2.34 (1.81–2.87). Thus, the odds of the presence of PEM being associated with an ME/CFS diagnosis is roughly 10.4 times more likely than the presence of PEM being associated with a non-ME/CFS diagnosis.
I'm not sure where the 10.4 figure comes from or what it means?
 
These findings suggest that PEM may discriminate ME/CFS from healthy or depressed individuals more strongly than it discriminates ME/CFS from other illness groups. This fits with previous literature suggesting that ME/CFS and MDD are distinct entities

MDD: major depressive disorder
 
Limitations

This study has a number of limitations. Most importantly, the number of studies that met inclusion criteria is relatively low (while still being appropriate for meta-analysis). The primary reasons studies were excluded was the lack of reporting on PEM. Many studies focused exclusively on the symptom of fatigue, missing the unique element of post-exertional sickness and symptom exacerbation that PEM describes.
 
Future directions

This meta-analysis was only focused on subjective presence of PEM. While method of PEM assessment (thresholding for frequency and severity versus occurrence alone) was considered as a moderator, it would also be important to meta-analyze PEM severity outcomes in patients versus controls. However, this may be difficult until more researchers begin reporting on the intensity of specific symptom domains rather than just reporting composite somatic symptom scores. Future meta-analyses of PEM should also focus on studies that investigate objective performance on exercise testing, and how well this testing may distinguish between patients and controls. Cognitive functioning has already been investigated meta-analytically (Cockshell and Mathias, 2010), but other core symptoms of ME and CFS (sleep dysfunction, autonomic dysfunction, pain, etc.) could be investigated in a similar way.
 
The moderators with non-significant findings within the meta-regression included: publication status, method of diagnosis, case definition, mode of PEM assessment, and thresholding.

Case definition is possibly a little surprising, but then these were the categories they used based on the data available:
Case definition
Fukuda 2.48 19 90.01**
Holmes 1.76 4 7.47**
Unknown 1.23 3 8.21**
Other 2.68 3 8.29**
Fukuda and Holmes 2.59 2 16.79
 
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