The Chest Australia Trial: a randomised controlled trial of an intervention to increase consultation rates in smokers at risk of lung cancer.

BACKGROUND: International research has focused on screening and mass media campaigns to promote earlier patient presentation and detect lung cancer earlier. This trial tested the effect of a behavioural intervention in people at increased risk of lung cancer on help-seeking for respiratory symptoms. METHODS: Parallel, individually randomised controlled trial. Eligible participants were long-term smokers with at least 20 pack-years, aged 55 and above. The CHEST intervention entailed a consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to encourage help-seeking for respiratory symptoms. The control group received a brief discussion about lung health. Both groups had baseline spirometry. Telephone randomisation was conducted, 1:1, stratified Medical Research Council (MRC) dyspnoea score and general practice. Participants could not be blinded; data extraction and statistical analyses were performed blinded to group assignment. The primary outcome was respiratory consultation rates. RESULTS: We randomised 551 participants (274 intervention, 277 control) from whom the primary outcome was determined for 542 (269 intervention, 273 control). There was a 40% relative increase in respiratory consultations in the intervention group: (adjusted rates (95% CI) intervention 0.57 (0.47 to 0.70), control 0.41 (0.32 to 0.52), relative rate 1.40 (1.08 to 1.82); p=0.0123). There were no significant differences in time to first respiratory consultation, total consultation rates or measures of psychological harm. The incremental cost-effectiveness ratio was $A1289 per additional respiratory consultation. CONCLUSIONS: A behavioural intervention can significantly increase consulting for respiratory symptoms in patients at increased risk of lung cancer. This intervention could have an important role in primary care as part of a broader approach to improve respiratory health in patients at higher risk. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (1261300039 3752). This was registered pre-results.

Reducing barriers to consulting a General Practitioner in patients at increased risk of lung cancer: a qualitative evaluation of the CHEST Australia intervention.

Background: Lung cancer has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is no longer possible, partly due to later presentation with symptoms to a healthcare provider. Objective: To explore the theoretical underpinning of the Scottish CHEST intervention in participants randomized to the intervention group within the CHEST Australia trial. Methods: A purposive maximum variation sample of participants who received the intervention in the CHEST trial in Perth, Western Australia (N = 13) and Melbourne, Victoria, (N = 7) were interviewed. Patients were asked about their experience of the CHEST consultation, their recall of the main messages, their symptom appraisal and issues relating to help seeking when they develop symptoms. Thematic analysis was conducted to draw common themes between the participants. Results: We identified themes consistent with the theoretical basis of the CHEST intervention. Barriers to consultation identified in the CHEST Australia trial participants were smoker stigmatization, guilt, fatalism and symptom normalization. We identified a general perceived mistrust of GPs based on previous negative experiences of visiting their GP in relation to their smoking. The intervention tackled barriers around lecturing and feelings of guilt and stigma related to smoking. We identified expected effects on salience and personal relevance of symptoms. Participants reported a clearer understanding of what to look out for and when to take action after the CHEST intervention. Conclusions: These findings suggest that the CHEST Australia intervention is achieving the desired objectives at the qualitative level through the proposed theoretical mechanisms.

An olfactory 'stress test' may detect preclinical Alzheimer's disease.

BACKGROUND: The olfactory bulb (OB) receives extensive cholinergic input from the basal forebrain and is affected very early in Alzheimer's disease (AD). We speculated that an olfactory 'stress test' (OST), targeting the OB, might be used to unmask incipient AD. We investigated if change in olfactory performance following intranasal atropine was associated with several known antecedents or biomarkers of AD. METHODS: We measured change in performance on the University of Pennsylvania Smell Identification Test (UPSIT) in the left nostril before (20-items) and after (remaining 20-items) intranasal administration of 1 mg of atropine. We administered cognitive tests, measured hippocampal volume from MRI scans and recorded Apolipoprotein E genotype as indices relevant to underlying AD. RESULTS: In a convenience sample of 56 elderly individuals (14 probable AD, 13 cognitive impairment no dementia, 29 cognitively intact) the change in UPSIT score after atropine ('atropine effect' = AE) correlated significantly with demographically scaled episodic memory score (r = 0.57, p < 0.001) and left hippocampal volume (LHCV) (r = 0.53, p < 0.001). Among non-demented individuals (n = 42), AE correlated with episodic memory (r = 0.52, p < 0.001) and LHCV (r = 0.49, p < 0.001) and hierarchical linear regression models adjusted for age, gender, education, and baseline UPSIT showed that the AE explained more variance in memory performance (24%) than did LHCV (15%). The presence of any APOE ϵ4 allele was associated with a more negative AE (p = 0.014). CONCLUSIONS: The OST using atropine as an olfactory probe holds promise as a simple, inexpensive screen for early and preclinical AD and further work, including longitudinal studies, is needed to explore this possibility.

Rapid quantification and taxonomic classification of environmental DNA from both prokaryotic and eukaryotic origins using a microarray.

A microarray has been designed using 62,358 probes matched to both prokaryotic and eukaryotic small-subunit ribosomal RNA genes. The array categorized environmental DNA to specific phylogenetic clusters in under 9 h. To a background of DNA generated from natural outdoor aerosols, known quantities of rRNA gene copies from distinct organisms were added producing corresponding hybridization intensity scores that correlated well with their concentrations (r=0.917). Reproducible differences in microbial community composition were observed by altering the genomic DNA extraction method. Notably, gentle extractions produced peak intensities for Mycoplasmatales and Burkholderiales, whereas a vigorous disruption produced peak intensities for Vibrionales, Clostridiales, and Bacillales.

Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of an intervention to reduce time-to-consult with symptoms of lung cancer.

INTRODUCTION: Lung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer. METHODS/ANALYSIS: The intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms. ETHICS AND DISSEMINATION: Ethical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry ACTRN 1261300039 3752.