[Show abstract][Hide abstract] ABSTRACT: Plain english summary
Myalgic encephalitis (M.E.) is a common condition, the cause of which is not known and there are no treatments available. In this study the national patient support group Action for M.E. sought the opinions of their members via an online survey as to what they felt should be future priorities for M.E. research.
Respondents were asked what they considered first, second and third research priorities to be from a list of 13 pre-defined options. Individuals were invited to provide additional free text comments about Action for M.E.’s research priorities in general.
Of the 1144 respondents: 822 had M.E.; 94 were a supporting a member of Action for M.E. ; 66 were carers for someone with M.E.; 26 were professionals with an interest in M.E.; 136 had a family member or colleague with M.E. Individuals selected more than one category as applicable.
The top five research priorities identified were: disease processes to achieve a better understanding of the causes of M.E.; more effective treatments; faster and more accurate diagnosis; clinical course of M.E.; outcomes and natural history; and severely affected patients. Least popular priorities were: sleep; economic research towards identifying the cost of ME; and psychological aspects. Much of the free text comments emphasised the importance of funding biomedical research into disease processes to achieve a better understanding of the causes of M.E. Three themes were identified in relation to this topic: accurate diagnosis and awareness; risk factors and causes; drug development and curative therapies.
In conclusion; individuals affected by M.E. have clear views regarding priorities for research investment. These have informed Action for M.E.’s ongoing research strategy and ultimately will inform national and international research priorities.
[Show abstract][Hide abstract] ABSTRACT: Background/Purpose: Primary Sjögren’s Syndrome (pSS) is an autoimmune disease which targets secretory glands and results in dryness. In addition pSS patients frequently experience symptoms of fatigue, pain, low mood and have difficulty performing daily activities and subsequently have poor quality of life. There is currently no curative treatment and medical interventions focus on the symptomatic management of dryness. The aim of this study is to identify independent predictors for each of the SF-36 domains in order to identify targets for future therapy interventions with pSS patients. The goal is to identify potential interventions to be delivered by non-medical health care professionals in order to improve the ability to perform daily activities, facilitate taking on life roles and improve quality of life.
Methods: 149 PSS patients diagnosed according to the American European Consensus Criteria were recruited from 12 sites across England. Participants completed the SF-36 questionnaire and measurements of anxiety and depression (Hospital Anxiety and Depression Scale HADs), functional status (ImprovedHAQ), pain (visual analogue scale (VAS), fatigue (VAS), mental fatigue (VAS), dryness (VAS), cognitive failures (Cognitive Failures Questionnaire) and recorded their age and disease duration. Significant correlates of each of the SF-36 domain were identified and multiple regression analysis performed for each of the domains to determine partial regression coefficients. Model robustness was determined by hierarchical regression analysis testing the sensitivity of the model to the order of inclusion.
Results: With one exception, PSS patients scored significantly worse than the norm-based scores for all domains of the SF-36, including Physical Functioning, Role Physical, Bodily Pain, Vitality, Social Functioning, Role Emotional and Mental Health (p<0.001). General Health was the exception and there was no significant difference between the pSS patients and the norm-based scores. All SF-36 domains correlated significantly with anxiety, depression, cognitive failures, mental fatigue, pain, fatigue and dryness (p<0.001).
Fatigue and depression were the main predictors of poorer Role Physical and Social Functioning domain scores (all p≤0.006). Fatigue was a predictor of Bodily Pain (p<0.001) and pain was an independent predictor of poor Physical Functioning (p<0.001). Depression and pain were the main independent predictors of the Vitality domain (p≤0.006) and the General Health domain (p≤0.043). The main predictors of the Role Emotional domain were fatigue, anxiety and depression (p≤0.037) and of the Mental Health domain were disease duration and cognitive failures (p≤0.026).
Conclusion: This study demonstrates that fatigue and depression, followed by anxiety and pain are key predictors of the reduced ability to perform daily activities, take on life roles and quality of life. These factors should be addressed during therapeutic interventions with PSS patients presenting with these symptoms. This in turn could support PSS patients to carry out daily activities, take on social and physical life roles and improve their quality of life.
[Show abstract][Hide abstract] ABSTRACT: Background/Purpose: Fatigue is a common symptom for people with inflammatory arthritis and associated auto-immune conditions. Its impact is wide-ranging and significantly reduces health-related quality of life. Research evidence, however, suggests that neither clinicians nor patients consistently raise the issue in clinic. In-depth discussion of fatigue and support from professionals to manage its impacts are rare. Arthritis Research UK developed a booklet, ‘Fatigue and Arthritis’, intended to help patients help themselves. Our study has explored patients’ approaches to managing fatigue and the impact this booklet has upon them.
