Barriers to recruitment in paediatric CFS research: "the focus of the study itself"

I want to mention the study results published by Maria Loades and colleagues [1] today. This piece of research focused on the issue of participant recruitment "in the context of an observational study of mental health problems in adolescents with paediatric Chronic Fatigue Syndrome (CFS/ME) presenting to a specialist paediatric CFS team" and the barriers faced when trying to recruit for such a study. Various obstacles to participation were noted, including an important variable: "the focus of the study itself."

The Loades article is open-access so doesn't need any long post from me. The main points: researchers asked researchers about their research experience specifically focused on "exploring healthcare professionals’ views of recruiting to studies, including the facilitators and barriers to recruitment to this study." 'This study', by the way was an "observational study of co-morbid mental health problems in adolescents with confirmed CFS/ME."

Results: based on interviews with six researchers, various qualitative results were provided. Some interesting points were raised. The ones that stood out for me were related to how researchers themselves talked about the research focus on mental health in relation to ME/CFS. A few choice quotes exemplify this: "…because it’s got depression in the title and um I think um you it just seems a little bit more explanation um by inviting them to take part I’m not suggesting that they are depressed…" and "because it is more objectively more obviously about the mental health side of things I have found it to be a different experience recruiting to this."

I'm sure that for those with some knowledge about the debates on-going in the context of ME/CFS you can perhaps see where I'm going with this. I speak of course about the 'application' of things like the biospychosocial (BPS) model to ME/CFS which has, I'm afraid to say, caused some significant distress down the years to patients, their loved ones and many researchers alike (see here and see here). Indeed, one could argue that the application of the BPS model to ME/CFS, where 'unhelpful thoughts' for example are deemed part-and-parcel of some peoples view of ME/CFS, has been so damaging to the concept of ME/CFS, that any study looking at mental health in the realm of CFS/ME is likely to be seen as 'tainted' by association.

And, as I write, still the BPS beat continues [2] although with scrutiny continuing to follow [3]...

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[1] Loades ME. et al. Obstacles to recruitment in paediatric studies focusing on mental health in a physical health context: the experiences of clinical gatekeepers in an observational cohort study. BMC Med Res Methodol. 2019 Apr 27;19(1):89.

[2] Gregorowski A. et al. Child and adolescent chronic fatigue syndrome/myalgic encephalomyelitis: where are we now? Curr Opin Pediatr. 2019 Apr 30.

[3] Vink M. & Vink-Niese A. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open. 2019;6(1):2055102919840614. 

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Rituximab for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a fail

"B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with ME/CFS [Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]."

That was the conclusion reached in the paper by Øystein Fluge and colleagues [1]. Their findings based on the use of rituximab, "a drug that is often used to treat inflammatory diseases (for example, rheumatoid arthritis) and lymphoma" were not entirely unexpected (see here) as a familiar theme of small scale results [2] being 'positive' but not translating into gains during more methodologically-sound study was rehashed.

The Fluge paper also has an accompanying easy-read summary of the results [3] which really aids my job. The long-and-short of it was that over 150 patients diagnosed with ME/CFS were enrolled into the study. Most had been ill with ME/CFS for several years. They were randomly assigned to receive either rituximab or saline (control) over the course of 1 year. Said timing and dosage of rituximab started with "2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months." Participants completed various 'self-reported' questionnaires about their fatigue and functioning over a 2-year period alongside some more objective measurement of physical activity. Results were collated, and well, there was very little difference between rituximab and saline use noted when comparisons were made. What was notable in the published findings were the quite high rates of side-effects observed: "Twenty patients (26.0%) in the rituximab group and 14 (18.9%) in the placebo group had serious adverse events" and over a third of those adverse events were considered 'possibly or probably related to' rituximab use.

What's more to say? Well, the discrepancy between these latest findings and other previous results suggests a couple of potentially important processes *might* be at work. First, the placebo response seems to be quite prominent in this patient group. I say that on the basis that the calculated placebo response among those receiving saline ranged between 25-50% across the various centres that recruited participants for this study. Other commentators (see here) have similarly mentioned how the placebo response seems to be typically quite high in ME/CFS, and how that might have also been on show in other studies too (see here). This could have lots and lots of implications for various intervention trials relevant to ME/CFS. Second, one has to consider that similar to various other labels that include some significant heterogeneity 'under them', there may be responders and non-responders [4] to consider in relation to the use of something like rituximab [5]. Third, and also quite important is to mention that although negative, these results don't invalidate the idea that immune function seems to have something of an important relationship with quite a few cases of ME/CFS (see here for example).

Having said all that, it is difficult to talk about further research on rituximab with ME/CFS in mind on the basis of the Fluge negative results. Not least because, like all medicines, there is a risk-benefit balance to be struck with such a preparation and failures using gold-standard experimental methodologies cannot be easily brushed under the scientific carpet...

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[1] Fluge Ø. et al. B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Annals of Internal Medicine. 2019. April 2.

[2] Fluge Ø. & Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28.

[3] Patient Summary: Rituximab for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Annals of Internal Medicine. 2019. April 2.

[4] Rekeland IG. et al. Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome. Clin Ther. 2018 Nov 28. pii: S0149-2918(18)30514-9.

[5] Morris MC. et al. Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically Relevant Phenotyping of Women With Chronic Fatigue Syndrome. Clin Ther. 2019 Mar 28. pii: S0149-2918(19)30112-2.

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Post-Exertional Malaise (PEM) in ME/CFS: what do patients say about it?

"The findings of this survey suggest that there are key domains of this symptom, including triggers, symptom onset, and duration, which have often not been comprehensively assessed in a previous PEM [post-exertional malaise] instrument."

So said the findings reported by Carly Holtzman and colleagues [1] (open-access available here) examining (yet again and yet again) an important part of the clinical profile of the conditions known as myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): post-exertional malaise or PEM.

Although still the source of some debate (see here), PEM basically refers to "a worsening of ME/CFS symptoms after minimal physical or mental exertion." Some authors have used other words to describe PEM - "payback" is one of them - but the sentiments remain the same: a physiological (and psychological) 'cost' following exertion. And said exertion does not necessarily have to be over-exertion either.

In light of the 'confusion' around PEM, Holtzman et al decided on a rather sensible course of action: "to try to develop a comprehensive measure [of PEM] with active collaboration of the patient community." This follows other independent research that has reaped the rewards of asking patients suffering with ME/CFS (yes, suffering) about their experience of their illness (see here for example). To do this, one of the rather famous authors on the Holtzman paper - Leonard Jason - started some conversations with various other patients who were unhappy with some of the descriptions of PEM that were being bounced around. Joined by Holtzman, things took off with regards to a questionnaire that was developed with PEM in mind [2] as we are told that: "comments and items received helped shape each new revision of the questionnaire."

