Publications by authors named "Bradbury C"

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation.

Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin.

Methods: Patients who received initial anticoagulation dosed consistently with randomization were included.

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Background: This paper describes and critically reflects on how children and young people (CYP) acted as public advisors to coproduce health information materials about Long Covid for younger audiences. This work was underpinned by the Lundy model, a framework which provides guidance on facilitating CYP to actively contribute to matters which affect them.

Methods: Coproduction activity sessions took place with CYP in schools as well as video conferences with a CYP stakeholder group and CYP with Long Covid.

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Background Stroke survivors are a population at increased risk of experiencing loneliness, thus exploring the effect of lockdown measures on stroke survivors is of paramount importance. We explored the personal experiences of loneliness among stroke survivors during lockdown in the COVID-19 pandemic and the lessons that can be learned from these experiences. Methods Seventeen stroke survivors from across the United Kingdom (10 females, 7 males; 45-83years old; M age =63.

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Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR).

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Background: Decisions about driving for individuals living with dementia (ILWD) can be challenging. There are limited evidence-based person-centred interventions in the United Kingdom that support decisions about transitioning to not driving or guidelines for developing decision aids for ILWD. This study aimed to understand the important features of a decision aid through the cultural adaptation of Australian dementia and driving decision aid (DDDA) for ILWD residing in the United Kingdom.

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Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA.

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Article Synopsis
  • Clinicians globally are managing research alongside their regular workloads, leading to the establishment of Clinical Trial Units (CTUs) that support high-quality Investigator Initiated Trials (IITs) and promote international standards.
  • The study aimed to identify the critical services that International Clinical Trial Center Network (ICN) members consider essential for effective clinical trial management, contributing to global harmonization.
  • Results indicated that services focused on quality management and coordination are prioritized, while operational services are viewed as less critical, suggesting CTUs should enhance their management expertise and training efforts for clinicians.
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Article Synopsis
  • The study aimed to evaluate the effectiveness of simvastatin in critically ill Covid-19 patients compared to a control group not receiving statins.
  • A total of 2684 patients were analyzed, showing a median of 11 organ support-free days in the simvastatin group versus 7 in the control group, with a high probability indicating simvastatin’s potential superiority.
  • However, the study was halted due to decreasing Covid-19 cases, and while simvastatin had some benefits, it also led to more reported serious adverse effects, such as elevated liver enzymes.
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Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.

Objective: To determine whether vitamin C improves outcomes for patients with COVID-19.

Design, Setting, And Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents.

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Regulatory B (Breg) cells are potentially implicated in the pathogenesis of immune thrombocytopenia (ITP). We analysed a prospective cohort of newly diagnosed steroid naïve ITP patients enrolled in the multicentre FLIGHT trial and found that the numbers of Bregs in their peripheral blood were similar to healthy controls. In contrast, Breg numbers were significantly reduced in ITP patients treated with systemic immunosuppression (glucocorticoids or mycophenolate mofetil).

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Aim: To determine the level of heterogeneity in delivery of computed tomography (CT) colonography services and develop a workforce calculator that accommodates the variation identified.

Materials And Methods: A national survey, based on the "WHO workforce indicators of staffing need", established activity standards for essential tasks in delivery of the service. From these data a workforce calculator was designed to guide the required staffing and equipment resource by service size.

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Article Synopsis
  • Overactivation of the renin-angiotensin system (RAS) could lead to worse outcomes for COVID-19 patients, prompting a study to see if ACE inhibitors or ARBs could help.
  • In a clinical trial with 721 patients, participants were randomly assigned to receive either an ACE inhibitor, an ARB, or no RAS inhibitor to evaluate their effects on patient recovery.
  • Results showed no significant improvement in organ support-free days among the treatment groups compared to the control, leading to the discontinuation of enrollment due to safety concerns.
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Social determinants of health (SDH), such as social isolation and loneliness, are often more frequently experienced in brain injury survivors. The paper explores the personal experiences of loneliness among brain injury survivors during lockdown to negate health inequalities and improve rehabilitation for this population in the future. Twenty-four brain injury survivors participated in semi-structured interviews and questionnaires relating to loneliness, resilience and wellbeing.

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Leptomeningeal metastases (LM) are a devastating complication of HER2 + metastatic breast cancer (MBC), with no effective treatments. In a case series of 8 patients with heavily pretreated HER2 + MBC and progressing LM, all 8 patients (100%) derived clinical benefit from Trastuzumab deruxtecan (TDXd), and 4 patients (50%) had an objective partial response based on formal neuroradiology MRI reads using the EORTC/RANO-LM Revised-Scorecard. T-DXd warrants further study in LM in HER2 + MBC and solid tumors where T-DXd may be active.

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Importance: Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making.

Objective: To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE.

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Objective: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking.

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Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.

Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.

Design, Setting, And Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries.

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Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear.

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Background: Adult primary immune thrombocytopenia (ITP) is a rare bleeding disorder of unknown cause. Recent estimates of its incidence and trend over time were acquired for England.

Method: The primary ITP population (using ICD 10 code D693 and excluding secondary ITP cases; positive predictive value: 82.

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Article Synopsis
  • The study aimed to assess whether antiplatelet therapy, specifically aspirin or P2Y12 inhibitors, improves outcomes for critically ill COVID-19 patients compared to no treatment.
  • Involved a total of 1557 adult patients across 105 sites in 8 countries, monitored over 90 days, with patients randomly assigned to receive either aspirin, a P2Y12 inhibitor, or no treatment.
  • Findings indicated that both aspirin and P2Y12 inhibitor groups showed similar efficacy in terms of organ support-free days, meeting criteria for equivalence in their effectiveness.
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