Detailed statistical analysis plan for a cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP), a novel school-based intervention to prevent obesity in school children

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: The Healthy Lifestyles Programme (HeLP) trial is being conducted to determine whether a novel school-based intervention is effective and cost-effective in preventing obesity in 9-10 year-old children. This article describes the detailed statistical analysis plan for the HeLP trial, including an amendment (and rationale for amendment) made to originally planned sensitivity analyses. METHODS AND DESIGN: The HeLP trial is a definitive, pragmatic, superiority, cluster randomised controlled trial with two parallel groups and blinded outcome assessment. This update article describes in detail (1) the primary and secondary outcomes, (2) the statistical analysis principles (including which children will be included in each analysis, how the clustered nature of the study design will be accounted for, which covariates will be included in each analysis, how the results will be presented), (3) planned sensitivity analyses, planned subgroup analyses and planned adherence-adjusted analyses for the primary outcome, (4) planned analyses for the secondary outcomes and (e) planned longitudinal analyses. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) register: ISRCTN15811706 . Registered on 1 May 2012.The definitive trial of HeLP is funded by the UK National Institute for Health Research (NIHR) Public Health Research Programme (10/3010/01) and a full report will be published on the NIHR website. KW and JL are partially supported by PenCLAHRC, the National Institute for Health Research (NIHR) CLAHRC for the Southwest Peninsul

Community-based Rehabilitation Training after stroke: Protocol of a pilot randomised controlled trial (ReTrain)

Introduction: The Rehabilitation Training (ReTrain) intervention aims to improve functional mobility, adherence to poststroke exercise guidelines and quality of life for people after stroke. A definitive randomised controlled trial (RCT) is required to assess the clinical and cost-effectiveness of ReTrain, which is based on Action for Rehabilitation from Neurological Injury (ARNI). The purpose of this pilot study is to assess the feasibility of such a definitive trial and inform its design. Methods and analysis: A 2-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed-methods process evaluation and economic evaluation. 48 participants discharged from clinical rehabilitation despite residual physical disability will be individually randomised 1:1 to ReTrain (25 sessions) or control (exercise advice booklet). Outcome assessment at baseline, 6 and 9 months include Rivermead Mobility Index; Timed Up and Go Test; modified Patient-Specific Functional Scale; 7-day accelerometry; Stroke Self-efficacy Questionnaire, exercise diary, Fatigue Assessment Scale, exercise beliefs and self-efficacy questionnaires, SF-12, EQ-5D-5L, Stroke Quality of Life, Carer Burden Index and Service Receipt Inventory. Feasibility, acceptability and process outcomes include recruitment and retention rates; with measurement burden and trial experiences being explored in qualitative interviews (20 participants, 3 intervention providers). Analyses include descriptive statistics, with 95% CI where appropriate; qualitative themes; intervention fidelity from videos and session checklists; rehearsal of health economic analysis. Ethics and dissemination: National Health Service (NHS) National Research Ethics Service approval granted in April 2015; recruitment started in June. Preliminary studies suggested low risk of serious adverse events; however (minor) falls, transitory muscle soreness and high levels of postexercise fatigue are expected. Outputs include pilot data to inform whether to proceed to a definitive RCT and support a funding application; finalised Trainer and Intervention Delivery manuals for multicentre replication of ReTrain; presentations at conferences, public involvement events; internationally recognised peer-reviewed journal publications, open access sources and media releases

Randomised controlled trial of an augmented exercise referral scheme using web-based behavioural support for inactive adults with chronic health conditions: the e-coachER trial.

OBJECTIVE: To determine whether adding web-based support (e-coachER) to an exercise referral scheme (ERS) increases objectively assessed physical activity (PA). DESIGN: Multicentre trial with participants randomised to usual ERS alone (control) or usual ERS plus e-coachER (intervention). SETTING: Primary care and ERS in three UK sites from 2015 to 2018. PARTICIPANTS: 450 inactive ERS referees with chronic health conditions. INTERVENTIONS: Participants received a pedometer, PA recording sheets and a user guide for the web-based support. e-coachER interactively encouraged the use of the ERS and other PA options. MAIN OUTCOME MEASURES: Primary and key secondary outcomes were: objective moderate-to-vigorous PA (MVPA) minutes (in ≥10 min bouts and without bouts), respectively, after 12 months. Secondary outcomes were: other accelerometer-derived and self-reported PA measures, ERS attendance, EQ-5D-5L, Hospital Anxiety and Depression Scale and beliefs about PA. All outcomes were collected at baseline, 4 and 12 months. Primary analysis was an intention to treat comparison between intervention and control arms at 12-month follow-up. RESULTS: There was no significant effect of the intervention on weekly MVPA at 12 months between the groups recorded in ≥10 min bouts (mean difference 11.8 min of MVPA, 95% CI: -2.1 to 26.0; p=0.10) or without bouts (mean difference 13.7 min of MVPA, 95% CI: -26.8 to 54.2; p=0.51) for 232 participants with usable data. There was no difference in the primary or secondary PA outcomes at 4 or 12 months. CONCLUSION: Augmenting ERS referrals with web-based behavioural support had only a weak, non-significant effect on MVPA. TRIAL REGISTRATION NUMBER: ISRCTN15644451

Refined saddle-point preconditioners for discretized Stokes problems

This paper is concerned with the implementation of efficient solution algorithms for elliptic problems with constraints. We establish theory which shows that including a simple scaling within well-established block diagonal preconditioners for Stokes problems can result in significantly faster convergence when applying the preconditioned MINRES method. The codes used in the numerical studies are available online

Optoelectronics with electrically tunable PN diodes in a monolayer dichalcogenide

One of the most fundamental devices for electronics and optoelectronics is the PN junction, which provides the functional element of diodes, bipolar transistors, photodetectors, LEDs, and solar cells, among many other devices. In conventional PN junctions, the adjacent p- and n-type regions of a semiconductor are formed by chemical doping. Materials with ambipolar conductance, however, allow for PN junctions to be configured and modified by electrostatic gating. This electrical control enables a single device to have multiple functionalities. Here we report ambipolar monolayer WSe2 devices in which two local gates are used to define a PN junction exclusively within the sheet of WSe2. With these electrically tunable PN junctions, we demonstrate both PN and NP diodes with ideality factors better than 2. Under excitation with light, the diodes show photodetection responsivity of 210 mA/W and photovoltaic power generation with a peak external quantum efficiency of 0.2%, promising numbers for a nearly transparent monolayer sheet in a lateral device geometry. Finally, we demonstrate a light-emitting diode based on monolayer WSe2. These devices provide a fundamental building block for ubiquitous, ultra-thin, flexible, and nearly transparent optoelectronic and electronic applications based on ambipolar dichalcogenide materials.Comment: 14 pages, 4 figure

Amp-PCR: Combining a Random Unbiased Phi29-Amplification with a Specific Real-Time PCR, Performed in One Tube to Increase PCR Sensitivity

In clinical situations where a diagnostic real-time PCR assay is not sensitive enough, leading to low or falsely negative results, or where detection earlier in a disease progression would benefit the patient, an unbiased pre-amplification prior to the real-time PCR could be beneficial. In Amp-PCR, an unbiased random Phi29 pre-amplification is combined with a specific real-time PCR reaction. The two reactions are separated physically by a wax-layer (AmpliWax®) and are run in sequel in the same sealed tube. Amp-PCR can increase the specific PCR signal at least 100×106-fold and make it possible to detect positive samples normally under the detection limit of the specific real-time PCR. The risk of contamination is eliminated and Amp-PCR could replace nested-PCR in situations where increased sensitivity is needed e.g. in routine PCR diagnostic analysis. We show Amp-PCR to work on clinical samples containing circular and linear viral dsDNA genomes, but can work well on DNA of any origin, both from non-cellular (virus) and cellular sources (bacteria, archae, eukaryotes)

A case of muscular bridge resulting in myocardial infraction following heavy effort: a case report

Muscular bridge (MB) is transient systolic coronary blockage occurring due to exposure of a portion of epicardial coronary arteries to compression during systole as a result of tunneling into the myocardium. Although rare, these patients may develop angina pectoris, severe arrhythmia and myocardial infraction (MI). A 30-year-old male patient presented to the emergency with severe pain with an onset at the front part of the chest followed by spreading to the back and arms, during a football match. The investigations performed revealed anterior wall infraction and thus thrombolytic treatment was administered. Patient's history was normal except for smoking. The patient was detected to play football occasionally since his childhood; however, we learnt that he had started playing without warm-up exercises at the last football match. Coronary angiography detected a lesion with an onset in the left anterior descending artery following the 1st diagonal and extending to the 2nd diagonal and exhibiting a significant contraction during systole. The patient was considered to have myocardial infraction secondary to myocardial bridge. Sudden deaths frequently occur in competitive sports requiring heavy effort