Methods: Twelve patients from a rheumatology outpatient service in north-east England took part in in-depth, qualitative interviews before and after being given the ‘Fatigue and Arthritis’ booklet. Patients were recruited purposively to ensure variation in diagnosis (rheumatoid arthritis (RA), ankylosing spondylitis (AS), and primary Sjögren’s Syndrome (pSS)), fatigue severity, and demographic characteristics. Data, in the form of transcripts, was analysed thematically using coding, mapping and memoing techniques.
Results: This study confirms both the impact of fatigue and evidence that neither clinicians nor patients routinely raise the matter in consultations. Our data suggests patients face significant barriers to communicating their fatigue, including: reliance on a diverse, colloquial vocabulary to define the problem; uncertainty how it relates to their condition; doubts to its place on the consultation agenda; and a belief that nothing can be done about it. These barriers affect both if and how patients raise their concerns and are reinforced where clinicians’ responses do not invite elaboration.
None of our participants, even those who had discussed fatigue with a clinician, reported having seen the ‘Fatigue and Arthritis’ booklet before. Not all found it of practical help in improving their day-to-day management and experience of fatigue (criticisms including the familiarity and/or unsuitability of advice). However, most reported gaining something from the booklet. Benefits included: improved understanding of a distressing symptom; validation of their concerns; and a sense that things could be done to manage fatigue. These gains made it easier to discuss fatigue and its impacts with clinicians and with family, friends and colleagues.
Conclusion: Our research adds to the limited evidence on barriers to fatigue communication in the rheumatology clinic. In detailing patients’ difficulties, it reinforces prior recommendations that clinicians need to be prepared both to initiate discussions and respond sensitively to concerns about fatigue. It suggests that information materials such as the booklet featuring in this study may be a useful tool for improving communication. We encourage clinicians to give this booklet (or a similar resource) to patients reporting fatigue, and to commit to discussing it at future appointments. More effective communication about fatigue would improve clinicians’ understanding of the burden of disease individual patients bear and facilitate improved (shared) decision-making about management options.
[Show abstract][Hide abstract] ABSTRACT: Few studies have compared symptomatology and functional differences experienced by patients with chronic fatigue syndrome (CFS) across cultures. The current study compared patients with CFS from the United States (US) to those from the United Kingdom (UK) across areas of functioning, symptomatology, and illness onset characteristics. Individuals in each sample met criteria for CFS as defined by Fukuda et al. (1994). These samples were compared on two measures of disability and impairment, the DePaul Symptom Questionnarie (DSQ) and the Medical outcomes study 36-item short-form health survey (SF-36). Results revealed that the UK sample was significantly more impaired in terms of mental health and role emotional functioning, as well as specific symptoms of pain, neurocognitive difficulties, and immune manifestations. In addition, the UK sample was more likely to be working rather than on disability. Individuals in the US sample reported more difficulties falling asleep, more frequently reported experiencing a sudden illness onset (within 24 hours), and more often reported that the cause of illness was primarily due to physical causes. These findings suggest that there may be important differences in illness characteristics across individuals with CFS in the US and the UK, and this has implications for the comparability of research findings across these two countries.
[Show abstract][Hide abstract] ABSTRACT: Background: Chronic fatigue syndrome (CFS) is heterogeneous in nature, yet no clear subclassifications currently exist. There is evidence of dysautonomia in almost 90% of patients and CFS is often co-morbid with conditions associated with autonomic nervous system (ANS) dysfunction, such as temporomandibular disorders (TMD). The present study examined the point prevalence of TMD in a sample of people with CFS and explored whether co-morbidity between the conditions is associated with greater ANS dysfunction than CFS alone. Method: Fifty-one patients and 10 controls underwent screening for TMD. They completed a self-report measure of ANS function (COMPASS-31) and objective assessment of heart rate variability during rest and standing (derived using spectral analysis). Frequency densities in the high-frequency (HF) and low-frequency (LF) band were calculated. Results: Patients with CFS were divided into those who screened positive for TMD (n = 16, 31%; CFS + TMD) and those who did not (n = 35, 69%; CFS − TMD). Both CFS groups had significantly higher self-rated ANS dysfunction than controls. CFS + TMD scored higher than CFS − TMD on the orthostatic and vasomotor subscales. The CFS + TMD group had significantly higher HF and significantly lower LF at rest than the other two groups. In discriminant function analysis, self-report orthostatic intolerance and HF units correctly classified 75% of participants. Conclusions: Almost one-third of CFS patients screened positive for TMD and this was associated with greater evidence of parasympathetic dysfunction. The presence of TMD shows potential as an effective screen for patients with CFS showing an autonomic profile and could help identify subgroups to target for treatment.
[Show abstract][Hide abstract] ABSTRACT: In late age, the autonomic nervous system (ANS) has diminished ability to maintain physiological homeostasis in the brain in response to challenges such as to systemic blood pressure changes caused by standing. We devised an fMRI experiment aiming to map the cerebral effects of an ANS challenge (Valsalva manoeuvre (VM)). We used dual-echo fMRI to measure the effective transverse relaxation rate (R2*, which is inversely proportional to brain tissue oxygenation levels) in 45 elderly subjects (median age 80 years old, total range 75-89) during performance of the VM. In addition, we collected fluid-attenuated inversion recovery (FLAIR) data from which we quantified white matter hyperintensity (WMH) volumes. We conducted voxelwise analysis of the dynamic changes in R2* during the VM to determine the distribution of oxygenation changes due to the autonomic stressor. In white matter, we observed significant decreases in oxygenation levels. These effects were predominantly located in posterior white matter and to a lesser degree in the right anterior brain, both concentrated around the border zones (watersheds) between cerebral perfusion territories. These areas are known to be particularly vulnerable to hypoxia and are prone to formation of white matter hyperintensities. Although we observed overlap between localisation of WMH and triggered deoxygenation on the group level, we did not find significant association between these independent variables using subjectwise statistics. This could suggest other than recurrent transient hypoxia mechanisms causing/contributing to the formation of WMH.
Journal of the American Aging Association 10/2015; 37(5). DOI:10.1007/s11357-015-9833-6 · 3.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ImportanceFatigue 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.DesignUsing a group concept mapping approach, we objectively identified the shared understanding of service users accessing this novel clinic.SettingNHS Clinics for Research & Service in Themed Assessment (CRESTA) Fatigue Clinic, Newcastle Upon Tyne, UK.ParticipantsPatients (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 measureWe mapped the needs of patients attending the CRESTA Fatigue Clinic and identified which high-priority needs were being successfully met and which were not.ResultsMultidimensional 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 RelevanceService 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.
Health expectations: an international journal of public participation in health care and health policy 08/2015; DOI:10.1111/hex.12405 · 3.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: and criteria for chronic fatigue syndrome (CFS), renaming the illness systemic
exertion intolerance disease (SEID). The new SEID case definition requires
substantial reductions or impairments in the ability to engage in pre-illness
activities, unrefreshing sleep, post-exertional malaise, and either cognitive
impairment or orthostatic intolerance. Purpose: In the current study, samples
were generated through several different methods and were used to compare this
new case definition to previous case definitions for CFS, the International
Consensus Criteria for myalgic encephalomyelitis (ME-ICC), the Canadian
myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) definition, as
well as a case definition developed through empirical methods. Methods: We
used a cross-sectional design with samples from tertiary care settings, a BioBank
sample, and other forums. Seven hundred and ninety-six patients from the USA,
Great Britain, and Norway completed the DePaul Symptom Questionnaire.
Results: Findings indicated that the SEID criteria identified 88% of participants
in the samples analyzed, which is comparable to the 92% that met the Fukuda
criteria. The SEID case definition was compared to a four-item empiric criteria,
and findings indicated that the four-item empiric criteria identified a smaller,
more functionally limited and symptomatic group of patients. Conclusion: The
recently developed SEID criteria appears to identify a group comparable in size
to the Fukuda et al. criteria, but a larger group of patients than the Canadian
ME/CFS and ME criteria, and selects more patients who have less impairment
and fewer symptoms than a four-item empiric criteria.
[Show abstract][Hide abstract] ABSTRACT: Background: Many people with primary Sjögren's syndrome (PSS) experience difficulty with participation1. There are currently few published studies of non-pharmacological therapy interventions aiming to improve participation in PSS patients. Group concept mapping is a robust, equitable, and systematic approach which has been successfully utilised to identify priorities in both healthcare and research2.
Objectives: To identify priority patient and stakeholder informed intervention targets for a future therapy intervention package which will aim to improve participation in people with PSS.
Methods: We conducted a mixed-methods group concept mapping exercise with PSS patients, adult household members (AHM) and health care professionals (HCP) (n=232). Patient and AHM participants were recruited from 12 sites in England and all the patients fulfilled the American European Consensus Group diagnosis criteria. HCP were recruited from across the UK via email distribution lists and at professional meetings. First participants completed a statement generation brainstorming activity to identify key barriers to being able to participate fully in daily activities of their choosing. Next an individual card sorting activity was completed with a refined statement set, where participants each sorted similar meaning statements into groups. Finally each statement was rated for importance on a 1-5 Likert scale.
Multi-dimensional scaling and hierarchical cluster analysis statistical techniques were applied to generate concept maps which are a visual representation of all stakeholders' ideas and priorities. The maps depicted the priority themed clusters of ideas and “Go-zones”, or bivariate plots of the priority ratings by group, which pinpoint the priority statements within each cluster. Potential priority therapy intervention targets were subsequently identified.
Results: The concept maps revealed 7 key themes: “Symptoms”, “Patient empowerment”, “Access and co-ordination of healthcare”, “Wellbeing”, “Family and friends”, “Knowledge and support” and “Public awareness”. The Symptoms and Patient empowerment clusters received the greater priority ratings. Within these clusters potential priority non-pharmacological intervention therapy targets included fatigue, pain, swallowing, sleep, support to self-manage and adherence to medication.
European League Against Rheumatism Congress 2015, Rome, Italy; 06/2015
[Show abstract][Hide abstract] ABSTRACT: To explore the point prevalence of painful temporomandibular disorders (TMD) in a well-characterized clinical cohort of postural orthostatic tachycardia syndrome (PoTS) sufferers and to understand the functional and physiologic impact of this comorbidity on the patient.
Patients with PoTS were retrospectively recruited from a previous study conducted in a UK hospital setting. Data had previously been collected on several parameters, including sociodemographic, physiologic, and functional. The participants were mailed a highly sensitive (99%) and specific (97%) self-report screening instrument for painful TMD. Simple descriptive statistics with Fisher Exact and Kruskal-Wallis tests were used to examine the data and draw inferences from it.
A total of 36 individuals responded (69% response rate). Just under half (47%) of the sample screened positive for painful TMD. There was no significant difference between the screening result for TMD or previously reported headaches or joint pain (P < .05). Chronic fatigue syndrome (CFS) was diagnosed by the Fukuda Criteria in 44% of the total sample and in 56% of those with painful TMD. There were no significant differences in physiologic parameters in CFS and TMD. TMD caused a significant decrease in quality of life as measured by the Patient-Reported Outcomes Measurement Information System, Health Assessment Questionnaire (P < .05).
TMD are common in patients with PoTS. They have a significant, additional impact on patients' quality of life and should therefore be screened for at an early stage in PoTS.
[Show abstract][Hide abstract] ABSTRACT: We obtained a time series of tongue/throat swabs from 90 patients with lower limb fracture, aged 65-101 in a general hospital in the North East of England between April 2009-July 2010. We used novel real-time multiplex PCR assays to detect S. aureus, MRSA, E. coli, P. aeruginosa, S. pneumoniae, H. influenza and Acinetobacter spp. We collected data on dental/denture plaque (modified Quigley-Hein index) and outcomes of clinician-diagnosed HAP.
The crude incidence of HAP was 10% (n = 90), with mortality of 80% at 90 days post discharge. 50% of cases occurred within the first 25 days. HAP was not associated with being dentate, tooth number, or heavy dental/denture plaque. HAP was associated with prior oral carriage with E. coli/S. aureus/P.aeruginosa/MRSA (p = 0.002, OR 9.48 95% CI 2.28-38.78). The incidence of HAP in those with carriage was 35% (4% without), with relative risk 6.44 (95% CI 2.04-20.34, p = 0.002). HAP was associated with increased length of stay (Fishers exact test, p=0.01), with mean 30 excess days (range -11.5-115). Target organisms were first detected within 72 hours of admission in 90% participants, but HAP was significantly associated with S. aureus/MRSA/P. aeruginosa/E. coli being detected at days 5 (OR 4.39, 95%CI1.73-11.16) or 14 (OR 6.69, 95%CI 2.40-18.60).
Patients with lower limb fracture who were colonised orally with E. coli/ S. aureus/MRSA/P. aeruginosa after 5 days in hospital were at significantly greater risk of HAP (p = 0.002).
PLoS ONE 04/2015; 10(4):e0123622. DOI:10.1371/journal.pone.0123622 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.
Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise.
In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16 h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16 h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.
EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.
PLoS ONE 04/2015; 10(4):e0122982.. DOI:10.1371/journal.pone.0122982 · 3.23 Impact Factor