Andrew Lloyd Wiff's on Chronic Fatigue Syndrome: the Decline and Fall of an ME/CFS Researcher

Cort

Founder of Health Rising and Phoenix Rising
Staff member
All longtime ME/CFS researcher and the creator of the Dubbo studies, Andrew Lloyd can say now apparently about ME/CFS is to engage in CBT and GET. He also makes some remarkable statements. What happened to Andrew Lloyd>
  • He says an exhaustive array of treatment trials (really- an exhaustive array? - really?) have failed to find benefits.
  • He says studies have failed to find convincing evidence of either persistent infection or immunological, endocrine, or metabolic change - really? no natural killer cell dysfunction - really?, no autonomic nervous system dysfunction - really?
  • No exercise dysfunction ????
  • he does say imaging studies indicate central nervous system problems are found
  • he states the PACE trial suggested recovery was possible but allowed for overly generous interpretations of "recovery"
http://www.bmj.com/content/350/bmj.h2087.short
 
Last edited:

MAC

Member
I have been so impressed with Andrew Lloyd's past work - I have quoted his Dubbo study to medical professionals. The idea was great; get a number of doctor's surgeries to track all the cases of people presenting with Q fever, Ross River fever and glandular fever and find out who stays sick. I found it very interesting just how common prolonged post-viral syndromes were found to be.

A little while ago I was wondering what Andrew Lloyd had been up to and googled - only to find his recent references to GET and CBT. That paper you've given the link to Cort, it is actually quite nuanced - it isn't saying that everyone with ME/CFS is a mood-disordered hypochondriac. But most readers will take that message away.

I'm so disappointed and puzzled about this. I know Andrew Lloyd and his team have worked on a range of studies in the years since that first Dubbo study. But surely just the fact that he hasn't been able to find anything should not have led him to this. How can he not be aware of recent advances made elsewhere.

I'm thinking I might email Professor Lloyd to help him understand how papers like this give ammunition to those in the medical profession who just dismiss us as having a psychological problem, leaving ill people without care and slowing down research efforts.

Unfortunately I haven't been able to get access to the paper that is quoted in the Lloyd paper as providing evidence of co-existing mood disorders yet.
 

MAC

Member
Yes, sdsu, what comes first, the mood disorder or having an illness that people tell you is caused by not trying hard enough to be well? :banghead:
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
I have been so impressed with Andrew Lloyd's past work - I have quoted his Dubbo study to medical professionals. The idea was great; get a number of doctor's surgeries to track all the cases of people presenting with Q fever, Ross River fever and glandular fever and find out who stays sick. I found it very interesting just how common prolonged post-viral syndromes were found to be.

A little while ago I was wondering what Andrew Lloyd had been up to and googled - only to find his recent references to GET and CBT. That paper you've given the link to Cort, it is actually quite nuanced - it isn't saying that everyone with ME/CFS is a mood-disordered hypochondriac. But most readers will take that message away.

I'm so disappointed and puzzled about this. I know Andrew Lloyd and his team have worked on a range of studies in the years since that first Dubbo study. But surely just the fact that he hasn't been able to find anything should not have led him to this. How can he not be aware of recent advances made elsewhere.

I'm thinking I might email Professor Lloyd to help him understand how papers like this give ammunition to those in the medical profession who just dismiss us as having a psychological problem, leaving ill people without care and slowing down research efforts.

Unfortunately I haven't been able to get access to the paper that is quoted in the Lloyd paper as providing evidence of co-existing mood disorders yet.
Well here it is. It's not all bad - he does warn about the limitations of CBT/GET, but in the whole - the message it sends, as you note, is horrible. I considered Lloyd as a seminal figure in ME/CFS - a creative and important researcher - but he throws some real howlers in here. I'm so upset I'm preparing a blog on of my formerly favorite researchers.

BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2087 (Published 05
May 2015) Cite this as: BMJ 2015;350:h2087

Andrew R Lloyd, professor,
Jos W M van der Meer, professor

Not over yet

There hasn’t been much good news for patients with the prevalent but enigmatic disorder chronic fatigue syndrome (also referred to as myalgic encephalomyelitis). Over decades, research into the pathophysiology has failed to find convincing evidence of either persistent infection or immunological, endocrine, or metabolic change, and has rejected simplistic notions of depression (typical or atypical) or primary sleep disorder. Several notable “breakthroughs” have failed independent replication. The most noteworthy is the recent rise and fall of xenotropic murine leukaemia virus related virus (XMRV) as the cause, which was ultimately established as a murine DNA laboratory contaminant.1 Similarly, an exhaustive array of randomised controlled trials seeking curative outcomes from antiviral, immunological, hormonal, antidepressant, and many other therapies have failed to show any benefit over placebo, or failed the replication test.

Where then is the progress? Firstly, there is reproducible evidence implicating certain infections as a trigger—notably, infectious
mononucleosis caused by Epstein-Barr virus, but also infection with other pathogens.2 Secondly, there is clear evidence that a substantial proportion of patients have a coexisting mood disorder, and sometimes a sleep-wake disorder, and that these conditions may exacerbate or perpetuate the illness.3 Thirdly, independent studies using both structural and functional imaging techniques have identifiedalterations in the brains of patients with chronic fatigue syndrome, implicating the central nervous system as the site of pathophysiology.4 Fourthly, there is solid evidence from multiple controlled studies that patients can gain control of symptoms and functional improvement through multidisciplinary interventions incorporating graded exercise therapy and cognitive behavioural therapy.

These interventions have clearly positive outcomes in systematic reviews and meta-analyses.5 6 7 For instance, the recent Cochrane review of graded exercise therapy5 states that “patients with CFS [chronic fatigue syndrome] may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed.”

How therapy works

Plausibly, graded exercise may reverse a perpetuator in the form of physical deconditioning. However, there is little evidence for loss of aerobic fitness in patients with chronic fatigue syndrome, and limited evidence for improved physical performance after successful graded exercise therapy.8 Instead, graded exercise has been proposed to act by desensitising an exaggerated central nervous system response to the physiological signals associated with exercise.9

In psychological terms, patients may avoid activity because of the prolonged exacerbation of symptoms that follows minor physical activity; this leads to an understandable conclusion that exercise is harmful or to a conditioned fear of such activity.10 In this respect, the recent mediation analysis of the outcomes of the PACE trial is of interest.11 This trial compared standard medical care, cognitive behavioural therapy, graded exercise, and adaptive pacing therapy, concluding that both cognitive behavioural and graded exercise therapy were more effective at reducing fatigue and improving physical disability than standard care or adaptive pacing.12 The mediation analysis suggested that both cognitive behavioural therapy and graded exercise worked by reducing avoidance of activity. This is broadly consistent with findings by others,13 although whether the effect simply relates to the behavioural change itself (that is, exercise) or reconditioning of the associated fear of activity remains unclear.

In addition, a substantial proportion of patients do not avoid activity but have repeated boom-bust cycles of overactivity when feeling relatively well (the boom) followed by reduced activity when symptoms are exacerbated thereafter (the bust). These data argue for a personalised approach to both therapies.

Cognitive behavioural therapy for patients with chronic fatigue syndrome is based on the premise that inappropriate cognitive
attributions (thinking patterns) and behaviours help perpetuate symptoms. It seeks to alter these attributions and modify the
associated behaviour, targeting activity patterns and sleep-wake behaviours. For example, although primary sleep disorders do not
explain chronic fatigue syndrome,14 patients typically report that their night-time sleep is unrefreshing, and as fatigue is the dominant symptom, patients may consider that increased sleep will relieve symptoms and aid recovery. This idea commonly leads to frequent daytime naps and a delayed sleep-wake cycle.

Prospects for cure

There has been recent contention about the possibility of cure after graded exercise and cognitive behavioural therapy. An analysis of the PACE trial suggested cure was possible, but recovery outcomes were defined post hoc using population norms with generous thresholds (such as the population mean plus one standard deviation for self reported fatigue).15 This analysis was criticised because of the limited assessments and less than full restoration of health,16 leading to a recommendation that trials use more accurate outcomes (such as clinically relevant improvement) defined in advance and capturing a broad based return to health with assessments of fatigue and function.

Trialists must also consider patients’ perceptions of their recovery.17 In this context, the increase in volume of grey matter associated with clinical response to cognitive behavioural therapy, as reported in one study, needs further investigation.18 Even with the unduly liberal designation of recovery, less than one quarter of patients “recovered” in the PACE trial.

