Victoria Strassheim

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 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.

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

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.

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

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

ABSTRACT 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

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

’ 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.

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

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

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

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.

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

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.

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

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. n nBackground: 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. n nMethod: 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. n nResults: 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. n nConclusion: The CRESTA fatigue clinic continues to successfully meet patient expectations and has made significant improvements in peer support.