How does cognitive behavior therapy for dissociative seizures work? A mediation analysis of the CODES trial.

BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Chronic fatigue syndrome and occupational status: a retrospective longitudinal study.

BACKGROUND: Few studies into chronic fatigue syndrome (CFS) have emphasized work-related consequences, including return to work after illness. AIMS: This paper explores socio-demographic, work and clinical characteristics that are associated with occupational status among patients who were assessed at baseline and a follow-up point. METHODS: Longitudinal data were assessed from patients affected by CFS who attended an outpatient CFS treatment service between 2007 and 2014. Employment status at baseline and follow-up was available for 316 patients. Data were also included on gender, age, duration of CFS, fatigue severity, type and number of treatment sessions, coping strategies, functional impairment, common mental disorders and physical functioning. RESULTS: Most patients were female (73%) and had been affected by CFS for longer than 2 years (66%). Patients were followed up for an average of 285 days and over this period 53% of patients who were working remained in employment. Of the patients who were not working at baseline, 9% had returned to work at follow-up. However, of those working at baseline, 6% were unable to continue to work at follow-up. Age, fatigue severity, functional impairment, cognitive and behavioural responses, and depressive symptoms impacted on a patients' work status at follow-up. CONCLUSIONS: The findings indicated that it is possible for people with CFS to remain in work or return to work, despite having had a disabling illness. Work-related outcomes should be targeted in all people of working age.

Understanding and addressing vaccine hesitancy in the context of COVID-19: development of a digital intervention.

OBJECTIVES: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) was identified in late 2019, spreading to over 200 countries and resulting in almost two million deaths worldwide. The emergence of safe and effective vaccines provides a route out of the pandemic, with vaccination uptake of 75-90% needed to achieve population protection. Vaccine hesitancy is problematic for vaccine rollout; global reports suggest only 73% of the population may agree to being vaccinated. As a result, there is an urgent need to develop equitable and accessible interventions to address vaccine hesitancy at the population level. STUDY DESIGN: & Method: We report the development of a scalable digital intervention seeking to address COVID-19 vaccine hesitancy and enhance uptake of COVID-19 vaccines in the United Kingdom. Guided by motivational interviewing (MI) principles, the intervention includes a series of therapeutic dialogues addressing 10 key concerns of vaccine-hesitant individuals. Development of the intervention occurred linearly across four stages. During stage 1, we identified common reasons for COVID-19 vaccine hesitancy through analysis of existing survey data, a rapid systematic literature review, and public engagement workshops. Stage 2 comprised qualitative interviews with medical, immunological, and public health experts. Rapid content and thematic analysis of the data provided evidence-based responses to common vaccine concerns. Stage 3 involved the development of therapeutic dialogues through workshops with psychological and digital behaviour change experts. Dialogues were developed to address concerns using MI principles, including embracing resistance and supporting self-efficacy. Finally, stage 4 involved digitisation of the dialogues and pilot testing with members of the public. DISCUSSION: The digital intervention provides an evidence-based approach to addressing vaccine hesitancy through MI principles. The dialogues are user-selected, allowing exploration of relevant issues associated with hesitancy in a non-judgmental context. The text-based content and digital format allow for rapid modification to changing information and scalability for wider dissemination.

Assessing functioning in adolescents with chronic fatigue syndrome: psychometric properties and factor structure of the School and Social Adjustment Scale and the Physical Functioning Subscale of the SF36.

BACKGROUND: Chronic fatigue syndrome (CFS) has a major impact on functioning. However, no validated measures of functioning for this population exist. AIMS: We aimed to establish the psychometric properties of the 5-item School and Social Adjustment Scale (SSAS) and the 10-item Physical Functioning Subscale of the SF-36 in adolescents with CFS. METHOD: Measures were completed by adolescents with CFS (n = 121). RESULTS: For the Physical Functioning Subscale, a 2-factor solution provided a close fit to the data. Internal consistency was satisfactory. For the SSAS, a 1-factor solution provided an adequate fit to the data. The internal consistency was satisfactory. Inter-item and item-total correlations did not indicate any problematic items and functioning scores were moderately correlated with other measures of disability, providing evidence of construct validity. CONCLUSION: Both measures were found to be reliable and valid and provide brief measures for assessing these important outcomes. The Physical Functioning Subscale can be used as two subscales in adolescents with CFS.

Psychometric properties of the Cognitive and Behavioural Responses Questionnaire (CBRQ) in adolescents with chronic fatigue syndrome.

BACKGROUND: To better understand the maintenance of chronic fatigue syndrome (CFS), a valid and reliable measure of cognitive and behavioural responses to symptoms is required. Such a measure could also assess beliefs and coping behaviours in the context of fatigue in other somatic conditions. AIMS: We aimed to establish the psychometric properties of both the Cognitive and Behavioural Responses Questionnaire (CBRQ) and its shortened version (CBRQ-S) in adolescents with CFS. METHOD: The full questionnaire was completed by a clinical cohort of adolescents (n = 121) presenting to specialist CFS units in the UK. RESULTS: Both the CBRQ and CBRQ-S had good internal consistency. The CBRQ scores were strongly associated with depression, anxiety, school and social functioning, but weakly associated with fatigue and physical functioning, providing evidence of validity. CONCLUSION: Both the 40-item and the 18-item versions of the CBRQ were found to be reliable and valid in adolescents with CFS. To minimize unnecessary burden, the 18-item version is favoured. Using this assessment tool in future studies, including intervention studies, may help to better target interventions during clinical practice and improve outcomes.

Protocol of a two arm randomised, multi-centre, 12-month controlled trial: evaluating the impact of a Cognitive Behavioural Therapy (CBT)-based intervention Supporting UPtake and Adherence to antiretrovirals (SUPA) in adults with HIV.

BACKGROUND: Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. METHODS: This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient's perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. DISCUSSION: The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. TRIAL REGISTRATION: The trial was retrospectively registered 21/02/2014, ISRCTN35514212 .

Factors associated with work status in chronic fatigue syndrome.

BACKGROUND: Work status in people with chronic fatigue syndrome (CFS) has not been extensively researched. AIMS: To explore occupational outcomes in patients with CFS by socio-demographic, well-being and disease characteristics. METHODS: We assessed cross-sectional data from patients attending a UK specialist CFS treatment service between 1 January 2007 and 31 December 2014. The main outcome was self-reported current employment status: currently in employment, temporarily interrupted employment or permanently interrupted employment. Other variables included sex, age, ethnicity, education, marital status, CFS duration, fatigue severity, anxiety, depression, activity limitations and functional impairment. We used multinominal logistic regression models to identify factors associated with current work status. RESULTS: Two hundred and seventy-nine (55%) patients were currently working, with 83 (16%) reporting temporarily interrupted employment and 146 (29%) stopping work altogether. Factors strongly associated with permanently interrupted employment were older age (adjusted odds ratio (AOR) 5.24; 95% CI 2.67-10.28), poorer functioning (AOR 6.41; 95% CI 3.65-11.24) and depressive symptoms (AOR 2.89; 95% CI 1.82-4.58) compared to patients currently working. Higher educated patients (AOR 0.60; 95% CI 0.37-0.97) and being in a relationship (AOR 0.34; 95% CI 0.21-0.54) were associated with being currently employed. Anxiety symptoms were common; 230 patients (45%) met caseness criteria. CONCLUSIONS: Many patients with CFS were not working. This was exacerbated by high levels of depressive symptoms. Health professionals should assess co-morbid mental health conditions and consider treatment options when patients with CFS present themselves. The early involvement of occupational health practitioners is recommended to maximize the chances of maintaining employment.

Cognitive-behavioural therapy for adult attention-deficit hyperactivity disorder: a proof of concept randomised controlled trial.

OBJECTIVE: To investigate efficacy, patient acceptability and feasibility of formulation-based cognitive-behavioural therapy (CBT) for adults with attention-deficit hyperactivity disorder (ADHD). NICE guidelines for adult ADHD recommend further research into psychological treatments. METHOD: Sixty participants with adult ADHD were randomly allocated to treatment as usual (TAU) vs. TAU plus up to 16 sessions of individual formulation-based CBT for ADHD. RESULTS: Adding formulation-based CBT to TAU for ADHD significantly improved ADHD symptoms on the Barkley Current Symptoms Scale and scores on the Work and Social Adjustment Scale. Adjusted effect sizes (ES) were 1.31 and 0.82 respectively. There were also significant improvements on secondary outcomes including independently evaluated clinical global improvement, self-rated anxiety, depression, global distress and patient satisfaction (adjusted effect sizes 0.52-1.01). CONCLUSIONS: This is the first randomised controlled trial to provide preliminary evidence of efficacy and acceptability of individual formulation-based CBT for ADHD when added to TAU over TAU alone. This approach now needs to be tested in a larger multicentred randomised controlled trial.