"A survey was ultimately developed and was subsequently completed by 1534 members of the patient community."

Findings? Well, first and foremost "94.4% reported being diagnosed by a medical doctor." Nearly three-quarters of participants reported 'symptom exacerbation' immediately following exertion. Nine out of ten participants "had experienced delayed onset after exertion." As to the triggers of PEM, well, "basic activities of daily living" was a big one, as was "emotional events (88.3%), noise (85.5%), and sensory overload (83.6%)." What sorts of symptoms were experienced? So: "reduced stamina and/or functional capacity (99.4%), physical fatigue (98.9%), cognitive exhaustion (97.4%), problems thinking (97.4%), unrefreshing sleep (95.0%), muscle pain (87.9%), insomnia (87.3%), muscle weakness/instability (87.3%), temperature dysregulation (86.9%), and flu-like symptoms (86.6%)." Quite a few. How long did PEM last for? An average of 3-6 days (that's days) and in some cases, an awful lot longer. Also: "67.1% of the sample had experienced a “crash” that never resolved." Most participants who answered the survey also felt that it pretty well reflected their experience of PEM.

There's quite a bit more to do in this area in terms of developing said questionnaire and hopefully putting more flesh on the descriptive bones of PEM. I'm also inclined to suggest that as well as describing PEM and how it is experienced by those diagnosed with ME/CFS, science needs to do a lot more on the biology of PEM and what could potentially help (yet again, minus the psychobabble). Still, 'asking patients' continues to be an important theme in ME/CFS research...

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[1] Holtzman CS. et al. Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A Patient-Driven Survey. Diagnostics (Basel). 2019 Mar 2;9(1). pii: E26.

[2] Jason LA. et al. The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Health Psychol. 2018 Oct 24:1359105318805819.

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"PEM, cognitive impairment, and orthostatic intolerance as core symptoms of pediatric ME/CFS"

There were a few rather familiar aspects to the study results published by Maria Roma and colleagues [1] investigating health-related quality of life (HRQOL) in relation to myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

Familiar because HRQOL was found to be "substantially lower in an ambulatory population of adolescents and young adults with ME/CFS than for healthy controls in North America" in the Roma study, in keeping with other studies looking at this important parameter (see here). Familiar also because PEM - post-exertional malaise - was found to be something really quite important to ME / CFS, again in line with other findings (see here for example). But don't think that the Roma findings aren't important, they are. Indeed, with mention of something called orthostatic intolerance in the context of CFS / ME, they provide some further directions for investigation.

So: "We enrolled 55 consecutive ME/CFS patients (46 F) aged 10–23 years." They all "satisfied the 1994 International Chronic Fatigue Syndrome Study Group criteria" (also called the Fukuda criteria). Importantly too: "Individuals with primary depression who were referred by psychiatrists for evaluation of chronic fatigue were excluded, but those who had developed depression sometime after the onset of ME/CFS were included." See those words 'developed depression... after the onset of ME/CFS'. Control participants (n=55) - asymptomatic and in good health - were also included for study. Quite a large battery of questionnaires and schedules were delivered to participants covering HRQOL and quite a bit more including fatigue and depression. Researchers also asked a few questions about "the type of onset for ME/CFS" as well as items pertinent to the IOM (United States Institute of Medicine) criteria for ME/CFS. Lots to see.

And indeed, the results were pretty revealing. Yes, HRQOL was lower - significantly lower - in the ME/CFS group, as talk about a percentage of those with ME/CFS having to change from regular schooling "to part-time schooling... [or] home tutoring" tells you everything you need to know (yet again). Also: "A novel finding of this study is the correlation of impairment in HRQOL with the frequency of PEM, at least for an ambulatory population with ME/CFS." PEM, or 'payback' as another study categorised it as (see here), is starting to get the clinical and research attention that it truly deserves. Researchers specifically mention how "as the frequency of PEM increased, the mean PedsQL [Pediatric Quality of Life Inventory] score fell and the mean FDI [Functional Disability Inventory] score increased, consistent with a significant association of PEM with worse overall function." Need I say anymore?

And then back to orthostatic intolerance (i.e. the "development of symptoms when standing upright which are relieved when reclining"). Researchers considered this present in participants if "(a) self-reported lightheadedness occurred at least several times per week, (b) there was a history of recurrent syncope in the presence of a structurally normal heart, considered consistent with NMH [neurally mediated hypotension]... or (c) previous upright tilt testing or a passive standing testing (performed in patients not being treated with medications for orthostatic intolerance) had confirmed the presence of NMH or POTS [postural tachycardia syndrome]." And present it was in 96% of participants. So much so that authors decided that with orthostatic intolerance being one of the core diagnostic criteria for the IOM diagnostic criteria for ME/CFS, 85% of their participants hit the diagnostic thresholds based on that scheme. Important stuff.

This takes us neatly back to the quote titling this post: "PEM, cognitive impairment, and orthostatic intolerance as core symptoms of pediatric ME/CFS." And perhaps a change is coming to research and clinical practice in this area. Having said that, change is going to be quite difficult for some groups it seems [2] as words like: "Parental representations could contribute to fatigue maintenance" still appear in the peer-reviewed science literature with CFS/ME in mind...

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[1] Roma M. et al. Impaired Health-Related Quality of Life in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Impact of Core Symptoms. Front. Pediatr. 2019. Feb 15.

[2] Loades ME. et al. Perfectionism and beliefs about emotions in adolescents with chronic fatigue syndrome and their parents: a preliminary investigation in a case control study nested within a cohort. Psychol Health. 2019 Mar 1:1-17.

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PACE trial for chronic fatigue syndrome (still) being put through its paces: a reply

I'm bringing the paper published by Michael Sharpe and colleagues [1] to your attention today in the interest of balance and peer-reviewed 'right to reply'.

The Sharpe paper concerns the PACE trial, the study which reported that "when added to specialist medical care, cognitive behaviour therapy and graded exercise therapy were more effective in improving both fatigue and physical function in participants with CFS [chronic fatigue syndrome], than both adaptive pacing therapy and specialised medical care alone."

Anyone with a little bit of knowledge about the PACE trial will know that it's a 'contentious' topic within CFS (and ME, myalgic encephalomyelitis) circles. Indeed, the Sharpe paper comes about as a direct result of a reanalysis paper (see here) which reported findings raising "serious concerns about the robustness of the claims made about the efficacy of CBT [cognitive behavioural therapy] and GET [graded exercise therapy]" in the context of CFS/ME. 'Serious concerns' is putting it mildly considering how others have described the PACE trial and some of its tenets (see here).