What then of the long awaited breakthrough? As is often the case in medical research, progress is predominantly made in modest increments not breakthroughs. The evidence for graded exercise and cognitive behavioural therapy is already clear, so this treatment should be made widely available. The next increments are to find ways to increase the symptom relief and functional improvement achieved by these treatments and to identify factors predicting clinically relevant improvement and non-response in order to increase the proportion of patients who benefit.

Notes
Cite this as: BMJ 2015;350:h2087

Footnotes
Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Provenance and peer review: Commissioned; not externally peer reviewed.

References

1. Van Kuppeveld FJ, van der Meer JW. XMRV and CFS—the sad end of a story. Lancet2012;379:e27-8.
2. Hickie I, Davenport T, Wakefield D, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ2006;333:575.
3. Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet2006;367:346-55.
4. Tanaka M, Ishii A, Watanabe Y. Neural mechanisms underlying chronic fatigue. Rev Neurosci2013;24:617-28.
5. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database SystRev2015;2:CD003200.
6. Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ 2000;320:292-6.
7. Knight SJ, Scheinberg A, Harvey AR. Interventions in pediatric chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Adolesc Health2013;53:154-65.
8. Moss-Morriss R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. J Health Psychol2005;10:245-59.
9. Nijs J, Meeus M, Van Oosterwijck J, et al. In the mind or the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome. Eur J Clin Invest2011;42:203-11.
10. Clark LV, White PD. The role of deconditioning and therapeutic exercise in chronic fatigue syndrome (CFS). J Mental
Health2005;14:237-52.
11. Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. Lancet Psychiatry2015;2:141-52.
12. White PD, Goldsmith KA, Johnson AL, 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. Lancet2011;377:823-36.
13. Wiborg JF, Knoop H, Prins JB, Bleijenberg G. Does a decrease in avoidance behavior and focusing on fatigue mediate the effect of cognitive behavior therapy for chronic fatigue syndrome? J Psychosom Res2011;70:306-10.
14. Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med2012;8:719-28.
15. White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med2013;43:2227-35.
16. Kindlon T, Baldwin A. Response to: reports of recovery in chronic fatigue syndrome may present less than meets the eye. Evid Based Mental Health2014. doi:10.1136/eb-2014-101961.
17. Adamowicz JL, Caikauskaite I, Friedberg F. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res2014;23:2407-16.
18. De Lange FP, Koers A, Kalkman JS, et al. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain2008;131:2172-80.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
  • Secondly, there is clear evidence that a substantial proportion of patients have a coexisting mood disorder,
As soon as I read the above I knew this had to be from a British publication. :banghead:
Indeed - as if they need more of the same over there. Those ideas already permeate the UK....Why pen an editorial like this? To get into print?
 

MAC

Member
Damn. I made a long post yesterday and it isn’t showing up even though I'm sure it was showing up as submitted last night. I’m having problems with the website thinking I’m not logged in when I come to submit a post even though my name shows at the top as being logged in. I then have to log in to submit the post.

It happened with that last post of mine above – an earlier draft posted rather than my final one. I’m not sure what I am doing wrong.I guess the second post is still lurking in the system somewhere?]

Anyway, I’ll try to redo the post.

Cort, thanks for the link. Actually it was the reference that Lloyd and van de Meer quoted as providing evidence of co-existing mood disorders that I was interested to see.
 

MAC

Member
I found a recent presentation of Professor Andrew Lloyd’s – 23 April 2014.


It’s long but quite entertaining in places – he had a tough crowd of people with ME/CFS.

Regarding the mood disorders – he is quite clear that the illness comes first. He rejected opportunities to blame past traumas (eg childhood abuse) as a cause of the illness. He says that mood disorders (anxiety, depression) are either caused by the illness directly and/or a result of living with a chronic poorly understood illness, in particular an illness that hits you every time you push a little with physical or cognitive effort. And he’s probably right in that.

That said, he does suggest that people who don’t do well in his fatigue clinic (which does CBT/GET/correction of sleep and mood problems) generally have a mood problem (presumably they are too irritable or unmotivated).

