Defining the road map to a UK national lung cancer screening programme.

Lung cancer screening with low-dose CT was recommended by the UK National Screening Committee (UKNSC) in September, 2022, on the basis of data from trials showing a reduction in lung cancer mortality. These trials provide sufficient evidence to show clinical efficacy, but further work is needed to prove deliverability in preparation for a national roll-out of the first major targeted screening programme. The UK has been world leading in addressing logistical issues with lung cancer screening through clinical trials, implementation pilots, and the National Health Service (NHS) England Targeted Lung Health Check Programme. In this Policy Review, we describe the consensus reached by a multiprofessional group of experts in lung cancer screening on the key requirements and priorities for effective implementation of a programme. We summarise the output from a round-table meeting of clinicians, behavioural scientists, stakeholder organisations, and representatives from NHS England, the UKNSC, and the four UK nations. This Policy Review will be an important tool in the ongoing expansion and evolution of an already successful programme, and provides a summary of UK expert opinion for consideration by those organising and delivering lung cancer screenings in other countries.

CREWS: improving specificity whilst maintaining sensitivity of the National Early Warning Score in patients with chronic hypoxaemia.

BACKGROUND: The National Early Warning Score (NEWS) is being introduced across the UK, but there are concerns about its specificity in patients with chronic hypoxaemia, such as some patients with COPD. This could lead to frequent clinically insignificant triggers and alarm fatigue. AIMS OF STUDY: To investigate whether patients with chronic hypoxaemia trigger excessively with NEWS, and to design a simple variant of NEWS for patients with chronic hypoxaemia: a Chronic Respiratory Early Warning Score (CREWS). METHODS: Data was collected from respiratory wards at two hospitals in North Wales. Components of NEWS and frequency of trigger thresholds being reached were recorded. CREWS was applied retrospectively to patients' observations. RESULTS: 196 admissions were analysed, including 78 for patients with chronic hypoxaemia. Patients with chronic hypoxaemia frequently exceeded trigger thresholds using NEWS during periods of stability/at discharge. Using CREWS, triggers during stability/at discharge were reduced from 32% of observations to 14% using a trigger threshold of a score greater than 6, and from 50% to 18% using a score greater than 5. All patients with chronic hypoxaemia who died within 30 days still reached CREWS trigger thresholds, and the area under receiver operated curves for NEWS and CREWS was comparable. CONCLUSION: CREWS is a simple variant of NEWS for patients with chronic hypoxaemia that could reduce clinically insignificant triggers and alarm fatigue, whilst still identifying the sickest patients.

Ghrelin induces abdominal obesity via GHS-R-dependent lipid retention.

Circulating ghrelin elevates abdominal adiposity by a mechanism independent of its central orexigenic activity. In this study we tested the hypothesis that peripheral ghrelin induces a depot-specific increase in white adipose tissue (WAT) mass in vivo by GH secretagogue receptor (GHS-R(1a))-mediated lipolysis. Chronic iv infusion of acylated ghrelin increased retroperitoneal and inguinal WAT volume in rats without elevating superficial sc fat, food intake, or circulating lipids and glucose. Increased retroperitoneal WAT mass resulted from adipocyte enlargement probably due to reduced lipid export (ATP-binding cassette transporter G1 mRNA expression and circulating free fatty acids were halved by ghrelin infusion). In contrast, ghrelin treatment did not up-regulate biomarkers of adipogenesis (peroxisome proliferator-activated receptor-gamma2 or CCAAT/enhancer binding protein-alpha) or substrate uptake (glucose transporter 4, lipoprotein lipase, or CD36) and although ghrelin elevated sterol-regulatory element-binding protein 1c expression, WAT-specific mediators of lipogenesis (liver X receptor-alpha and fatty acid synthase) were unchanged. Adiposity was unaffected by infusion of unacylated ghrelin, and the effects of acylated ghrelin were abolished by transcriptional blockade of GHS-R(1a), but GHS-R(1a) mRNA expression was similar in responsive and unresponsive WAT. Microarray analysis suggested that depot-specific sensitivity to ghrelin may arise from differential fine tuning of signal transduction and/or lipid-handling mechanisms. Acylated ghrelin also induced hepatic steatosis, increasing lipid droplet number and triacylglycerol content by a GHS-R(1a)-dependent mechanism. Our data imply that, during periods of energy insufficiency, exposure to acylated ghrelin may limit energy utilization in specific WAT depots by GHS-R(1a)-dependent lipid retention.