Sharpe et al, who were authors listed on the original PACE trial paper [2], have had to defend their work/findings before in the peer-reviewed realm (see here). Same as before, the name Carolyn Wilshire is addressed and her teams reanalysis of the PACE trial data [3]. Said data was, I might add, (partially) released only following intervention from the Information Commissioners Office (ICO) here in Blighty (see here). More recent events have similarly reiterated that 'access to raw study data' is something that CFS/ME researchers perhaps need to bear in mind at study conception (see here).

I'm not going to clinically dissect the Sharpe paper in this post because (a) 'interpretation' forms quite a bit of the reply to the Wilshire reanalysis, and (b) your opinion on the scientific quality of the Sharpe reply is most likely going to be shaped by where you stand in terms of the whole CBT/GET for CFS/ME discussion. Indeed, a peer-reviewer of the Sharpe paper also said as much (see here). What I will comment on is how the Wilshire reanalysis paper and the more recent Sharpe reply to the reanalysis paper might further inform research more generally with CFS/ME in mind.

Oh, and it's probably just a coincidence that the Sharpe paper comes out only days after a news headline reads "Online activists are silencing us, scientists say" talking about a familiar topic.

So:

• Point 1: Design a good trial analysis plan and stick to it. From my 'outsider looking in' perspective, the changes made to "the scoring of the pre-specified outcomes" regarding fatigue and physical functioning in the PACE trial, however innocent they might have been, have created tension. Lots of tension. Such changes, whether agreed by "Trial Data Monitoring and Steering Committees" or not, can be construed in various different ways. It's better not to make such changes in the first place.
• Point 2: If you are going to study something like physical functioning in relation to CFS/ME, don't just rely on things like questionnaires and Likert scales; use actigraphy too. Self-report is always a good thing but I've never understood why, with the wide range of cost-effective technology out there (available I believe, even in the early 2000s), wearable trackers such as pedometers or similar were not also utilised during such studies (see here). If you're spending £5 million on a trial, a few quid for some pedometers is not exactly going to break the bank and will inevitably bring some further quality data to the table.
• Point 3: Recovery. As per other discussions (see here), most people would characterise recovery as a complete remission of symptoms and/or return to typical functioning. If you're not going to use this description, don't use the word recovery. Use something else instead. Indeed, use 'partial remission' or 'improvement' if you need to but don't call anything less than the complete remission of symptoms 'recovery'.
• Point 4: Long-term outcomes. It's probably best to avoid any sweeping statements after the arms of a trial - a "randomised trial" not necessarily a "randomised controlled trial" according to Wilshire et al - have been completed. More so when you're measuring such long-term outcomes via a postal question minus any objective measure(s) (see point 2). It's probably also a good idea to ask patients about their quality of life too and whether that has changed (see here).
• Point 5: Even if your paper states in no uncertain terms that: "The effectiveness of behavioural treatments does not imply that the condition is psychological in nature" the use of something like CBT for CFS/ME implies that you probably think there is a substantial psychological 'component' to the condition. This is compounded when you're for example, a Professor of Psychological Medicine. If you were pitting CBT in particular against a specific pharmacological or biological intervention 'for CFS/ME' (see here for example), I'd be more inclined to see your view in a more 'rounded sense'. Indeed, if you were to study one or two biological parameters as well as behavioural ones looking for any change following intervention, you might convince more people that psychology is not the primary line you take. And whilst on the topic of psychology and CFS/ME, it's probably also best not to use 'psychobabble' terms like 'deconditioning' in your research. Such terms are pretty much scientifically untestable and, given the recent discussions about the legacy of some adherents to something like psychosomatic research (see here), is likely to be consigned to the scientific dustbin as some later point.

I think I've covered the main points as I see them. Please feel free to agree/disagree as you wish.

End of Line.

Addition: 26 March 2019. Not quite 'End of Line' it seems, as a reply to a reply to a reply emerges [4]. Peer reviewed science is far from slow...

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[1] Sharpe M. et al. The PACE trial of treatments for chronic fatigue syndrome: a response to WILSHIRE et al. BMC Psychology. 2019; 7: 15.

[2] White PD. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011; 377(9768):823-36.

[3] Wilshire CE. et al. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychology. 2018; 6: 6.

[4] Wilshire CE. & Kindlon T. Response: Sharpe, Goldsmith and Chalder fail to restore confidence in the PACE trial findings. BMC Psychology. 2019; 7: 19.

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"The most common peri-onset events reported by subjects were infection-related episodes (64%)"

The quote titling this post - "The most common peri-onset events reported by subjects were infection-related episodes (64%)" - comes from the (open-access) findings reported by Lily Chu and colleagues [1] continuing something of a research theme from this authorship group examining myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) (see here).

Indeed, it's probably no coincidence that the Chu cohort of "150 subjects fitting Fukuda 1994 CFS criteria" is the same as that used in their other research [2] when discussing another important issue: "post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome."

On this most recent publishing occasion, Chu et al set out to: "Describe ME/CFS onset and course in one United States-based cohort." They did this via the use of "a detailed survey" that asked various questions about the first stages of participants' illness and what this eventually led to. The results obtained weren't exactly unexpected, but yet again stress how lots of things 'assumed' about ME/CFS really need to be properly verbalised in the peer-reviewed science literature (see here and see here for other examples). Of particular note in the Chu findings pertinent to inquiry on the 'course' of ME/CFS is this important snippet of information: "Based on available data, the median age of illness onset was 36.6 ± 12.3 years and median duration of illness was 12.5 ± 10.1 years." That's 'median duration of illness was 12.5± 10.1 years'.

Results: "The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%)." Infection or rather 'infection-related episodes' came out top of the pops with regards to possible onset events. I've said 'possible onset events' in that last sentence not to be belittle the first-hand reports obtained, but rather to emphasise how we're still in a bit of a 'not knowing' state when it comes to definite causative infective agents and ME/CFS onset. Yes, there is some quite strong evidence that infections caused as a result of Epstein–Barr virus (EBV) seem to be involved in some cases of ME/CFS (see here) but more often that not, people aren't screened for every possible viral or bacterial agent. At this point, I'd also hark back to the viral 'hit-and-run' hypothesis that has been talked about in some ME/CFS circles recently (see here and see here) and what this also means.