My sense is that Prof Lloyd started out enthusiastic, without judgement of people with post-infective fatigue and keen to find the answer to the problem. Then, years of doing experiments and finding nothing has ground him down. He has watched lots of possible theories on cause and treatment be proven wrong and he has grown very sceptical. He probably burned his professional reputation a bit by being associated with CFS and has been criticised by those grumpy frustrated people with CFS too.

He seems to have decided that, for post-infective fatigue, all the problems are in the brain arising from it getting stuck in the ‘acute sickness response’ (sickness behaviour) mode. And I think he has lost interest and isn’t keeping up with recent advances.

He rejects the finding of poorer physical performance on the second day of exercise trials as simply a result of deconditioning and lack of motivation. This is because he did an experiment with electrical stimulation of muscles that found no difference in performance on day 2.

More to come..
 

Who Me?

Well-Known Member
@MAC

"Then, years of doing experiments and finding nothing has ground him down."

How does he think we feel, years of being sick with no help. If anyone has the right to feel ground down it's us.
 

MAC

Member
More from Prof Lloyd’s 2014 presentation:

He said that there is no good evidence of inflammation of the brain. When someone mentioned a recent imaging study that did show inflammation, he was sceptical.

Regarding the fatigue clinic, Prof Lloyd reported that around 30% of the patients attending improved as a result of the ‘intervention’. He said that he thought that about 70% of the participants have CFS. The clinic relies on the diagnosis made by GPs (primary care physicians) and they don’t do any checking of that. He wasn’t worried that patients with say just depression were turning up at the clinic as he felt that the clinic could help them too.

There hasn't been any rigorous analysis of the outcomes of his fatigue clinic.

He noted that many CFS patients get better on their own early in the course of the illness – his Dubbo study showed that. He said that the average number of years of illness of the patients attending the clinic is 5.5 years, so he felt that they were getting the patients with more resistant illness (although that average allows for a significant proportion of people who have had the illness for less than 5.5 years).

It was very interesting to hear from the fatigue clinic clinician about what is actually done in the clinic. The GET sounded much more like gentle pacing. The clinician actually mentioned that they often have to get people to do less activity rather than more. The two patients touted as success stories appeared to have had quite mild CFS cases when they started the intervention and are still sick now. What they reported was gaining an understanding of their own illness and how to live better within the energy constraints imposed by the illness.

The fatigue clinic clinician was very sweet and empathetic. It would be a very irritable patient indeed who would report, in the 12-week questionnaire, that all her effort for the patient had achieved nothing at all. There doesn’t seem to be any long-term follow-up.

I found it interesting that Prof Lloyd felt (at 57 mins) that there was little evidence for a higher prevalence of women than men of post-infective fatigue, certainly not the high ratios that are often claimed. He puts this down to men being more reluctant to see doctors. I think there is something in this.

He also noted that there is no difference between the incidence of post-infective fatigue with culture or geography – something that is often disputed when CFS is claimed to be a fashionable diagnosis.
 

MAC

Member
Looking at Prof Lloyd's website at the University of New South Wales now, there is no mention at all of Chronic Fatigue Syndrome apart from in the list of past publications. Post-infective fatigue states appears way down the bottom of the list of research interests. Prof Lloyd is currently running a Hepatitis C trial in a prison.
 

MAC

Member
@Minx
Certainly we have a right to feel aggrieved at our treatment by the medical profession.
And if you watch that video, you will see there are things to feel aggrieved about specifically with respect to Prof Lloyd's approach to CFS.

But what I also got from the video was the sense of a basically good intelligent man who did, for many years, probably try quite hard to make the lives of CFS patients better. This is in an environment where most people in the medical profession have thought CFS a bogus disease and those doctors involved with it either stupid or charlatans.
 

Strike me lucky

Well-Known Member
Sounds like prof Lloyd is depressed because he cant find the answer, so does what most drs do and blame the patient and or say they are depressed
 

Justarose123

Active Member
Yes, sdsu, what comes first, the mood disorder or having an illness that people tell you is caused by not trying hard enough to be well? :banghead:
You said it well my friend! Had no depression in the beginning, but almost every other system he listed? How ironic, Rita
 

Justarose123

Active Member
More from Prof Lloyd’s 2014 presentation:

He said that there is no good evidence of inflammation of the brain. When someone mentioned a recent imaging study that did show inflammation, he was sceptical.

