Smoking, attitudes to smoking and provision of smoking cessation advice in two teaching hospitals in Ireland: do smoke-free policies matter?

Brief cessation advice from health-care professionals in the hospital setting significantly increases the likelihood of patients quitting smoking, yet patients are not routinely provided with this advice. Smoke-free hospital policies aim to protect individuals from the adverse effects of smoking; however, it is unclear if such policies encourage systematic delivery of cessation advice by health-care professionals. The study’s aim was to determine the prevalence of smoking and cessation advice received by in-patients in two teaching hospitals in Ireland which have implemented smoke-free hospital policies, and to examine patient attitudes towards smoking cessation. Change in smoking prevalence and delivery of smoking cessation advice prior to and post-policy implementation was also examined in one hospital. This study surveyed 466 in-patients across 2 hospital sites, over a 3-week and 5- week period, respectively. Data were also compared to a survey completed prior to the implementation of the smoke-free policy in one of the hospital sites. Smoking prevalence was 17% in Beaumont Hospital and 28% in Connolly Hospital. Overall, nicotine dependence was low (Mean Fagerström Test for Nicotine Dependence = 4.21, ±2.9). Overall, 62% of smokers did not receive smoking cessation advice from a health professional, although 55% indicated a willingness to engage with this type of service. The before-and-after analysis of Beaumont Hospital showed a reduction in smoking prevalence (17% vs 21%) amongst hospital in-patients, and a 6% increase in reported cessation advice provided following the introduction of the hospital smoke-free policy. Smoke-free hospital policies play a role in decreasing the prevalence of in-patient smokers, but further intervention is needed to increase rates of cessation advice provided. Positive attitudes to smoking cessation, coupled with low average nicotine dependence, suggest that lowintensity interventions would be beneficial for most smokers. A systematic focus on provision of brief smoking cessation advice is needed in hospitals

Holistic Perspective

Background: Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing. The study described here was a double-blind, double-dummy, randomised, placebo-controlled trial, the aim of which was to assess the efficacy of once-daily VI compared with placebo in patients with persistent asthma. The primary endpoint was change from baseline in 24-hour weighted mean forced expiratory volume in 1 second after 12 weeks of treatment vs. placebo. An active control arm received salmeterol (SAL) twice daily. All patients were maintained on a stable background dose of ICS. Results: Patients (n = 347) received VI, placebo or SAL (1:1:1). For the primary endpoint, substantial improvements in lung function were seen with VI (359 ml), SAL (283 ml) and placebo (289 ml). There were no statistically significant treatment differences between either the VI (70 ml, P = 0.244) or SAL (-6 ml, P = 0.926) groups and placebo. Both active treatments were well tolerated, with similarly low rates of treatment-related adverse events compared with placebo. No treatment-related serious adverse events occurred. Conclusions: This study failed to show a treatment difference between VI and placebo for the primary endpoint, in the presence of a placebo response of unforeseen magnitude. Because the placebo response was so large, it is not possible to draw meaningful conclusions from the data. The reason for this magnitude of effect is unclear but it may reflect increased compliance with the anti-inflammatory therapy regimen during the treatment period. Trial registration: NCT01181895 at ClinicalTrials.gov

Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma

Abstract Background Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients. Methods Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical development programme in asthma. Safety data from 10 parallel-group, randomised, double-blind Phase II and III studies (including 3345 patients who received at least one dose of fluticasone furoate) were integrated to provide information on adverse events, withdrawals, laboratory assessments, vital signs and hypothalamic-pituitary-adrenal axis function. The efficacy of once-daily fluticasone furoate was evaluated in all included studies. Results Once-daily fluticasone furoate 100 μg and 200 μg safety profiles were consistent with those reported for other inhaled corticosteroids, and both doses consistently demonstrated efficacy versus placebo. In the integrated analysis, no dose-response relationship was observed for the overall incidence of adverse events and there were no significant effects of fluticasone furoate on hypothalamic-pituitary-adrenal axis function. Conclusion Once-daily fluticasone furoate 100 μg and 200 μg had acceptable safety profiles and was efficacious in adult and adolescent patients with asthma. There was no evidence of cortisol suppression at studied doses. Trial registrations GSK (NCT01499446/FFA20001, NCT00398645/FFA106783, NCT00766090/112202, NCT00603746/FFA109684, NCT00603278/FFA109685, NCT00603382/FFA109687, NCT01436071/115283, NCT01436110/115285, NCT01159912/112059, NCT01431950/114496, NCT01165138/HZA106827, NCT01086384/106837, NCT01134042/HZA106829 and NCT01244984/1139879)

Australian consensus statement for best practice ROS1 testing in advanced non-small cell lung cancer

Lung cancer is the most commonly diagnosed malignancy and the leading cause of death from cancer globally. Diagnosis of advanced non-small cell lung cancer (NSCLC) is associated with 5-year relative survival of 3.2%. ROS proto-oncogene 1 (ROS1) is an oncogenic driver of NSCLC occurring in up to 2% of cases and commonly associated with younger age and a history of never or light smoking. Results of an early trial with the tyrosine kinase inhibitor (TKI) crizotinib that inhibits tumours that harbour ROS1 rearrangements have shown an objective response rate (ORR) of 72% (95% CI 58–83%), median progression free survival (PFS) of 19.3 months (95% CI 15.2–39.1 months) and median overall survival (OS) of 51.4 months (95% CI 29.3 months to not reached). Therefore, with the availability of highly effective ROS1-targeted TKI therapy, upfront molecular testing for ROS1 status alongside EGFR and ALK testing is recommended for all patients with NSCLC. We review the tissue requirements for ROS1 testing by immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) and we present a testing algorithm for advanced NSCLC and consider how the future of pathology testing for ROS1 may evolve.</p

Most nocturnal asthma symptoms occur outside of exacerbations and associate with morbidity

BACKGROUND: Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied. OBJECTIVE: To determine the clinical consequences of nocturnal asthma symptom(s) requiring albuterol in children with mild-to-moderate persistent asthma outside of periods when oral corticosteroids were used for worsening asthma symptoms. METHODS: 285 children ages 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of three controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of nocturnal asthma symptoms requiring albuterol. RESULTS: Nocturnal asthma symptoms requiring albuterol occurred in 72.2% of participants at least once and in 24.3% ≥13 times. 81.3% of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use (56.9% of days preceded by nocturnal symptoms versus 18.1% of days not preceded by nocturnal symptoms, Relative Risk (RR) 2.3, 95%CI: 2.2,2.4), school absence (5.0% versus 0.3%, RR 10.6, 95%CI: 7.8,14.4), and doctor contact (3.7% versus 0.2%, RR 8.8, 95%CI:6.1,12.5). Similar findings were noted during exacerbation periods (RR 1.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contact). Nocturnal symptoms did not predict the onset of exacerbations. CONCLUSION: Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies.METHODS: Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients.RESULTS: Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza.CONCLUSION: Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.</p

Assessing cough symptom severity in refractory or unexplained chronic cough:findings from patient focus groups and an international expert panel

BACKGROUND: Cough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity. OBJECTIVE: The aim of this study was to establish items and domains that would inform development of a new cough severity instrument. METHODS: Three focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity. RESULTS: The patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, and provided an additional subdomain related to cough triggers. The final conceptual framework comprised 51 items in the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: triggers, control, frequency, fit/bout duration, intensity, quality and associated features/sequelae). CONCLUSIONS: Consensus findings from patients and international experts established domains of urge-to-cough and cough symptom with associated subdomains and relevant items. The results support item generation and content validity for a novel patient-reported outcome measure for use in health research and clinical practice

Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma

This study was funded by GSK (NCT01563029)