Treatment of fatigue with physical activity and behavioural change support in vasculitis: Study protocol for an open-label randomised controlled feasibility study

© 2018 Author(s) (or their employer(s)). Introduction Fatigue is a major cause of morbidity, limiting quality of life, in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The aetiology of fatigue is multifactorial; biological and psychosocial mediators, such as sleep deprivation, pain and anxiety and depression, are important and may be improved by increasing physical activity. Current self-management advice is based on expert opinion and is poorly adhered to. This study aims to investigate the feasibility of increasing physical activity using a programme of direct contact and telephone support, to provide patient education, encourage behaviour self-monitoring and the development of an individual change plan with defined goals and feedback to treat fatigue compared with standard of care to inform the design of a large randomised controlled trial to test the efficacy and cost effectiveness of this programme. Methods and analysis Patients with AAV and significant levels of fatigue (patient self-report using multidimensional fatigue index score questionnaire ≥14) will be randomised in a 1:1 ratio to the physical activity programme supported by behavioural change techniques or standard of care. The intervention programme will consist of 8 visits of supervised activity sessions and 12 telephone support calls over 12 weeks with the aim of increasing physical activity to the level advised by government guidelines. Assessment visits will be performed at baseline, 12, 24 and 52 weeks. The study will assess the feasibility of recruitment, retention, the acceptability, adherence and safety of the intervention, and collect data on various assessment tools to inform the design of a large definitive trial. A nested qualitative study will explore patient experience of the trial through focus groups or interviews. Ethics and dissemination All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, patient networks and academic publications

Management of fatigue with physical activity and behavioural change support in vasculitis: A feasibility study

OBJECTIVE: Patients with ANCA-associated vasculitis (AAV) experience high levels of fatigue, despite disease remission. This study assessed the feasibility and acceptability of a definitive randomized controlled trial of a behavioural-based physical activity intervention to support fatigue self-management in AAV patients. METHODS: AAV patients in disease remission with fatigue (Multidimensional Fatigue Inventory-20 general fatigue domain ≥14) were randomly allocated to intervention or standard care in this single-centre open-label randomized controlled feasibility study. The intervention lasted 12 weeks and comprised eight face-to-face physical activity sessions with a facilitator and 12 weekly telephone calls. Participants were encouraged to monitor their physical activity using a tracker device (Fitbit). Standard care involved sign-posting to fatigue websites. The primary outcome was feasibility of a phase III trial assessed against three stop/go traffic light criteria, (recruitment, intervention adherence and study withdrawal). A qualitative study assessed participant views about the intervention. RESULTS: A total of 248 patients were screened and 134 were eligible to participate (54%). Stop/go criteria were amber for recruitment; 43/134 (32%, 95% CI: 24, 40) eligible participants randomized, amber for adherence; 73% of participants attended all eight physical activity sessions, but only 11/22 (50%, 95% CI: 29, 71%) completed the intervention as per the intended schedule, and green for study withdrawal; 2/43 participants withdrew before 24 weeks (5%, 95% CI: 0, 11). Qualitative results suggested the intervention was acceptable. CONCLUSION: This study suggests a behavioural-based physical activity intervention targeting fatigue self-management was acceptable to patients with AAV, although recruitment and protocol adherence will need modification prior to a definitive trial. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11929227

Supplementary information files for Management of fatigue with physical activity and behavioural change support in vasculitis: a feasibility study

OBJECTIVE: Patients with ANCA-associated vasculitis (AAV) experience high levels of fatigue, despite disease remission. This study assessed the feasibility and acceptability of a definitive randomized controlled trial of a behavioural-based physical activity intervention to support fatigue self-management in AAV patients. METHODS: AAV patients in disease remission with fatigue (Multidimensional Fatigue Inventory-20 general fatigue domain ≥14) were randomly allocated to intervention or standard care in this single-centre open-label randomized controlled feasibility study. The intervention lasted 12 weeks and comprised eight face-to-face physical activity sessions with a facilitator and 12 weekly telephone calls. Participants were encouraged to monitor their physical activity using a tracker device (Fitbit). Standard care involved sign-posting to fatigue websites. The primary outcome was feasibility of a phase III trial assessed against three stop/go traffic light criteria, (recruitment, intervention adherence and study withdrawal). A qualitative study assessed participant views about the intervention. RESULTS: A total of 248 patients were screened and 134 were eligible to participate (54%). Stop/go criteria were amber for recruitment; 43/134 (32%, 95% CI: 24, 40) eligible participants randomized, amber for adherence; 73% of participants attended all eight physical activity sessions, but only 11/22 (50%, 95% CI: 29, 71%) completed the intervention as per the intended schedule, and green for study withdrawal; 2/43 participants withdrew before 24 weeks (5%, 95% CI: 0, 11). Qualitative results suggested the intervention was acceptable. CONCLUSION: This study suggests a behavioural-based physical activity intervention targeting fatigue self-management was acceptable to patients with AAV, although recruitment and protocol adherence will need modification prior to a definitive trial. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11929227

Management of fatigue with physical activity and behavioural change support in vasculitis: a feasibility study

OBJECTIVE: Patients with ANCA-associated vasculitis (AAV) experience high levels of fatigue, despite disease remission. This study assessed the feasibility and acceptability of a definitive randomized controlled trial of a behavioural-based physical activity intervention to support fatigue self-management in AAV patients. METHODS: AAV patients in disease remission with fatigue (Multidimensional Fatigue Inventory-20 general fatigue domain ≥14) were randomly allocated to intervention or standard care in this single-centre open-label randomized controlled feasibility study. The intervention lasted 12 weeks and comprised eight face-to-face physical activity sessions with a facilitator and 12 weekly telephone calls. Participants were encouraged to monitor their physical activity using a tracker device (Fitbit). Standard care involved sign-posting to fatigue websites. The primary outcome was feasibility of a phase III trial assessed against three stop/go traffic light criteria, (recruitment, intervention adherence and study withdrawal). A qualitative study assessed participant views about the intervention. RESULTS: A total of 248 patients were screened and 134 were eligible to participate (54%). Stop/go criteria were amber for recruitment; 43/134 (32%, 95% CI: 24, 40) eligible participants randomized, amber for adherence; 73% of participants attended all eight physical activity sessions, but only 11/22 (50%, 95% CI: 29, 71%) completed the intervention as per the intended schedule, and green for study withdrawal; 2/43 participants withdrew before 24 weeks (5%, 95% CI: 0, 11). Qualitative results suggested the intervention was acceptable. CONCLUSION: This study suggests a behavioural-based physical activity intervention targeting fatigue self-management was acceptable to patients with AAV, although recruitment and protocol adherence will need modification prior to a definitive trial. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11929227

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease