Delay and Pay? Healthcare Costs Associated with Late Oral Anti-coagulant Prescribing in People with Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with increased morbidity and mortality and exerts an increasingly significant burden on global healthcare resources, with its prevalence rising with an ageing population. Despite a substantial thromboembolic risk, particularly in the period immediately following diagnosis, oral anti-coagulation is frequently not initiated or is delayed. The aim of this study was to evaluate healthcare costs in people with AF, comparing those who were commenced on oral anti-coagulation in the immediate period following the index diagnosis date with those in whom initiation was late and those who never started anti-coagulation.

Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation.

Aims: Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start.

Methods And Results: This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHADS-VASC score of ≥2.

Undertaking multi-centre randomised controlled trials in primary care: learnings and recommendations from the PULsE-AI trial researchers.

Background: Conducting effective and translational research can be challenging and few trials undertake formal reflection exercises and disseminate learnings from them. Following completion of our multicentre randomised controlled trial, which was impacted by the COVID-19 pandemic, we sought to reflect on our experiences and share our thoughts on challenges, lessons learned, and recommendations for researchers undertaking or considering research in primary care.

Methods: Researchers involved in the Prediction of Undiagnosed atriaL fibrillation using a machinE learning AlgorIthm (PULsE-AI) trial, conducted in England from June 2019 to February 2021 were invited to participate in a qualitative reflection exercise.

Can we collect health-related quality of life information from anticoagulated atrial fibrillation participants who have recently experienced a bleed? An observational feasibility study in primary and secondary care in Wales and through a UK online forum.

Objective: To evaluate the feasibility of recruiting participants diagnosed with atrial fibrillation (AF) taking oral anticoagulation therapies (OATs) and recently experiencing a bleed to collect health-related quality of life (HRQoL) information.

Design: Observational feasibility study. The study aimed to determine the feasibility of recruiting participants with minor and major bleeds, the most appropriate route for recruitment and the appropriateness of the patient-reported outcome measures (PROMs) selected for collecting HRQoL information in AF patients, and the preferred format of the surveys.

A Novel Risk Prediction Score for Clinically Significant Bleeding in Patients Anticoagulated for Venous Thromboembolism with Active Cancer.

Background:  Cancer-associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction.

Methods:  UK Clinical Practice Research Datalink data (2008-2020) were used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE.

The association between brain volume loss and disability in multiple sclerosis: A systematic review.

Background: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, degenerative disease of the central nervous system that affects approximately 2.8 million people worldwide. Compelling evidence from observational studies and clinical trials indicates a strong association between brain volume loss (BVL) and the accumulation of disability in MS.

Sex Differences in Oral Anticoagulation Therapy in Patients Hospitalized With Atrial Fibrillation: A Nationwide Cohort Study.

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study.

Identification of undiagnosed atrial fibrillation using a machine learning risk-prediction algorithm and diagnostic testing (PULsE-AI) in primary care: a multi-centre randomized controlled trial in England.

Aims: The aim of the PULsE-AI trial was to assess the effectiveness of a machine learning risk-prediction algorithm in conjunction with diagnostic testing for identifying undiagnosed atrial fibrillation (AF) in primary care in England.

Methods And Results: Eligible participants (aged ≥30 years without AF diagnosis;  = 23 745) from six general practices in England were randomized into intervention and control arms. Intervention arm participants, identified by the algorithm as high risk of undiagnosed AF ( = 944), were invited for diagnostic testing ( = 256 consented); those who did not accept the invitation, and all control arm participants, were managed routinely.

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK.

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.

Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study.

Objective: Hepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival.

Methods: Incident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016-2017) and then a subset by National Health Service (NHS) regions.

Investigating the feasibility of recruitment to an observational, quality-of-life study of patients diagnosed with atrial fibrillation (AF) who have experienced a bleed while anticoagulated: EQUAL-AF feasibility study protocol.

Background: Oral anticoagulation therapies (OATs) are often prescribed in conjunction with medications to restore normal heart rate rhythm which can limit the risk of an atrial fibrillation (AF) related stroke and systemic thromboembolism. However, they are associated with the serious side effect of bleeding. Both clinically relevant nonmajor bleeding (CRNMB) and major bleeding while anticoagulated are believed to have a significant impact on patient quality of life (QoL).

Identification of undiagnosed atrial fibrillation using a machine learning risk prediction algorithm and diagnostic testing (PULsE-AI) in primary care: cost-effectiveness of a screening strategy evaluated in a randomized controlled trial in England.

Objective: The PULsE-AI trial sought to determine the effectiveness of a screening strategy that included a machine learning risk prediction algorithm in conjunction with diagnostic testing for identification of undiagnosed atrial fibrillation (AF) in primary care. This study aimed to evaluate the cost-effectiveness of implementing the screening strategy in a real-world setting.

Methods: Data from the PULsE-AI trial - a prospective, randomized, controlled trial conducted across six general practices in England from June 2019 to February 2021 - were used to inform a cost-effectiveness analysis that included a hybrid screening decision tree and Markov AF disease progression model.

