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.

Survival of patients with SSc-PAH in the modern treatment era is better than in historical series. A significant proportion of patients with mild functional impairment or exercise-induced SSc-PAH have evidence of disease progression. Survival of patients with respiratory disease-associated pulmonary hypertension is inferior. SLE-PAH has a better prognosis than SSc-PAH.

The prognosis in nonsurgical disease has improved. We have confirmed the previously described good outcome in surgically treated disease. However, we have also demonstrated that the long-term prognosis for patients who have persistent pulmonary hypertension at 3 months after surgery is good. The observed improvements in outcome during the modern treatment era reinforce the importance of identifying patients with this increasingly treatable condition.

BackgroundThe EQ-5D has been extensively used to assess patient utility in trials of new treatments within the cardiovascular field. The aims of this study were to review evidence of the validity and reliability of the EQ-5D, and to summarise utility scores based on the use of the EQ-5D in clinical trials and in studies of patients with cardiovascular disease.MethodsA structured literature search was conducted using keywords related to cardiovascular disease and EQ-5D. Original research studies of patients with cardiovascular disease that reported EQ-5D results and its measurement properties were included.ResultsOf 147 identified papers, 66 met the selection criteria, with 10 studies reporting evidence on validity or reliability and 60 reporting EQ-5D responses (VAS or self-classification). Mean EQ-5D index-based scores ranged from 0.24 (SD 0.39) to 0.90 (SD 0.16), while VAS scores ranged from 37 (SD 21) to 89 (no SD reported). Stratification of EQ-5D index scores by disease severity revealed that scores decreased from a mean of 0.78 (SD 0.18) to 0.51 (SD 0.21) for mild to severe disease in heart failure patients and from 0.80 (SD 0.05) to 0.45 (SD 0.22) for mild to severe disease in angina patients.ConclusionsThe published evidence generally supports the validity and reliability of the EQ-5D as an outcome measure within the cardiovascular area. This review provides utility estimates across a range of cardiovascular subgroups and treatments that may be useful for future modelling of utilities and QALYs in economic evaluations within the cardiovascular area.