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.

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 rehabilitationOrthostatic 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 phenotype.

MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants.

Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (CFS) is a debilitating condition. There is growing interest in a possible etiologic or pathogenic role of mitochondrial dysfunction and mitochondrial DNA (mtDNA) variation in ME/CFS. Supporting such a link, fatigue is common and often severe in patients with mitochondrial disease. We investigate the role of mtDNA variation in ME/CFS. No proven pathogenic mtDNA mutations were found. We then investigated population variation. Two cohorts were analysed, one from the UK (n = 89 moderately affected; 29 severely affected) and the other from South Africa (n = 143 moderately affected). For both cohorts, ME/CFS patients had an excess of individuals without a mildly deleterious population variant. The differences in population variation might reflect a mechanism important to the pathophysiology of ME/CFS.

Defining the prevalence and symptom burden of those with self-reported severe chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a two-phase community pilot study in the North East of England.

OBJECTIVES: To define the prevalence of severe chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and its clinical characteristics in a geographically defined area of Northern England. To understand the feasibility of a community-based research study in the severely affected CFS/ME group. DESIGN: A two-phase clinical cohort study to pilot a series of investigations in participants own homes. SETTING: Participants were community living from the area defined by the Northern clinical network of the UK. PARTICIPANTS: Adults with either a medical or a self-reported diagnosis of CFS/ME. Phase 1 involved the creation of a database. Phase 2: five participants were selected from database, dependent on their proximity to Newcastle. INTERVENTIONS: The De Paul fatigue questionnaire itemised symptoms of CFS/ME, the Barthel Functional Outcome Measure and demographic questions were collected via postal return. For phase 2, five participants were subsequently invited to participate in the pilot study. RESULTS: 483 questionnaire packs were requested, 63 were returned in various stages of completion. 56 De Paul fatigue questionnaires were returned: all but 12 met one of the CFS/ME criteria, but 12 or 22% of individuals did not fulfil the Fukuda nor the Clinical Canadian Criteria CFS/ME diagnostic criteria but 6 of them indicated that their fatigue was related to other causes and they barely had any symptoms. The five pilot participants completed 60% of the planned visits. CONCLUSIONS: Severely affected CFS/ME individuals are keen to participate in research, however, their symptom burden is great and quality of life is poor. These factors must be considered when planning research and methods of engaging with such a cohort.

Managing fatigue in postural tachycardia syndrome (PoTS): The Newcastle approach.

Fatigue is a significant symptom that is frequently reported by those with postural tachycardia syndrome (PoTS). There are a variety of reasons why those with PoTS might experience fatigue and as a consequence an individualised approach to management is most appropriate. In this chapter we will examine the prevalence of fatigue in those with PoTS, its overlap with conditions such as chronic fatigue syndrome and describe a clinical approach to the management of fatigue in those with PoTS.

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.

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.

A Novel Approach to Proactive Primary Care-Based Case Finding and Multidisciplinary Management of Falls, Syncope, and Dizziness in a One-Stop Service: Preliminary Results.

National and international evidence and guidelines on falls prevention and management in community-dwelling elderly adults recommend that falls services should be multifactorial and their interventions multicomponent. The way that individuals are identified as having had or being at risk of falls in order to take advantage of such services is far less clear. A novel multidisciplinary, multifactorial falls, syncope, and dizziness service model was designed with enhanced case ascertainment through proactive, primary care-based screening (of individual case notes of individuals aged ≥60) for individual fall risk factors. The service model identified 4,039 individuals, of whom 2,232 had significant gait and balance abnormalities according to senior physiotherapist assessment. Significant numbers of individuals with new diagnoses ranging from cognitive impairment to Parkinson's disease to urgent indications for a pacemaker were discovered. More than 600 individuals were found who were at high risk of osteoporosis according to World Health Association Fracture Risk Assessment Tool score, 179 with benign positional paroxysmal vertigo and 50 with atrial fibrillation. Through such screening and this approach, Comprehensive Geriatric Assessment Plus (Plus falls, syncope and dizziness expertise), unmet need was targeted on a scale far outside the numbers seen in clinical trials. Further work is needed to determine whether this approach translates into fewer falls and decreases in syncope and dizziness.

Droxidopa for orthostatic hypotension: a systematic review and meta-analysis.

OBJECTIVE: The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States. METHODS: MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis. RESULTS: Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)]. CONCLUSION: Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension. REGISTRATION: PROSPERO ID CRD42015024612.

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.

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

OBJECTIVE: To evaluate the effects of non-pharmacological interventions for primary SS (pSS) on outcomes falling within the World Health Organization International Classification of Functioning Disability and Health domains. METHODS: 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 randomized controlled trials of any non-pharmacological intervention. Two authors independently reviewed titles and abstracts against the inclusion/exclusion criteria and independently assessed trial quality and extracted data. RESULTS: A total of 1463 studies were identified, from which 17 full text articles were screened and 5 studies were included in the review; a total of 130 participants were randomized. The included studies investigated the 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, the sample size was relatively small. CONCLUSION: Further high-quality studies to evaluate non-pharmacological interventions for PSS are needed.