A survey to determine usual care after cancer treatment within the United Kingdom national health service.

BACKGROUND: Approximately one third of cancer survivors in the United Kingdom face ongoing and debilitating psychological and physical symptoms related to poor quality of life. Very little is known about current post-cancer treatment services. METHODS: Oncology healthcare professionals (HCPs) were invited to take part in a survey, which gathered both quantitative and free text data about the content and delivery of cancer aftercare and patient needs. Analysis involved descriptive statistics and content analysis. RESULTS: There were 163 complete responses from 278 survey participants; 70% of NHS acute trusts provided data. HCPs views on patient post-cancer treatment needs were most frequently: fear of recurrence (95%), fatigue (94%), changes in physical capabilities (89%), anxiety (89%) and depression (88%). A median number of 2 aftercare sessions were provided (interquartile range: 1,4) lasting between 30 and 60 min. Usually these were provided face-to-face and intermittently by a HCP. However, sessions did not necessarily address the issues HCPs asserted as important. Themes from free-text responses highlighted inconsistencies in care, uncertain funding for services and omission of some evidence based approaches. CONCLUSION: Provision of post-cancer treatment follow-up care is neither universal nor consistent in the NHS, nor does it address needs HCPs identified as most important.

Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

BACKGROUND: Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. METHOD: We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. RESULTS: The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. CONCLUSIONS: In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

An attention and interpretation bias for illness-specific information in chronic fatigue syndrome.

BACKGROUND: Studies have shown that specific cognitions and behaviours play a role in maintaining chronic fatigue syndrome (CFS). However, little research has investigated illness-specific cognitive processing in CFS. This study investigated whether CFS participants had an attentional bias for CFS-related stimuli and a tendency to interpret ambiguous information in a somatic way. It also determined whether cognitive processing biases were associated with co-morbidity, attentional control or self-reported unhelpful cognitions and behaviours. METHOD: A total of 52 CFS and 51 healthy participants completed self-report measures of symptoms, disability, mood, cognitions and behaviours. Participants also completed three experimental tasks, two designed specifically to tap into CFS salient cognitions: (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) v. neutral words; (ii) interpretive bias task measuring positive v. somatic interpretations of ambiguous information; and (iii) the Attention Network Test measuring general attentional control. RESULTS: Compared with controls, CFS participants showed a significant attentional bias for fatigue-related words and were significantly more likely to interpret ambiguous information in a somatic way, controlling for depression and anxiety. CFS participants had significantly poorer attentional control than healthy individuals. Attention and interpretation biases were associated with fear/avoidance beliefs. Somatic interpretations were also associated with all-or-nothing behaviour and catastrophizing. CONCLUSIONS: People with CFS have illness-specific biases which may play a part in maintaining symptoms by reinforcing unhelpful illness beliefs and behaviours. Enhancing adaptive processing, such as positive interpretation biases and more flexible attention allocation, may provide beneficial intervention targets.

Same, Same But Different? Cognitive Behavioural Treatment Approaches for Paediatric CFS/ME and Depression.

BACKGROUND: Approximately one in three children and young people with chronic fatigue syndrome (CFS/ME) also have probable depression. Cognitive behaviour therapy (CBT) has a growing evidence base as an effective treatment approach for CFS/ME and for depression in this population. AIMS: Given the high degree of co-morbidity, this discussion paper aims to compare and contrast CBT for CFS/ME and CBT for depression in children and young people. METHOD: The existing literature on CBT for depression and CBT for CFS/ME, in relation to children and young people was reviewed. RESULTS: Whilst there are commonalities to both treatments, the cognitive behavioural model of CFS/ME maintenance includes different factors and has a different emphasis to the cognitive behavioural model of depression, resulting in different intervention targets and strategies in a different sequence. CONCLUSIONS: A collaborative, formulation-driven approach to intervention should inform the intervention targets and treatment strategies.

A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset.

BACKGROUND: It is well established that people with irritable bowel syndrome (IBS) have higher levels of anxiety and depression compared with controls. However, the role of these as risk factors is less clearly established. The aims of this systematic review were to investigate: (1) whether anxiety and/or depression predict IBS onset; (2) the size of the relative risk (RR) of anxiety versus depression in IBS onset. Subgroup analyses explored if methodological factors affected the overall findings. METHOD: Prospective cohort or case-control studies were included if they: (1) focused on the development of IBS in population-based or gastroenteritis cohorts; (2) explored the effects of anxiety and/or depression at baseline as predictors of IBS onset at a future point. In all, 11 studies were included of which eight recruited participants with a gastrointestinal infection. Meta-analyses were conducted. RESULTS: The risk of developing IBS was double for anxiety cases at baseline compared with those who were not [RR 2.38, 95% confidence interval (CI) 1.58-3.60]. Similar results were found for depression (RR 2.06, 95% CI 1.44-2.96). Anxiety and depression seemed to play a stronger role in IBS onset in individuals with a gastrointestinal infection although this could be attributed to other differences in methodology, such as use of diagnostic interviews rather than self-report. CONCLUSIONS: The findings suggest that self-reported anxiety and depression provide a twofold risk for IBS onset. There is less support for the role of anxiety or depressive disorder diagnosed using clinical interview. These findings may have implications for the development of interventions focused on IBS prevention and treatment.

Establishing how psychological therapies work: the importance of mediation analysis.

This editorial reviews the literature regarding psychological studies that are designed to address the question of not just whether, psychological interventions effect change, but how. The practicalities and implications of assessing mechanisms of treatments are considered with examples from the fields of Cognitive Behavioural Therapy (CBT) and Mindfulness. The potential for elucidating theoretical mechanisms, developing new theoretical models and modifying treatment approaches are described. In addition an overview of different types of statistical methods available to researchers for assessing mediation is given. Structural Equation Modelling (SEM) is a recommended approach. The review concludes with a summary of optimum study conditions adopted by researchers for establishing mediating effects.

Mechanisms of change underlying the efficacy of cognitive behaviour therapy for chronic fatigue syndrome in a specialist clinic: a mediation analysis.

BACKGROUND: Several randomized controlled trials (RCTs) have shown that cognitive behavioural psychotherapy (CBT) is an efficacious treatment for chronic fatigue syndrome (CFS). However, little is known about the mechanisms by which the treatment has its effect. The aim of this study was to investigate potential mechanisms of change underlying the efficacy of CBT for CFS. We applied path analysis and introduce novel model comparison approaches to assess a theoretical CBT model that suggests that fearful cognitions will mediate the relationship between avoidance behaviour and illness outcomes (fatigue and social adjustment). METHOD: Data from 389 patients with CFS who received CBT in a specialist service in the UK were collected at baseline, at discharge from treatment, and at 3-, 6- and 12-month follow-ups. Path analyses were used to assess possible mediating effects. Model selection using information criteria was used to compare support for competing mediational models. RESULTS: Path analyses were consistent with the hypothesized model in which fear avoidance beliefs at the 3-month follow-up partially mediate the relationship between avoidance behaviour at discharge and fatigue and social adjustment respectively at 6 months. CONCLUSIONS: The results strengthen the validity of a theoretical model of CBT by confirming the role of cognitive and behavioural factors in CFS.

Childhood stressors in the development of fatigue syndromes: a review of the past 20 years of research.

BACKGROUND: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both highly prevalent conditions associated with extreme disability and with the development of co-morbid psychiatric disorders, such as depression and anxiety. Childhood stressors have been shown to induce persistent changes in the function of biological systems potentially relevant to the pathogenesis of both CFS and FM, such as the inflammatory system and the hypothalamic-pituitary-adrenal (HPA) axis. In this review, we examined whether multiple forms of childhood stressors are contributing factors to the development of these disorders, and of the associated psychiatric symptoms. METHOD: Using PubMed, we identified 31 papers relevant to this narrative review. We included cohort studies and case-control studies, without any exclusion in terms of age and gender. No study characteristics or publication date restrictions were imposed. RESULTS: Most studies across the literature consistently show that there is a strong association between experiences of childhood stressors and the presence of CFS and FM, with rates of CFS/FM being two- to three-fold higher in exposed than in unexposed subjects. We also found evidence for an increased risk for the development of additional symptoms, such as depression, anxiety and pain, in individuals with CFS and FM with a previous history of childhood stressors, compared with individuals with CFS/FM and no such history. CONCLUSIONS: Our review confirms that exposure to childhood stressors is associated with the subsequent development of fatigue syndromes such as CFS and FM, and related symptoms. Further studies are needed to identify the mechanisms underlying these associations.

Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial.

BACKGROUND: Pain is a common symptom of chronic fatigue syndrome (CFS). We investigated the effects of the treatments used in the PACE trial [cognitive behavioural therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT) and specialist medical care (SMC)] on pain in CFS. METHOD: We compared pain outcomes including individual painful symptoms, taken from the CDC criteria for CFS and co-morbid fibromyalgia. We modelled outcomes adjusting for baseline variables with multiple linear regression. RESULTS: Significantly less frequent muscle pain was reported by patients following treatment with CBT compared to SMC (mean difference = 0.38 unit change in frequency, p = 0.02), GET versus SMC (0.42, p = 0.01) and GET versus APT (0.37, p = 0.01). Significantly less joint pain was reported following CBT versus APT (0.35, p = 0.02) and GET versus APT (0.36, p = 0.02). Co-morbid fibromyalgia was less frequent following GET versus SMC (0.03, p = 0.03). The effect sizes of these differences varied between 0.25 and 0.31 for muscle pain and 0.24 and 0.26 for joint pain. Treatment effects on pain were independent of 'change in fatigue'. CONCLUSIONS: CBT and GET were more effective in reducing the frequency of both muscle and joint pain than APT and SMC. When compared to SMC, GET also reduced the frequency of co-morbid fibromyalgia; the size of this effect on pain was small.

Cognitions, behaviours and co-morbid psychiatric diagnoses in patients with chronic fatigue syndrome.

BACKGROUND: Specific cognitions and behaviours are hypothesized to be important in maintaining chronic fatigue syndrome (CFS). Previous research has shown that a substantial proportion of CFS patients have co-morbid anxiety and/or depression. This study aims to measure the prevalence of specific cognitions and behaviours in patients with CFS and to determine their association with co-morbid anxiety or depression disorders. METHOD: A total of 640 patients meeting Oxford criteria for CFS were recruited into a treatment trial (i.e. the PACE trial). Measures analysed were: the Cognitive Behavioural Response Questionnaire, the Chalder Fatigue Scale and the Work and Social Adjustment Scale. Anxiety and depression diagnoses were from the Structured Clinical Interview for DSM-IV. Multivariate analysis of variance was used to explore the associations between cognitive-behavioural factors in patients with and without co-morbid anxiety and/or depression. RESULTS: Of the total sample, 54% had a diagnosis of CFS and no depression or anxiety disorder, 14% had CFS and one anxiety disorder, 14% had CFS and depressive disorder and 18% had CFS and both depression and anxiety disorders. Cognitive and behavioural factors were associated with co-morbid diagnoses; however, some of the mean differences between groups were small. Beliefs about damage and symptom focussing were more frequent in patients with anxiety disorders while embarrassment and behavioural avoidance were more common in patients with depressive disorder. CONCLUSIONS: Cognitions and behaviours hypothesized to perpetuate CFS differed in patients with concomitant depression and anxiety. Cognitive behavioural treatments should be tailored appropriately.

Recovery from chronic fatigue syndrome after treatments given in the PACE trial.

BACKGROUND: A 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. METHOD: We 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. RESULTS: The 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) 1.64­6.88] and for GET 3.38 (95% CI 1.65­6.93), when compared to APT, and after CBT 3.69 (95% CI 1.77­7.69) and GET 3.71 (95% CI 1.78­7.74), when compared to SMC (p values < or =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. CONCLUSIONS: This study confirms that recovery from CFS is possible, and that CBT and GET are the therapies most likely to lead to recovery.