Title: Fatigue: acute fatigue Assessment and Management in Everyday practice (FAME)
Funder: Department of Health and Social Care

Abstract: WP1 initial development of a web based intervention. Theoretical modelling. The intervention will be based on the current theoretical and empirical literature on the development of post infectious chronic fatigue. There is an existing cognitive behavioural model of the development of chronic fatigue post glandular fever13 and this will be modified if necessary by broader findings of post infectious fatigue. We will also draw on the expertise gained in other fatigue management programmes. Initial Intervention Development. Previous work will enable us to begin the initial development of the web materials rapidly, using the LifeGuide software, and website-adapted versions of the core fatigue self-management we have developed and trialled for fatigue previously30. Key intervention components will include behavioural education and graded activity, and optional features such as improving sleep patterns if this is identified as contributing to fatigue. Education for behaviour change will include the importance of avoiding all-or-nothing behaviour and how a gradual return to activity aids recovery. Graded physical activity will include setting and monitoring small goals for recovery and use of pedometers and charts of physical activity for the user to complete that then gives automated tailored feedback. Patients who show particularly negative illness beliefs and high personal expectations will be provided opportunities to identify and challenge these thoughts. Tailoring is achieved by the website by algorithms linking responses to key questions about the website user s circumstances, beliefs, preferences and progress to a library of messages, so that website users automatically receive a unique combination of messages tailored to their particular situation. We will also map out a draft health professional training package which is likely to consist of a brief self-training module to provide nurses with the skills to guide and support the patients using the intervention, using non-directive and non-evaluative communication to assist patients to identify their own goals and solutions to problems43. Example patient scenarios will be used to rehearse skills and build confidence in patient management35. We anticipate resources of the PDG will not extend to creating a web version of the nurse training module. Qualitative methods to refine the intervention. Following the theoretical modelling stage we will collect feedback on our patient intervention materials - presented as web pages once they have been created, or paper-based format. In depth semi-structured interviews with up to 15 patients will inductively explore attitudes to fatigue and physical activity, consider feasibility and process issues, and elicit views of the intervention materials and use think-aloud methods44to encourage interviewees to express their immediate reactions to the materials WP2 pilot cohort Patients. Inclusion criteria: patients presenting in primary care with fatigue (4+ on the Chalder scale), less than 3 months (for interventions, once developed, to be able to limit the progression to chronic fatigue). We anticipate three basic clinical presentations based on previous cohorts (1) glandular fever (the clinical syndrome of sore throat, enlarged cervical glands, fever irrespective of EBV status)4 2) other apparent acute infective precipitants10 and 3)) no clear infective precipitant11;25. We will explore a variety of recruitment methods Exclusions: Patients unable to consent (e.g. dementia, severe uncontrolled psychosis), or where there is an alternative clear non infective and short term cause for fatigue (e.g. pregnancy, clinical hypothyroidism, drug induced). Web portal. We will develop a web portal which will have two functions a) data collection system for the clinical record form and b) for patients to complete questionnaires. Patients will also have the option to use paper based questionnaires, and can to save computer responses at any time to enable completion over a few sessions to facilitate participation. Clinical Record form Data: Respiratory symptoms; phenotype (musculoskeletal; neurocognitive; etc)25;fatigue severity (VAS); myalgia severity; prior duration of symptoms; gender, ethnicity, age, comorbidities; brief screening questions for distress and depression7;11;45; MYMOP questionnaire46 (3 item questionnaire to quantify key symptoms for patients); and exercise tolerance. Patient completed data (baseline, 6 months unless specified): Fatigue questionnaire47 (also at 2 weeks) and repeat of the VAS for fatigue and MYMOP Sociodemographic (baseline only) and lifestyle data (food frequency; short IPAQ questionnaire for exercise)48 SF12 for quality of life. Mental health mediators:PHQ9 and GAD7(for anxiety and depression) 49; Cohen perceived stress and BRUGHA life events (baseline only); Jenkins sleep questionnaire, short Wellbeing scale (WEMWBS) and PHQ15 for somatisation50 The Brief Illness perception questionnaire51Belief about Emotions scale52Modified enablement scale53;54The all-or-nothing subscale from the Behavioural Responses to Illness Questionnaire (BRIQ) 55The negative subscale from the Positive and Negative