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Chronic Fatigue Syndrome: HELP
Articles by Andrew R. Lloyd
Based on 24 articles published since 2010
(Why 24 articles?)
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Between 2010 and 2020, A. Lloyd wrote the following 24 articles about Fatigue Syndrome, Chronic.
 
+ Citations + Abstracts
1 Editorial The long wait for a breakthrough in chronic fatigue syndrome. 2015

Lloyd, Andrew R / Meer, Jos W M van der. ·Inflammation and Infection Research Centre, University of New South Wales, Sydney 2052, Australia a.lloyd@unsw.edu.au. · Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. ·BMJ · Pubmed #25944462.

ABSTRACT: -- No abstract --

2 Editorial A controversial consensus--comment on article by Broderick et al. 2012

van der Meer, J W M / Lloyd, A R. · ·J Intern Med · Pubmed #21988219.

ABSTRACT: -- No abstract --

3 Review Response to Commentary: 'Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches'. 2019

Beilharz, Jessica E / Fatt, Scott J / Cvejic, Erin / Lloyd, Andrew R / Vollmer-Conna, Ute. ·School of Psychiatry, University of New South Wales, Sydney, Australia. j.beilharz@unsw.edu.au. · School of Psychiatry, University of New South Wales, Sydney, Australia. · School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia. · Viral Immunology Systems Program, The Kirby Institute, University of New South Wales, Sydney, Australia. ·Curr Rheumatol Rep · Pubmed #30955109.

ABSTRACT: -- No abstract --

4 Review The Invisible Burden of Chronic Fatigue in the Community: a Narrative Review. 2019

Fatt, Scott J / Cvejic, Erin / Lloyd, Andrew R / Vollmer-Conna, Ute / Beilharz, Jessica Elise. ·Department of Human Behaviour, School of Psychiatry, University of New South Wales, Level 1 30 Botany Street, UNSW, Sydney, NSW, 2052, Australia. s.fatt@unsw.edu.au. · Department of Human Behaviour, School of Psychiatry, University of New South Wales, Level 1 30 Botany Street, UNSW, Sydney, NSW, 2052, Australia. · School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, 2006, Australia. · Viral Immunology Systems Program, The Kirby Institute, University of New South Wales, Sydney, 2052, Australia. · Department of Human Behaviour, School of Psychiatry, University of New South Wales, Level 1 30 Botany Street, UNSW, Sydney, NSW, 2052, Australia. j.beilharz@unsw.edu.au. ·Curr Rheumatol Rep · Pubmed #30741357.

ABSTRACT: PURPOSE OF REVIEW: Unexplained fatigue is commonly reported in the general population, with varying severity. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) sits at the extreme of the fatigue continuum, yet more individuals experience unexplained prolonged fatigue (1-6-month duration) or chronic fatigue (> 6 months) that, although debilitating, does not fulfil ME/CFS criteria. This review examines the empirical literature comparing symptoms for those with prolonged fatigue, chronic fatigue and ME/CFS. RECENT FINDINGS: Substantial overlap of self-reported psychological, physical and functional impairments exists between chronic fatigue and ME/CFS. The conversion rate from prolonged or chronic fatigue to ME/CFS is not understood. Current research has failed to uncover factors accounting for differences in fatigue trajectories, nor incorporate comprehensive, longitudinal assessments extending beyond self-reported symptoms. Distinguishing factors between prolonged fatigue, chronic fatigue and ME/CFS remain poorly understood, highlighting a need for longitudinal studies integrating biopsychosocial approaches to inform early management and targeted rehabilitation strategies.

5 Clinical Trial Outcomes and predictors of response from an optimised, multidisciplinary intervention for chronic fatigue states. 2016

Sandler, C X / Hamilton, B A / Horsfield, S L / Bennett, B K / Vollmer-Conna, U / Tzarimas, C / Lloyd, A R. ·Fatigue Clinic, Lifestyle Clinic, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. · National Centre for Cancer Survivorship, University of New South Wales, Sydney, New South Wales, Australia. · Department of Human Behaviour, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia. · Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. ·Intern Med J · Pubmed #27620986.

ABSTRACT: BACKGROUND: Medically unexplained chronic fatigue states are prevalent and challenging to manage. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are effective in clinical trials. The evaluation of delivery in a standard healthcare setting is rare. An integrated treatment programme with individualised allocation of resources to patients' needs was developed and implemented through an academic outpatient clinic. It was hypothesised that the programme would result in similar responses to those observed in the clinical trials. AIM: To evaluate the outcomes of an integrated, 12-week CBT and GET programme delivered by exercise physiologists and clinical psychologists. METHODS: Consecutive eligible patients (n = 264) who met the diagnostic criteria for chronic fatigue syndrome or post-cancer fatigue were evaluated with self-report measures of fatigue, functional capacity and mood disturbance at baseline, end-of-treatment (12 weeks) and follow-up (24 weeks). A semi-structured interview recording the same parameters was conducted pre- and post-treatment by an independent clinician. Primary outcome was analysed by repeated measures analysis of variance and predictors of response were analysed by logistic regression. RESULTS: The intervention produced sustained improvements in symptom severity and functional capacity. A substantial minority of patients (35%) gained significant improvement, with male gender and higher pain scores at baseline predicting non-response. A small minority of patients (3%) worsened. CONCLUSION: The manualised protocol of integrated CBT and GET was successfully implemented, confirming the generally positive findings of clinical trials. Assessment and treatment protocols are available for dissemination to allow standardised management. The beneficial effects described here provide the basis for ongoing studies to optimise the intervention further and better identify those most likely to respond.

6 Article Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome. 2020

Fatt, Scott J / Beilharz, Jessica E / Joubert, Michael / Wilson, Chloe / Lloyd, Andrew R / Vollmer-Conna, Uté / Cvejic, Erin. ·School of Psychiatry, Faculty of Medicine, University of New South Wales Sydney, New South Wales, Australia. · Viral Immunology Systems Program, The Kirby Institute, University of New South Wales Sydney, New South Wales, Australia. · The University of Sydney, School of Public Health, Faculty of Medicine and Health, New South Wales, Australia. ·J Clin Sleep Med · Pubmed #31957647.

ABSTRACT: STUDY OBJECTIVES: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS. METHODS: Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants' homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality. RESULTS: Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep. Poorer self-reported wellbeing and sleep quality was associated with reduced parasympathetic signaling during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS. CONCLUSIONS: Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.

7 Article Personalised relaxation practice to improve sleep and functioning in patients with chronic fatigue syndrome and depression: study protocol for a randomised controlled trial. 2018

Macnamara, Claire L / Cvejic, Erin / Parker, Gordon B / Lloyd, Andrew R / Lee, Gina / Beilharz, Jessica E / Vollmer-Conna, Ute. ·Department of Human Behaviour (Psychiatry), UNSW, Level 1, 30 Botany Street, Sydney, NSW, 2052, Australia. · School of Public Health, University of Sydney, Sydney, Australia. · Black Dog Institute, Prince of Wales Hospital, Randwick, Sydney, Australia. · Viral Immunology Systems Program, The Kirby Institute, University of New South Wales, Sydney, Australia. · Department of Human Behaviour (Psychiatry), UNSW, Level 1, 30 Botany Street, Sydney, NSW, 2052, Australia. ute@unsw.edu.au. ·Trials · Pubmed #29996933.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) are both debilitating but heterogeneous conditions sharing core features of fatigue, unrefreshing sleep, and impaired functioning. The aetiology of these conditions is not fully understood, and 'best-practice' treatments are only moderately effective in relieving symptoms. Unrecognised individual differences in the response to such treatments are likely to underlie poor treatment outcomes. METHODS/DESIGN: We are undertaking a two-group, parallel, randomised controlled trial (RCT) comparing the effects of a personalised relaxation intervention on sleep quality, daytime symptoms, and functioning in patients with CFS (n = 64) and MDD (n = 64). Following identification of the method that best enhances autonomic responding (such as heart rate variability), participants randomised to the active intervention will practise their recommended method nightly for 4 weeks. All participants will keep a sleep diary and monitor symptoms during the trial period, and they will complete two face-to-face assessments, one at baseline and one at 4 weeks, and a further online assessment to evaluate lasting effects of the intervention at 2 months. Assessments include self-report measures of sleep, wellbeing, and function and monitoring of autonomic responses at rest, in response to the relaxation method and during nocturnal sleep. Treatment outcomes will be analysed using linear mixed modelling. DISCUSSION: This is the first RCT examining the effects of a personalised relaxation intervention, pre-tested to maximise the autonomic relaxation response, in patients with unrefreshing sleep and fatigue attributed to CFS or MDD. Detailed monitoring of sleep quality and symptoms will enable sensitive detection of improvements in the core symptoms of these debilitating conditions. In addition, repeated monitoring of autonomic functioning can elucidate mechanisms underlying potential benefits. The findings have translational potential, informing novel, personalised symptom management techniques for these conditions, with the potential for better clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616001671459 . Registered on 5 December 2016.

