Is there any evidence that deconditioning alone causes pain and fatigue?

[Insomniac]

It's a shame that this information is hidden in an obscure thread in this forum. I wish I could put it in a permanent website that always goes top of google results and is translated in every language for everyone to see.

Goodness knows what harm has been done to newly diagnosed people.

I saw a doctor/researcher yesterday who has the power to ask the ministry of health where I live to make a special case for me to receive Rituximab as a one off case. Before I could bring it up the doc goes into the exact PACE thing that is quoted above.
He believes it, and even if he didn't he would probably have to recommend it anyway because CBT is the official recommended treatment for CFS/ME. CBT is in most of the fibro and CFS research papers he reads, other than Cymbalta and Lyrica which were unhelpful for me. He offered to get me Rituximab at the end but I have no desire to try this experimental drug with someone so ignorant.

This information you've all got together should really not be stuck in this thread alone.

 

[biophile]

I have a present for you oceanblue, enjoy ...

p23 GET therapist manual:

MODEL AND RATIONALE BEHIND GET

GET has been shown to improve muscle strength, cardiovascular endurance, and symptoms in a wide variety of illnesses,[4] including fibromyalgia, a painful fatiguing illness related to CFS/ME.[5] Three systematic reviews have concluded that GET is a promising treatment for outpatients with CFS/ME.[6-8] Five randomised controlled trials (RCTs) have found improved fatigue and disability with differing graded exercise programmes compared to no treatment or control treatments.[1,2,9-11] Three randomised controlled trials of graded exercise suggest that GET improves symptoms or disability more than relaxation or supportive therapy.[1,10,11]

The rationale behind GET stems from both physical and behavioural understanding of CFS/ME. Physical deconditioning, exercise intolerance and avoidance caused by relative inactivity are reversed by gradually and carefully re-introducing regular physical exercise, aiming to return a patient to normal health and ability. This model has been used in previous trials.[1,2,11] Exercise also has a role to play in improving the sleep disturbance, mood, and cognitive problems found in people with CFS/ME.[10]

The most prominent symptom of CFS/ME is post-exertional fatigue, resulting in avoidance of exercise, exercise intolerance, and reduced aerobic capacity.[12-14] One study has also shown significantly lower isometric quadriceps strength.[14] Prolonged inactivity can perpetuate or worsen fatigue and its associated symptoms in both healthy volunteers [13] and in people recovering from a viral illness.[15]

Physical deconditioning is characterised by reduced muscle strength and aerobic capacity.[13] This has been supported by a number of exercise studies that have shown reduced exercise tolerance in CFS/ME patients compared to controls. Five case-control studies have found that exercise tolerance was significantly reduced in CFS/ME participants.[14,16,17,18,19]. A further small study found nearly two minutes difference in an exercise test compared to controls.[20] A seventh study also concluded that exercise tolerance was reduced, although time spent exercising was not given.[21] Six of these studies also found that people with CFS/ME were either more deconditioned than healthy controls or at least as deconditioned as sedentary healthy controls [14,16-20]. Only two studies found no significant differences from healthy controls,[22,23] although both patients and controls were less fit than predicted.[22] However, CFS/ME participants in these two studies had significant correlations between deconditioning and both fatigue and functional impairment, and a negative correlation with physical activity,[22] suggesting that deconditioning was important even in these apparently negative studies.[22,23] Studies also show exercise incapacity was significantly correlated with reduced muscle strength and/or higher heart-rate response to sub-maximal exercise in people with CFS/ME.[11,14] The latter may be related to reduced left ventricular mass found in CFS/ME.[24] A graded exercise programme produced a 13 per cent increase in peak VO2 and a 26 per cent increase in quadriceps muscle strength.[1,14] Improved exercise capacity was also correlated with reduced heart-rate response to sub-maximal exercise.[14]

1. Fulcher KY & White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ 1997;314:1647-52.

2. Powell P et al. A randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. BMJ 2001;322:387-92.

3. Fulcher KY & White PD. Chronic fatigue syndrome: a description of graded exercise treatment. Physiotherapy 1998;84:223-6.

4. Basmajian JV & Wolf SL. Therapeutic Exercise. Baltimore, Williams & Wilkins, 1990.

5. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev 2002; 3:CD003786.

6. Whiting P, Bagnall A, Sowden A, Cornell J, Mulrow C, Ramirez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA 2001;286:1360-8.

7. Bagnall AM et al. A systematic review of interventions for the treatment and management of chronic fatigue syndrome and/or myalgic encephalomyelitis. www.york.ac.uk/inst/crd/cfs.htm 2001.

