343 research outputs found

    Does a Healthy Weight Body Mass Index at Onset of Idiopathic Intracranial Hypertension Change the Outcomes? A United Kingdom Prospective Cohort Study

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    Idiopathic intracranial hypertension (IIH) predominantly affects reproductive-aged females with obesity. However, the prevalence and impact of a healthy weight body mass index (BMI) at disease presentation is not known. This study aimed to evaluate the visual and headache outcomes stratified by the presenting BMI. This was a longitudinal prospective cohort study (IIH Life) based on a tertiary neuro-ophthalmology IIH service, University Hospitals Birmingham NHS Trust, United Kingdom, recruiting consecutive patients living with IIH between 2012 and 2021. Those with a presenting BMI were included. The outcome measures included visual outcomes of LogMAR visual acuity, Humphrey visual field perimetric mean deviation (PMD), optical coherence tomography (OCT) measurements, and headache outcomes of frequency, severity, and Headache Impact Test-6 score. Three hundred seventy-five people with IIH and a documented baseline BMI. About 3.7% of the entire cohort had a healthy weight BMI at IIH presentation and 15.5% BMI < 30 kg/m2. The baseline PMD was worse in patients without obesity; however, OCT papilloedema measures were similar. The presence of obesity was associated with a small but significant greater worsening in visual acuity but slower macular ganglion cell layer loss. There was no impact on PMD or papilloedema prognosis related to baseline obesity. The headache outcomes showed heterogeneity, with worse baseline headache frequency in patients with obesity. No BMI group was associated with worse headache outcomes. Patients with a healthy weight BMI or those without obesity at baseline make up a small proportion of IIH patients. BMI at presentation does not appear to influence long-term visual or headache outcomes

    Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial

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    Simple SummaryPatients with medulloblastoma receive treatment according to a risk stratification, which is a combination of clinical and biological factors. To date there have been a limited number of trials for high-risk disease in children older than 3 years, with a wide range of treatment philosophies that usually involve higher doses of radiotherapy delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, to date, trials in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international, biomarker-driven, randomised clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens.AbstractMedulloblastoma patients receive adapted therapies stratified according to their risk-profile. Favourable, standard, and high disease-risk groups are each defined by the status of clinical and pathological risk factors, alongside an evolving repertoire of diagnostic and prognostic biomarkers. Medulloblastoma clinical trials in Europe are coordinated by the International Society for Paediatric Oncology (SIOP-Europe) brain tumour group. Favourable and standard-risk patients are eligible for the SIOP-PNET5-MB clinical trial protocol. In contrast, therapies for high-risk disease worldwide have, to date, encompassed a range of different treatment philosophies, with no clear consensus on approach. Higher radiotherapy doses are typically deployed, delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, trials to date in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international biomarker-driven, randomised, clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens. The HR-MB patient population is molecularly and clinically defined, and upfront assessments incorporate a standardised central review of molecular pathology, radiology, and radiotherapy quality assurance. Secondary objectives include the assessment of (i) novel therapies within an upfront ‘window’ and (ii) therapy-associated neuropsychology, toxicity, and late effects, alongside (iii) the collection of materials for comprehensive integrated studies of biological determinants within the SIOP-HR-MB cohort

    X-ray Variability and Evidence for Pulsations from the Unique Radio Pulsar/X-ray Binary Transition Object FIRST J102347.6+003841

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    We report on observations of the unusual neutron-star binary system FIRST J102347.6+003841 carried out using the XMM-Newton satellite. This system consists of a radio millisecond pulsar in an 0.198-day orbit with a ~0.2 solar-mass Roche-lobe-filling companion, and appears to have had an accretion disk in 2001. We observe a hard power-law spectrum (\Gamma = 1.26(4)) with a possible thermal component, and orbital variability in X-ray flux and possibly hardness of the X-rays. We also detect probable pulsations at the pulsar period (single-trial significance ~4.5 sigma from an 11(2)% modulation), which would make this the first system in which both orbital and rotational X-ray pulsations are detected. We interpret the emission as a combination of X-rays from the pulsar itself and from a shock where material overflowing the companion meets the pulsar wind. The similarity of this X-ray emission to that seen from other millisecond pulsar binary systems, in particular 47 Tuc W (PSR J0024-7204W) and PSR J1740-5340, suggests that they may also undergo disk episodes similar to that seen in J1023 in 2001.Comment: 14 pages, 5 figures, 1 table; accepted to Ap

    Chandra Observation of the Globular Cluster NGC 6440 and the Nature of Cluster X-ray Luminosity Functions

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    As part of our campaign to determine the nature of the various source populations of the low-luminosity globular cluster X-ray sources, we have obtained a Chandra X-ray Observatory ACIS-S3 image of the globular cluster NGC 6440. We detect 24 sources to a limiting luminosity of ~2 times 10^31 erg/s (0.5-2.5keV) inside the cluster's half-mass radius, all of which lie within ~2 core radii of the cluster center. We also find excess emission in and around the core which could be due to unresolved point sources. Based upon X-ray luminosities and colors, we conclude that there are 4-5 likely quiescent low-mass X-ray binaries and that most of the other sources are cataclysmic variables. We compare these results to Chandra results from other globular clusters and find the X-ray luminosity functions differ among the clusters.Comment: 9 pages, 4 figures, accepted by ApJ, minor changes, added table of clusters' physical parameter

    Early phase clinical trials extension to the guidelines for the content of statistical analysis plans

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    This paper reports guidelines for the content of statistical analysis plans for early phase clinical trials, ensuring specification of the minimum reporting analysis requirements, by detailing extensions (11 new items) and modifications (25 items) to existing guidance after a review by various stakeholders

    Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis

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    INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757
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