Perfectionism Scale (PANPS) 56 Resource use: Notes review at follow-up for reconsultations and patient completed questionnaires for social/societal resource implications (particularly for impact on work, family and employment). The rationale for the 2 week appointment is on clinical grounds - the time it takes normal acute illness to resolve (more than 90% of those resolving will do so57) and so potentially a key time to contrast individuals who will or will not have prolonged fatigue and/or progress to CFS/ME Clinical outcomes. We will document the development of chronic fatigue and of CFS/ME. The primary continuous outcome will be the Chalder fatigue score. Although there are several overlapping definitions of CFS/ME we propose using the Fukuda criteria 32 (see appendix) since this is the most widely used definition. This will also allow us to explore the implications of using other criteria (e.g. Oxford; NICE)28;33 and chronic fatigue that does not meet the definition of CFS/ME. Nested sample collection (sample collection only for this application). Our patient group has emphasised the fundamental importance of better understanding of the basic physiological and pathophysiological mechanisms in the generation of chronic fatigue. We will take blood samples from patients who are happy opt in to sampling at baseline, 2 weeks and 6 months for future analysis (for which we will apply to the MRC) Sample size. 100 participants in each of our three clinical groups should be sufficient to estimate the duration of fatigue with 95% confidence intervals of +/- 0.2 SD (approximately 1 week) or detect a difference in duration of fatigue between groups of 0.4 SD ( approximately 2 weeks). For proportions we will have less precision but assuming the development of CFS/ME is likely for 5% (in a lower risk group which we anticipate the other group may be) we will have sufficient precision to estimate this within +/-4% i.e. to be reasonably sure the true figure is not much higher at 10% (which is where we anticipate the estimate of the glandular fever group will be). Feasibility. To recruit another 200 individuals i.e. over and above the number we anticipate being able to recruit from the pump priming grant from SPCR we will need to go to more practices (we anticipate another 5-10) which will be possible if we employ an RA for 3 days instead of 1 and paying for CLRN nurse time to support recruitment in practices.

Lay abstract: Our overarching aims are: 1) To develop and validate a clinical scoring system in patients presenting with acute fatigue which will help predict the development of chronic fatigue (lasting 6 months or more) or Chronic Fatigue Syndrome/ myalgic encephalomyelitis (CFS/ME). 2) To modify an existing more intensive intervention for chronic fatigue, in order to help patients with acute fatigue, and which is suitable for use by trained CBT (cognitive behavioural therapy) therapists. 3) To develop an internet version of the intervention that could also be used by practice nurses as a briefer intervention in supporting patients with acute fatigue. 4) To assess whether the intensive or briefer interventions are effective and cost effective in reducing the duration of acute fatigue among patients at risk of Chronic fatigue or CFS/ME Fatigue is one of the most intrusive but often hidden symptoms, with patients often not telling their doctors about it. The longer terms aims of this research, should a future Programme grant be awarded, are to try and better understand and predict which patients with short term ( acute ) fatigue go on to develop chronic fatigue or CFS/ME. We also hope to show whether helping patients manage acute fatigue symptoms using internet based support helps shorten the duration of fatigue. However, preliminary research is needed before full funding can be justified. The current grant will enable us to explore how long fatigue lasts in the different groups of fatigue presenting in primary care. To do this we aim to recruit 100 individuals with acute fatigue in each of three groups: those with fatigue after glandular fever, after other infections, or where no obvious infection occurred. This will allow us to decide which groups of patients would be suitable to include in the proposed future larger study. The grant will also enable us to do sufficient intervention development work based on the existing intervention, which has been shown to helps patient with chronic fatigue who have multiple sclerosis, and see if it can be applied to patients with acute fatigue. We will do this by collecting feedback on our draft patient intervention materials - presented as web pages once they have been created, or paper-based format. In depth interviews with up to 15 patients will explore attitudes to fatigue and physical activity, consider feasibility and process issues, and most importantly find out what people think of the intervention materials - particularly their immediate reactions to the materials. The research is a multicentre collaboration lead by Southampton University and the team includes a very broad range of study and condition expertise necessary to successfully complete the research. There are no major ethical issues involved in this research.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFECTION;DISPUTED AETIOLOGY AND OTHER