Uptake and 4-week quit rates from an opt-out co-located smoking cessation service delivered alongside community-based low-dose computed tomography screening within the Yorkshire Lung Screening Trial.

BACKGROUND: Up to 50% of those attending for low-dose computed tomography screening for lung cancer continue to smoke and co-delivery of smoking cessation services alongside screening may maximise clinical benefit. Here we present data from an opt-out co-located smoking cessation service delivered alongside the Yorkshire Lung Screening Trial (YLST). METHODS: Eligible YLST participants were offered an immediate consultation with a smoking cessation practitioner (SCP) at their screening visit with ongoing smoking cessation support over subsequent weeks. RESULTS: Of 2150 eligible participants, 1905 (89%) accepted the offer of an SCP consultation during their initial visit, with 1609 (75%) receiving ongoing smoking cessation support over subsequent weeks. Uptake of ongoing support was not associated with age, ethnicity, deprivation or educational level in multivariable analyses, although men were less likely to engage (adjusted OR (ORadj) 0.71, 95% CI 0.56-0.89). Uptake was higher in those with higher nicotine dependency, motivation to stop smoking and self-efficacy for quitting. Overall, 323 participants self-reported quitting at 4 weeks (15.0% of the eligible population); 266 were validated by exhaled carbon monoxide (12.4%). Multivariable analyses of eligible smokers suggested 4-week quitting was more likely in men (ORadj 1.43, 95% CI 1.11-1.84), those with higher motivation to quit and previous quit attempts, while those with a stronger smoking habit in terms of cigarettes per day were less likely to quit. CONCLUSIONS: There was high uptake for co-located opt-out smoking cessation support across a wide range of participant demographics. Protected funding for integrated smoking cessation services should be considered to maximise programme equity and benefit.

Short-term psychosocial outcomes of adding a non-contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening.

OBJECTIVES: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. SUBJECTS AND METHODS: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. RESULTS: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. CONCLUSION: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings.

Diagnoses and treatments for participants with interstitial lung abnormalities detected in the Yorkshire Lung Screening Trial.

INTRODUCTION: Interstitial lung abnormalities (ILA) are relatively common incidental findings in participants undergoing low-dose CT screening for lung cancer. Some ILA are transient and inconsequential, but others represent interstitial lung disease (ILD). Lung cancer screening therefore offers the opportunity of earlier diagnosis and treatment of ILD for some screening participants. METHODS: The prevalence of ILA in participants in the baseline screening round of the Yorkshire Lung Screening Trial is reported, along with the proportion referred to a regional ILD service, eventual diagnoses, outcomes and treatments. RESULTS: Of 6650 participants undergoing screening, ILA were reported in 169 (2.5%) participants. Following review in a screening review meeting, 56 participants were referred to the ILD service for further evaluation (0.8% of all screening participants). 2 participants declined referral, 1 is currently awaiting review and the remaining 53 were confirmed as having ILD. Eventual diagnoses were idiopathic pulmonary fibrosis (n=14), respiratory bronchiolitis ILD (n=4), chronic hypersensitivity pneumonitis (n=2), connective tissue disease/rheumatoid arthritis-related ILD (n=4), asbestosis (n=1), idiopathic non-specific interstitial pneumonia (n=1), sarcoidosis (n=1) and pleuroparenchymal fibroelastosis (n=1). Twenty five patients had unclassifiable idiopathic interstitial pneumonia. Overall, 10 people received pharmacotherapy (7 antifibrotics and 3 prednisolone) representing 18% of those referred to the ILD service and 0.15% of those undergoing screening. 32 people remain under surveillance in the ILD service, some of whom may require treatment in future. DISCUSSION: Lung cancer screening detects clinically significant cases of ILD allowing early commencement of disease-modifying treatment in a proportion of participants. This is the largest screening cohort to report eventual diagnoses and treatments and provides an estimate of the level of clinical activity to be expected by ILD services as lung cancer screening is implemented. Further research is needed to clarify the optimal management of screen-detected ILD. TRIAL REGISTRATION NUMBER: ISRCTN42704678.

Measuring spirometry in a lung cancer screening cohort highlights possible underdiagnosis and misdiagnosis of COPD.

