Progressive functional exercise versus best practice advice for adults aged 50 years or over after ankle fracture: protocol for a pilot randomised controlled trial in the UK - the Ankle Fracture Treatment: Enhancing Rehabilitation (AFTER) study

Introduction Ankle fractures result in significant morbidity in adults, with prognosis worsening with increasing age. Previous trials have not found evidence supporting supervised physiotherapy sessions, but these studies have not focused on older adults or tailored the exercise interventions to the complex needs of this patient group. The Ankle Fracture Treatment: Enhancing Rehabilitation study is a pilot randomised controlled trial to assess feasibility of a later definitive trial comparing best-practice advice with progressive functional exercise for adults aged 50 years and over after ankle fracture. The main objectives are to assess: (i) patient engagement with the trial, measured by the participation rate of those eligible; (ii) establish whether the interventions are acceptable to participants and therapists, assessed by intervention adherence levels, participant interviews and a therapist focus group; (iii) participant retention in the trial, measured by the proportion of participants providing outcome data at 6 months; (iv) acceptability of measuring outcomes at 3 and 6 month follow-up. Methods and analysis A multicentre pilot randomised controlled trial with an embedded qualitative study. At least 48 patients aged 50 years and over with an ankle fracture requiring surgical management, or non-operative management by immobilisation for at least 4 weeks, will be recruited from a minimum of three National Health Service hospitals in the UK. Participants will be allocated 1:1 via a central web-based randomisation system to: (i) best-practice advice (one session of face-to-face self-management advice delivered by a physiotherapist and up to two optional additional sessions) or (ii) progressive functional exercise (up to six sessions of individual face-to-face physiotherapy). An embedded qualitative study will include one-to-one interviews with up to 20 participants and a therapist focus group. Ethics and dissemination Hampshire B Research Ethics Committee (18/SC/0281) gave approval on 2nd July 2018. Trial registration number ISRCTN1661233

Progressive exercise versus best practice advice for adults aged 50 years or over after ankle fracture: the AFTER pilot randomised controlled trial

Objective The aim of the Ankle Fracture Treatment: Enhancing Rehabilitation (AFTER) study, a multicentre external pilot parallel-group randomised controlled trial (RCT), was to assess feasibility of a definitive trial comparing rehabilitation approaches after ankle fracture. Setting Five UK National Health Service hospitals. Participants Participants were aged 50 years and over with an ankle fracture requiring immobilisation for at least 4 weeks. Interventions Participants were allocated 1:1 via a central web-based randomisation system to: (1) best practice advice (one session of physiotherapy, up to two optional additional advice sessions) or (2) progressive exercise (up to six sessions of physiotherapy). Primary outcome measures Feasibility: (1) participation rate, (2) intervention adherence and (3) retention. Results Sixty-one of 112 (54%) eligible participants participated, exceeding progression criteria for participation of 25%. Recruitment progression criteria was 1.5 participants per site per month and 1.4 was observed. At least one intervention session was delivered for 28/30 (93%) of best practice advice and 28/31 (90%) of progressive exercise participants, exceeding the 85% progression criteria. For those providing follow-up data, the proportion of participants reporting performance of home exercises in the best practice advice and the progressive exercise groups at 3 months was 20/23 (87%) and 21/25 (84%), respectively. Mean time from injury to starting physiotherapy was 74.1 days (95% CI 53.9 to 94.1 days) for the best practice advice and 72.7 days (95% CI 54.7 to 88.9) for the progressive exercise group. Follow-up rate (6-month Olerud and Molander Ankle Score) was 28/30 (93%) for the best practice advice group and 26/31 (84%) in the progressive exercise group with an overall follow-up rate of 89%. Conclusions This pilot RCT demonstrated that a definitive trial would be feasible. The main issues to address for a definitive trial are intervention modifications to enable earlier provision of rehabilitation and ensuring similar rates of follow-up in each group. Trial registration number ISRCTN16612336

Behaviour change physiotherapy intervention to increase physical activity following hip and knee replacement (PEP-TALK): study protocol for a pragmatic randomised controlled trial.

INTRODUCTION: While total hip replacement (THR) and total knee replacement (TKR) successfully reduce pain associated with chronic joint pathology, this infrequently translates into increased physical activity. This is a challenge given that over 50% of individuals who undergo these operations are physically inactive and have medical comorbidities such as hypertension, heart disease, diabetes and depression. The impact of these diseases can be reduced with physical activity. This trial aims to investigate the effectiveness of a behaviour change physiotherapy intervention to increase physical activity compared with usual rehabilitation after THR or TKR. METHODS AND ANALYSIS: The PEP-TALK trial is a multicentre, open-labelled, pragmatic randomised controlled trial. 260 adults who are scheduled to undergo a primary unilateral THR or TKR and are moderately inactive or inactive, with comorbidities, will be recruited across eight sites in England. They will be randomised post-surgery, prior to hospital discharge, to either six, 30 min weekly group-based exercise sessions (control), or the same six weekly, group-based, exercise sessions each preceded by a 30 min cognitive behaviour approach discussion group. Participants will be followed-up to 12 months by postal questionnaire. The primary outcome is the University of California, Los Angeles (UCLA) Physical Activity Score at 12 months. Secondary outcomes include: physical function, disability, health-related quality of life, kinesiophobia, perceived pain, self-efficacy and health resource utilisation. ETHICS AND DISSEMINATION: Research ethics committee approval was granted by the NRES Committee South Central (Oxford B - 18/SC/0423). Dissemination of results will be through peer-reviewed, scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN29770908

Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial

BACKGROUND: The antibacterial, anti-inflammatory, and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-to-moderate disease are not available. We assessed whether azithromycin is effective in reducing hospital admission in patients with mild-to-moderate COVID-19. METHODS: This prospective, open-label, randomised superiority trial was done at 19 hospitals in the UK. We enrolled adults aged at least 18 years presenting to hospitals with clinically diagnosed, highly probable or confirmed COVID-19 infection, with fewer than 14 days of symptoms, who were considered suitable for initial ambulatory management. Patients were randomly assigned (1:1) to azithromycin (500 mg once daily orally for 14 days) plus standard care or to standard care alone. The primary outcome was death or hospital admission from any cause over the 28 days from randomisation. The primary and safety outcomes were assessed according to the intention-to-treat principle. This trial is registered at ClinicalTrials.gov (NCT04381962) and recruitment is closed. FINDINGS: 298 participants were enrolled from June 3, 2020, to Jan 29, 2021. Three participants withdrew consent and requested removal of all data, and three further participants withdrew consent after randomisation, thus, the primary outcome was assessed in 292 participants (145 in the azithromycin group and 147 in the standard care group). The mean age of the participants was 45·9 years (SD 14·9). 15 (10%) participants in the azithromycin group and 17 (12%) in the standard care group were admitted to hospital or died during the study (adjusted OR 0·91 [95% CI 0·43-1·92], p=0·80). No serious adverse events were reported. INTERPRETATION: In patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death. Our findings do not support the use of azithromycin in patients with mild-to-moderate COVID-19. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford and Pfizer

Progressive exercise versus best practice advice for adults aged 50 years or over after ankle fracture: the AFTER pilot randomised controlled trial

