A concept mapping study evaluating the UK's first NHS generic fatigue clinic.

Importance - Fatigue is a significant and debilitating symptom affecting 25% of the population. It occurs in those with a range of chronic diseases, can be idiopathic and in 0.2-0.4% of the UK population occurs in combination with other symptoms that together constitute chronic fatigue syndrome (CFS). Until recently, NHS clinical services only focussed upon CFS and excluded the majority of fatigued patients who did not meet the CFS diagnostic criteria. The CRESTA Fatigue interdisciplinary clinic was established in 2013 in response to this unmet need. Objective - To identify the service needs of the heterogeneous group of patients accessing the CRESTA Fatigue Clinic, to prioritize these needs, to determine whether each is being met and to plan targeted service enhancements. Design - Using a group concept mapping approach, we objectively identified the shared understanding of service users accessing this novel clinic. Setting - NHS Clinics for Research & Service in Themed Assessment (CRESTA) Fatigue Clinic, Newcastle Upon Tyne, UK. Participants - Patients (n = 30) and referrers (n = 10) to the CRESTA Fatigue Clinic contributed towards a statement generation exercise to identify ways the clinic could support service users to improve their quality of life. Patients (n = 46) participated in the sorting and rating task where resulting statements were sorted into groups similar in meaning and rated for 'importance' and 'current success'. Main outcome and measure - We mapped the needs of patients attending the CRESTA Fatigue Clinic and identified which high-priority needs were being successfully met and which were not. Results - Multidimensional scaling and hierarchical cluster analysis depicted the following eight themed clusters from the data which related to various service-user requirements: 'clinic ethos', 'communication', 'support to self-manage', 'peer support', 'allied health services', 'telemedicine', 'written information' and 'service operation'. Service improvement targets were identified within value bivariate plots of the statements. Conclusion and relevance - Service development concepts were grouped into thematic clusters and prioritized for both importance and current success. The resulting concept maps depict where the CRESTA Fatigue Clinic successfully addresses issues which matter to patients and highlights areas for service enhancement. Unmet needs of patients have been identified in a rigorous service evaluation, and these are currently being addressed in collaboration with a service-user group

Experiences of Living with Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a rare disease with no known etiology. It affects 0.4% of the population, 25% of which experience the severe and very severe categories; these are defined as being wheelchair-, house-, and bed-bound. Currently, the absence of biomarkers necessitates a diagnosis by exclusion, which can create stigma around the illness. Very little research has been conducted with the partly defined severe and very severe categories of CFS/ME. This is in part because the significant health burdens experienced by these people create difficulties engaging in research and healthcare provision as it is currently delivered. This qualitative study explores the experiences of five individuals living with CFS/ME in its most severe form through semi-structured interviews. A six-phase themed analysis was performed using interview transcripts, which included identifying, analysing, and reporting patterns amongst the interviews. Inductive analysis was performed, coding the data without trying to fit it into a pre-existing framework or pre-conception, allowing the personal experiences of the five individuals to be expressed freely. Overarching themes of ‘Lived Experience’, ‘Challenges to daily life’, and ‘Management of the condition’ were identified. These themes highlight factors that place people at greater risk of experiencing the more severe presentation of CFS/ME. It is hoped that these insights will allow research and clinical communities to engage more effectively with the severely affected CFS/ME population

A systematic review of non-pharmacological interventions for primary Sjögren’s syndrome

The objective of this systematic review was to assess the efficacy of non-pharmacological interventions for the management of primary Sjögren’s syndrome. We searched the following databases from inception to September 2014; Cochrane Database of Systematic Reviews; Medline; Embase; PsychINFO; Cinahl and clinical trials registers. We included randomised controlled trials of any non-pharmacological interventions. Two review authors independently reviewed titles and abstracts against the inclusion/exclusion criteria and independently assessed trial quality and extracted data. 1463 studies were identified of which 17 full text articles were screened and 5 studies were included in the review with a total of 130 participants randomised. The included studies investigated effectiveness of an oral lubricating device for dry mouth, acupuncture for dry mouth, lacrimal punctum plugs for dry eyes and psychodynamic group therapy for coping with symptoms. Overall the studies were of low quality and at high risk of bias. Although one study showed punctum plugs to improve dry eyes it was too small for the findings to be conclusive. Overall we identified no evidence to support any non-pharmacological interventions to improve PSS. The area needs quality large randomised controlled trials that are reported according to CONSORT guidelines and address important issues to patients

A comprehensive service re-evaluation of the UK's first NHS generic fatigue clinic four years following its inception: a mixed methods study

Objective: To identify if the Newcastle CRESTA (Clinics for Research in Themed Assessment) fatigue clinic continues to meet patient expectations, two years since an initial evaluation in 2015, following changes to the original service model. Background: The CRESTA fatigue clinic was established in 2013 to fulfil the unmet needs of patients with long-term conditions and the symptom of chronic fatigue who did not have access to fatigue management support. The service was previously evaluated using a group concept mapping (GCM) approach and found to successfully meet patients’ expectations. To ensure these needs continued to be met following change to the original service model, we re-evaluated the service using a similar approach. GCM is a mixed method approach. Statements are generated from stakeholders, sorted into themed clusters, and then rated. Method: 146 assessment tools were posted to consecutive clinic patients containing statements generated during the original study. Patients rated each statement for ‘current success’ on a 1-5 Likert scale and provided for free-text feedback. Unpaired t-tests were used to compare cluster success scores from both the previous evaluation and the current cohort of patients. Thematic analysis was used to evaluate the qualitative comments. Results: 46 questionnaires were returned. Comparison of the cluster success scores revealed the clinic has maintained its previous success and made significant improvements in peer support (p≥0.001). The free-text comments were mainly positive and patients found the service to be invaluable. Conclusion: The CRESTA fatigue clinic continues to successfully meet patient expectations and has made significant improvements in peer support