Budget impact analysis of a machine learning algorithm to predict high risk of atrial fibrillation among primary care patients.

Aims: We investigated whether the use of an atrial fibrillation (AF) risk prediction algorithm could improve AF detection compared with opportunistic screening in primary care and assessed the associated budget impact.

Methods And Results: Eligible patients were registered with a general practice in UK, aged 65 years or older in 2018/19, and had complete data for weight, height, body mass index, and systolic and diastolic blood pressure recorded within 1 year. Three screening scenarios were assessed: (i) opportunistic screening and diagnosis (standard care); (ii) standard care replaced by the use of the algorithm; and (iii) combined use of standard care and the algorithm.

Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation.

To compare the efficacy and safety of apixaban and rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) by way of a meta-analysis informed by real-world evidence. Systematic review and meta-analysis of observational studies including patients with NVAF on apixaban and rivaroxaban, which reported stroke/systemic embolism and/or major bleeding. Prospero registration number: CRD42021251719.

Mind the gap: From recommendation to practice in crisis management. Exploring the gap between the "lessons identified" during exercise cygnus and the UK government response to COVID-19.

The failure to learn lessons from crises is a common observation. The UK Government has been criticized for its response to the COVID-19 crisis. Many critics have highlighted the Government's apparent failure to learn the lessons from Exercise Cygnus, which made recommendations to improve the UK's response to a pandemic.

G-Quadruplex Assembly by Ribosomal DNA: Emerging Roles in Disease Pathogenesis and Cancer Biology.

Unique repetitive elements of the eukaryotic genome can be problematic for cellular DNA replication and transcription and pose a source of genomic instability. Human ribosomal DNA (rDNA) exists as repeating units clustered together on several chromosomes. Understanding the molecular mechanisms whereby rDNA interferes with normal genome homeostasis is the subject of this review.

Application of a machine learning algorithm for detection of atrial fibrillation in secondary care.

Atrial fibrillation (AF) is the most common sustained heart arrhythmia and significantly increases risk of stroke. Opportunistic AF testing in high-risk patients typically requires frequent electrocardiogram tests to capture the arrhythmia. Risk-prediction algorithms may help to more accurately identify people with undiagnosed AF and machine learning (ML) may aid in the diagnosis of AF.

Detecting undiagnosed atrial fibrillation in UK primary care: Validation of a machine learning prediction algorithm in a retrospective cohort study.

Aims: To evaluate the ability of a machine learning algorithm to identify patients at high risk of atrial fibrillation in primary care.

Methods: A retrospective cohort study was undertaken using the DISCOVER registry to validate an algorithm developed using a Clinical Practice Research Datalink (CPRD) dataset. The validation dataset included primary care patients in London, England aged ≥30 years from 1 January 2006 to 31 December 2013, without a diagnosis of atrial fibrillation in the prior 5 years.

Outcomes in rheumatoid arthritis patients treated with abatacept: a UK multi-centre observational study.

Background: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic synovitis, resulting in progressive joint destruction and functional disability and affects approximately 400,000 people in the UK. This real-world study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients who received abatacept in UK clinical practice.

Methods: This was a multi-centre, retrospective, observational study of patients with RA treated with abatacept at four UK centres between 01 January 2013 and 31 December 2017.

Total Defence Resilience: Viable or Not During COVID-19? A Comparative Study of Norway and the UK.

The total defence (TD) concept aims to provide an effective crisis response structure by increasing society resilience. However, the complexity of its structure regarding resource mobilization and management process highlights the need for a complexity-oriented approach in the operationalising of TD. We study the application of TD during the COVID-19 crisis and explore what makes the TD a viable system with resilience capabilities in the face the crisis.

Influence of weather and climate on cryptosporidiosis-A review.

Studies have shown that climatic factors can significantly influence transmission of many waterborne diseases. However, knowledge of the impact of climate variability on cryptosporidiosis is much less certain. Associations between the incidence of cryptosporidiosis and climatic variables have been reported in several countries.

Identification of undiagnosed atrial fibrillation patients using a machine learning risk prediction algorithm and diagnostic testing (PULsE-AI): Study protocol for a randomised controlled trial.

Atrial fibrillation (AF) is associated with an increased risk of stroke, enhanced stroke severity, and other comorbidities. However, AF is often asymptomatic, and frequently remains undiagnosed until complications occur. Current screening approaches for AF lack either cost-effectiveness or diagnostic sensitivity; thus, there is interest in tools that could be used for population screening.

Real-world utility of HCV core antigen as an alternative to HCV RNA testing: Implications for viral load and genotype.

Following positive serology, the gold standard confirmatory test of hepatitis C virus (HCV) infection is detection of HCV RNA by PCR. We assessed the utility of HCV core antigen testing to identify active infection among those positive for anti-HCV antibodies, when introduced to routine testing. We identified serum samples that were tested at a single laboratory in Scotland from June 2011to December 2017.