"I'm quite proud of how we've handled it": health professionals' experiences of returning additional findings from the 100,000 genomes project.

Participants in the 100,000 Genomes Project (100kGP) could consent to receive additional finding (AF) results, individual variants relating to genes associated with susceptibility to cancer and familial hypercholesterolemia (FH). In the study reported here, qualitative interviews were used to explore the experiences of National Health Service (NHS) professionals from across England who were tasked with returning over 80,000 "no AF" results and 700 positive AF results to 100kGP participants. Interviews were conducted with 45 professionals from a range of backgrounds, including Genetic Counsellors, Clinical Geneticists, FH Clinical Nurse Specialists and Clinical Scientists.

A review of UK primary care pathways for acute ophthalmic conditions.

Care pathways for the management of acute ophthalmic conditions have developed and transformed significantly over recent years, owing to a combination of legislative changes, policy implementation and the pressing requirement to redistribute increased demand away from traditional secondary care providers through collaboration with primary care. Following UK healthcare devolution in 1999, each nation has developed and implemented their own strategies for managing the growing demands on acute ophthalmology services. Local commissioning across England has seen Enhanced Service Pathways develop to provide acute eye care by primary care optometrists, with provision and access dependent upon locality.

cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.

We report the first, and so far, only index patient with neonatal onset MoCD type A who was diagnosed and treated early enough with cPMP to avoid severe brain injury and disability. The child presented with hypoglycemia at the age of 10 h and was diagnosed because of the incidental finding of severely decreased L-cystine in plasma. Due to a high level of awareness and excellent co-operation between metabolic laboratory and clinical services, cPMP substitution could be initiated before severe encephalopathy set in, and the child subsequently had a normal motor development.

Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS).

Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation in the phase 3 BOREAS trial.

Objective: To assess clinical outcomes in patients from BOREAS by emphysema status.

Methods: Patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/μL) on maximal inhaled therapy were randomized to add-on dupilumab 300 mg or placebo every 2 weeks for 52 weeks.

Evaluating the Effectiveness of Virtual Fracture Clinics in Managing Toe Fractures: Patient Demographics and Outcomes.

Background Virtual fracture clinics (VFCs) offer a remote alternative to traditional fracture clinics, potentially reducing the burden on in-person services. This is particularly relevant for fractures that typically do not require follow-up, such as toe fractures, which are commonly managed conservatively. Methods This study evaluated the effectiveness of VFCs in managing toe fractures.

Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD.

Unlabelled: Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively.

Methods: Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene.

Proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline.

Clinical Question: In adult patients with inflammatory bowel disease, inflammatory arthritis (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis), or psoriasis taking biologic drugs, does proactive therapeutic drug monitoring (TDM) improve outcomes as compared with standard care?

Context And Current Practice: Standard care for immune mediated inflammatory diseases includes prescribing biologic drugs at pre-determined doses. Dosing may be adjusted reactively, for example with increased disease activity. In proactive TDM, serum drug levels and anti-drug antibodies are measured irrespective of disease activity, and the drug dosing is adjusted to achieve target serum drug levels, usually within pre-specified therapeutic ranges.

Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis: The EVOLVED Randomized Clinical Trial.

Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis.

Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis.

Design, Setting, And Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia.

The CO-produced Psychosocial INtervention delivered by GPs to young people after self-harm (COPING): protocol for a feasibility study.

Background: Self-harm in young people is a growing concern and reducing rates a global priority. Rates of self-harm documented in general practice have been increasing for young people in the UK in the last two decades, especially in 13-16-year-olds. General practitioners (GPs) can intervene early after self-harm but there are no effective treatments presently available.

Rapid Access Diagnostics for Asthma (RADicA): protocol for a prospective cohort study to determine the optimum series of investigations to diagnose asthma using conventional and novel tests.

Introduction: The diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend including confirmation of variable airflow obstruction. Some recommend using a sequence of objective tests; however the tests used, the specific cut-off values and the specified order are yet to be validated.

BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

Treatment strategies with electrochemotherapy for limb in-transit melanoma: Real-world outcomes from a European, retrospective, cohort study.

Background: This study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM).

Methods: We audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006-2020) within the International Network for Sharing Practices of ECT (InspECT).

Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS)/perioperative quality initiative (POQI) consensus statement on prehabilitation in oesophagogastric surgery.

Background: Prehabilitation is safe, feasible and may improve a range of outcomes in patients with oesophago-gastric cancer (OGC). Recent studies have suggested the potential of prehabilitation to improve body composition, sarcopenia and physical fitness, reduce surgical complications and improve quality of life. Despite this, prehabilitation services are not offered throughout all OGC centres in the UK.

Simultaneous quantification of serum symmetric dimethylarginine, asymmetric dimethylarginine and creatinine for use in a routine clinical laboratory.

Background: Symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) are naturally occurring amino acids classed as uraemic toxins by the European Uremic Toxins Work Group. SDMA is principally excreted through the kidneys and is a well-known renal function marker, and ADMA is a potent inhibitor of nitric oxide production. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry method for simultaneous measurement of SDMA, ADMA and creatinine.