Graded exercise in chronic fatigue syndrome. Patients were selected group

Comment on: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Editor—Kathy Y Fulcher and Peter D White conclude that their findings support the use of graded aerobic exercise in the management of the chronic fatigue syndrome.1 Those readers who delve no further than the abstract and key points may welcome this “take home message.”

Several flaws in the paper, however, make accurate interpretation of the findings difficult and greatly limit its applicability. Firstly, less than two fifths of those screened for the trial actually entered it. Many of those who did not enter it were excluded on the basis of current psychiatric disorder, even though the Oxford criteria used by the authors do not specifically exclude patients with anxiety and depression.2 Given that this is already a subgroup selected by their referral to psychiatric outpatient departments, to select out those with a current psychiatric disorder makes them an unusual group indeed.

Secondly, successful randomisation should make the intervention and control groups similar. Such comparability should enable the problem of confounders, known or unknown, to be accounted for. Evidence of the comparability of cases and controls should be presented.3 Age and sex are almost universal confounders. In this study one might also add body mass index, duration of illness, and even previous athletic training as other possible confounders. The paper does not break down the age and sex of the two groups to enable comparison.

Thirdly, the main outcome measure is the self rated clinical global impression change score. This score is a validated measure of overall change.4 However, the validity of the subsequent categorisation of patients into those with a score of 1 or 2 and those with a score of 3-7, and whether this was a post hoc categorisation, is not stated. A categorisation into 1-3 (all scores representing an improvement) and 4-7 (the rest) would not have produced a significant change. Numerous other physiological outcome measures are provided, but more clinically relevant would have been consultation rates, use of drug treatment, and time off work (time off work was measured only at one year, after the crossover). In short, for those considering the options for managing this condition, especially those who commission services, the message should be that we need more information before we can tell if graded exercise will help most patients with the chronic fatigue syndrome.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127633/pdf/9361551.pdf

 

Source: Sadler M. Graded exercise in chronic fatigue syndrome. Patients were selected group. BMJ. 1997 Oct 11;315(7113):947-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127633/

 

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results

Comment on:

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

Managing chronic fatigue syndrome in children. [BMJ. 1997]

 

Editor—“Editor’s choice” in the issue of 7 June states, “we agree that myalgic encephalomyelitis (or chronic fatigue syndrome) is a serious condition” and “all conditions have a mental and physical component.” This is the stance of the patient organisations supporting patients with this condition. Unfortunately, some doctors have trivialised this illness; ridiculed patients and their supporters; and subjected a few of them, including children, to oppressive, perhaps even abusive, forms of treatment. Hopefully, this is now a thing of the past. We need, as Harvey Marcovitch says, to explore what might be done to help them.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127632/pdf/9361550.pdf

 

Source: Franklin AJ. Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. BMJ. 1997 Oct 11;315(7113):947; author reply 948. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127632/

 

Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity

Erratum in: BMJ 1997 Nov 1;315(7116):1165.

Comment on: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Editor—We remain firmly opposed to exercise programmes that encourage patients with the chronic fatigue syndrome to increase their levels of physical activity progressively without making allowance for fluctuating levels of disablement. Nevertheless, we welcome Kathy Y Fulcher and Peter D White’s finding that an individually tailored programme can produce benefits in a carefully selected subset.1 We have concerns, however, about the way in which these results have been oversimplified in the media and may now be put into practice by health professionals with no experience of this approach to management.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127628/pdf/9361549.pdf

 

Source: Shepherd C, Macintyre A. Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity. BMJ. 1997 Oct 11;315(7113):947; author reply 948. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127628/

 

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome

Abstract:

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome.

DESIGN: Randomised controlled trial with control treatment crossover after the first follow up examination.

SETTING: Chronic fatigue clinic in a general hospital department of psychiatry.

SUBJECTS: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance.

INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards.

MAIN OUTCOME MEASURE: The self rated clinical global impression change score, “very much better” or “much better” being considered as clinically important.

RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion. 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment.

CONCLUSION: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.

Comment in:

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. [BMJ. 1997]

Managing chronic fatigue syndrome in children. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Chronic fatigue syndrome is heterogeneous condition. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Patients were selected group. [BMJ. 1997]

 

Source: Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ. 1997 Jun 7;314(7095):1647-52. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126868/ (Full article)

 

Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology

Abstract:

Physical fatigability and avoidance of physically demanding tasks in chronic fatigue syndrome (CFS) were assessed by the achievement or nonachievement of 85% of age-predicted maximal heart rate (target heart rate, THR) during incremental exercise. The association with functional status impairment, somatization, and psychopathology was examined.