Regarding the fatigue clinic, Prof Lloyd reported that around 30% of the patients attending improved as a result of the ‘intervention’. He said that he thought that about 70% of the participants have CFS. The clinic relies on the diagnosis made by GPs (primary care physicians) and they don’t do any checking of that. He wasn’t worried that patients with say just depression were turning up at the clinic as he felt that the clinic could help them too.

There hasn't been any rigorous analysis of the outcomes of his fatigue clinic.

He noted that many CFS patients get better on their own early in the course of the illness – his Dubbo study showed that. He said that the average number of years of illness of the patients attending the clinic is 5.5 years, so he felt that they were getting the patients with more resistant illness (although that average allows for a significant proportion of people who have had the illness for less than 5.5 years).

It was very interesting to hear from the fatigue clinic clinician about what is actually done in the clinic. The GET sounded much more like gentle pacing. The clinician actually mentioned that they often have to get people to do less activity rather than more. The two patients touted as success stories appeared to have had quite mild CFS cases when they started the intervention and are still sick now. What they reported was gaining an understanding of their own illness and how to live better within the energy constraints imposed by the illness.

The fatigue clinic clinician was very sweet and empathetic. It would be a very irritable patient indeed who would report, in the 12-week questionnaire, that all her effort for the patient had achieved nothing at all. There doesn’t seem to be any long-term follow-up.

I found it interesting that Prof Lloyd felt (at 57 mins) that there was little evidence for a higher prevalence of women than men of post-infective fatigue, certainly not the high ratios that are often claimed. He puts this down to men being more reluctant to see doctors. I think there is something in this.

He also noted that there is no difference between the incidence of post-infective fatigue with culture or geography – something that is often disputed when CFS is claimed to be a fashionable diagnosis.
More from Prof Lloyd’s 2014 presentation:

He said that there is no good evidence of inflammation of the brain. When someone mentioned a recent imaging study that did show inflammation, he was sceptical.

Regarding the fatigue clinic, Prof Lloyd reported that around 30% of the patients attending improved as a result of the ‘intervention’. He said that he thought that about 70% of the participants have CFS. The clinic relies on the diagnosis made by GPs (primary care physicians) and they don’t do any checking of that. He wasn’t worried that patients with say just depression were turning up at the clinic as he felt that the clinic could help them too.

There hasn't been any rigorous analysis of the outcomes of his fatigue clinic.

He noted that many CFS patients get better on their own early in the course of the illness – his Dubbo study showed that. He said that the average number of years of illness of the patients attending the clinic is 5.5 years, so he felt that they were getting the patients with more resistant illness (although that average allows for a significant proportion of people who have had the illness for less than 5.5 years).

It was very interesting to hear from the fatigue clinic clinician about what is actually done in the clinic. The GET sounded much more like gentle pacing. The clinician actually mentioned that they often have to get people to do less activity rather than more. The two patients touted as success stories appeared to have had quite mild CFS cases when they started the intervention and are still sick now. What they reported was gaining an understanding of their own illness and how to live better within the energy constraints imposed by the illness.

The fatigue clinic clinician was very sweet and empathetic. It would be a very irritable patient indeed who would report, in the 12-week questionnaire, that all her effort for the patient had achieved nothing at all. There doesn’t seem to be any long-term follow-up.

I found it interesting that Prof Lloyd felt (at 57 mins) that there was little evidence for a higher prevalence of women than men of post-infective fatigue, certainly not the high ratios that are often claimed. He puts this down to men being more reluctant to see doctors. I think there is something in this.

He also noted that there is no difference between the incidence of post-infective fatigue with culture or geography – something that is often disputed when CFS is claimed to be a fashionable diagnosis.
Really because I had 3 or 4 MRI's of my neck and brain, in 2007 found right Mastoiditis some fluid signal in mastoid air cells, and enhancement post-gadolinium it has should progression from previous study in 2005 also. In 2012 there is prominence of cystic adenoid lymphoid tissue, isn't this all bacteria of right inner ear which had been swollen behind off and on quite abit and treated with antibiotics once. Could this have spread? I have pineal cyst. But hypopitituary problems?? Or am I reading these reports all wrong because they are mri's of the brain? Rita
 

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