Getting Recovery Right After Neck Dissection (GRRAND-F): Mixed-methods feasibility study to design a pragmatic randomised controlled trial.

Objective: To determine the feasibility of a randomised controlled trial to estimate the effectiveness and cost-effectiveness of a rehabilitation intervention following neck dissection (ND) after head and neck cancer (HNC). Design: Two-arm, open, pragmatic, parallel, multicentre, randomised controlled feasibility trial. Setting: Two UK NHS hospitals. Participants: People who had HNC in whom a ND was part of their care. We excluded those with a life expectancy of six months or less, pre-existing, long-term neurological disease affecting the shoulder and cognitive impairment. Intervention: Usual care (standard care supplemented with a booklet on postoperative self-management) was received by all participants. The GRRAND intervention programme consisted of usual care plus up to six individual physiotherapy sessions including neck and shoulder range of motion and progressive resistance exercises, advice and education. Between sessions, participants were advised to complete a home exercise programme. Randomisation: 1:1 randomisation. Allocation was based on minimisation, stratified by hospital site and spinal accessory nerve sacrifice. It was not possible to mask treatment received. Main outcome measures: Primary: Participant recruitment, retention and fidelity to the study protocol and interventions from study participants and staff at six months post-randomisation (and 12 months for those reaching that time-point). Secondary: clinical measures of pain, function, physical performance, health-related quality of life, health utilisation and adverse events. Results: 36 participants were recruited and enrolled. The study achieved five of its six feasibility targets. These included consent - 70% of eligible participants were consented; intervention fidelity - 78% participants discharged completed the intervention sessions; contamination - none - no participants in the control arm received the GRRAND-F intervention and retention - 8% of participants were lost to follow-up. The only feasibility target that was not achieved was the recruitment target where only 36 of the planned 60 participants were recruited over 18 months. This was principally due to the COVID-19 pandemic which caused all research activity to be paused or reduced, with a subsequent reduction in. Conclusions: Based on the findings a full-trial can now be designed to better understand whether this proposed intervention is effective. Clinical Trial Registration: https://www.isrctn.com/ISRCTN1197999, identifier ISRCTN11979997.

Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: primary report from the HOPE-e randomised, placebo-controlled, feasibility study.

Background: Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of hormone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. Methods: The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40-65 years, for whom 1-10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. Findings: From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63-92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0·50 [95% CI 0·25-0·75]). The trial met the prespecified criteria for progression to a full trial. Interpretation: This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Funding: Research for Patient Benefit programme, National Institute for Health Research.

Randomised controlled trial of a behaviour change physiotherapy intervention to increase physical activity following hip and knee replacement: the PEP-TALK trial.

OBJECTIVE: To test the effectiveness of a behaviour change physiotherapy intervention to increase physical activity compared with usual rehabilitation after total hip replacement (THR) or total knee replacement (TKR). DESIGN: Multicentre, pragmatic, two-arm, open, randomised controlled, superiority trial. SETTING: National Health Service providers in nine English hospitals. PARTICIPANTS: 224 individuals aged ≥18 years, undergoing a primary THR or TKR deemed 'moderately inactive' or 'inactive'. INTERVENTION: Participants received either six, 30 min, weekly, group-based exercise sessions (usual care) or the same six weekly, group-based, exercise sessions each preceded by a 30 min cognitive behaviour discussion group aimed at challenging barriers to physical inactivity following surgery (experimental). RANDOMISATION AND BLINDING: Initial 75 participants were randomised 1:1 before changing the allocation ratio to 2:1 (experimental:usual care). Allocation was based on minimisation, stratifying on comorbidities, operation type and hospital. There was no blinding. MAIN OUTCOME MEASURES: Primary: University of California Los Angeles (UCLA) Activity Score at 12 months. Secondary: 6 and 12-month assessed function, pain, self-efficacy, kinesiophobia, psychological distress and quality of life. RESULTS: Of the 1254 participants assessed for eligibility, 224 were included (139 experimental: 85 usual care). Mean age was 68.4 years (SD: 8.7), 63% were women, 52% underwent TKR. There was no between-group difference in UCLA score (mean difference: -0.03 (95% CI -0.52 to 0.45, p=0.89)). There were no differences observed in any of the secondary outcomes at 6 or 12 months. There were no important adverse events in either group. The COVID-19 pandemic contributed to the reduced intended sample size (target 260) and reduced intervention compliance. CONCLUSIONS: There is no evidence to suggest attending usual care physiotherapy sessions plus a group-based behaviour change intervention differs to attending usual care physiotherapy alone. As the trial could not reach its intended sample size, nor a proportion of participants receive their intended rehabilitation, this should be interpreted with caution. TRIAL REGISTRATION NUMBER: ISRCTN29770908.

Getting Recovery Right After Neck Dissection (GRRAND-F): mixed-methods feasibility study to design a pragmatic randomised controlled trial protocol.

