Do graded activity therapies cause harm in chronic fatigue syndrome?

Background Both Peak Oxygen Uptake (peak VO2), from cardiopulmonary exercise testing (CPET) and the distance walked during a Six-Minute Walk Test (6 MWD) are used for following the natural history of various diseases, timing of procedures such as transplantation and for assessing the response to therapeutic interventions. However, their relationship has not been clearly defined. Methods We determined the ability of 6 MWD to predict peak VO2 using data points from 1,083 patients with diverse cardiopulmonary disorders. The patient data came from a study we performed and 10 separate studies where we were able to electronically convert published scattergrams to bivariate points. Using Linear Mixed Model analysis (LMM), we determined what effect factors such as disease entity and different inter-site testing protocols contributed to the magnitude of the standard error of estimate (SEE). Results The LMM analysis found that only 0.16 ml/kg/min or about 4% of the SEE was due to all of the inter-site testing differences. The major source of error is the inherent variability related to the two tests. Therefore, we were able to create a generalized equation that can be used to predict peak VO2 among patients with different diseases, who have undergone various exercise protocols, with minimal loss of accuracy. Although 6 MWD and peak VO2 are significantly correlated, the SEE is unacceptably large for clinical usefulness in an individual patient. For the data as a whole it is 3.82 ml/kg/min or 26.7% of mean peak VO2. Conversely, the SEE for predicting the mean peak VO2 from mean 6 MWD for the 11 study groups is only 1.1 ml/kg/min. Conclusions A generalized equation can be used to predict peak VO2 from 6 MWD. Unfortunately, like other prediction equations, it is of limited usefulness for individual patients. However, the generalized equation can be used to accurately estimate mean peak VO2 from mean 6 MWD, among groups of patients with diverse diseases without the need for cardiopulmonary exercise testing. The equation is:

Background There is a concern in the literature that harm from interventions is insufficiently documented in clinical trials in general, and in those assessing psychological treatments in particular. A recent decision by a trial steering committee to stop recruitment into a randomized controlled trial (RCT) of a psychological intervention for personality disorder led to an investigation of the recording of harm in trials funded by the National Institute for Health Research (NIHR). Methods The protocols and final reports of all 82 NIHR trials funded between 1995 and 2013 were examined for the reporting of adverse events. These were subdivided by category of intervention. Results None of the psychological intervention trials mentioned the occurrence of an adverse event in their final report. Trials of drug treatments were more likely to mention adverse events in their protocols compared with those using psychological treatments. When adverse events were mentioned, the protocols of psychological interventions relied heavily on severe adverse events guidelines from the National Research Ethics Service (NRES), which were developed for drug rather than psychological interventions and so may not be appropriate for the latter. Conclusions This survey supported the belief that the reporting of adverse events in psychological treatments is weak and the criteria used may not be appropriate. Recommendations are made as to how current practice might be improved.

Background Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis/encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations' surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone. Methods/Design 600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current comorbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a 'booster session' at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures. Discussion The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.