Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. METHODS AND ANALYSIS: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. ETHICS AND DISSEMINATION: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110

Community Nurses' Judgement for the Management of Venous Leg Ulceration: A Judgement Analysis

Background: Nurses caring for the large numbers of people with leg ulceration play a key role in promoting quality in health via their diagnostic and treatment clinical judgements. In the UK, audit evidence suggests that the quality of these judgements is often sub optimal. Misdiagnosis and incorrect treatment choices are likely to affect healing rates, patients’ quality of life, patient safety and healthcare costs. Objectives: To explore the diagnostic judgements and treatment choices of UK community nurses managing venous leg ulceration. Design: A judgement analysis based on Brunswik's psychological Lens Model theory. Setting: UK community and primary care nursing services. Participants: 18 community generalist nurses working in district (home) nursing teams and general practitioner services and 18 community tissue viability specialist nurses. Methods: During 2011 and 2012, 36 nurses made diagnostic judgements and treatment choices in response to 110 clinical scenarios. Scenarios were generated from real patient cases and presented online using text and wound photographs. The consensus judgements of a panel of nurses with advanced knowledge of leg ulceration judged the same scenarios and provided a standard against which to compare the participants. Correlations and logistic regression models were constructed to generate various indices of judgement and decision “performance”: accuracy (Ra), consistency (Rs) and information use (G) and uncertainty (Re). Results: Taking uncertainty into account, nurses could theoretically have achieved a diagnostic level of accuracy of 0.63 but the nurses only achieved an accuracy of 0.48. For the treatment judgement (whether applying high compression was warranted) nurses could have achieved an accuracy of 0.88 but achieved only an accuracy of 0.49. This may have been due to the nurses giving insufficient weight to the diagnostic cues of medical history and appearance of the leg and ulcer and insufficient weight to the treatment cues of type of leg ulcer and pain. Conclusion: Clinical judgements and decisions made by nurses managing leg ulceration are complex and uncertain and some of the variability in judgements and choices can be explained by the ways in which nurses process the information and handle the uncertainties, present in clinical encounters

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

The effect of low-dye taping on rearfoot motion and plantar pressure during the stance phase of gait

Background: Low-dye (LD) taping is commonly used to reduce rearfoot pronation. No studies have previously investigated the effectiveness of LD taping using both plantar pressure distribution (F-Scan) and 3-D (CODA) analysis of rearfoot motion. Methods: 20 healthy subjects with a navicular drop test exceeding 10 mm participated in the study. T tests were used to determine whether significant (p < 0.05) differences in plantar pressure and rearfoot motion occurred with LD taping. Results: LD taping resulted in statistically significant increases in peak plantar pressure in the lateral midfoot (p = 0.000), along with significant decreases in pressure in the medial forefoot (p = 0.014), and the medial (p = 0.000) and lateral hindfoot (p = 0.007). No significant changes occurred in the medial midfoot (p = 0.794) or lateral forefoot (p = 0.654). When assessed using motion analysis, taping resulted in a statistically significant decrease in rearfoot pronation (p = 0.006), supination (p = 0.025) and total rearfoot range of motion (p = 0.000). The mean rearfoot position during stance was not significantly different however (p = 0.188). Conclusion: LD taping is associated with alterations in peak plantar pressure in the midfoot and forefoot that indicate reduced pronation with LD taping. However, LD taping appears to reduce both pronation and supination in the rearfoot, rather than simply reducing pronation, when assessed using 3D motion analysis. Therefore, it would appear that LD taping does indeed reduce pronation, by restricting rearfoot motion in general, rather than pronation specifically. The degree of change observed with LD taping was however very small, and further research is needed to clarify the clinical significance of these initial findings