A statistically significant association was demonstrated between this physical fatigability variable and impairment, and a trend was found for an association with somatization. No association was demonstrated with psychopathology. These results are in accordance with the cognitive-behavioral model of CFS, suggesting a major contribution of avoidance behavior to functional status impairment; however, neither anxiety nor depression seem to be involved in the avoidance behavior.

Aerobic work capacity was compared between CFS and healthy controls achieving THR. Physical deconditioning with early involvement of anaerobic metabolism was demonstrated in this CFS subgroup.

Half of the CFS patients who did not achieve THR did not reach the anaerobic threshold. This finding argues against an association in CFS between avoidance of physically demanding tasks and early anaerobic metabolism during effort.

 

Source: 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, somatization and psychopathology. J Psychosom Res. 1997 Apr;42(4):369-78. http://www.ncbi.nlm.nih.gov/pubmed/9160276

 

Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if patients with the chronic fatigue syndrome have less vagal power during walking and rest periods following walking, in comparison to a group of healthy controls.

Eleven patients (ten women and one man) who fulfilled the case definition for chronic fatigue syndrome modified to reduce heterogeneity and eleven healthy, but sedentary, age- and sex-matched controls walked on a treadmill at 2.5 mph four times each for 4 min duration. Between each period of walking, subjects were given a 4-min seated rest period. Vagal power, a Fourier-based measure of cardiac, parasympathetic activity in the frequency range of 0.15 to 1.0 Hz, was computed.

In each period of walking and in one period of rest, patients had significantly less vagal power than the control subjects despite there being no significant group-wise differences in mean heart rate, tidal volume, minute volume, respiratory rate, oxygen consumption or total spectrum power. Further, patients had a significant decline in resting vagal power after periods of walking.

These results suggest a subtle abnormality in vagal activity to the heart in patients with the chronic fatigue syndrome and may explain, in part, their post-exertional symptom exacerbation.

 

Source: Cordero DL, Sisto SA, Tapp WN, LaManca JJ, Pareja JG, Natelson BH. Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome. Clin Auton Res. 1996 Dec;6(6):329-33. http://www.ncbi.nlm.nih.gov/pubmed/8985621

 

Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression

Abstract:

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force.

MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal.

The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects.

 

Source: Samii A, Wassermann EM, Ikoma K, Mercuri B, George MS, O’Fallon A, Dale JK, Straus SE, Hallett M. Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression. Neurology. 1996 Dec;47(6):1410-4. http://www.ncbi.nlm.nih.gov/pubmed/8960719

 

Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome

Abstract:

PURPOSE: To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria.

RESULTS: Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads.

CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Comment in:

Exercise limits in chronic fatigue syndrome. [Am J Med. 1997]

Graded exercise testing and chronic fatigue syndrome. [Am J Med. 1997]

 

Source: Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, Boda WL, Tapp WN, Natelson BH. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. 1996 Jun;100(6):634-40. http://www.ncbi.nlm.nih.gov/pubmed/8678084

 

Reduced oxidative muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15).

CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14).

In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Comment in: Chronic fatigue syndrome and skeletal muscle mitochondrial function. [Muscle Nerve. 1997]

 

Source: McCully KK, Natelson BH, Iotti S, Sisto S, Leigh JS Jr. Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. 1996 May;19(5):621-5. http://www.ncbi.nlm.nih.gov/pubmed/8618560

 

Use of exercise for treatment of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a condition that results in moderate to severe disability, the primary feature of which is fatigue of unknown origin. There is a lot of interest in classifying, characterising and treating patients with CFS. Currently, the two major theories of a medical cause of CFS are viral infection and immune dysregulation.

Patients report critical reductions in levels of physical activity, and many experience ‘relapses’ of severe symptoms following even moderate levels of exertion. Despite this, most studies report CFS patients to have normal muscle strength and either normal or slightly reduced muscle endurance.

Histological and metabolic studies report mixed results: CFS patients have either no impairment or mild impairment of mitochondria and oxidative metabolism compared with sedentary controls.

Current treatments for CFS are symptom-based, with psychological, pharmacological and rehabilitation treatments providing some relief but no cure. Immunological and nutritional treatments have been tried but have not provided reproducible benefits. Exercise training programmes are thought to be beneficial (if ‘relapses’ can be avoided), although few controlled studies have been performed.

CFS is a long-lasting disorder that can slowly improve with time, but often does not. Further studies are needed to better understand the multiple factors that can cause chronic fatigue illness, as well as the effect that exercise training has on the symptoms of CFS.

 

Source: McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of chronic fatigue syndrome. Sports Med. 1996 Jan;21(1):35-48. http://www.ncbi.nlm.nih.gov/pubmed/8771284