Onward: "For the overwhelming majority of patients (96%, n = 141), their illness did not improve with time although different patterns of illness were seen." That last sentence really speaks for itself in terms of what ME/CFS means in the long-term. That's not to say that symptoms did not 'fluctuate' - "59%, fluctuating (symptoms could change in severity but were always present)" - but participants on the whole did not 'shake off' their disability. And when it came to some details about how symptoms ebbed and flowed over the course of time, Chu et al have some data on that too: "Over time, flu-like symptoms, fatigue, unrefreshing sleep, and exertion-related items decreased the most, by between 12 and 25%... Cognitive symptoms present at the beginning of the illness tended to persist, declining by only 4–10%." Further focus on 'cognitive symptoms' is perhaps important [3].

Further: "Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions." The authors phrase this in the context that "patients with co-morbid medical or psychiatric conditions are the rule rather than the exception" when it comes to ME/CFS. But just before anyone starts making noises that anxiety and depression are so significantly present in this cohort and probably beyond, such findings does not open the door to any psychobabble 'biopsychosocial' (BPS) explanations about the cause/perpetuation of ME/CFS. I think many patients (and researchers) have had quite enough of all that (see here).

The Chu paper is a comprehensive one and adds to our knowledge about ME/CFS. It has its limitations - "reliance on subject self-report, recall bias, and relative superficiality of some survey items" - but no more or less than lots of other ME/CFS research. It hopefully will open the door to a lot more similar study; perhaps also including the odd biological measure also.

And just before you go, I'll draw your attention to the findings reported by Katherine Rowe [4] who also asked a cohort of participants with ME/CFS about their illness experiences. There's a few important matching details included in the paper - "Eighty percent reported a defined onset following an infection" - but also some other noteworthy information. One such observation was that: "Many indicated the need to be sensitive about when psychological assistance is offered... They were sensitive as to whether this was implying that psychological issues were the “cause.”." It's not difficult to see why patients with ME/CFS would think such [BPS] things.

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[1] Chu L. et al. Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome. Front. Pediatr. 2019. Jan 16.

[2] Chu L. et al. Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey. PLoS One. 2018;13(6):e0197811.

[3] Robinson LJ. et al. Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction. PLoS One. 2019 Feb 5;14(2):e0210394.

[4] Rowe KS. Long Term Follow up of Young People With Chronic Fatigue Syndrome Attending a Pediatric Outpatient Service. Front Pediatr. 2019 Feb 21;7:21.

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"Having accessed treatment was associated with reporting lower levels of work/school attendance"

I have to admit that I did a bit of a double-take when I came across the quote titling this post - "Having accessed treatment was associated with reporting lower levels of work/school attendance" - in the paper published by Sheila Ali and colleagues [1] (open-access available here).

The findings came from a study that set out to investigate the "factors associated with fatigue, disability and school attendance in young people with severe CFS/ME [chronic fatigue syndrome/myalgic encephalomyelitis]." Part of the study also looked (in a preliminary manner) at whether some of the therapeutic options offered 'for ME/CFS' were up to scratch based on participants' responses and views.

"Questionnaire data were collected in two waves: at baseline (T1), and at follow-up (T2), which was 3–9 months later" as such data were collected from 51 young people "required to have a self-reported diagnosis of CFS/ME." Researchers mention how they focused on participants with "severe CFS" as measured by a self-report 'functional ability scale'. That being said, recruitment phases for the Ali study were not uniform, as two different thresholds for severity were eventually used in different recruitment phases.

No mind, Ali et al asked participants to complete various questionnaires around things like mobility, meaningful education and/or work (including attendance), and level of fatigue. Bearing in mind the use of words like 'fear avoidance' in the Ali paper (possibly denoting the biopsychosocial (BPS) 'sway' of some of the authors), various 'psychological' concepts were also included for study. The data were collated and analysed.

Results: although data for 51 participants were eventually analysed, nearly 400 young people were sent a letter inviting them to participate in the Ali study. Only 56 responses (consent forms and questionnaires) were eventually received which, even taking into account the 'severe CFS' inclusion criteria, represents a pretty low study turnout. This seems to follow a trend among certain types of study of ME/CFS (see here) which is starting to become quite noticeable.

"Thirty-seven (72.5%) participants reported using assistive equipment such as crutches, walking frames, ramps, stair-lifts and shower chairs. Thirty-three participants (64.7%) reported that they used a wheelchair. Nine participants (17.6%) reported that they were bed-bound." Contained within those sentences is the real cost of ME/CFS to something like mobility. On top of all that, researchers also observed that approaching 90% of their cohort were also taking some form of medication (I assume pertinent to things like mobility issues and beyond). In terms of how things like mobility issues impacted on participation in 'meaningful' education and/or work, we are told that only a quarter of participants "had been able to attend school, college or work in the past year." That's 'in the past year'.

Then back to those 'treatments' and their effects. So: "Although this was a naturalistic study and not an evaluation of treatment, it is notable that the majority of participants reported that they had accessed some form of treatment, and yet the mean scores for fatigue and social functioning had not changed considerably by T2." What sorts of treatments had they tried I hear you ask? Well, table 1 (see here) provides some details. The most popular treatment 'accessed' was "CBT, GET or both with at least one other treatment" closely followed by "CBT, GET or both." Allied to other independent data suggesting that cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are failing many patients with ME/CFS (see here and see here and see here), and the case grows ever stronger for new treatment directions to be pursued. Such research directions should perhaps also be minus words like 'fear avoidance' or other psychobabble inclinations that have pervaded ME/CFS thought down the years. Indeed, one has to ask who would advocate for treatments that are seemingly at best ineffective and at worst downright detrimental to the patient group who are 'accessing' them?

There are some other points noted in the Ali paper including things like how "low mood is a consequence of having CFS/ME" and how "symptoms of CFS/ME and levels of functioning can fluctuate over time." These follow similar sentiments expressed in other research (see here and see here) along the lines of CFS/ME being very much a real physical illness with both physical and psychological effects.

There are some obvious caveats to mention about the Ali study, specifically around the sole use of questionnaires without any other 'actigraphic' form of inquiry (to measure something like activity levels), the representativeness of results, and the reliance on self-report when it came to diagnoses. Although I've also been pretty harsh on the effectiveness of the treatment options accessed, I will direct you to some author comments on this issue and how "the effects of treatment would not be seen within such a short period of time." I'm not too sure about such sentiments but, in the interests of balance, give them airtime in this study write-up.

Despite all that, the Ali findings add further to our knowledge about ME/CFS in young adults. They demonstrate how 'life-destroying' the illness is (are) and can be, and what that means to those who suffer with it (them). They also add to the multiple voices - research and patient voices - demanding a greater clinical focus on ME/CFS, and how objective, biological science in particular, needs to be front-and-centre of any new direction. But I'll also reiterate that any new focus and new direction needs to be minus the psychobabble; indeed it may be unethical not to [2]...

