ME/CFS Science

9) The contested RACGP guideline is part of the Handbook of Non-Drug Interventions (HANDI) project and can be found here:

Is the RACGP HANDI recommendation of incremental physical activity for chronic fatigue syndrome The Handbook of Non-Drug interventions (HANDI) is an online formulary of non-drug interventions, enabling GPs to offer to a greater choice of interventions to their patients.

8 ) The original article can be found here:

Stallard et al. 2026. Is the RACGP HANDI recommendation of incremental physical activity for chronic fatigue syndrome/myalgic encephalomyelitis harming patients?

Invited response to viewpoint article Response to a Viewpoint article about the Handbook of Non-Drug interventions (HANDI).

7) There's also an invited counterargument by Dr. Daniel Ewald with the support of Paul Glasziou and RACGP staff. It can be read here:

6) The letter also states: "Graded exercise therapy misconstrues ME/CFS as deconditioning combined with a psychological fear of exercise. Therefore, therapists actively suppress reports of harm, and worsening symptoms are not recorded."

5) The authors refer to the problems with the PACE trial, the outdated Cochrane review, the lack of blinding in exercise trials and high risk of bias, and reports of harm in patient surveys.

4) These quotes are taken from a new article in the Australian Journal of General Practice.

It's a critique of the guideline "Incremental physical activity for chronic fatigue syndrome/myalgic encephalomyelitis" by The Royal Australian College of General Practitioners (RACGP).

RACGP logo AJGP Logo Advertising AJGP > March > Is the RACGP HANDI recommendation of incremental physical activity for chronic fatigue syndrome Viewpoint Volume 55, Issue 3, March 2026 Is the RACGP HANDI recommendation of incremental physical activity for chronic fatigue syndrome/myalgic encephalomyelitis harming patients? Jacqueline Stallard Stephan Praet Sandeep Gupta Angela Smith doi: 10.31128/AJGP-03-25-7614 | Download article Cite this article BIBTEX REFER RIS

Well done and thanks to the authors of this piece which seems to be well researched 👍👏

Is the RACGP HANDI recommendation of incremental physical activity for chronic fatigue syndrome / myalgic encephalomyelitis harming patients?

www1.racgp.org.au/ajgp/2026/ma...

#MEcfs #CFS #PwME

3) "In the meantime, for evidence-based recommendations regarding the management of ME/CFS, general practitioners can refer to the UK’s NICE and BMJ Best Practice guidelines."

2) "Furthermore, graded exercise therapy should be contraindicated as per the BMJ Best Practice guideline until the National Health and Medical Research Council (NHMRC) has completed its review of ME/CFS guidelines in 3 years’ time."

1) "Given the lack of sound research support for graded exercise therapy in ME/CFS, the contraindication of graded exercise therapy by best practice guidelines in the US and the UK and patient reports of iatrogenic harm, the RACGP guideline [..] should be withdrawn immediately."

Who receives a diagnostic label for fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome? A study in the lifelines cohort Functional Somatic Syndrome (FSS) is characterized by persistent bothersome symptoms not fully explained by known medical abnormalities. FSS includes …

9) Link to the paper:

Tatten et al. 2026. Who receives a diagnostic label for fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome? A study in the lifelines cohort.

8 ) A bit curious that depression and anxiety were associated with lower instead of higher odds of FSS diagnosis. The authors speculate that this may reflect diagnostic overshadowing: somatic symptoms of FSS might have been attributed to a psychiatric diagnosis.

7) Older age, smoking, and reporting a depressive or an anxiety disorder were associated with lower odds of receiving an FSS diagnostic label.

6) Female sex, having lower education levels, various comorbidities, higher healthcare use, and current employment were positively associated with getting a FSS diagnosis.

(see the odds ratios from multiple logistic regression analysis in table below)

5) The rest of the paper looks at factors that differ between patients that received a diagnosis versus those that didn't. They not only looked at ME/CFS but at "Functional Somatic Syndrome (FSS)" which also includes fibromyalgia and irritable bowel syndrome.

4) The prevalence of ME/CFS in this cohort was 1.8% (2,793 out of 152,807 participants), which seems substantially higher than sound epidemiological estimates (which are usually below 1%).

3) So rather than a large number of people with CFS being undiagnosed, it could also be that this CFS Symptom Inventory selects a high number of false positives who don't actually have CFS.

2) A big caveat, however, is that cases were selected using a questionnaire (the CDC's CFS Symptom Inventory) not a clinical examination. Most diagnostic criteria for ME/CFS require a clinical examination to assess symptoms and exclude alternative causes.

1) A new paper from the Lifelines cohort reports that only 14% of people with ME/CFS received a formal diagnosis.

7) Link to the paper:

Tuzzolino. et al. 2026. Identifying post-exertional malaise subtypes: Differentiating physical and mental PEM manifestations
journals.sagepub.com...

6) To digg deeper into PEM manifestations, I think we need better questions than those from the DePaul symptom questionnaire - these focus too much on fatigue after exertion and fatiguability, not on becoming sicker much later after the (over)exertion.

5) The paper claims that "these results indicate distinct PEM subtypes" but I think it looks like the opposite: the difference between groups were not that clear and most (almost 80%) of patients fell in the group with both physical and mental PEM.

4) There was also data on how well patients managed to stay inside their energy envelope using a ratio of estimated expended and available energy * 100. Those under 94 were considered under-exerted, those above 119 over-exerted.

3) Turns out the vast majority (78%) of ME/CFS patients had both mental and physical PEM.

Only 5% fell in the mental PEM only subgroup. This tended to have more males. Otherwise the differences between groups do not look that big.

2) A score of 2 out 4 for both severity and frequency was needed for the following:

- "Mentally tired after the slightest effort", was used for mental PEM.
- “Minimum exercise makes you physically tired", was used for physical PEM.

1) A large study of ca. 2000 ME/CFS patients analyzed post-exertional malaise (PEM) scores and differences between ME/CFS subgroups that mostly experience physical or mental PEM.

This is from Lenny Jason's group in Chicago.

ICD-10 Diagnoses prior to ME/CFS diagnosis in children and young people suggest potential early diagnostic indicators Scientific Reports - ICD-10 Diagnoses prior to ME/CFS diagnosis in children and young people suggest potential early diagnostic indicators

10) Link to the paper:

Wirth et al. 2026. ICD-10 Diagnoses prior to ME/CFS diagnosis in children and young people suggest potential early diagnostic indicators.

9) "Need for vaccination against unspecified infectious disease" had a negative association with ME/CFS while the need for vaccination against influenza or COVID-19 was positively associated with ME/CFS.

Obesity on the other hand, had a negative association (OR: 0.84).

8 ) Some results are interesting though: ADHD had a negative association (OR: 0.80) while attention deficit disorder (without hyperactivity) had a positive association (OR: 1.5) - perhaps because of the cognitive dysfunction.

7) I suspect that for most of these diagnoses the patient might have already had the illness ME/CFS (even if they didn't get a ME/CFS diagnosis G93.3 yet). So the diagnoses given before might be misdiagnoses or comorbidities, rather than risk factors.