8 Article Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome. 2017

Cvejic, Erin / Sandler, Carolina X / Keech, Andrew / Barry, Benjamin K / Lloyd, Andrew R / Vollmer-Conna, Uté. ·School of Psychiatry, University of New South Wales, NSW, Australia; University of Sydney, School of Public Health, NSW, Australia. Electronic address: erin.cvejic@sydney.edu.au. · UNSW Fatigue Clinic, University of New South Wales, NSW, Australia. Electronic address: c.sandler@unsw.edu.au. · School of Medical Sciences, University of New South Wales, NSW, Australia. Electronic address: a.keech@unsw.edu.au. · School of Medical Sciences, University of New South Wales, NSW, Australia; Neuroscience Research Australia, NSW, Australia. Electronic address: ben.barry@unsw.edu.au. · UNSW Fatigue Clinic, University of New South Wales, NSW, Australia; Viral Immunology Systems Program, The Kirby Institute, University of New South Wales, NSW, Australia. Electronic address: a.lloyd@unsw.edu.au. · School of Psychiatry, University of New South Wales, NSW, Australia. Electronic address: ute@unsw.edu.au. ·J Psychosom Res · Pubmed #29167053.

ABSTRACT: OBJECTIVE: To explore changes in autonomic functioning, sleep, and physical activity during a post-exertional symptom exacerbation induced by physical or cognitive challenge in participants with chronic fatigue syndrome (CFS). METHODS: Thirty-five participants with CFS reported fatigue levels 24-h before, immediately before, immediately after, and 24-h after the completion of previously characterised physical (stationary cycling) or cognitive (simulated driving) challenges. Participants also provided ratings of their sleep quality and sleep duration for the night before, and after, the challenge. Continuous ambulatory electrocardiography (ECG) and physical activity was recorded from 24-h prior, until 24-h after, the challenge. Heart rate (HR) and HR variability (HRV, as high frequency power in normalized units) was derived from the ECG trace for periods of wake and sleep. RESULTS: Both physical and cognitive challenges induced an immediate exacerbation of the fatigue state (p<0.001), which remained elevated 24-h post-challenge. After completing the challenges, participants spent a greater proportion of wakeful hours lying down (p=0.024), but did not experience significant changes in sleep quality or sleep duration. Although the normal changes in HR and HRV during the transition from wakefulness to sleep were evident, the magnitude of the increase in HRV was significantly lower after completing the challenge (p=0.016). CONCLUSION: Preliminary evidence of reduced nocturnal parasympathetic activity, and increased periods of inactivity, were found during post-exertional fatigue in a well-defined group of participants with CFS. Larger studies employing challenge paradigms are warranted to further explore the underlying pathophysiological mechanisms of post-exertional fatigue in CFS.

9 Article Cognitive remediation training improves performance in patients with chronic fatigue syndrome. 2017

McBride, Richard L / Horsfield, Sarah / Sandler, Carolina X / Cassar, Joanne / Casson, Sally / Cvejic, Erin / Vollmer-Conna, Uté / Lloyd, Andrew R. ·UNSW Fatigue Clinic, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. · School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia; University of Sydney, School of Public Health, Camperdown, NSW 2006, Australia. Electronic address: erin.cvejic@sydney.edu.au. · School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia. · UNSW Fatigue Clinic, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: a.lloyd@unsw.edu.au. ·Psychiatry Res · Pubmed #28830024.