8. Edmonds M, McGuire H, Price J. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2004(3):CD003200.

9. Wearden AJ et al. A randomised, double-blind, placebo-controlled trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry 1998;172:485-90.

10. Wallman K, Morton A, Goodman C, et al. Randomised controlled trial of graded exercise therapy for chronic fatigue syndrome. Med J Australia 2004;180:444-8.

11. Moss-Morris R, Wash C, Tobin R, Baldi JC. A randomised controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. J Health Psychol (in press).

12. Royal Colleges. Chronic Fatigue Syndrome; Report of a joint working group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. London, Royal College of Physicians, CR54, 1996.

13. Sandler H, Vernikos J. Inactivity: physiological effects. London: Academic Press, 1986.

14. Fulcher KY & White PD. Strength and physiological response to exercise in patients with the chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 2000;69:302-7.

15. Dalrymple W. Infectious mononucleosis: 2. Relation of bed rest and activity to prognosis. Postgrad Med 1961;35:345-349.

16. DeBecker P et al. Exercise capacity in chronic fatigue syndrome. Arch Intern Med 2000;160:3270-7.

17. Fischler, B, Dendale P, Michiels V, Cluydts R, Kaufman L, De Meirleir K. Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatisation and psychopathology. J Psychosom Res 1997;42:369-78.

18. Riley MS, O’Brien CJ, McCluskey DR, Bell NP, Nicholls DP. Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990;301:953-6.

19. Sisto SA, Lamanca J, Cordero DL et al. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med 1996;100:634-40.

20. Gibson J, Carroll N, Clague JE, Edwards RHT. Exercise performance in fatiguability in patients with chronic fatigue syndrome. J Neurol Neursurg Psychiatry 1993;56:993-8.

21. Inbar O, Dlin R, Rootstein A, Whipp BJ. Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med Sci Sports Exerc 2001;33:1463-70.

22. Bazelmans E, Bleijenberg G, Van Der Meer JWM, Folgering H. Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A control study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychol Med 2001;31:107-14.

23. Sargent C, Scroop GC, Nemeth BN, Burnet RB, Buckley JD. Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc 2002;34:51-6.

24. De Lorenzo F, Xiao H, Mukherjee M et al. Chronic fatigue syndrome: physical and cardiovascular deconditioning. Q J Med 1998;91:475-81.

p24 claims that, the deconditioning model "should apply equally if not more to" the severely affected patients who were excluded from the trial, and that the major objective of GET is to exercise adequately for full health and to prevent disease ie "30-45 minute sessions of moderate intensity physical activity at least five times a week". This is even more physical activity than most healthy people achieve.

It is odd how they state that the "most prominent symptom of CFS/ME is post-exertional fatigue", considering how their definition of CFS is baseline fatigue as the only main symptom, not post-exertional fatigue which they do not even require for diagnosis. And as they attribute post-exertional symptoms to deconditioning, this implies that the most prominent characteristic of CFS is deconditioning, which would be a ridiculous generalization for high functioning patients.

 

[oceanblue]

It's a shame that this information is hidden in an obscure thread in this forum. I wish I could put it in a permanent website that always goes top of google results and is translated in every language for everyone to see.

This information you've all got together should really not be stuck in this thread alone.

The plan is to write a summary of this, which might become a blog, but first I need to deal with Biophile's challenge. . .

 

[oceanblue]

I have a present for you oceanblue, enjoy ...

just what I wanted, thanks!

It feels like a test: 'can you spot the 25 sleights of hands in this creative misinterpretation?'. It certainly reads like a convincing argument.

I'll have a bash now and might do some more tomorrow.

GET therapist manual: MODEL AND RATIONALE BEHIND GET

GET has been shown to improve muscle strength, cardiovascular endurance, and symptoms in a wide variety of illnesses,[4] including fibromyalgia, a painful fatiguing illness related to CFS/ME.[5]

None of these are CFS so are not directly relevant, but it's worth noting that the effects in other diseases generally are rather modest, eg a Cochrane review of exercise for cancer fatigue found an effect size of only 0.23, which is small.

Three systematic reviews have concluded that GET is a promising treatment for outpatients with CFS/ME.[6-8] . . . Three randomised controlled trials of graded exercise suggest that GET improves symptoms or disability more than relaxation or supportive therapy.[1,10,11]

The most authoritative GET evidence now comes from the PACE trial, which found only modest improvements in self-reported fatigue and function, while the sole objective measure of fitness, the 6MWT, found only a tiny improvement over 12 months compared with the control group - leaving CFS patients on average figures typical of those with serious chronic illness. Telling results, when GET aimed to "return a patient to normal health and ability".

Physical deconditioning is characterised by reduced muscle strength and aerobic capacity.[13] This has been supported by a number of exercise studies that have shown reduced exercise tolerance in CFS/ME patients compared to controls. Five case-control studies have found that exercise tolerance was significantly reduced in CFS/ME participants.[14,16,17,18,19]

This is where it really falls down. Although the authors claimed exercise tolerance was less than sedentary controls, the controls were dodgy. Fortunately, there are population norms for the measure of deconditioning used in all these studies, VO2max, and in 4 out of 5 of these studies the CFS VO2max scores were at the low end of normal, but not abnormal by any means. Only 1 of the studies (De Becker [16]) did find evidence of deconditioning. They acknowledge that 2 further studies found no evidence of deconditioning and neglected to mention that a third study, Wallman, which they cite in another context, found that submaximal VO2 levels (more relevant to normal life) in CFS patients were no different than well-matched sedentary controls. So another way to summarise this evidence is:
"7 out of 8 studies found exercise tolerance was normal in CFS/ME participants".

 

[oceanblue]

rebuttal continued . . .

GET therapist manual: MODEL AND RATIONALE BEHIND GET

. . . Prolonged inactivity can perpetuate or worsen fatigue and its associated symptoms in both healthy volunteers [13] and in people recovering from a viral illness.[15]

Unfortunately I can't access the book [13] they reference, but if you read the rest of this thread you'll see that prolonged bed rest in healthy volunteers doesn't seem to cause fatigue, apart from mild fatigue in bed rest studies over 6 months. As for post-viral fatigue, it looks a bit desperate if they can only find a reference from 1961 [15. Dalrymple W. Infectious mononucleosis: 2. Relation of bed rest and activity to prognosis, 1961]. The title implies that longer bed rest correlates with more post-infectious fatigue, but correlation does not mean causation; longer bed rest might be a marker of a more severe initial illness. The recent Dubbo studies found that the initial severity of the infection (with infectious mononucleosis and 2 other infections) was a strong predictor of later fatigue.

. . . Studies also show exercise incapacity was significantly correlated with reduced muscle strength and/or higher heart-rate response to sub-maximal exercise in people with CFS/ME.[11,14] The latter may be related to reduced left ventricular mass found in CFS/ME.[24]

11 & 14 are both the Fulcher & White study: exercise incapacity is correlated with muscle strength and sub-maximal heart-rate response in healthy people too, so I'm not sure what point they are trying to make. The heart mass study they quote, Lorenzo, is quite large but unfortunately didn't use matched sedentary controls so doesn't necessarily tell us anything either.

A graded exercise programme produced a 13 per cent increase in peak VO2 and a 26 per cent increase in quadriceps muscle strength.[1,14] Improved exercise capacity was also correlated with reduced heart-rate response to sub-maximal exercise.[14]

Fulcher & White again. What they don't mention is that this study found the post-GET increases didn't correlate with any improvement in patients: "we found no significant association between feeling better after graded exercise treatment and becoming stronger or fitter". That does rather contradict their deconditioning argument. See above for correlation between exercise capacity and sub-maximal heart rate in healthy people too.

Did I miss anything?

So yes, the pitch in the PACE GET Therapist manual does look quite convincing, until you lift the lid. Then it's clear they've used the usual approach of closing one eye and squinting with the other until they can see what they want to see.

 

[Sean]

leaving CFS patients on average [with] figures typical of those with serious chronic illness.

And IIRC that includes some terminal illnesses (End Stage Lung Disease, Chronic Obstructive Pulmonary Disorders, etc). Some therapy.

"we found no significant association between feeling better after graded exercise treatment and becoming stronger or fitter". That does rather contradict their deconditioning argument.

And then some. Not that it will stop them invoking 'deconditioning' as a central critical assumption for their model.

For all their claims to be the 'evidence-based' side of the debate, they are remarkably willing to persistently ignore evidence seriously inconvenient to their agenda. How surprisement.

 

[biophile]

So yes, the pitch in the PACE GET Therapist manual does look quite convincing, until you lift the lid. Then it's clear they've used the usual approach of closing one eye and squinting with the other until they can see what they want to see.

Good work oceanblue, I just knew you couldn't resist, hehe. Anything worth adding to the thread "Examples of misleading statements in CFS papers from biopsychosocialists"? Also, don't knock the one eye squinting method, I have a headache right now which is about the force me off the PC and I'm using that method to post!

And IIRC that includes some terminal illnesses (End Stage Lung Disease, Chronic Obstructive Pulmonary Disorders, etc). Some therapy.