This is the final version. Available from BMJ Publishing Group via the DOI in this record. Data are available upon reasonable request. Data sharing requests can be considered via contact with the corresponding author.OBJECTIVE: The aim of the Ankle Fracture Treatment: Enhancing Rehabilitation (AFTER) study, a multicentre external pilot parallel-group randomised controlled trial (RCT), was to assess feasibility of a definitive trial comparing rehabilitation approaches after ankle fracture. SETTING: Five UK National Health Service hospitals. PARTICIPANTS: Participants were aged 50 years and over with an ankle fracture requiring immobilisation for at least 4 weeks. INTERVENTIONS: Participants were allocated 1:1 via a central web-based randomisation system to: (1) best practice advice (one session of physiotherapy, up to two optional additional advice sessions) or (2) progressive exercise (up to six sessions of physiotherapy). PRIMARY OUTCOME MEASURES: Feasibility: (1) participation rate, (2) intervention adherence and (3) retention. RESULTS: Sixty-one of 112 (54%) eligible participants participated, exceeding progression criteria for participation of 25%. Recruitment progression criteria was 1.5 participants per site per month and 1.4 was observed. At least one intervention session was delivered for 28/30 (93%) of best practice advice and 28/31 (90%) of progressive exercise participants, exceeding the 85% progression criteria. For those providing follow-up data, the proportion of participants reporting performance of home exercises in the best practice advice and the progressive exercise groups at 3 months was 20/23 (87%) and 21/25 (84%), respectively. Mean time from injury to starting physiotherapy was 74.1 days (95% CI 53.9 to 94.1 days) for the best practice advice and 72.7 days (95% CI 54.7 to 88.9) for the progressive exercise group. Follow-up rate (6-month Olerud and Molander Ankle Score) was 28/30 (93%) for the best practice advice group and 26/31 (84%) in the progressive exercise group with an overall follow-up rate of 89%. CONCLUSIONS: This pilot RCT demonstrated that a definitive trial would be feasible. The main issues to address for a definitive trial are intervention modifications to enable earlier provision of rehabilitation and ensuring similar rates of follow-up in each group. TRIAL REGISTRATION NUMBER: ISRCTN16612336.National Institute for Health and Care Research (NIHR

Effects of temporarily suspending low- dose methotrexate treatment for 2 weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions: protocol for a multicentre randomised controlled trial and nested mechanistic substudy (Vaccine Response On/Off Methotrexate (VROOM) study)

Introduction It is unknown if a temporary break in long-term immune-suppressive treatment after vaccination against COVID-19 improves vaccine response. The objective of this study was to evaluate if a 2-week interruption in low-dose weekly methotrexate treatment after SARS-CoV-2 vaccine boosters enhances the immune response compared with continuing treatment in adults with autoimmune inflammatory conditions. Methods and analysis An open-label, pragmatic, prospective, parallel group, randomised controlled superiority trial with internal feasibility assessment and nested mechanistic substudy will be conducted in rheumatology and dermatology clinics in approximately 25 UK hospitals. The sample size is 560, randomised 1:1 to intervention and usual care arms. The main outcome measure is anti-spike receptor-binding domain (RBD) antibody level, collected at prebooster (baseline), 4 weeks (primary outcome) and 12 weeks (secondary outcome) post booster vaccination. Other secondary outcome measures are patient global assessments of disease activity, disease flares and their treatment, EuroQol 5- dimention 5-level (EQ-5D-5L), self-reported adherence with advice to interrupt or continue methotrexate, neutralising antibody titre against SARS-CoV-2 (mechanistic substudy) and oral methotrexate biochemical adherence (mechanistic substudy). Analysis of B-cell memory and T-cell responses at baseline and weeks 4 and 12 will be investigated subject to obtaining additional funding. The principal analysis will be performed on the groups as randomised (ie, intention to treat). The difference between the study arms in anti-spike RBD antibody level will be estimated using mixed effects model, allowing for repeated measures clustered within participants. The models will be adjusted for randomisation factors and prior SARS-CoV-2 infection status. Ethics and dissemination This study was approved by the Leeds West Research Ethics Committee and Health Research Authority (REC reference: 21/HRA/3483, IRAS 303827). Participants will be required to give written informed consent before taking part in the trial. Dissemination will be via peer review publications, newsletters and conferences. Results will be communicated to policymakers

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN