'He just gave up': an exploratory study into the perspectives of paid carers on supporting older people living in care homes with depression, self-harm, and suicide ideation and behaviours

This study explored the concept of ‘giving up’ from the perspective of care staff working in care homes, and their everyday communication and hidden knowledge concerning what they think about this taboo topic and the context it reflects. Moving to a care home is a major transition where cumulative losses can pose risks to mental health in later life. If not recognised, this vulnerability can lead to depression which extends to suicide ideation and behaviours in the form of self-harm and self-neglect. Care homes are a significant place of care until death, yet a discourse of silence means that self-harm and suicide is under-reported or not attended to with specialist expertise. The layperson’s concept of an older person ‘giving up’ on life is hardly discussed in the literature. This co-produced qualitative study used an inductive approach to explore this phenomenon through focus groups with 33 care staff across four care homes in South-East England. Findings paint a complex picture, highlighting tensions in providing the right support and creating spaces to respond to such challenging situations. ‘Giving up’ requires skilled detailed assessment to respond to risks alongside improved training and support for paid carers, to achieve a more holistic strategy which capitalises on significant relationships within a wider context

Persistent reduced ecosystem respiration after insect disturbance in high elevation forests

Amid a worldwide increase in tree mortality, mountain pine beetles (Dendroctonus ponderosae Hopkins) have led to the death of billions of trees from Mexico to Alaska since 2000. This is predicted to have important carbon, water and energy balance feedbacks on the Earth system. Counter to current projections, we show that on a decadal scale, tree mortality causes no increase in ecosystem respiration from scales of several square metres up to an 84 km2 valley. Rather, we found comparable declines in both gross primary productivity and respiration suggesting little change in net flux, with a transitory recovery of respiration 6–7 years after mortality associated with increased incorporation of leaf litter C into soil organic matter, followed by further decline in years 8–10. The mechanism of the impact of tree mortality caused by these biotic disturbances is consistent with reduced input rather than increased output of carbon

A systematic review on the qualitative experiences of people living with lung cancer in rural areas.

PURPOSE: To synthesize the qualitative literature exploring the experiences of people living with lung cancer in rural areas. METHODS: Searches were performed in MEDLINE, CINAHL, and PsycINFO. Articles were screened independently by two reviewers against pre-determined eligibility criteria. Data were synthesized using Thomas and Harden's framework for the thematic synthesis of qualitative research. The CASP qualitative checklist was used for quality assessment and the review was reported in accordance with the ENTREQ and PRISMA checklists. RESULTS: Nine articles were included, from which five themes were identified: (1) diagnosis and treatment pathways, (2) travel and financial burden, (3) communication and information, (4) experiences of interacting with healthcare professionals, (5) symptoms and health-seeking behaviors. Lung cancer diagnosis was unexpected for some with several reporting treatment delays and long wait times regarding diagnosis and treatment. Accessing treatment was perceived as challenging and time-consuming due to distance and financial stress. Inadequate communication of information from healthcare professionals was a common concern expressed by rural people living with lung cancer who also conveyed dissatisfaction with their healthcare professionals. Some were reluctant to seek help due to geographical distance and sociocultural factors whilst others found it challenging to identify symptoms due to comorbidities. CONCLUSIONS: This review provides a deeper understanding of the challenges faced by people with lung cancer in rural settings, through which future researchers can begin to develop tailored support to address the existing disparities that affect this population

A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation

The angiotensin type 1 receptor (AT1R) transactivates the epidermal growth factor receptor (EGFR) to mediate cellular growth, however, the molecular mechanisms involved have not yet been resolved. To address this, we performed a functional siRNA screen of the human kinome in human mammary epithelial cells that demonstrate a robust AT1R-EGFR transactivation. We identified a suite of genes encoding proteins that both positively and negatively regulate AT1R-EGFR transactivation. Many candidates are components of EGFR signalling networks, whereas others, including TRIO, BMX and CHKA, have not been previously linked to EGFR transactivation. Individual knockdown of TRIO, BMX or CHKA attenuated tyrosine phosphorylation of the EGFR by angiotensin II stimulation, but this did not occur following direct stimulation of the EGFR with EGF, indicating that these proteins function between the activated AT1R and the EGFR. Further investigation of TRIO and CHKA revealed that their activity is likely to be required for AT1R-EGFR transactivation. CHKA also mediated EGFR transactivation in response to another G protein-coupled receptor (GPCR) ligand, thrombin, indicating a pervasive role for CHKA in GPCR-EGFR crosstalk. Our study reveals the power of unbiased, functional genomic screens to identify new signalling mediators important for tissue remodelling in cardiovascular disease and cancer.This work was supported by the Australian National Health and Medical Research Council project grants [grant numbers 472640, 1024726 to W.G.T. and R.D.H]; and a project grant awarded to R.D.H, funded in Australia by the Captain Courageous Foundation (http://www.captaincourageousfoundation.com). R.D.H also holds an NHMRC senior research fellowship [grant number 1022402]

Yorkshire Enhanced Stop Smoking (YESS) study: a protocol for a randomised controlled trial to evaluate the effect of adding a personalised smoking cessation intervention to a lung cancer screening programme

Introduction: Integration of smoking cessation (SC) into lung cancer screening is essential to optimise clinical and cost effectiveness. The most effective way to use this ‘teachable moment’ is unclear. The Yorkshire Enhanced Stop Smoking study will measure the effectiveness of an SC service integrated within the Yorkshire Lung Screening Trial (YLST) and will test the efficacy of a personalised SC intervention, incorporating incidental findings detected on the low-dose CT scan performed as part of YLST. / Methods and analysis: Unless explicitly declined, all smokers enrolled in YLST will see an SC practitioner at baseline and receive SC support over 4 weeks comprising behavioural support, pharmacotherapy and/or a commercially available e-cigarette. Eligible smokers will be randomised (1:1 in permuted blocks of random size up to size 6) to receive either an enhanced, personalised SC support package, including CT scan images, or continued standard best practice. Anticipated recruitment is 1040 smokers (January 2019–December 2020). The primary objective is to measure 7-day point prevalent carbon monoxide (CO) validated SC after 3 months. Secondary outcomes include CO validated cessation at 4 weeks and 12 months, self-reported continuous cessation at 4 weeks, 3 months and 12 months, attempts to quit smoking and changes in psychological variables, including perceived risk of lung cancer, motivation to quit smoking tobacco, confidence and efficacy beliefs (self and response) at all follow-up points. A process evaluation will explore under which circumstances and on which groups the intervention works best, test intervention fidelity and theory test the mechanisms of intervention impact. / Ethics and dissemination: This study has been approved by the East Midlands-Derby Research Ethics Committee (18/EM/0199) and the Health Research Authority/Health and Care Research Wales. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via the YLST website. / Trial registration numbers: ISRCTN63825779, NCT03750110

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

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

Introduction: Lung cancer is the world’s leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. / Methods and analysis: Using a single-consent Zelen’s design, ever-smokers aged 55–80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. / Ethics and dissemination: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. / Trial registration numbers: ISRCTN42704678 and NCT03750110

End-point definition and trial design to advance tuberculosis vaccine development

Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgently needed. There are several new vaccine candidates at different stages of clinical development. Given the limited funding for vaccine development, it is crucial that trial designs are as efficient as possible. Prevention of infection (POI) approaches offer an attractive opportunity to accelerate new candidate vaccines to advance into large and expensive prevention of disease (POD) efficacy trials. However, POI approaches are limited by imperfect current tools to measure Mycobacterium tuberculosis infection end-points. POD trials need to carefully consider the type and number of microbiological tests that define TB disease and, if efficacy against subclinical (asymptomatic) TB disease is to be tested, POD trials need to explore how best to define and measure this form of TB. Prevention of recurrence trials are an alternative approach to generate proof of concept for efficacy, but optimal timing of vaccination relative to treatment must still be explored. Novel and efficient approaches to efficacy trial design, in addition to an increasing number of candidates entering phase 2-3 trials, would accelerate the long-standing quest for a new TB vaccine