What is known about severe and very severe chronic fatigue syndrome? A scoping review

Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) affects 0.4% of the population. It is characterised by disabling fatigue and a combination of self-reported symptoms which include impairments in concentration, short-term memory, sleep disturbances, post-exertional malaise and musculoskeletal pain. There are four categories of severity in the CFS/ME population: mild; moderate; severe; and very severe which are expanded on elsewhere and adopted by the National Institute for Health and Care Excellence [NICE. Chronic fatigue syndrome/myalgic encephelomyelitis diagnosis and management in adults and children; 2007]. Objective: Identify research relating to those severely and very severely affected by CFS/ME. Methods: We searched electronic databases for relevant studies using pre-defined search terms: ‘chronic fatigue syndrome’ and ‘sever$’ which covers ‘severe’ and ‘severely’. Included were English language papers published in full that discretely identified severely and very severely affected CFS/ME populations from the broader CFS/ME population. Results: Over 2000 papers were reviewed and 21 papers met the selection criteria. The capture produced both adult and paediatric populations with a variety of methodologies. Wide differences in illness characterisation, definition and measurement were found. Case studies reported that in extreme presentations very severe CFS/ME individuals may be confined to bed, requiring reduced light and noise exposure. Conclusion: This review highlights the limited research focusing on the severely affected CFS/ME population. The heterogeneity of the condition contributes to the lack of consensus concerning definitive diagnostic criteria and functional measures to assess disability. Focused research to understand the disease characteristics of the most severely ill will help to advance our understanding of possible phenotypes associated with distinct severity categories

Understanding severely affected chronic fatigue syndrome (CFS): the gravity of the situation

Objective: To describe how the effects of gravity may adversely affect the neuro-cardiovascular physiology of individuals with severe Chronic Fatigue Syndrome (CFS). Design: A narrative review of the literature relating to microgravity, orthostatic intolerance and severe CFS. Emphasis is placed on the clinical significance and implications for the management of patients with severe CFS, with suggestions for future rehabilitation and physical interventions. Results: Physiological functions in humans have evolved to counter the effects of gravity, in particular the neuro-cardiovascular system. Reducing exposure to gravity will result in deconditioning of these systems. Many of the symptoms experienced by astronauts returning to Earth are shared by those with severe CFS. Prolonged periods in the supine position create an environment similar to microgravity – the mechanism through which we propose orthostatic intolerance develops in CFS. However, there are also some physiological changes present in CFS which may exacerbate these changes. Studies have shown that some CFS individuals have hypovolaemia unrelated to deconditioning. This pre-existing hypovolaemia may make the neuro-cardiovascular system more vulnerable to the effects of bed rest in those individuals with CFS. Conclusion: Severely affected CFS individuals may be more susceptible to a specific type of deconditioning, related to reduced exposure to gravity, due to pre-existing vulnerabilities in their cardiovascular and autonomic nervous systems. Rehabilitation which targets the neuro-cardiovascular system and its response to upright posture may improve function and symptoms of severely affected CFS individuals

Conceptualizing the benefits of a group exercise program developed for those with chronic fatigue: a mixed methods clinical evaluation

Purpose: Fatigue is a disabling and prevalent feature of many long-term conditions. Orthostatic dizziness is a commonly experienced by those with fatigue. The purpose was; to evaluate factors contributing to successful delivery of a novel group exercise program designed for people with chronic fatigue and orthostatic symptoms and identify targets to improve future program content and delivery. Research methods: We used group concept mapping methodology. Participants of the exercise program with a long-term physical health condition and chronic fatigue- contributed ideas in response to a focus question. They sorted these ideas into themed piles and rated them for importance and success of the program delivery. Multidimensional scaling and cluster analysis were applied to the sort data to produce ideas clusters within a concept map. Value ratings were compared to evaluate the success of the program. Results: The resulting concept map depicted seven key themed clusters of ideas: Exercises, Group atmosphere, Physical benefits, Self-management of symptoms, Acceptance and Education. Value plots of the rating data identified important and successful conceptual ideas. Conclusions: The concept maps have depicted key concepts relating to the successful delivery of a novel exercise program for people with fatigue and identified specific targets for future program enhancements. Implications for rehabilitation Orthostatic symptoms are common in those with fatigue and might be a target for group-based exercise programs. People with fatigue value a group-based exercise program that targets orthostatic symptoms. The key concepts of a group-based exercise program valued by those with fatigue are the exercises, group atmosphere, physical benefits, self-management support, acceptance, education and support with looking forwards following the program

The effect of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function

Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts. This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotyp

Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.

[This corrects the article DOI: 10.1371/journal.pone.0186802.]

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

<div><p>Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.</p></div