Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome

Objective

Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them.

Methods

AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts.

Results

Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P = .47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P < .001), with no significant differences in worsening fatigue.

Conclusions

The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data.     

Therapist effects in routine psychotherapy practice: An account from chronic fatigue syndrome

Abstract

The effect of therapists in psychotherapy is a much debated topic, with a number of studies showing therapist variance being large while other studies show little or no variability in outcomes due to therapists. The aim of this study was to investigate therapist effects in a well-defined sample of patients and therapists from an outpatient service which specializes in providing cognitive behaviour therapy (CBT) for patients with chronic fatigue syndrome (CFS). Therapy was provided in a highly specialized clinical setting for CFS and was delivered by qualified CBT therapists with at least 2 years experience with this client group. Three hundred and seventy-four patients with CFS and 12 cognitive behavioural psychotherapists took part. Therapist effects on the primary outcomes of fatigue and disability were investigated with multilevel random effects models and variance component analysis. Different models were computed and compared. Results showed a reduction in fatigue and disability scores after therapy. Variance explained by therapists, when demographic covariates were accounted for, was 0% for fatigue and under 2% for disability. A number of important factors may have played a significant role in minimizing therapist effects in our study. These are: specialist setting, single centre, patients with the same primary diagnosis, therapists of the same orientation and training, shared environment and supervision. Future studies may stress the importance of these factors in the investigation of the therapist effect in psychotherapy.     

Correction to: Faintly tired: a systematic review of fatigue in patients with orthostatic syncope

Clinical Autonomic Research -     

Gulf War Illness: lessons from medically unexplained symptoms

Service in the Persian Gulf in 1991 is associated with increased reporting of symptoms and distress in a proportion of those who served there. Yet despite clear evidence of an increase in symptom burden and a decrease in well being, exhaustive clinical and laboratory based scientific research has failed to document many reproducible biomedical abnormalities in this group. Likewise, there has been no evidence of an increase in disease related mortality. Formal psychiatric disorders are twice as common in Gulf War veterans, as might be expected in the aftermath of any conflict, but this too is insufficient to explain the ill-health observed. Many service personnel who returned unwell believe that they have Gulf War Syndrome, and that their ill-health is due to exposures that they encountered in theatre. Research on multiple exposures to date has not generated a plausible aetiological mechanism for veterans' ill-health. Even if medical research has failed to provide a satisfactory explanation, it remains the case that many of those affected continue to be unwell and disabled some 15 years after returning from combat. For this reason, it is time that more attention is given to developing effective interventions to relieve their ill-health and distress. In this review we discuss the importance of the wider social context, individual illness beliefs and attributions and go on to outline a model of continuing ill-health in Gulf veterans. The review concludes with some suggestions for future research priorities, in particular the need for further qualitative studies to further our understanding of the illness, in order that better treatments may be developed.     

Non-Epileptic attacks: A Cognitive Behavioural Approach in a Single Case with a Four-Year Follow-up

A fear avoidance model is used to understand and treat a 57-year-old man with non-epileptic attacks during which he had a sudden paroxysmal experience which was interpreted by others as epileptic. The principal component of treatment was graded exposure to avoided activities. At discharge the attacks had stopped and the associated avoidances were markedly improved. Treatment gains were maintained at 4-year follow-up.     

Childhood experiences of illness and parenting in adults with chronic fatigue syndrome

OBJECTIVE: There are many similarities between chronic fatigue syndrome (CFS), the somatoform disorders and problems otherwise known as "medically unexplained symptoms." There is some evidence to suggest that a combination of inadequate parenting and early illness experience may predispose the individual to develop medically unexplained symptoms in adult life. The aim of this investigation was to compare the contributions of childhood experiences of illness and parenting in adults with CFS with a fracture clinic control group. METHOD: A retrospective case control design was used. Thirty patients with a diagnosis of CFS and 30 patients attending a fracture clinic in an inner London teaching hospital completed questionnaires measuring parental care and protection and were interviewed about childhood experiences of illness. RESULTS: There were no differences in childhood experience of illness in the two groups. However, logistic regression revealed that maternal overprotection and depression were associated with the diagnosis of CFS. CONCLUSION: The findings may represent risk factors for the development of CFS in adult life. It is possible that maternal overprotection in particular is related to the formation of belief systems about avoiding activity that operate to adversely influence behaviour in patients with CFS.     

Inhibition of chronic vascular rejection by donor-specific blood transfusion is associated with a reduction in transforming growth factor-beta1 expression

BACKGROUND: Concentric intimal thickening and the infiltration of inflammatory cells in cardiac allografts are the pathological hallmark characteristics of chronic vascular rejection (CVR), the leading cause of long-term graft failure. The precise mechanisms involved in the development and pathogenesis of CVR remain elusive. In the PVG-R23 to PVG-RT1u rat model of CVR, prior administration of a donor-specific transfusion (DST) was previously shown to prolong graft survival indefinitely and abolish the vascular lesions associated with CVR. The present study investigates in more depth the underlying mechanisms involved in the subsequent prolongation of allograft survival and inhibition of CVR by DST. METHODS: R23 heart grafts were monitored in nontransfused and transfused RT1u recipients injected 2 weeks before transplantation with 1.5 ml of R23 blood. Severity of arteriosclerosis, transplant infiltrate, transforming growth factor (TGF)-beta1 protein expression within the graft, plasma TGF-beta1 levels, class II MHC expression, tenascin protein expression, and serum alloantibody levels were measured. RESULTS: There was no significant difference in donor MHC class II, myocardial TGF-beta1, or tenascin expression between DST and non-DST-treated recipients. However, DST-pretreated recipients showed greatly reduced histological evidence of CVR and had lower titers of R23-specific IgG subclasses. Furthermore, DST-treated allograft recipients showed significant decreases in circulating TGF-beta1 levels and a reduction in TGF-beta1 and tenascin expression within coronary arteries of the allografts. CONCLUSION: The results suggested that DST inhibited CVR by altering and regulating the expression of TGF-beta1, thereby preventing the fibrogenic effects associated with TGF-beta1.