INTRODUCTION: We will evaluate the feasibility of a randomised controlled trial to estimate the effectiveness and cost-effectiveness of a rehabilitation intervention on pain, function and health-related quality of life following neck dissection (ND) after head and neck cancer (HNC). METHODS AND ANALYSIS: This is a pragmatic, multicentred, feasibility study. Participants are randomised to usual care (control) or usual care plus an individualised, rehabilitation programme (Getting Recovery Right After Neck Dissection, GRRAND intervention). Adults aged over 18 with HNC for whom ND is part of their care will be recruited from specialist clinics. Participants are randomised in 1:1 ratio using a web-based service. The target sample size is 60 participants. Usual care will be received by all participants during their postoperative inpatient stay consisting standard National Health Service care supplemented with a booklet advising on postoperative self-management strategies. The GRRAND intervention programme consists of usual care plus up to six individual physiotherapy sessions including neck and shoulder range of motion (ROM) and progressive resistance exercises, advice and education. Between sessions participants will be advised to complete a home exercise programme. The primary outcome is to determine recruitment and retention rates from study participants across sites. Outcomes will be measured at 6 and 12 months. Participants and physiotherapists will be invited to an optional qualitative interview at the completion of their involvement in the study. The target qualitative sample size is 15 participants and 12 physiotherapists. Interviews aim to further investigate the feasibility and acceptability of the intervention and to determine wider experiences of the study design and intervention from patient and physiotherapist perspectives. ETHICS AND DISSEMINATION: Ethical approval was given on 29 October 2019 (National Research Ethics Committee Number: 19/SC/0457). Results will be reported at conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN11979997. STATUS: Trial recruitment is ongoing and is expected to be completed by 30 August 2021.

Statistical analysis plan for a pragmatic phase III randomised controlled trial examining behaviour change physiotherapy intervention to increase physical activity following hip and knee replacements: the PEP-TALK trial.

BACKGROUND: Total hip (THR) and total knee replacements (TKR) are two highly successful orthopaedic procedures that reduce pain for people with osteoarthritis. Previous evidence suggests that physical activity, at best, remains the same pre- to post-operatively, and in some instances declines. The PEP-TALK trial evaluates the effects of a group-based, behaviour change intervention on physical activity following a THR or TKR. METHODS: PEP-TALK is an open, phase III, pragmatic, multi-centre, parallel, two-arm, two-way superiority randomised controlled trial investigating the effectiveness of usual care plus a behaviour change therapy compared with usual care alone following primary THR or TKR. The primary outcome is the UCLA Activity Score at 12 months post-randomisation which will be analysed using a linear mixed effects model. Secondary outcomes measured at 6 months and 12 months after randomisation include the UCLA Activity Score, Lower Extremity Functional Scale, Oxford Hip/Knee Score, Numerical Rating Scale for Pain, Generalised Self-Efficacy Scale, Tampa Scale for Kinesiophobia, Hospital Anxiety and Depression Scale, EuroQoL EQ-5D-5L index and EQ-VAS and complications or adverse events. Full details of the planned analysis approaches for the primary and secondary outcomes, as well as the planned sensitivity analyses to be undertaken due to the COVID-19 pandemic, are described here. The PEP-TALK study protocol has been published previously. DISCUSSION: This paper provides details of the planned statistical analyses for the PEP-TALK trial. This is aimed to reduce the risk of outcome reporting bias and enhance transparency in reporting. TRIAL REGISTRATION: International Standard Randomised Controlled Trials database, ISRCTN Number: 29770908 . Registered on October 2018.

Rehabilitation to enable recovery from COVID-19: a rapid systematic review.

OBJECTIVES: To establish the evidence for rehabilitation interventions tested in populations of patients admitted to ICU and critical care with severe respiratory illness, and consider whether the evidence is generalizable to patients with COVID-19. METHODS: The authors undertook a rapid systematic review. Medline (via OvidSP), CINAHL Complete (via EBSCOhost), Cochrane Library, Cochrane Database of Systematic Reviews and CENTRAL (via Wiley), Epistemonikos (via Epistemonikos.org), PEDro (via pedro.org.au) and OTseeker (via otseeker.com) searched to 7 May 2020. The authors included systematic reviews, RCTs and qualitative studies involving adults with respiratory illness requiring intensive care who received rehabilitation to enhance or restore resulting physical impairments or function. Data were extracted by one author and checked by a second. TIDier was used to guide intervention descriptions. Study quality was assessed using Critical Skills Appraisal Programme (CASP) tools. RESULTS: Six thousand nine hundred and three titles and abstracts were screened; 24 systematic reviews, 11 RCTs and eight qualitative studies were included. Progressive exercise programmes, early mobilisation and multicomponent interventions delivered in ICU can improve functional independence. Nutritional supplementation in addition to rehabilitation in post-ICU hospital settings may improve performance of activities of daily living. The evidence for rehabilitation after discharge from hospital following an ICU admission is inconclusive. Those receiving rehabilitation valued it, engendering hope and confidence. CONCLUSIONS: Exercise, early mobilisation and multicomponent programmes may improve recovery following ICU admission for severe respiratory illness that could be generalizable to those with COVID-19. Rehabilitation interventions can bring hope and confidence to individuals but there is a need for an individualised approach and the use of behaviour change strategies. Further research is needed in post-ICU settings and with those who have COVID-19. Registration: Open Science Framework https://osf.io/prc2y.