Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in and Vici syndrome patients.

Epilepsy is a common neurological condition that arises from dysfunctional neuronal circuit control due to either acquired or innate disorders. Autophagy is an essential neuronal housekeeping mechanism, which causes severe proteotoxic stress when impaired. Autophagy impairment has been associated to epileptogenesis through a variety of molecular mechanisms.

Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access.

Purpose And Scope: The aim of this position statement is to provide recommendations regarding the delivery of genomic testing to patients with rare disease in the UK and Ireland. The statement has been developed to facilitate timely and equitable access to genomic testing with reporting of results within commissioned turnaround times.

Methods Of Statement Development: A 1-day workshop was convened by the UK Association for Clinical Genomic Science and attended by key stakeholders within the NHS Genomic Medicine Service, including clinical scientists, clinical geneticists and patient support group representatives.

Standards for research in NHS Wales critical care units: A modified Delphi study.

Introduction: The importance of research and development in all aspects of healthcare is well acknowledged. Within critical care, national guidelines provide a limited number of standards and series of recommendations on Research and Development (R&D) activity. The aim of this study was to create a broader set of standards in support of R&D activity in critical care departments.

Intraoperative parathyroid hormone assay benefits surgery for primary hyperparathyroidism when preoperative localisation is negative or not performed.

Introduction: Parathyroid localisation is now routine before first-time surgery for patients with primary hyperparathyroidism (PHPT). The aim of this study was to investigate the contribution of intraoperative parathyroid hormone (PTH) (ioPTH) in patients in whom localisation was either not undertaken or negative for a tumour.

Methods: This was a retrospective study of patients undergoing first-time parathyroidectomy for PHPT in a regional endocrine centre.

Challenges and opportunities for identifying people with Familial hypercholesterolaemia in the UK: Evidence from the National FH PASS database.

Background: Familial Hypercholesterolaemia (FH) is a monogenic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol. Cascade testing, where relatives of known individuals with FH ('index') are genetically tested, is effective and cost-effective, but implementation in the UK varies.

Objective: This study aims to provide evidence on current UK FH cascade yields and to identify common obstacles cascade services face and individual- and service-level predictors of success.

Consistency in the Assessment of Dried Blood Spot Specimen Size and Quality in U.K. Newborn Screening Laboratories.

In 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm.

Orphan and paediatric medical devices in Europe: recommendations to support their availability for on-label and off-label clinical indications.

Introduction: The Medical Device Regulation (EU)745/2017, increased the regulatory requirements and thus the time and the cost associated with marketing medical devices. For a majority of medical device manufacturers, this has lead to reconsiderations of their product portfolio. The risk of important or essential devices being withdrawn is particularly relevant for pediatric patients and other rare disease patients where limited numbers of devices can be sold and hence the investment needed may not be recovered.

Lodestar DX, an evaluation: loop-mediated isothermal amplification (LAMP) for the diagnosis of urinary tract infection in symptomatic adult females.

Background: Over 404.6 million people are affected worldwide each year by urinary tract infections (UTIs), with ∼237 000 associated deaths globally in 2019. Much more common in women than men, acute UTI occurs in up to 50% of the female population.

fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study.

Background: The safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs).

Methods: This phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly.

Hip fracture projections up to the year 2060: an analysis based on data from the National Hip Fracture Database (NHFD) for England, Wales, and Northern Ireland.

Introduction: Hip fractures are common and cause a huge socioeconomic burden to patients, their carers, and healthcare services worldwide. Our aim was to examine how much hip fracture numbers would be expected to rise over coming decades, simply as a consequence of the ageing of the population.

Methods: We used data from the National Hip Fracture Database on the volume of hip fractures occurring in England, Wales and Northern Ireland in the year 2019 (n = 67,210).

Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.

Background: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

Safety and efficacy of itacitinib, a selective JAK1 inhibitor, in advanced hepatocellular cancer: Phase 1b trial (JAKAL).

Overactivation of the JAK/STAT pathway is one of the drivers for the pathophysiology of hepatocellular carcinoma (HCC). We propose a Phase Ib study to evaluate the safety and efficacy of itacitinib, a selective JAK1 inhibitor, as a second-line treatment for patients with advanced or metastatic HCC.Twenty-five patients will receive 400 mg itacitinib orally daily, 28-day cycle.

Characterizing medication safety incidents in surgical patients: a retrospective cross-sectional analysis of incident reports.

Background: Medication-related safety incidents (MSIs) are among the most frequent contributors to preventable harm in hospital patients. There is a paucity of research that explores the factors that contribute to MSIs across the departments of high-risk specialties such as surgery.

Objectives: To characterize MSIs involving surgical patients across two secondary care sites at a University Health Board.

Progress on nonculture based diagnostic tests for invasive mould infection.

Purpose Of Review: This review describes the current status of diagnosing invasive mould disease and Pneumocystis pneumonia using nonconventional diagnostics methods.

Recent Findings: There has been significant development in the range of nonculture mycological tests. Lateral flow tests (LFTs) for diagnosing aspergillosis complement galactomannan ELISA testing, and LFTs for other fungal diseases are in development.

Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.

Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals.

Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report From the Pulmonary Embolism Research Collaborative.

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment.

PRECIOUS study (PREterm Caesarean/vaginal birth and IVH/OUtcomeS): does mode of birth reduce the risk of death or brain injury in very preterm babies? A cohort and emulated target trial protocol.

Introduction: Very preterm babies are at risk of poor neurodevelopmental outcomes and death. Intraventricular haemorrhage (IVH) after birth is the most prevalent cause of this. Birth by caesarean section may protect against IVH in very preterm babies, but the evidence is limited.