Introduction: COPD is underdiagnosed, and measurement of spirometry alongside low-dose computed tomography (LDCT) screening for lung cancer is one strategy to increase earlier diagnosis of this disease. Methods: Ever-smokers at high risk of lung cancer were invited to the Yorkshire Lung Screening Trial for a lung health check (LHC) comprising LDCT screening, pre-bronchodilator spirometry and a smoking cessation service. In this cross-sectional study we present data on participant demographics, respiratory symptoms, lung function, emphysema on imaging and both self-reported and primary care diagnoses of COPD. Multivariable logistic regression analysis identified factors associated with possible underdiagnosis and misdiagnosis of COPD in this population, with airflow obstruction defined as forced expiratory volume in 1 s/forced vital capacity ratio <0.70. Results: Out of 3920 LHC attendees undergoing spirometry, 17% had undiagnosed airflow obstruction with respiratory symptoms, representing potentially undiagnosed COPD. Compared to those with a primary care COPD code, this population had milder symptoms, better lung function and were more likely to be current smokers (p≤0.001 for all comparisons). Out of 836 attendees with a primary care COPD code who underwent spirometry, 19% did not have airflow obstruction, potentially representing misdiagnosed COPD, although symptom burden was high. Discussion: Spirometry offered alongside LDCT screening can potentially identify cases of undiagnosed and misdiagnosed COPD. Future research should assess the downstream impact of these findings to determine whether any meaningful changes to treatment and outcomes occur, and to assess the impact on co-delivering spirometry on other parameters of LDCT screening performance such as participation and adherence. Additionally, work is needed to better understand the aetiology of respiratory symptoms in those with misdiagnosed COPD, to ensure that this highly symptomatic group receive evidence-based interventions.

Diagnosis and treatment outcomes from prebronchodilator spirometry performed alongside lung cancer screening in a Lung Health Check programme.

INTRODUCTION: Incorporating spirometry into low-dose CT (LDCT) screening for lung cancer may help identify people with undiagnosed chronic obstructive pulmonary disease (COPD), although the downstream impacts are not well described. METHODS: Participants attending a Lung Health Check (LHC) as part of the Yorkshire Lung Screening Trial were offered spirometry alongside LDCT screening. Results were communicated to the general practitioner (GP), and those with unexplained symptomatic airflow obstruction (AO) fulfilling agreed criteria were referred to the Leeds Community Respiratory Team (CRT) for assessment and treatment. Primary care records were reviewed to determine changes to diagnostic coding and pharmacotherapy. RESULTS: Of 2391 LHC participants undergoing prebronchodilator spirometry, 201 (8.4%) fulfilled the CRT referral criteria of which 151 were invited for further assessment. Ninety seven participants were subsequently reviewed by the CRT, 46 declined assessment and 8 had already been seen by their GP at the time of CRT contact. Overall 70 participants had postbronchodilator spirometry checked, of whom 20 (29%) did not have AO. Considering the whole cohort referred to the CRT (but excluding those without AO postbronchodilation), 59 had a new GP COPD code, 56 commenced new pharmacotherapy and 5 were underwent pulmonary rehabilitation (comprising 2.5%, 2.3% and 0.2% of the 2391 participants undergoing LHC spirometry). CONCLUSIONS: Delivering spirometry alongside lung cancer screening may facilitate earlier diagnosis of COPD. However, this study highlights the importance of confirming AO by postbronchodilator spirometry prior to diagnosing and treating patients with COPD and illustrates some downstream challenges in acting on spirometry collected during an LHC.

The Yorkshire Kidney Screening Trial (YKST): protocol for a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal pathology within a trial of community-based CT screening for lung cancer.

INTRODUCTION: Kidney cancer (renal cell cancer (RCC)) is the seventh most common cancer in the UK. As RCC is largely curable if detected at an early stage and most patients have no symptoms, there is international interest in evaluating a screening programme for RCC. The Yorkshire Kidney Screening Trial (YKST) will assess the feasibility of adding non-contrast abdominal CT scanning to screen for RCC and other abdominal pathology within the Yorkshire Lung Screening Trial (YLST), a randomised trial of community-based CT screening for lung cancer. METHODS AND ANALYSIS: In YLST, ever-smokers aged 55-80 years registered with a general practice in Leeds have been randomised to a Lung Health Check assessment, including a thoracic low-dose CT (LDCT) for those at high risk of lung cancer, or routine care. YLST participants randomised to the Lung Health Check arm who attend for the second round of screening at 2 years without a history of RCC or abdominal CT scan within the previous 6 months will be invited to take part in YKST. We anticipate inviting 4700 participants. Those who consent will have an abdominal CT immediately following their YLST thoracic LDCT. A subset of participants and the healthcare workers involved will be invited to take part in a qualitative interview. Primary objectives are to quantify the uptake of the abdominal CT, assess the acceptability of the combined screening approach and pilot the majority of procedures for a subsequent randomised controlled trial of RCC screening within lung cancer screening. ETHICS AND DISSEMINATION: YKST was approved by the North West-Preston Research Ethics Committee (21/NW/0021), and the Health Research Authority on 3 February 2021. Trial results will be disseminated at clinical meetings, in peer-reviewed journals and to policy-makers. Findings will be made available to participants via the study website (www.YKST.org). TRIAL REGISTRATION NUMBERS: NCT05005195 and ISRCTN18055040.

Participation in community-based lung cancer screening: the Yorkshire Lung Screening Trial.

BACKGROUND: Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality; however, the most effective strategy for optimising participation is unknown. Here we present data from the Yorkshire Lung Screening Trial, including response to invitation, screening eligibility and uptake of community-based LDCT screening. METHODS: Individuals aged 55-80 years, identified from primary care records as having ever smoked, were randomised prior to consent to invitation to telephone lung cancer risk assessment or usual care. The invitation strategy included general practitioner endorsement, pre-invitation and two reminder invitations. After telephone triage, those at higher risk were invited to a Lung Health Check (LHC) with immediate access to a mobile CT scanner. RESULTS: Of 44 943 individuals invited, 50.8% (n=22 815) responded and underwent telephone-based risk assessment (16.7% and 7.3% following first and second reminders, respectively). A lower response rate was associated with current smoking status (adjusted OR 0.44, 95% CI 0.42-0.46) and socioeconomic deprivation (adjusted OR 0.58, 95% CI 0.54-0.62 for the most versus the least deprived quintile). Of those responding, 34.4% (n=7853) were potentially eligible for screening and offered a LHC, of whom 86.8% (n=6819) attended. Lower uptake was associated with current smoking status (adjusted OR 0.73, 95% CI 0.62-0.87) and socioeconomic deprivation (adjusted OR 0.78, 95% CI 0.62-0.98). In total, 6650 individuals had a baseline LDCT scan, representing 99.7% of eligible LHC attendees. CONCLUSIONS: Telephone risk assessment followed by a community-based LHC is an effective strategy for lung cancer screening implementation. However, lower participation associated with current smoking status and socioeconomic deprivation underlines the importance of research to ensure equitable access to screening.

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.

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.

A Single Site Population Study to Investigate CYP2D6 Phenotype of Patients with Persistent Non-Malignant Pain.

Background and Objectives: Codeine requires biotransformation by the CYP2D6 enzyme, encoded by the polymorphic CYP2D6 gene, to morphine for therapeutic efficacy. CYP2D6 phenotypes of poor, intermediate, and ultra-rapid metabolisers are at risk of codeine non-response and adverse drug reactions due to altered CYP2D6 function. The aim of this study was to determine whether genotype, inferred phenotype, and urinary and oral fluid codeine O-demethylation metabolites could predict codeine non-response following a short course of codeine. Materials and Methods: There were 131 Caucasians with persistent pain enrolled. Baseline assessments were recorded, prohibited medications ceased, and DNA sampling completed before commencing codeine 30 mg QDS for 5 days. Day 4 urine samples were collected 1-2 h post morning dose for codeine O-demethylation metabolites analysis. Final pain assessments were conducted on day 5. Results: None of the poor, intermediate, ultra-rapid metabolisers and only 24.5% of normal metabolisers responded to codeine. A simple scoring system to predict analgesic response from day 4 urinary metabolites was devised with overall prediction success of 79% (sensitivity 0.8, specificity 0.78) for morphine and 79% (sensitivity 0.76, specificity 0.83) for morphine:creatinine ratio. Conclusions: In conclusion, this study provides tentative evidence that day 4 urinary codeine O-demethylation metabolites could predict non-response following a short course of codeine and could be utilised in the clinical assessment of codeine response at the point of care to improve analgesic efficacy and safety in codeine therapy. We offer a scoring system to predict codeine response from urinary morphine and urinary morphine:creatinine ratio collected on the morning of day 4 of codeine 30 mg QDS, but this requires validation before it could be considered for use to assess codeine response in clinical practice.

All That Glitters Is Not Grit: Three Studies of Grit in University Students.

The present research looked at the importance of the concept of grit in University students based on a mixed-method approach. Study 1 comprised 440 University students. All were given the Grit Scale, the Perceived Stress Scale, the short Warwick-Edinburgh Mental Well-being Scale, the Office of National Statistics Well-being items and the Self-Control Scale. Levels of grit were significantly higher in female students, older students and postgraduates. Grit correlated highest with self-control. Study 2 looked at 340 University students. In addition to measuring self-control, mental well-being and grit, measures of resilience and mindsets were also added. A construct validity test of the Grit Scale showed that high grit scorers had significantly higher levels of self-control and mental well-being, were more resilient and were more likely to have a more growth oriented mindset. Grit varies with age and is most closely associated with the concept of self-control. The third study was a qualitative investigation with 10 successful graduates. Semi-structured interviews were coded using thematic analysis. Three broad themes emerged. The first, Passion and Perseverance, included themes of having short and long terms goals, resilience, dedication, and endurance. The second, Self-Control, included time management, self-awareness, prioritizing tasks and knowing strengths and weaknesses. The third theme identified was Positive Mindsets. This included having a positive attitude toward learning, the importance of feedback and constructive criticism and that success is not materialistic. The qualitative research has helped "unpack" concepts from the grit research and may enable University tutors to guide students better. Though these studies were only conducted in one English University, they have been stepping stones in our quest to discover what are the most important factors in determining student academic success? The development and piloting of our new Uni-Stride Scale, is the next step in this process.

Skeletal complications and survival in renal cancer patients with bone metastases.

Skeletal metastases occur in around one third of patients with advanced or metastatic renal cell carcinoma (RCC). Skeletal involvement is commonly an aggressive, lytic process which causes substantial morbidity through skeletal complications and occurrence of skeletal related events (SREs). However, compared with bone metastases in breast and prostate cancer, there is a paucity of data relating to the demographics of bone metastases in RCC and their sequelae in terms of SREs and survival. The study population included all patients (N=803) with advanced or metastatic RCC treated in a tertiary centre serving a regional population of 2.6 million between 1998 and 2007. Demographic and survival data and information relating to metastatic disease were extracted from electronic records. Thirty-two percent (N=254) of the study population presented with (N=131) or later developed (N=123) bone metastases and 83% of these (N=210) also developed metastases elsewhere. The mean number of SREs experienced by the bone metastatic patients over the course of their disease was 2.4 and only 37 patients experienced no SRE. A high proportion of patients (80%) received radiotherapy for bone pain and there was a surprising and strikingly high incidence of spinal cord/nerve root compression, which was experienced by 28% patients. Although bisphosphonate use increased following the availability of zoledronic acid in 2004, approximately 50% patients with bone metastases did not receive bisphosphonate treatment. The skeletal morbidity rate (number of SREs per patient years at risk) was 1.0 and 1.4 for patients who received or did not receive bisphosphonates, respectively. The median survival following diagnosis of RCC was similar in patients who developed bone metastases (20.4 months) and those who did not (20.9 months). Median survival from diagnosis of metastases was 13.3 months for those who never developed bone metastases, 10.6 months for those who presented with them, 19.6 months for those who developed them later and 22.6 months for patients who had bone only metastases. This is the largest study to date focusing specifically on skeletal complications in RCC. A striking finding was the high incidence of spinal cord/nerve root compression and more research into this area is needed. Clearer, internationally accepted guidelines are recommended for the management of this patient group.