130 research outputs found

    The Sweep of Indiana History

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    The Sweep of Indiana History

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    Successful recruitment to trials : findings from the SCIMITAR+ Trial

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    BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. RESULTS: Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment

    Unified View of Scaling Laws for River Networks

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    Scaling laws that describe the structure of river networks are shown to follow from three simple assumptions. These assumptions are: (1) river networks are structurally self-similar, (2) single channels are self-affine, and (3) overland flow into channels occurs over a characteristic distance (drainage density is uniform). We obtain a complete set of scaling relations connecting the exponents of these scaling laws and find that only two of these exponents are independent. We further demonstrate that the two predominant descriptions of network structure (Tokunaga's law and Horton's laws) are equivalent in the case of landscapes with uniform drainage density. The results are tested with data from both real landscapes and a special class of random networks.Comment: 14 pages, 9 figures, 4 tables (converted to Revtex4, PRE ref added

    FES-UPP: A Flexible Functional Electrical Stimulation System to Support Upper Limb Functional Activity Practice

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    There is good evidence supporting highly intensive, repetitive, activity-focused, voluntary-initiated practice as a key to driving recovery of upper limb function following stroke. Functional electrical stimulation (FES) offers a potential mechanism to efficiently deliver this type of therapy, but current commercial devices are too inflexible and/or insufficiently automated, in some cases requiring engineering support. In this paper, we report a new, flexible upper limb FES system, FES-UPP, which addresses the issues above. The FES-UPP system consists of a 5-channel stimulator running a flexible FES finite state machine (FSM) controller, the associated setup software that guides therapists through the setup of FSM controllers via five setup stages, and finally the Session Manager used to guide the patient in repeated attempts at the activities(s) and provide feedback on their performance. The FSM controller represents a functional activity as a sequence of movement phases. The output for each phase implements the stimulations to one or more muscles. Progression between movement phases is governed by user-defined rules. As part of a clinical investigation of the system, nine therapists used the FES-UPP system to set up FES-supported activities with twenty two patient participants with impaired upper-limbs. Therapists with little or no FES experience and without any programming skills could use the system in their usual clinical settings, without engineering support. Different functional activities, tailored to suit the upper limb impairment levels of each participant were used, in up to 8 sessions of FES-supported therapy per participant. The efficiency of delivery of the therapy using FES-UPP was promising when compared with published data on traditional face-face therapy. The FES-UPP system described in this paper has been shown to allow therapists with little or no FES experience and without any programming skills to set up state-machine FES controllers bespoke to the patient’s impairment patterns and activity requirements, without engineering support. The clinical results demonstrated that the system can be used to efficiently deliver high intensity, activity-focused therapy. Nevertheless, further work to reduce setup time is still required

    Does home oxygen therapy (HOT) in addition to standard care reduce disease severity and improve symptoms in people with chronic heart failure? A randomised trial of home oxygen therapy for patients with chronic heart failure

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    Background: Home oxygen therapy (HOT) is commonly used for patients with severe chronic heart failure(CHF) who have intractable breathlessness. There is no trial evidence to support its use.Objectives: To detect whether or not there was a quality-of-life benefit from HOT given as long-termoxygen therapy (LTOT) for at least 15 hours per day in the home, including overnight hours, comparedwith best medical therapy (BMT) in patients with severely symptomatic CHF.Design: A pragmatic, two-arm, randomised controlled trial recruiting patients with severe CHF. It includeda linked qualitative substudy to assess the views of patients using home oxygen, and a free-standingsubstudy to assess the haemodynamic effects of acute oxygen administration.Setting: Heart failure outpatient clinics in hospital or the community, in a range of urban andrural settings.Participants: Patients had to have heart failure from any aetiology, New York Heart Association (NYHA)class III/IV symptoms, at least moderate left ventricular systolic dysfunction, and be receiving maximallytolerated medical management. Patients were excluded if they had had a cardiac resynchronisation therapydevice implanted within the past 3 months, chronic obstructive pulmonary disease fulfilling the criteria forLTOT or malignant disease that would impair survival or were using a device or medication that wouldimpede their ability to use LTOT.Interventions: Patients received BMT and were randomised (unblinded) to open-label LTOT, prescribed for15 hours per day including overnight hours, or no oxygen therapy.Main outcome measures: The primary end point was quality of life as measured by the Minnesota Livingwith Heart Failure (MLwHF) questionnaire score at 6 months. Secondary outcomes included assessing theeffect of LTOT on patient symptoms and disease severity, and assessing its acceptability to patientsand carers.Results: Between April 2012 and February 2014, 114 patients were randomised to receive either LTOT orBMT. The mean age was 72.3 years [standard deviation (SD) 11.3 years] and 70% were male. Ischaemicheart disease was the cause of heart failure in 84%; 95% were in NYHA class III; the mean left ventricularejection fraction was 27.8%; and the median N-terminal pro-B-type natriuretic hormone was 2203 ng/l.The primary analysis used a covariance pattern mixed model which included patients only if they provided datafor all baseline covariates adjusted for in the model and outcome data for at least one post-randomisationtime point (n = 102: intervention, n = 51; control, n = 51). There was no difference in the MLwHF questionnairescore at 6 months between the two arms [at baseline the mean score was 54.0 (SD 18.4) for LTOT and54.0 (SD 17.9) for BMT; at 6 months the mean score was 48.1 (SD 18.5) for LTOT and 49.0 (SD 20.2) forBMT; adjusted mean difference –0.10, 95% confidence interval (CI) –6.88 to 6.69; p = 0.98]. At 3 months,the adjusted mean MLwHF questionnaire score was lower in the LTOT group (–5.47, 95% CI –10.54 to–0.41; p = 0.03) and breathlessness scores improved, although the effect did not persist to 6 months.There was no effect of LTOT on any secondary measure. There was a greater number of deaths in the BMTarm (n = 12 vs. n = 6). Adherence was poor, with only 11% of patients reporting using the oxygenas prescribed.Conclusions: Although the study was significantly underpowered, HOT prescribed for 15 hours per dayand subsequently used for a mean of 5.4 hours per day has no impact on quality of life as measured bythe MLwHF questionnaire score at 6 months. Suggestions for future research include (1) a trial of patientswith severe heart failure randomised to have emergency oxygen supply in the house, supplied by cylindersrather than an oxygen concentrator, powered to detect a reduction in admissions to hospital, and (2) astudy of bed-bound patients with heart failure who are in the last few weeks of life, powered to detectchanges in symptom severity.Trial registration: Current Controlled Trials ISRCTN60260702.Funding: This project was funded by the NIHR Health Technology Assessment programme and will bepublished in full in Health Technology Assessment; Vol. 19, No. 75. See the NIHR Journals Library websitefor further project information

    A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

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    Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

    Cohort Profile: Post-Hospitalisation COVID-19 (PHOSP-COVID) study

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    Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

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    Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study