ABSTRACT: Neurocognitive disturbance with subjectively-impaired concentration and memory is a common, disabling symptom reported by patients with chronic fatigue syndrome (CFS). We recently reported preliminary evidence for benefits of cognitive remediation as part of an integrated cognitive-behavioral therapy (CBT)/ graded exercise therapy (GET) program. Here, we describe a contemporaneous, case-control trial evaluating the effectiveness of an online cognitive remediation training program (cognitive exercise therapy; CET) in addition to CBT/GET (n=36), compared to CBT/GET alone (n=36). The study was conducted in an academic, tertiary referral outpatient setting over 12 weeks (11 visits) with structured, home-based activities between visits. Participants self-reported standardized measures of symptom severity and functional status before and after the intervention. Those in the CET arm also completed standardized neurocognitive assessment before, and following, treatment. The addition of formal CET led to significantly greater improvements in self-reported neurocognitive symptoms compared to CBT/GET alone. Subjective improvement was predicted by CET group and lower baseline mood disturbance. In the CET group, significant improvements in objectively-measured executive function, processing speed, and working memory were observed. These subjective and objective performance improvements suggest that a computerized, home-based cognitive training program may be an effective intervention for patients with CFS, warranting randomized controlled trials.

10 Article Randomised controlled trial of online continuing education for health professionals to improve the management of chronic fatigue syndrome: a study protocol. 2017

Li, Sophie H / Sandler, Carolina X / Casson, Sally M / Cassar, Joanne / Bogg, Tina / Lloyd, Andrew R / Barry, Benjamin K. ·School of Medical Sciences, University of New South Wales, Sydney, Australia. · School of Psychology, The University of New South Wales, Sydney, Australia. · The Kirby Institute, University of New South Wales, Sydney, Australia. · Neuroscience Research Australia, University of New South Wales, Sydney, Australia. · School of Clinical Medicine, University of Queensland, Brisbane, Australia. ·BMJ Open · Pubmed #28495811.

ABSTRACT: INTRODUCTION: Chronic fatigue syndrome (CFS) is a serious and debilitating illness that affects between 0.2%-2.6% of the world's population. Although there is level 1 evidence of the benefit of cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for some people with CFS, uptake of these interventions is low or at best untimely. This can be partly attributed to poor clinician awareness and knowledge of CFS and related CBT and GET interventions. This trial aims to evaluate the effect of participation in an online education programme, compared with a wait-list control group, on allied health professionals' knowledge about evidence-based CFS interventions and their levels of confidence to engage in the dissemination of these interventions. METHODS AND ANALYSIS: A randomised controlled trial consisting of 180 consenting allied health professionals will be conducted. Participants will be randomised into an intervention group (n=90) that will receive access to the online education programme, or a wait-list control group (n=90). The primary outcomes will be: 1) knowledge and clinical reasoning skills regarding CFS and its management, measured at baseline, postintervention and follow-up, and 2) self-reported confidence in knowledge and clinical reasoning skills related to CFS. Secondary outcomes include retention of knowledge and satisfaction with the online education programme. The influence of the education programme on clinical practice behaviour, and self-reported success in the management of people with CFS, will also be assessed in a cohort study design with participants from the intervention and control groups combined. ETHICS AND DISSEMINATION: The study protocol has been approved by the Human Research Ethics Committee at The University of New South Wales (approval number HC16419). Results will be disseminated via peer-reviewed journal articles and presentations at scientific conferences and meetings. TRIAL REGISTRATION: ACTRN12616000296437.

11 Article Gene Expression in Response to Exercise in Patients with Chronic Fatigue Syndrome: A Pilot Study. 2016

Keech, Andrew / Vollmer-Conna, Ute / Barry, Benjamin K / Lloyd, Andrew R. ·School of Medical Sciences, University of New South Wales Sydney, NSW, Australia. · School of Psychiatry, University of New South Wales Sydney, NSW, Australia. · School of Medical Sciences, University of New South WalesSydney, NSW, Australia; Neuroscience Research AustraliaSydney, NSW, Australia. · Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales Sydney, NSW, Australia. ·Front Physiol · Pubmed #27713703.

ABSTRACT: Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterized by fatigue, which is exacerbated after minimal exercise. We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signaling as an under-pinning of the fatigue state. A carefully-characterized sample of patients with CFS (

12 Article Fatigue Exacerbation by Interval or Continuous Exercise in Chronic Fatigue Syndrome. 2016

Sandler, Carolina X / Lloyd, Andrew R / Barry, Benjamin K. ·1Fatigue Clinic, Lifestyle Clinic, School of Medical Sciences, University of New South Wales, Sydney, NSW, AUSTRALIA; 2Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, AUSTRALIA; and 3Neuroscience Research Australia, University of New South Wales, Sydney, AUSTRALIA. ·Med Sci Sports Exerc · Pubmed #27183124.

ABSTRACT: PURPOSE: The objective of this study is to determine whether the typical exacerbation of symptoms in patients with chronic fatigue syndrome (CFS) after a bout of exercise differs between high-intensity interval training (HIIT) or continuous (CONT) aerobic exercise of the same duration and mechanical work. METHODS: Participants with specialist-diagnosed CFS performed two 20-min bouts of cycling in a randomized crossover study. The bouts were either moderate-intensity continuous (70% age-predicted HR maximum) or high-intensity interval exercise, separated by at least 2 wk. Self-report questionnaires capturing fatigue, the related symptoms, and actigraphy were collected across 2 d before and 4 d after the exercise. Comparisons between exercise bouts were made using paired sample t-tests. RESULTS: Fourteen moderately affected participants who were unable to work, but not bed bound, completed the study (nine female, 32 ± 10 yr, 67 ± 11 kg). Mechanical work was matched successfully between the exercise bouts (HIIT, 83,037, vs CONT, 83,348 J, P = 0.84). Mean HR (HIIT, 76% ± 5%, vs CONT, 73% ± 6% age-predicted HR maximum, P < 0.05) and RPE (6-20) in the legs (HIIT, 15.4 ± 1.4, vs CONT, 13.2 ± 1.2, P < 0.001) were higher for the interval compared with continuous exercise. Mean fatigue scores (0-10) were similar before each exercise challenge (HIIT, 4.5 ± 1.8, vs CONT, 4.1 ± 1.7, P = 0.43). Participants reported an increase in fatigue scores after both challenges (mean difference: HIIT, 1.0 ± 1.3, P < 0.01; CONT, 1.5 ± 0.7, P < 0.001), but these exacerbations in fatigue were not statistically or clinically different (P = 0.20). CONCLUSIONS: High-intensity interval exercise did not exacerbate fatigue any more than continuous exercise of comparable workload. This finding supports evaluation of HIIT in graded exercise therapy interventions for patients with CFS.

13 Article Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions. 2016

Cvejic, Erin / Lloyd, Andrew R / Vollmer-Conna, Uté. ·School of Psychiatry, University of New South Wales, Australia. Electronic address: e.cvejic@unsw.edu.au. · Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Australia. Electronic address: a.lloyd@unsw.edu.au. · School of Psychiatry, University of New South Wales, Australia. Electronic address: ute@unsw.edu.au. ·Compr Psychiatry · Pubmed #26995250.

ABSTRACT: BACKGROUND: Neurocognitive difficulties are commonly reported by patients suffering from chronic fatigue syndrome (CFS). Moderate improvements from 'best practice' therapy are promising, but to date reported efficacy is based entirely on subjective measures. This is problematic, given the well-documented divergence between subjective perceptions and actual neurocognitive performance, including in this patient group. MATERIAL AND METHODS: Subjective and objective measures of neurocognitive performance were obtained from 25 patients with well-characterized CFS before and after the completion of a 12-week graded-activity program incorporating a cognitive training component. Additionally, self-reported symptoms, cardiac autonomic activity (a relevant biomarker of stress responsivity), and their relation to neurocognitive improvements were examined. RESULTS: Substantive post-intervention improvements in subjective (p=0.006) and objective (including faster responses speeds and greater accuracy, p's<0.001) neurocognitive performance were documented. Participants also demonstrated reduced autonomic reactivity to the cognitive challenge at follow-up (p's≤0.01). These improvements were accompanied by improvements in symptom ratings (p's≤0.01). However, subjective ratings of neurocognitive difficulties, and CFS-related symptoms were not linked to objective performance improvements. CONCLUSIONS: These initial data provide the first evidence of objective neurocognitive performance improvements accompanied by a significant reduction in responsiveness in stress-related neural pathways consequent to cognitive-behavioral/graded exercise therapy programs. These findings provide support for the effectiveness of such programs in remediating clinical status. These promising findings warrant further investigation, including replication in a larger sample utilizing more controlled study designs.

14 Article Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome. 2015

Keech, Andrew / Sandler, Carolina X / Vollmer-Conna, Ute / Cvejic, Erin / Lloyd, Andrew R / Barry, Benjamin K. ·School of Medical Sciences, University of New South Wales, Sydney, Australia. Electronic address: andrew.keech@unsw.edu.au. · School of Medical Sciences, University of New South Wales, Sydney, Australia. · School of Psychiatry, University of New South Wales, Sydney, Australia. · Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, Australia. · School of Medical Sciences, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia. ·J Psychosom Res · Pubmed #26359713.

ABSTRACT: OBJECTIVE: To design and validate an instrument to capture the characteristic post-exertional exacerbation of fatigue in patients with chronic fatigue syndrome (CFS). METHODS: Firstly, patients with CFS (N=19) participated in five focus group discussions to jointly explore the nature of fatigue and dynamic changes after activity, and inform development of a self-report instrument - the Fatigue and Energy Scale (FES). The psychometric properties of the FES were then examined in two case-control challenge studies: a physically-demanding challenge (moderate-intensity aerobic exercise; N=10 patients), and a cognitively-demanding challenge (simulated driving; N=11 patients). Finally, ecological validity was evaluated by recording in association with tasks of daily living (N=9). RESULTS: Common descriptors for fatigue included 'exhaustion', 'tiredness', 'drained of energy', 'heaviness in the limbs', and 'foggy in the head'. Based on the qualitative data, fatigue was conceptualised as consisting of 'physical' and 'cognitive' dimensions. Analysis of the psychometric properties of the FES showed good sensitivity to the changing symptoms during a post-exertional exacerbation of fatigue following both physical exercise and driving simulation challenges, as well as tasks of daily living. CONCLUSION: The 'fatigue' experienced by patients with CFS covers both physical and cognitive components. The FES captured the phenomenon of a post-exertional exacerbation of fatigue commonly reported by patients with CFS. The characteristics of the symptom response to physical and cognitive challenges were similar. Both the FES and the challenge paradigms offer key tools to reliably investigate biological correlates of the dynamic changes in fatigue.

15 Article Characterization of fatigue states in medicine and psychiatry by structured interview. 2014

Bennett, Barbara Kaye / Goldstein, David / Chen, Michelle / Davenport, Tracey A / Vollmer-Conna, Ute / Scott, Elizabeth M / Hickie, Ian B / Lloyd, Andrew R. · ·Psychosom Med · Pubmed #25076512.

ABSTRACT: CONTEXT: Unexplained fatigue states are prevalent, with uncertain diagnostic boundaries. OBJECTIVE: Patients with fatigue-related illnesses were investigated by questionnaire and a novel semistructured interview to identify discriminatory features. METHODS: Cross-sectional samples of women from specialist practices with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or major depression (n = 16) were recruited. Additionally, two longitudinal samples were studied: women with fatigue associated with acute infection who subsequently developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n = 21), and women undergoing adjuvant therapy for breast cancer experiencing treatment-related fatigue who subsequently developed PCF (n = 16) or recovered uneventfully (n = 16). Patients completed self-report questionnaires, and trained interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The receiver operating characteristics curves of the interview were measured against clinician-designated diagnoses. Cluster analyses were performed to empirically partition participants by symptom characteristics. RESULTS: The interview had good internal consistency (Cronbach alpha "fatigue" = .83), and diagnostic sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major depression (100% and 72%), with reasonable parameters for PCF (72% and 58%). Empirical clustering by "fatigue" or "neurocognitive difficulties" items allocated most patients to one group, whereas "mood disturbance" items correctly classified patients with depression only. CONCLUSIONS: The Semi-structured Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing fatigue-related conditions. The symptom domains of fatigue and neurocognitive difficulties are shared across medical and psychiatric boundaries, whereas symptoms of depression such as anhedonia are distinguishing.

16 Article Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. 2012

Beaumont, Alison / Burton, Alexander R / Lemon, Jim / Bennett, Barbara K / Lloyd, Andrew / Vollmer-Conna, Uté. ·School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia. ·PLoS One · Pubmed #23166694.

ABSTRACT: BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed. RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.

17 Article Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections. 2011

Galbraith, Sally / Cameron, Barbara / Li, Hui / Lau, Diana / Vollmer-Conna, Ute / Lloyd, Andrew R. ·School of Mathematics and Statistics, Faculty of Science, University of New South Wales, Sydney, Australia. ·J Infect Dis · Pubmed #21964398.

ABSTRACT: BACKGROUND: Several infections trigger postinfective fatigue syndromes, which share key illness characteristics with each other and with chronic fatigue syndrome (CFS). Previous cross-sectional case-control studies of CFS have suggested that unique gene expression signatures are evident in peripheral blood samples. METHODS: Peripheral blood transcriptomes in samples collected longitudinally, in 18 subjects with a fatigue syndrome lasting ≥ 6 months after acute infection due to Epstein-Barr virus, Ross River virus, or Coxiella burnetii (Q fever), and 18 matched control subjects who had recovered promptly, were studied by microarray (n = 127) and confirmatory quantitative polymerase chain reaction (PCR). Gene expression patterns associated with CFS were sought by univariate statistics and regression modeling. RESULTS: There were 23 genes with modest differential expression (0.6-2.3-fold change) in within-subject comparisons of early, symptomatic time points with late, recovered time points. There were modest differences found in 63 genes, either in cross-sectional comparison of cases and controls at 6 months after infection onset or in the regression model. There were 223 genes significantly correlated with individual symptom domains. Quantitative PCR confirmed 33 (73%) of 45 genes-none were consistent across cohorts. CONCLUSIONS: Although the illness characteristics of patients with postinfective fatigue syndromes have more similarities than differences, no reliable peripheral blood gene expression correlate is evident.

18 Article Sleep-wake behavior in chronic fatigue syndrome. 2011

Rahman, Khairunnessa / Burton, Alexander / Galbraith, Sally / Lloyd, Andrew / Vollmer-Conna, Ute. ·School of Psychiatry, University of NSW, Sydney, Australia. ·Sleep · Pubmed #21532961.

ABSTRACT: STUDY OBJECTIVES: Disturbances of the internal biological clock manifest as fatigue, poor concentration, and sleep disturbances-symptoms reminiscent of chronic fatigue syndrome (CFS) and suggestive of a role for circadian rhythm disturbance in CFS. We examined circadian patterns of activity, sleep, and cortisol secretion in patients with CFS. DESIGN: Case-control study, 5-day behavioral observation. SETTING: Natural setting/home environment PARTICIPANTS: 15 patients with CFS and 15 healthy subjects of similar age, sex, body mass index (BMI), and activity levels. INTERVENTIONS: N/A. MEASUREMENTS: Self-report questionnaires were used to obtain medical history and demographic information and to assess health behaviors, somatic and psychological symptoms, and sleep quality. An actiwatch accelerometer recorded activity and sleep patterns over 5 days with concurrent activity and symptom logs. Diurnal salivary cortisol secretion was measured. Additionally, overnight heart rate monitoring and pain sensitivity assessment was undertaken. RESULTS: Ratings of symptoms, disability, sleep disturbance, and pain sensitivity were greater in patients with CFS. No between-group differences were found in the pattern or amount of sleep, activity, or cortisol secretion. Afternoon activity levels significantly increased evening fatigue in patients but not control subjects. Low nocturnal heart rate variability was identified as a biological correlate of unrefreshing sleep. CONCLUSIONS: We found no evidence of circadian rhythm disturbance in CFS. However, the role of autonomic activity in the experience of unrefreshing sleep warrants further assessment. The activity symptom-relationship modelled here is of clinical significance in the approach to activity and symptom management in the treatment of CFS.

19 Article Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome. 2010

Cameron, Barbara / Flamand, Louis / Juwana, Hedy / Middeldorp, Jaap / Naing, Zin / Rawlinson, William / Ablashi, Dharam / Lloyd, Andrew. ·Center for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. b.cameron@unsw.edu.au ·J Med Virol · Pubmed #20827765.

ABSTRACT: Multiple previous studies have sought evidence for ongoing, active infection with, or reactivation of, Herpesviruses in patients with chronic fatigue syndrome (CFS), with conflicting results. This study aimed to clarify this by studying 20 patients enrolled in a well-characterized model of the onset and evolution of CFS, the prospective cohort of the Dubbo Infection Outcomes Study (DIOS). The patients selected for examination included five CFS patients with primary Epstein-Barr virus (EBV) infection; five CFS patients with acute viral infection not caused by EBV; and 10 matched controls with prompt resolution of primary EBV infection. Serum samples from three timepoints were assayed using a comprehensive range of serological assays for EBV, HHV-6, and CMV. Viral genomes were assessed using quantitative PCR assays. All patients were seropositive for HHV-6, and 10 were seropositive for CMV at infection baseline (five patients and five controls). Low titer CMV IgM antibodies were found at infection baseline in two of these cases and three control patients. HHV-6 IgG antibody titers were highest at infection baseline but did not differ between the CFS cases and the control patients. There were increases in EBV IgG VCA p18, EBNA-1 IgG, and EA IgG titers over time, but these did not differ between CFS cases and control patients. EBV and HHV6 DNA levels were at control levels in a minority of samples, and CMV was undetectable in all samples. These data do not support the hypothesis of ongoing or reactivated EBV, HHV-6, or CMV infection in the pathogenesis of CFS.

20 Article Autonomic hyper-vigilance in post-infective fatigue syndrome. 2010

Kadota, Yumiko / Cooper, Gavin / Burton, Alexander R / Lemon, Jim / Schall, Ulrich / Lloyd, Andrew / Vollmer-Conna, Ute. ·School of Psychiatry, University of NSW, Sydney, Australia. ·Biol Psychol · Pubmed #20678991.

ABSTRACT: This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation. Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.

21 Article Reduced heart rate variability predicts poor sleep quality in a case-control study of chronic fatigue syndrome. 2010

Burton, A R / Rahman, K / Kadota, Y / Lloyd, A / Vollmer-Conna, U. ·School of Psychiatry, University of NSW, Sydney, Australia. ·Exp Brain Res · Pubmed #20502886.

ABSTRACT: Parasympathetic function is important in the induction and maintenance of sleep. We examined whether nocturnal vagal modulation of heart rate is related to the poor sleep quality commonly reported in chronic fatigue syndrome (CFS). Heart rate (HR, as R-R intervals) was continuously monitored during sleep in 20 patients with CFS and 20 matched control subjects. Questionnaires assessed demographic information, symptoms, functional impairment, and subjective sleep quality. CFS was associated with more sleep problems in general and poorer subjective sleep quality on the study night (all p < 0.003), and reports of repeated awakening during the night were 7 times more likely compared to healthy subjects (p = 0.017). Time and frequency-domain parameters of HR variability during sleep were significantly lower in patients with CFS (all p < 0.006). Multiple regression analyses revealed that heart rate variability (HRV) parameters were the best predictors of subjective sleep measures. This study identified significant reductions in vagal modulation of heart rate during sleep in CFS. Low HRV strongly predicted sleep quality-suggesting a pervasive state of nocturnal sympathetic hypervigilance in CFS.

22 Article Comment on "Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome". 2010

Lloyd, Andrew / White, Peter / Wessely, Simon / Sharpe, Michael / Buchwald, Dedra. ·Centre for Infection and Inflammation Research, University of New South Wales, Sydney, Australia 2052. a.lloyd@unsw.edu.au ·Science · Pubmed #20466905.

ABSTRACT: Lombardi et al. (Reports, 23 October 2009, p. 585) reported a significant association between the human retrovirus XMRV and chronic fatigue syndrome (CFS). However, the cases with CFS and the control subjects in their study are poorly described and unlikely to be representative. Independent replication is a critical first step before accepting the validity of this finding.

23 Minor Cytokine signature in chronic fatigue syndrome. 2017

Roerink, Megan E / Buckland, Matthew / Lloyd, Andrew R / van der Meer, Jos W M. ·Radboud University Medical Center, Nijmegen 6500 HB, The Netherlands. · Barts Health Trust, London E1 1BB, United Kingdom. · Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia. · Radboud University Medical Center, Nijmegen 6500 HB, The Netherlands; jos.vandermeer@radboudumc.nl. ·Proc Natl Acad Sci U S A · Pubmed #29087342.

ABSTRACT: -- No abstract --

24 Minor Apology. 2013

Lloyd, A R. · ·J Intern Med · Pubmed #23647317.

ABSTRACT: -- No abstract --