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[1] Ali S. et al. Psychological and demographic factors associated with fatigue and social adjustment in young people with severe chronic fatigue syndrome/myalgic encephalomyelitis: a preliminary mixed-methods study. J Behav Med. 2019 Jan 25.

[2] O'Leary D. et al. Ethical classification of ME/CFS in the United Kingdom. Bioethics. 2019 Feb 8.

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"A 4-Day Mindfulness-Based Cognitive Behavioral Intervention Program for CFS/ME" but...

I did um-and-ah about whether I should blog about the findings reported by Bjarte Stubhaug and colleagues [1] observing that "a brief, concentrated treatment program for CFS/ME might be highly beneficial."

The reasoning behind my reticence was primarily to do with the study design whereby "a 4-day group intervention program, comprised by education, cognitive group therapy sessions, mindfulness sessions, physical activity and writing sessions, within a context of cognitive behavioral therapy, mindfulness, acceptance and commitment model" was delivered to over 300 people diagnosed with Chronic Fatigue Syndrome/Myalgic Encephalopathy (CFS/ME) and self-report results plotted "1 week before and 1 week after the intervention program, and at 3 months and 1 year after the intervention" without any control group or any kind of blinding. Even the researchers themselves wrote that their study design make "conclusion of the actual effect of the treatment program [in part or whole] and its impact on the clinical course through the follow-up period difficult." But, here I am...

As you can see from the picture accompanying this post, others are also just a little bit critical of the Stubhaug paper and findings. Although I can't speak for anyone else, I imagine some of the 'criticism' of the study and results rightly follows on from the methodology employed by the authors. I did also wonder if some feeling might also be there because of the subject matter, and specifically, the continuing idea in some quarters that the application of the biopsychosocial (BPS) model to CFS/ME should carry weight. To quote from the authors: "The therapeutic rationale behind the program was to increase the medical knowledge and interpretation of bodily distress, challenge and modify dysfunctional illness perceptions as well as illness behavior, and through acceptance and commitment strategies contribute to behavioral change and clinical improvement." Sounds about as BPS as you can get I reckon.

Focusing for now on the methodological and related side of the Stubhaug paper, the starting point for the study was the authors' observation that: "The most promising treatment so far seem to be cognitive-behavioral treatment programs... and graded exercise." Just before anyone gets angry about this, authors do also highlight how "the effectiveness of interventions and robustness of findings are continuously being questioned" in this area. Yes, yes they are being questioned (see here and see here for examples) and by lots and lots of different people. Nonetheless, researchers decided to test whether their 4-day program, encompassing quite a few elements, might impact on some of the signs and symptoms of CFS/ME in their cohort. Said program included education: an "introduction to stress medicine with focus on physiological and psychological stress", cognitive group therapy, mindfulness and writing experience ("patients were instructed to write for 15 min about positive experiences and emotions"). They also talk about the use of "daily walking sessions of 60–90 min, in low to moderate pace" which, considering other research (see here), sounds pretty 'full on' to me, in light of some of principal issues that define CFS/ME (see here).

Relying on self-report measures such as the Chalder Fatigue Scale and the Short Form Health Survey-36 (SF-36), researchers reported their results as per the timescales already mentioned. The picture that emerged was a fairly positive one as various statistically significant group changes (improvements) were noted across the testing sessions, even when taking into account different ways of diagnosing CFS and across the various instruments used. Most participants also said that they were pretty satisfied with the intervention program and the service they received. In short, the study met it's aims quite successfully.

But... not to pour cold water on the findings, one cannot forget about the 'open study' shortcomings of the study design. So on top of what has already been mentioned: "Many patients with CFS/ME tend to be critical to biopsychosocial interventions, and possibly most of these patients did not accept referral to the clinic, contributing to the possible selection bias." I'd say that this was another quite important *issue* that faced the Stubhaug study. The authors go on to note that their results "clearly represent a CFS population, albeit not representing the total body of CFS/ME patients" so perhaps clarifying the caution needed in this area of science specifically around any sweeping generalisations. And as an example: "At 1 year follow-up, half of the patients completing assessments (56%) still report levels of fatigue representing substantial fatigue." Such an intervention is therefore no panacea for CFS/ME.

What else? Well, the continued focus on subjective questionnaires over and above more objective measures is also apparent in the Stubhaug findings (see here). As I've mentioned on more than one occasion, it's perfectly acceptable to ask patients how they are feeling and about related issues like quality of life for example (see here). But when it comes to a condition or set of conditions like ME/CFS defined by fatigue and other symptoms that very much impact on core issues such as activity, it strikes me that one should really include an objective measure of activity if one wants to study it in its entirety. So yes, actigraphy would have been a good feature to see in this study (with before and after results). Even a pedometer costing a few quid, used a few times a week over a number of different weeks would be something at least. And once again, how about also including some biological parameters into such studies too? Y'know, just on the off-chance that things like mindfulness, minus any grand sweeping claims, for example, could have possible biological effects too [2]?

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[1] Stubhaug B. et al. A 4-Day Mindfulness-Based Cognitive Behavioral Intervention Program for CFS/ME. An Open Study, With 1-Year Follow-Up. Front Psychiatry. 2018;9:720.

[2] Hoge EA. et al. The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder. Psychiatry Res. 2018 Apr;262:328-332.

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"Fatigue, fluctuation and payback were described by all adolescents with CFS/ME in this study"

The quote titling this post - "Fatigue, fluctuation and payback were described by all adolescents with CFS/ME in this study" - comes from the findings reported by Roxanne Parslow and colleagues [1] during their study designed "to explore outcomes important in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) and what improvements in fatigue and disability are key."

Indeed, this latest study seems to follow a theme of looking at the personal experiences of CFS/ME [2] by members of this authorship team, potentially onward to the development of a PROM (Patient Reported Outcome Measure) [3] specifically with children and adolescents in mind. If this was a goal, I wondered if perhaps this *could* also be linked to some other work from some of the Parslow paper authors that has also been previously discussed on this blog too (see here)?

I specifically wanted to talk about this paper because of the word 'payback' and it's particular use to mean an "increase in fatigue and symptoms following activity." Mentioning it only twice in their article (one of those occasions being the use of a reference), I think the authors mean post-exertional malaise (PEM) (see here and see here for more discussion of this concept). They however, seemed a little reluctant to use that term. In answering one of the reviewers of their paper prior to acceptance for publication, the authors did say: "Payback is defined as a core symptom in NHS guidance, and is used in the clinical setting." They also clarified how "the term ‘payback’ was used instead of exhaustion."

No mind, based on interviews with "21 adolescents and their parents (20 mothers and 2 fathers)", most adolescents being female with a mean age of around 14 years, several key themes emerged. To reiterate: "All adolescents with CFS/ME report fatigue, a natural fluctuation of the condition, as well as an increase in fatigue and symptoms after activity (payback)." Several sub-themes also emerged from such reporting including how: "Adolescents and parents reflected on how CFS/ME naturally fluctuates" and "Adolescents and parents recognised patterns of good and bad days" and "Adolescents were limited in the amount of time they could spend on activities, which ranged from minutes, ‘5 min’ to hours, ‘an hour at the most’." These aren't exactly novel findings by any means but it's always useful to see them described in the peer-reviewed research domain.

Heading back to that 'payback' issue, researchers mention how their results are "consistent with previous research where children described the intensity of symptoms fluctuating as well as ‘overextension’ making it worse, resulting in ‘paying the price’." Accepting that such payback or PEM or 'payback exhaustion resulting in fatigue and other symptoms following activity' if you prefer, is widely present in CFS/ME (albeit individual and 'variable' in nature), one might see the Parslow results perhaps as further justification for being slightly critical of the use of something like graded exercise therapy (GET) in relation to CFS/ME (see here). GET relies on the assumption that increasing or grading in physical activity will eventually 'help' facets of CFS/ME. Unfortunately, whilst still expounded in some circles, there is accumulating (peer-reviewed) evidence that many patients with CFS/ME experience GET as more of a hindrance rather than a help for their symptoms (see here). Indeed, allied to terms like 'deconditioning' as part of suite of 'psychobabble' that seems to have enveloped CFS/ME down the years, the idea that CFS/ME is something that can be just 'exercised out of' seems to have been a truly damaging policy that has not seemingly served many patients particularly well.

The Parslow findings are revealing and add something further to the idea that an overhaul of current thinking on CFS/ME in children and adults is perhaps required (see here). Obviously the results are small-scale and require some follow-up, but listening to patients and their parents/caregivers and their collected experiences is a good idea in my book; particularly when it comes to a group of conditions like CFS/ME that have seen more than their fair share of 'assumptions' down the years.

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[1] Parslow RM. et al. Adolescent’s descriptions of fatigue, fluctuation and payback in chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): interviews with adolescents and parents. BMJ Paediatr Open. 2018;2(1):e000281.

[2] Parslow RM. et al. Children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies. BMJ Open. 2017 Jan 13;7(1):e012633.

[3] Parslow RM. et al. Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services. BMC Pediatr. 2017 Feb 1;17(1):43.

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"by the time ongoing fatigue was established, the immune activation was no longer present"

The quote heading this post - "by the time ongoing fatigue was established, the immune activation was no longer present" - comes from some media coverage of the paper published by Alice Russell and colleagues [1]. Said paper observed some interesting results in relation to the use of interferon-alpha (IFN-α) "used in the treatment of chronic Hepatitis C Virus (HCV) infection" and what this *could* mean in relation to a "proxy model of chronic fatigue syndrome."

The long-and-short of the Russell results and their possible application to chronic fatigue syndrome (CFS) is that for quite a few years now there have been rumblings that at least some cases of CFS (also known as myalgic encephalomyelitis, ME) might be *associated* with a viral hit-and-run encounter. By saying 'hit-and'run' I mean that an initial viral or bacterial infection is experienced which induces the symptoms of CFS. Said infection then eventually disappears for whatever reason(s) but leaves persisting symptoms such as long-term fatigue and more. Further explanation of this hypothesis can be seen in another of my posts on CFS (see here).

So: "Fifty-five patients undergoing IFN-α treatment for chronic HCV were assessed at baseline, during the 6–12 months of IFN-α treatment, and at six-months post-treatment." The use of IFN-α is clinically indicated for HCV infection as part of an antiviral therapeutic regime ("IFN-α and ribavirin"). Various biological parameters were assessed in the 55 participants as well as in separate groups of those diagnosed with CFS and so-called "healthy volunteers."

Treatment with IFN-α induced fatigue in quite a few of those being treated for HCV infection. Most cases of fatigue resolved at 6-months post-treatment but for some, fatigue remained and for about 30%, levels of fatigue were "higher six-months post-treatment than at baseline." The authors looked at the biological results obtained for those with 'persistent fatigue' (PF) and compared them with those with 'resolved fatigue' (RF) to see if they could discern some differences.

They came up with a few important group observations: "Subjects who later develop PF have higher fatigue in response to IFN-α", "Subjects who later develop PF have higher IL-10 levels before treatment, and IL-6 and IL-10 levels in response to IFN-α", and "Psychosocial and clinical risk factors do not distinguish PF from RF subjects." What this all amounts to is that within quite a small participant group: "findings from this study support the hypothesis that abnormal immune mechanisms are important in CFS, but only early in the course of the illness, around the time of the trigger, rather than when the syndrome is established." Further the study: "confirms the importance of the acute fatigue response to the trigger, rather than of the recovery period preceding the illness."

There is more to do in this area bearing in mind that CFS is a pretty heterogeneous condition both in terms of symptom onset and the course of the illness. Researchers also admit that they "can only speculate at this stage on whether or not the mechanisms underlying the persistence of fatigue in CFS and IFN-α induced PF are related" and their suggestion of a proxy model. Others who have covered this study have said similar things (see here). This is also important given other results reported by the authors on those diagnosed with CFS compared with those 'healthy' controls/volunteers.

Still, there are some interesting observations made by Russell et al and once again, such results hopefully move CFS further away from the biopsychosocial (BPS) model of old that has seemingly done considerable damage to those diagnosed (see here and see here). Indeed, such post-infective thinking kinda brings CFS back full circle...

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[1] Russell A. et al. Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome. Psychoneuroendocrinology. 2018 Dec 17.

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The DePaul Symptom Questionnaire for chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME)

It's another short descriptive post today as I bring the paper by Len Jason & Madison Sunnquist [1] to your attention charting "the development of the DePaul Symptom Questionnaire (DSQ) to assess symptoms of the major chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) case definitions."

I say this is a descriptive post because the Jason/Sunnquist paper provides some important technical details about the DSQ and its evolution; all from a research group who seem to be pretty clued into ME/CFS and its very wide range of clinical presentation (see here).

There are some important aspects included in the paper; not least a focus on the issue of post-exertional malaise (PEM), something which has been a real focus to these researchers (see here). The other very welcomed side to the Jason/Sunnquist paper are the various links to the DSQ derivatives all provided free of charge.

'Nuff said.

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[1] Jason LA. & Sunnquist M. The Development of the DePaul Symptom Questionnaire: Original, Expanded, Brief, and Pediatric Versions. Front Pediatr. 2018;6:330.

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"a 256-peptide immunosignature with the ability to separate ME/CFS cases from controls"

The findings reported by Oliver Günther and colleagues [1] (open-access available here) really interested me. They interested me because they talked about the "hit and run" hypothesis being pertinent to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where "a pathogen or other immunological insult experienced by a subject may be gone, but leaves behind physiological disequilibrium." They interested me because researchers turned to "an immunosignature assay (ISA) that employs a microarray of thousands of random-sequence peptides to interrogate antibodies in a broad and unbiased fashion" to try and pick out the biological effects of the 'hit and run' hypothesis in relation to ME/CFS. And they interested me because researchers reported that they were able to identify "a 256-peptide signature that separates ME/CFS samples from healthy controls, suggesting that the hit-and-run hypothesis of immune dysfunction merits further investigation." Lots of interesting things (honest!).

The Günther paper is open-access so doesn't really need too grand an explanation from me. The long-and-short of it was that following the adoption of a discovery and validation methodology (an increasingly favoured option in ME/CFS research circles), authors came up with a sort of 'biological fingerprint' "optimally separating ME/CFS cases and controls" based on the examination of serum samples. They also noted that in amongst their 256-peptide signature, one particular peptide - "LRVVWLSGVASG" - was also mentioned in another independent study with similar aims [2] perhaps therefore requiring further research focus. For those who might not be totally au fait with peptide designation, that string of letters is not meant to be pronounced, but rather each letter corresponds to an amino acid making up that particular peptide.

Whilst this is great work and indeed, represents some really quite detailed analysis, the authors caution that the science is not quite there yet when it comes to a 'biological test' for ME/CFS. So: "the heterogenous nature of ME/CFS clinical presentation and the variance natural present amongst control samples means that group labels in the Discovery and Validation Sets are not based on any gold standard." Diagnosis of ME/CFS still remains a point of real contention in various circles (see here) given the variety of diagnostic criteria available. Indeed, some commentators have suggested that the combination of 'ME/CFS' as a unified diagnostic label simply cannot ever exist (see here). The authors further note that: "Even the best research case definitions are often subjective and—in the absence of clear biomarkers—any group of ME/CFS cases likely comprise a heterogeneous set of pathologies."

I'm also minded to suggest that as per the lessons being learned in connection to autism biomarker research for example (see here), one needs to perhaps think about getting different research groups together who are looking at ME/CFS from different angles (see here). Y'know, sort of combining various different biomarker studies looking at various different biological 'angles' and sorta meta-analysing all the collected data to see if a larger, grander, range of variables might provide a more accurate biomarker picture of the condition(s)...

Still, the Günther study represents some good science and good value-for-research-money. It stresses how, by utilising the pretty sophisticated analytical equipment available these days, one can start creeping ever closer to some of the possible biochemistry that underpins ME/CFS (or at least some ME/CFS) and perhaps then also start some conversations centred on what can be done to alleviate symptoms and cure such a devastating illness.

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[1] Günther OP. et al. Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Mol Neurobiol. 2018 Oct 8.

[2] Singh S. et al. Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity. Mol Neurobiol. 2018 Jan;55(1):633-641.

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"contrary to its findings, there is no evidence that graded exercise therapy is effective" for myalgic encephalomyelitis / chronic fatigue syndrome

Things can sometimes move pretty fast in the world of peer-reviewed science. I had originally scheduled this post to appear in November (2018) but there's been some recent 'movement' in this area (see here) so I've decided to publish it now.

The original post is shown below. And below that are a few extra thoughts in light of the reported decision to remove the Larun article (at least for now)...

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The re-analysis paper published by Mark Vink & Alexandra Vink-Niese [1] makes for some really interesting reading. Not only because it adds to other voices in the peer-reviewed domain (see here) questioning the usefulness and safety of the intervention known as graded exercise therapy (GET) 'for' myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but also because it kinda fits in with a narrative suggesting that 'trusted evidence' is almost always open to interpretation (see here).

So, graded exercise therapy (GET) and ME/CFS. I have to say that out of all the interventions / treatments that I've come across down the years that have been indicated for various diagnostic labels, GET is probably one of the most reviled by the population it is supposed to be aimed at. The reasons for such a scenario are multiple and complex, but one of the more vocal arguments seems to be the lack of regard for harm caused by the use of a stepped physical activity schedule on a population whose illness is defined by boom-bust symptom profiles caused by physical exertion. Of particular importance to this line of thinking is the idea that post-exertional malaise (PEM) needs to have a lot more prominence attached to it when it comes to ME/CFS, minus any psychobabble 'deconditioning' chatter or related explanations.

The Vink-Vink-Niese paper is based on a Cochrane review paper of GET published by Lillebeth Larun and colleagues [2]. Yes, the same Cochrane that is going through a bit of turmoil at the moment. The Larun paper concluded a few things such as: "Exercise therapy did not worsen symptoms for people with CFS" and "Moderate‐quality evidence showed exercise therapy was more effective at reducing fatigue compared to ‘passive’ treatment or no treatment." This based on the examination of "eight randomised controlled studies" with "reported data from 1518 participants." To be fair to the Larun review paper, the authors did also mention that: "Serious side effects were rare in all groups, but limited information makes it difficult to draw firm conclusions about the safety of exercise therapy" and "further studies should be carried out to discover what type of exercise is most beneficial for people affected by CFS, which intensity is best, the optimal length, as well as the most beneficial delivery method." This, on the basis that CFS/ME is best described as a heterogeneous condition and accepting that exercise can come in various different forms, some of which might be more applicable than others when it comes to individuals with fatigue-related labels (see here for example) minus any sweeping generalisations.

Some familiar themes crop up in the Vink re-review paper - "Entry score requirements were not sufficiently strict" and "The review used subjective fatigue measured by questionnaires as the primary outcome" - which have quite notably hindered the research in this area. I note also that authors mention about attrition (dropout) rates in the reviewed studies and how, in some studies, over a third of participants placed in exercise conditions withdrew from such investigations. Such statistics will no doubt have an important influence on any final results, as well as providing an important clue that such an intervention might not be sufficiently well tolerated by quite a few [3].

Vink concludes by saying that: "The GET trials reviewed here are inherently biased: use of exercise may attract only the mildly affected and may deter the more disabled patients from participating" and that: "The flaws in the review and the trials... all created a bias in favour of the exercise intervention."

On the basis of their interpretation of the scientific data, I'm in agreement with Vink & Vink-Niese that the evidence base for the universal application of GET to ME/CFS is by no means indicated. You might well say that GET is not universally rolled out for everyone with ME/CFS but, as things currently stand at the time of writing, it is still part of the clinical guidance for the condition(s) here in Blighty (for now) and hence potentially something that can be suggested for anyone diagnosed with ME/CFS. The ethos behind GET also being tied into another biopsychosocial (BPS) favourite - CBT - also makes for a good reason why psychology really shouldn't be let anywhere near such clinical issues, particularly when the evidence against such 'interventions' is seemingly mounting (see here). Indeed, although little comfort to those currently living with ME/CFS, I'm sure one day we'll look back at the whole BPS 'involvement' with ME/CFS and truly say WTF?

And finally, whilst on the topic of 'not listening to your target population' I would also draw your attention to the recent findings from McManimen and colleagues [4] highlighting what could happen when those with ME/CFS face stigma (and dogma). Oh, and because the Cochrane name is part-and-parcel of today's post, I'll also draw your attention to an important message concerning some of their other advice pertinent to CFS...

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What else to add to this post? Well, a quote appearing in that Reuters report on the decision to temporarily withdraw the Larun review suggesting that "the withdrawal decision set a worrying precedent for scientific evidence being over-ridden by the opinions of activists" is, to my mind, inappropriate. Aside from the feedback received regarding the Larun article (see here) the Vink paper for example, is peer-reviewed science and published peer-reviewed science at that. It's not some activist randomly throwing around allegations and the like on social media or blogs(!). It's published peer-reviewed-science that calmly calls into question the conclusions of the original Larun analysis. Indeed, it's part of a trend for serious scientific conversations being held in the peer-reviewed science domain concerning some of the science and clinical practice around ME/CFS (see here). Nothing vexatious.

As I mentioned, given that other Cochrane reviews covering the topic of CFS have also been recently withdrawn [5] (see here for more on the withdrawal notice) it strikes me that Cochrane is perhaps also wisely ensuring that it's previous high standards are maintained and confidence restored in its 'evidence-based' name particularly when it comes to research into ME/CFS. Given also the turbulent few weeks that have just passed (see here) and seemingly, are still continuing (see here) for the 'collaboration', it's also a timely reappraisal that fits the important narrative that ME/CFS is a long-term physical health condition (see here) and not a mental disorder or worse. And intervention options need to recognise this fact...

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[1] Vink M. & Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychology Open. 2018;5(2):2055102918805187.

[2] Larun L. et al. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2016 Jun 24;(6):CD003200.

[3] Cheshire A. et al. Guided graded Exercise Self-help for chronic fatigue syndrome: patient experiences and perceptions. Disabil Rehabil. 2018 Oct 16:1-10.

[4] McManimen SL. et al. Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Community Psychol. 2018 Nov;46(8):959-971.

[5] Adams D. et al. WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev. 2018 Oct 15;10:CD006348.

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On the question of suicide risk and chronic fatigue syndrome / myalgic encephalomyelitis continued

The paper by Andrew Devendorf and colleagues [1] brought me back to a complicated and sensitive topic previously discussed on this blog (see here) regarding the issue of suicide risk in the context of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, the Devendorf findings provide some potentially important information about the possible reasoning behind suicide risk in the context of ME/CFS: "(1) feeling trapped and (2) loss of self, loss of others, stigma and conflict."

Based on discussions with 29 people diagnosed with ME/CFS "who endorsed suicidal ideation but did not meet depression criteria" researchers, including one Leonard Jason (see here), discussed some of the hows-and-whys of such suicidal ideation. As per the 'did not meet depression criteria' sentiments of the research, this work was less about 'mental health diagnoses affecting suicide risk' and more about how thoughts, feelings and situational factors might play a role. And as per the two variables highlighted by the study - 'feeling trapped' and 'loss of self & others and the stigma and conflict' generated by this incapacitating condition(s), some clear areas for further research and clinical attention emerged.

I've covered the sensitive issue of suicide (risk, ideation, completion) quite a few times on this blog for all-manner of different reasons (see here and see here for examples). In the most part, my musings have been on research into suicide where a specific label/condition/disorder has been diagnosed, and how facets of such labels/conditions/disorders *might* at least partially, 'intrinsically' elevate the risk of suicide ideation or beyond. The Devendorf findings kinda deviate from such 'intrinsic' sentiments, insofar as examining the implications of an acquired physical disability (see here and see here) and the onward the physical (and mental) restrictions of a condition seemingly elevating the risk of suicidality. By saying all that, I'm not making any sweeping generalisations...

I don't think anyone should really be surprised by the Devendorf results. With ME/CFS you have a condition that literally steals life from people; for example, rendering previously fit and active people to sometimes being bed-bound for days and days (or even longer) at a time. Add in a 'boom-bust' pattern of symptoms (see here) and the various 'environmental' effects (to employment, finances, social life, etc) of the condition, and well, I'm often surprised how resilient people with ME/CFS are.

I noted also how the words 'stigma' and 'conflict' were also detailed in the Devendorf study, and what implications this might have for quite a few areas of current research and clinical practice in relation to ME/CFS. I'm thinking specifically about the whole 'biopsychosocial (BPS) thing' that seems to have pervaded ME/CFS thinking down the years (see here), and how psychology in particular, seems to have over-stepped it's usefulness in relation to ME/CFS. It's kind of a coincidence that as I write this post, another article including Keith Geraghty [2] on the authorship list, is published discussing how some ME/CFS patients and patient groups have been labelled as 'militant' (or similar words and phrases) on the basis of them pushing back against medical dogma as a function of their own experiences of BPS-backed 'intervention' for example (see here). Militant is one word that has been used, 'vexatious' is another (see here).

"Participants emphasized that they were not depressed, but felt trapped by the lack of treatments available." This sentence serves to reiterate that suicidality in the context of ME/CFS is perhaps not something that should necessarily be thought of as intrinsic to the condition(s). It emphasises how issues like 'hopelessness' at the state of medical knowledge about ME/CFS, about the lack of biological explanation for the condition, and the lack of intervention options (not BPS guided I might add) may play a role in thoughts and feelings related to suicidality. It also provides another rather pressing reason why less 'psychologising' and more biological science needs to be dedicated to the hows-and-whys of ME/CFS and the search for a cure...

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[1] Devendorf AR. et al. Suicidal ideation in non-depressed individuals: The effects of a chronic, misunderstood illness. J Health Psychol. 2018 Jul 1:1359105318785450.

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