Julia L Newton

NIHR Oxford Biomedical Research, Oxford, England, United Kingdom

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Publications (280)1454.66 Total impact

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    Nicola Childs · Lisa Robinson · Sonya Chowdhury · Clare Ogden · Julia L Newton ·
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    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.
    12/2015; 1(11). DOI:10.1186/s40900-015-0011-x
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    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.
    ACR/ARHP, San Francisco; 11/2015
  • Ruth Hart · Katie L Hackett · Julia L Newton · Wan-Fai Ng · Ben Thompson ·
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    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.
    ACR/ARHP, San Francisco; 11/2015
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    Dataset: nihms685208

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    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.
    10/2015; 2015(52):98-107. DOI:10.5923/j.ijpbs.20150502.07
  • Lucy J. Robinson · Justin Durham · Laura L. MacLachlan · Julia L. Newton ·
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    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.
    10/2015; 3(4):205-219. DOI:10.1080/21641846.2015.1091152
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    Iwo Bohr · Claire McDonald · Jiabao He · Simon Kerr · Julia L. Newton · Andrew M. Blamire ·
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    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
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    ABSTRACT: Greater ambulatory blood pressure variability (ABPV) is associated with end-organ damage and increased mortality. Age-related changes in the cardiovascular and autonomic nervous systems make age-associated increases in ABPV likely. Cross-sectional studies support this hypothesis, showing greater ABPV among older compared to younger adults. The only longitudinal study to examine changes in ABPV, however, found ABPV decreased over 5 years follow-up. This unexpected observation probably reflected the highly selected nature of the study participants. In this longitudinal study, we assessed changes in ABPV over 10 years in a community-cohort of older people. In addition, we examined the extent to which ABPV was predicted by demographics, cardiovascular risk factors, and medication. Clinical examination and 24-hour ambulatory blood pressure monitoring were carried out at baseline and at 10 years follow-up in 83 people, median age 70 years. ABPV was calculated using SD and coefficient of variation (Cv). Three time periods were examined: daytime, nighttime, and 24 hours. Daytime and 24-hour, systolic and diastolic, SD, and Cv were significantly greater at follow-up than at baseline (P < 0.001 in all cases). Mean BP did not change. Multilevel modeling showed follow-up interval had a significant, positive effect on SD and Cv (P < 0.004), independent of age, sex, and medication.ABPV increased over a 10-year follow-up despite stable mean BP. ABPV may therefore be an additional target for treatment in older people. Future studies should examine what degree of ABPV is harmful and if control of ABPV reduces adverse outcome. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    American Journal of Hypertension 08/2015; DOI:10.1093/ajh/hpv150 · 2.85 Impact Factor
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    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
  • James Frith · Julia L Newton ·
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    ABSTRACT: To validate a new patient-reported outcome measure for routine clinical use. A total of 50 older individuals with orthostatic hypotension who attended a falls and syncope clinic completed three questionnaires, the recently developed Orthostatic Hypotension Questionnaire, the existing Orthostatic Grading Scale and the quality of life measure EQ-5D-5L. Validity of the Orthostatic Hypotension Questionnaire was tested against the aforementioned questionnaires for symptoms and for quality of life. Comorbidity was quantified using the Charlson Comorbidity Index. The cohort of 50 individuals had a median age of 67 years (interquartile range 26-89 years) with a median Charlson Comorbidity Index of 3 (interquartile range 2-5). The total Orthostatic Hypotension Questionnaire Symptom Assessment score correlated strongly with the Orthostatic Grading Scale (0.616, P < 0.001) and the Orthostatic Hypotension Questionnaire Daily Activity Scale correlated strongly with daily activity on the EQ-5D-5L (0.61, P < 0.001). Using the Orthostatic Grading Scale, individuals' symptoms were categorized as mild, moderate or severe, the Orthostatic Hypotension Questionnaire scores were significantly different between these groups (P < 0.001). Internal consistency was high (Cronbach's apha 0.882), and ceiling or floor effects did not limit the total scores. The Orthostatic Hypotension Questionnaire is a valid patient report tool to quantify the symptom burden of people with orthostatic hypotension. Because the symptoms associated with orthostatic hypotension are frequently non-specific, it will be a clinically useful tool to measure and quantify symptom load in people with orthostatic hypotension. Geriatr Gerontol Int 2015; ●●: ●●-●●. © 2015 Japan Geriatrics Society.
    Geriatrics & Gerontology International 07/2015; DOI:10.1111/ggi.12553 · 2.19 Impact Factor
  • James Frith · Ayat S Bashir · Julia L Newton ·
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    ABSTRACT: Orthostatic hypotension (OH) affects 6% of community-dwelling older people. This increases to 60% when non-invasive, continuous blood pressure (BP) monitoring is used, due to identification of transient drops in BP which recover rapidly. To determine the clinical relevance of these transient orthostatic BP drops. 5-year clinical observational study. 103 consecutive new patients attending a Falls and Syncope Clinic in the UK from 1(st) February 2009 underwent continuous BP monitoring during an active stand. BP profiles were analysed to quantify all reductions in BP, measuring the duration of any drop below diagnostic criteria. Five-year follow-up data was extracted from hospital clinical records to assess clinical outcomes. Systolic BP (sBP) dropped ≥20 mmHg in 76 (74%) individuals, with 65 (63%) having ≥10 mmHg drop in diastolic BP. However, only 22 (21%) cases were diagnosed clinically with OH. A sustained reduction in BP (≥30 seconds) had a sensitivity of 0.91 and specificity of 0.88 for a clinical diagnosis of OH, being more accurate than absolute BP reduction alone. A sustained reduction in sBP was associated with greater use of vasopressors (36%, p 0.001) and an independent, significantly greater risk of death (45% at 5 years, p 0.009). An orthostatic reduction in sBP lasting ≥30 seconds improves accuracy of diagnosis. Moreover, given the significant adverse outcomes with a sustained reduction, clinicians should consider this when diagnosing and treating patients, as transient OH does not appear to be clinically significant. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    QJM: monthly journal of the Association of Physicians 07/2015; DOI:10.1093/qjmed/hcv126 · 2.50 Impact Factor
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    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.
    06/2015; 3(3). DOI:10.1080/21641846.2015.1051291
  • Katie L Hackett · K.H.O. Deane · T. Rapley · V. Deary · S. Bowman · E. Price · Julia L Newton · W-F. Ng ·
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    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

  • 13th International Symposium on Sjögren's Syndrome, Bergen, Norway; 05/2015

  • 13th International Symposium on Sjögren's Syndrome, Bergen, Norway; 05/2015
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    13th International Symposium on Sjogren's syndrome, Bergen, Norway; 05/2015
  • Justin Durham · Claire McDonald · Luke Hutchinson · Julia L Newton ·
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    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.
    05/2015; 29(2):152-7. DOI:10.11607/ofph.1396
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    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
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    ABSTRACT: Perceived fatigue is a prominent symptom in patients with mitochondrial disease but to date its prevalence, impact and aetiology are poorly understood. Our aim was to determine the prevalence and assess for comorbidities associated with clinically relevant fatigue in patients with mitochondrial disease. A cross-sectional postal survey of patients with mitochondrial disease was undertaken using a validated self-completion, patient-reported outcome measures (response rate: 60%; n = 132). The prevalence and perceived functional impact of experienced fatigue were assessed using the Fatigue Impact Scale. Other putative biological mechanisms were evaluated using the Hospital Anxiety Depression scale and Epworth sleepiness scale. Data were compared with those for healthy control subjects and patients with Myalgic Encephalopathy/Chronic Fatigue Syndrome matched for age and gender. Sixty-two per cent of patients with mitochondrial disease reported excessive symptomatic fatigue (Fatigue Impact Scale ≥ 40); whilst 32% reported severe, functionally limiting fatigue symptoms (Fatigue Impact Scale ≥ 80) comparable to perceived fatigue in patients with Myalgic Encephalopathy/Chronic Fatigue Syndrome. Fatigue is common and often severe in patients with mitochondrial disease irrespective of age, gender or genotype. Future evaluation of causal factors in mitochondrial disease-associated fatigue is warranted with the potential to guide future treatment modalities. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Neuromuscular Disorders 04/2015; 25(7). DOI:10.1016/j.nmd.2015.03.001 · 2.64 Impact Factor
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    Audrey E Brown · David E Jones · Mark Walker · Julia L Newton ·
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    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. Methods: 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. Results: 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. Conclusion: 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

Publication Stats

3k Citations
1,454.66 Total Impact Points


  • 2012-2015
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 1997-2015
    • Newcastle University
      • • Institute of Cellular Medicine
      • • Institute for Ageing and Health
      • • Institute for Cell and Molecular Biosciences
      Newcastle-on-Tyne, England, United Kingdom
  • 1997-2014
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Department of Geriatric Medicine
      Newcastle-on-Tyne, England, United Kingdom
  • 2013
    • Nicolaus Copernicus University
      • Faculty of Medicine
      Toruń, Kujawsko-Pomorskie, Poland
    • Newcastle College
      Newcastle-on-Tyne, England, United Kingdom
    • DePaul University
      • Center for Community Research
      Chicago, IL, United States
  • 2008-2010
    • University of Newcastle
      Newcastle, New South Wales, Australia
  • 2007
    • University of Padova
      Padua, Veneto, Italy
  • 2005
    • University of Liverpool
      • Department of Public Health and Policy
      Liverpool, England, United Kingdom
  • 2004
    • Repatriation General Hospital
      Tarndarnya, South Australia, Australia
  • 2003
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom