SummaryBackgroundTrial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients' organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.MethodsIn our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.FindingsWe recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p=0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p=0·0003), but did not differ for APT (0·7 [−0·9 to 2·3] points lower; p=0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p=0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p=0·0005), but did not differ for APT (3·4 [−1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p=0·0027; GET p=0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.InterpretationCBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.FundingUK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

A retrospective analysis of 220 cases fulfilling criteria for cryptogenic fibrosing alveolitis (CFA) attending the Brompton Hospital between 1955 and 1973 has been carried out and patients have been followed for between four and 21 years. The frequency of various clinical features confirms previous reports. The 2 :1 male preponderance was similar in all age groups.The mean age at presentation was 54 years ± 12 SD; 202 (92%) of the patients presented with dyspnoea, the severity of which was related to the reduction in vital capacity (p < 0 003) and to the radiographic profusion score (p < 0.01) but not to its duration. Twenty-one per cent of the 220 had joint symptoms, 10% having clinical rheumatoid arthritis. Eleven showed much greater fibrosis and less acute inflammatory cellularity in spite of an interval between onset of symptoms and death of less than four years in 21 of 26 patients. One hundred and fifty-six patients have died (mean survival 3 -2 years). Eleven (5 %) are believed to be alive but have been lost to follow-up. Fifty-five per cent of deaths were attributable directly or indirectly to CFA. There was also an excess of deaths from cardiovascular disease and lung cancer. Using a life-table analysis and a log rank test, longer survival was seen in younger patients (p < 0 001) and women (p < 0.01). After correction for age and sex, lesser grades of dyspnoea (p <0 03) and lesser radiographic abnormality (p < 0-001), absence of right axis deviation (p < 0-001), and a higher Pao2 (p < 0-01) also related to longer survival. Subjects with more cellular histology also survived longer (p <0 02). Factors having no influence on survival included duration of dyspnoea before presentation, degree of reduction of FEV1, FVC, and TLC, the presence of "connective tissue"

BackgroundA multi-centre, four-arm trial (the PACE trial) found that rehabilitative cognitive behaviour therapy (CBT) and graded exercise therapy (GET) were more effective treatments for chronic fatigue syndrome (CFS) than specialist medical care (SMC) alone, when each was added to SMC, and more effective than adaptive pacing therapy (APT) when added to SMC. In this study we compared how many participants recovered after each treatment.MethodWe defined recovery operationally using multiple criteria, and compared the proportions of participants meeting each individual criterion along with two composite criteria, defined as (a) recovery in the context of the trial and (b) clinical recovery from the current episode of the illness, however defined, 52 weeks after randomization. We used logistic regression modelling to compare treatments.ResultsThe percentages (number/total) meeting trial criteria for recovery were 22% (32/143) after CBT, 22% (32/143) after GET, 8% (12/149) after APT and 7% (11/150) after SMC. Similar proportions met criteria for clinical recovery. The odds ratio (OR) for trial recovery after CBT was 3.36 [95% confidence interval (CI) 1.64–6.88] and for GET 3.38 (95% CI 1.65–6.93), when compared to APT, and after CBT 3.69 (95% CI 1.77–7.69) and GET 3.71 (95% CI 1.78–7.74), when compared to SMC (p values ⩽0.001 for all comparisons). There was no significant difference between APT and SMC. Similar proportions recovered in trial subgroups meeting different definitions of the illness.ConclusionsThis study confirms that recovery from CFS is possible, and that CBT and GET are the therapies most likely to lead to recovery.