Comparison of Reporting Quality in National Cystic Fibrosis Patient Registries: Implications for Identifying Use of Novel CFTR Modulators.

Introduction: Advances in development of cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapies mean that now people who are heterozygous (instead of having to be homozygous) for the common F508del variant can benefit from these therapies. Recent economic estimates suggest only approximately 15% of the global population have CFTRm access, yet it is unknown how prevalence of F508del and economic factors may affect this availability.

Methods: Data related to prevalence of cystic fibrosis (CF), CFTRm usage, and prevalence of F508del in 10 countries were extracted from publicly accessible registry reports from 2021.

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.

Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations.

Autosomal recessive coding variants are well-known causes of rare disorders. We quantified the contribution of these variants to developmental disorders in a large, ancestrally diverse cohort comprising 29,745 trios, of whom 20.4% had genetically inferred non-European ancestries.

'I Live With Lynch. Cancer Worry Ebbs Into the Background, Then Something Brings It to the Fore.' A Qualitative Interview Study Exploring How Lynch Syndrome Carriers Make Sense of Their Cancer Risks and Implications to Support Decision Making.

Background: Lynch syndrome carriers ('carriers') are presented with complex, emotionally laden choices regarding management of increased genetic cancer risks. Decision aids encourage active involvement in values-based health decisions. This paper aimed to address the research question: How do Lynch syndrome carriers make sense of their chances of developing cancer, and what are the implications for providing support with decision making about genetic cancer risk management?

Methods: Adult carriers were recruited through a genetics service or involvement with Lynch Syndrome UK.

Why do mobile genetic elements transfer DNA of their hosts?

The prokaryote world is replete with mobile genetic elements (MGEs) - self-replicating entities that can move within and between their hosts. Many MGEs not only transfer their own DNA to new hosts but also transfer host DNA located elsewhere on the chromosome in the process. This could potentially lead to indirect benefits to the host when the resulting increase in chromosomal variation results in more efficient natural selection.

Mitochondria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways.

Metabolic diseases that include obesity and metabolic-associated fatty liver disease (MAFLD) are a rapidly growing worldwide public health problem. The pathogenesis of MAFLD includes abnormally increased lipogenesis, chronic inflammation, and mitochondrial dysfunction. Mounting evidence suggests that hydrogen sulfide (HS) is an important player in the liver, regulating lipid metabolism and mitochondrial function.

Cost-effectiveness of adding a smartphone app (BlueIce) to the mental health care of adolescents who repeatedly self-harm.

Digital interventions can offer crises support although their cost-effectiveness is unknown. We undertook an economic evaluation alongside a two-arm, single blind, randomised controlled trial. 170 adolescents aged 12-17, receiving child and adolescent mental health care who had self-harmed ≥2 in the past 12 months were randomised to usual care with or without an app (BlueIce).

Prehabilitation for frail patients undergoing hip and knee replacement in the UK: Joint PREP feasibility study for a randomised controlled trial.

Objective: To determine the feasibility of conducting a randomised controlled trial (RCT) to evaluate a prehabilitation programme for frail patients undergoing total hip replacement (THR) or total knee replacement (TKR).

Design: Randomised feasibility study with embedded qualitative work.

Setting: Three National Health Service hospitals.

Endothelial Cell-Derived Soluble CD200 Determines the Ability of Immune Cells to Cross the Blood-Brain Barrier.

The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion.

Improving the Clinical Utility of Platelet Count for Cancer Detection in Primary Care: A Cohort Study in England, Canada, and Australia.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 10/L; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England, Canada, and Australia.

What types of objective measures have been used to assess core ADHD symptoms in children and young people in naturalistic settings? A scoping review.

Objectives: We described the range and types of objective measures of attention-deficit/hyperactivity disorder (ADHD) in children and young people (CYP) reported in research that can be applied in naturalistic settings.

Design: Scoping review using best practice methods.

Data Sources: MEDLINE, APA PsycINFO, Embase, (via OVID); British Education Index, Education Resources Information Centre, Education Abstracts, Education Research Complete, Child Development and Adolescent Papers, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychology and Behavioural Sciences Collection (via EBSCO) were searched between 1 December 2021 and 28 February 2022.

Tobacco and COPD: presenting the World Health Organization (WHO) Tobacco Knowledge Summary.

The WHO recently published a Tobacco Knowledge Summary (TKS) synthesizing current evidence on tobacco and COPD, aiming to raise awareness among a broad audience of health care professionals. Furthermore, it can be used as an advocacy tool in the fight for tobacco control and prevention of tobacco-related disease. This article builds on the evidence presented in the TKS, with a greater level of detail intended for a lung-specialist audience.

Searching for studies: A guide to information retrieval for Campbell systematic reviews.

This guide outlines general issues in searching for studies; describes the main sources of potential studies; and discusses how to plan the search process, design, and carry out search strategies, manage references found during the search process and document and report the search process.

A lifetime economic model of mortality and secondary care use for patients discharged from hospital following acute stroke.

Background: The long-term health-economic consequences of acute stroke are typically extrapolated from short-term outcomes observed in different studies, using models based on assumptions about longer-term morbidity and mortality. Inconsistency in these assumptions and the methods of extrapolation can create difficulties when comparing estimates of lifetime cost-effectiveness of stroke care interventions.

Aims: To develop a long-term model consisting of a set of equations to estimate the lifetime effects of stroke care interventions to promote consistency in extrapolation of short-term outcomes.

Aortic reservoir-excess pressure parameters are associated with worse cognitive function in people with untreated stage II/III hypertension.

Objective: Hypertension is a recognized risk factor for the development of cognitive impairment and dementia in older adults. Aortic stiffness and altered haemodynamics could promote the transmission of detrimental high pressure pulsatility into the cerebral circulation, potentially damaging brain microvasculature and leading to cognitive impairment. We determined whether reservoir-excess pressure parameters were associated with cognitive function in people with hypertension (HT) and normotension (NT).