You may be recalling the paper which pooled the results from 11 different studies on a range of cardiopulmonary diseases, including end stage lung disease (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882364/table/T1). The average 6WMD across all studies was 393+/-115m (higher than the GET group in PACE at 52 weeks ie 379+/-100m) but the specific study on ESLD was lower, at 294+/-139m, which is still closer to the PACE GET group than the latter is to a healthy group. Also, there are many other studies on COPD cohorts which score higher in 6MWD than the GET group in PACE, but this is probably not for end stages of COPD, which can be much lower (eg http://www.ncbi.nlm.nih.gov/pubmed/20040883).

For all their claims to be the 'evidence-based' side of the debate, they are remarkably willing to persistently ignore evidence seriously inconvenient to their agenda. How surprisement.

Perhaps they are practicing "citation-based medicine", where all that matters is making it look like there is a reference to back up a questionable statement which most people will never bother to investigate for themselves (ironically this often even seems to include the peer reviewers of the papers in question).

 

[Sean]

"citation-based medicine"

c-i-r-c-l-e j-e-r-k



And thanks for the 6MWT comparison diseases ref. The PACE 6MWT results might not be quite as bad as for the end stage of terminal lung or cardio-pulmonary disease, but not by much. Still leaves ME/CFS patients clearly down at the very sick end of the spectrum.

 

[oceanblue]

Good work oceanblue, I just knew you couldn't resist, hehe. ..

Also, don't knock the one eye squinting method, I have a headache right now which is about the force me off the PC and I'm using that method to post!

Perhaps they are practicing "citation-based medicine", where all that matters is making it look like there is a reference to back up a questionable statement which most people will never bother to investigate for themselves (ironically this often even seems to include the peer reviewers of the papers in question).

You know me too well. And I now wonder if biopsychosocialists have a perpetual headache.

Love 'citation-based medicine'.

 

[Esther12]

Another +1 for 'citation based medicine'.

 

[user9876]

And IIRC that includes some terminal illnesses (End Stage Lung Disease, Chronic Obstructive Pulmonary Disorders, etc). Some therapy.


And then some. Not that it will stop them invoking 'deconditioning' as a central critical assumption for their model.

For all their claims to be the 'evidence-based' side of the debate, they are remarkably willing to persistently ignore evidence seriously inconvenient to their agenda. How surprisement.

It seems to me that too many people are doing 'evidence based medicine' with no underlying theory or model that they are trying to validate/invalidate. This means that their trials find correlation or a lack of correlation within a given situation. They or others then extrapolate to different situations and claim that this backs their views. This becomes easy to do since there is a lack of formal definition about what was tested and how that relates to the hypothesis and how that relates to any control.This lack of formality make reasoning about results hard, it means that you need to carefuly read all the papers to understand the detail of exactly what the trial was. It also makes it hard to talk about uncertanty associated with the evidence.

There is a danger in going the oposite way and being overly formal. This is what some economists have tended to do where they describe the world in a set of equations and have a tend to ignore effects that make the maths to complex.

 

[oceanblue]

From what I've read recently, I've got the impression that few psychosocial types are still defending the notion that deconditioning is a significant cause of disability in CFS... even if they still want to be paid to recondition patients. It's not quackery though... it's sophisticated biopsychosocial pragmatism.

Think I mentioned already this is very much the Nijmegen perspective, and this seems to be is the key paper, concluding: "Physical deconditioning does not seem a perpetuating factor in CFS"

The key figures are:
VO2max (ml O2/ml/kg)
CFS= 27.9
Control=31.7
The difference was non-significant, and, crucially, that CFS figure is within the low normal range for populations.

Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? full text
a controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity Bazelmans 2001

ABSTRACT
Background. Chronic fatigue syndrome (CFS) patients often complain that physical exertion
produces an increase of complaints, leading to a greater need for rest and more time spent in
bed. It has been suggested that this is due to a bad physical fitness and that physical deconditioning
is a perpetuating factor in CFS. Until now, studies on physical deconditioning in CFS
have shown inconsistent results.

Methods. Twenty CFS patients and 20 matched neighbourhood controls performed a maximal
exercise test with incremental load. Heart rate, blood pressure, respiratory tidal volume,
O2 saturation, O2 consumption, CO2 production, and blood-gas values of arterialized capillary
blood were measured. Physical fitness was quantified as the difference between the actual and
predicted ratios of maximal workload versus increase of heart rate. Fatigue, impairment and
physical activity were assessed to study its relationship with physical fitness.

Results. There were no statistically significant differences in physical fitness between CFS patients
and their controls. Nine CFS patients had a better fitness than their control. A negative
relationship between physical fitness and fatigue was found in both groups. For CFS patients
a negative correlation between fitness and impairment and a positive correlation between fitness
and physical activity was found as well. Finally, it was found that more CFS patients than
controls did not achieve a physiological limitation at maximal exercise.

Conclusion. Physical deconditioning does not seem a perpetuating factor in CFS.

I am still planning to write a summary of this thread but I've been engrossed by the Tour de France recently (why am I drawn to watching such an extreme endurance event?) which has given me better things to do. The Brits have finally arrived in Cycling.

 

[CJB]

I don't know if someone else mentioned this, but the webinar just presented by the CAA spotlighted the Pacific Fatigue Lab and they said unequivocally that their testing ruled out deconditioning, motivation, depression and one other thing in their CFS patients.

 

[alex3619]

The PACE 6MWT results might not be quite as bad as for the end stage of terminal lung or cardio-pulmonary disease, but not by much. Still leaves ME/CFS patients clearly down at the very sick end of the spectrum.

Yes, and that might indeed be the case, but remember that severe patients are excluded from their studies. For a full account, for ME, CFS, COPD or whatever, the full spectrum of patients have to be taken into account. For a very severe ME patient thats a 6MWT of what, zero to ten meters? What will that do to the averages? Bye, Alex

 

[oceanblue]

Some interesting comments from the Bazelmans discussion section
a) arguing against exercise programmes and
b) concluding that factors other than deconditioning account for fatigue, impairment and low levels of activity in CFS patients

Wagenmakers11 suggests that the abnormal physiology found in CFS may well be a consequence of the lack of exercise in CFS patients. For this reason he suggests that exercise programmes have to be brought into practice. However, this explanation does not seem plausible: in our study the controls also had a lower physical fitness than predicted while they were not less active or fatigued.

Considering the above mentioned correlations as well, it seems more likely that low levels of activity are an adaptation to a lower physical fitness of some CFS patients [my note: or could be due to a physiological limitation] but not for controls, rather than that low levels of activity lead to a worse physical fitness. Besides, Fulcher & White14 showed that there was no relationship between improvement in CFS after an exercise treatment programme and increase of peak aerobic capacity produced by exercise after this programme. This finding adds to the hypothesis that factors other than physical fitness determine a lower level of activity, fatigue and impairment in CFS.

... However, based on the results of our study, it must be concluded that a worse physical fitness does not seem to be a perpetuating factor in CFS.

 

[Esther12]

And the Bazelman's from 2001? You'd have thought it would have given pause for thought.

 

[user9876]

Yes, and that might indeed be the case, but remember that severe patients are excluded from their studies. For a full account, for ME, CFS, COPD or whatever, the full spectrum of patients have to be taken into account. For a very severe ME patient thats a 6MWT of what, zero to ten meters? What will that do to the averages? Bye, Alex

Only around 70% of all patients actually did the 6mwt in the pace trial. Not sure why but this could bias results significantly.

 

[biophile]

Only around 70% of all patients actually did the 6mwt in the pace trial. Not sure why but this could bias results significantly.

Coincidently, the lowest participation rate just happened to be in the GET group too.

 

[oceanblue]

And the Bazelman's from 2001? You'd have thought it would have given pause for thought.

I'm confused, those quotes are from the Bazelman 2001 paper.


I normally try to ignore inflammatory comments in these papers but the Fulcher & White first paper (1997) deserved a special mention for being so extreme:

Patients with the chronic fatigue syndrome perceive
greater fatigue than healthy controls taking the same
exercise.1 2 This may be caused by physical deconditioning,1
or sleep deprivation,3 or psychological
distress,4 or a combination of the three.

Or something else, perhaps?

I find the timing of this interesting as in 1997 I was very severely affected and facing some very extreme attitudes from those 'treating' me. I actually think the researchers may have mellowed a teeny bit since, or become a little more circumspect.

 

[oceanblue]

Another paper, this time for Adolescents, Katz 2010.
Exercise tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis. Full text inc tables available here

The study compared patients with a diagnosis of CFS 6 months after IM with a matched group of controls who had recovered from IM. Just wanted to pull out the deconditioning/fitness levels as VO2 max from the paper:

VO2max, ml/min/kg
CFS patients: 37.4
Recovered: 40.9

The difference was not statistically significant. Population norms for group of this age that is 85% female is around 40-49, so recovered patients (after 6 months) are scraping average while CFS patients are a bit below average, but by no means abnormal. This pattern must be looking pretty familiar by now.