Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study.

BACKGROUND: Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD). We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers. METHODS: Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 µg and placebo or FF/VI 100/25 µg + UMEC 62.5 µg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning. Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24. The non-inferiority margin for the lower 95% confidence limit was set at - 50 mL. RESULTS: A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528). Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI's was considered non-inferior to FF/VI + UMEC. At Week 24, the proportion of responders based on St George's Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups). A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12). The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC). CONCLUSIONS: Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks. Results were similar on all other measures of efficacy, health-related quality of life, and safety. TRIAL REGISTRATION: GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016).

Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial.

BACKGROUND: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting ß2 agonist (LABA). METHODS: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. RESULTS: 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. CONCLUSIONS: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. TRIAL REGISTRATION NUMBER: NCT01513460.

A patient preference study that evaluated fluticasone furoate and mometasone furoate nasal sprays for allergic rhinitis.

BACKGROUND: Corticosteroid nasal sprays are the mainstay of treatment for allergic rhinitis. These sprays have sensory attributes such as scent and/or odor, taste and aftertaste, and run down the throat and/or the nose, which, when unpleasant, can affect patient preference for, and compliance with, treatment. OBJECTIVE: This study examined patient preference for fluticasone furoate nasal spray (FFNS) or mometasone furoate nasal spray (MFNS) based on their sensory attributes after administration in patients with allergic rhinitis. METHODS: This was a multicenter, randomized, double-blind, cross-over study. Patient preferences were determined by using three questionnaires (Overall Preference, Immediate Attributes, and Delayed Attributes). RESULTS: Overall, 56% of patients stated a preference for FFNS versus 32% for MFNS (p < 0.001); the remaining 12% stated no preference. More patients stated a preference for FFNS versus MFNS for the attributes of "less drip down the throat" (p < 0.001), "less run out of the nose" (p < 0.05), "more soothing" (p < 0.05), and "less irritating" (p < 0.001). More patients responded in favor of FFNS versus MFNS for the immediate attributes, "run down the throat" (p < 0.001), and "run out of the nose" (p < 0.001), and, in the delayed attributes, "run down the throat" (p < 0.001), "run out of the nose" (p < 0.01), "presence of aftertaste" (p < 0.01), and "no nasal irritation" (p < 0.001). CONCLUSION: Patients with allergic rhinitis preferred FFNS versus MFNS overall and based on a number of individual attributes, including "less drip down the throat," "less run out of the nose," and "less irritating." Greater preference may improve patient adherence and thereby improve symptom management of the patient's allergic rhinitis.

Is there an association between chronic lung disease and abdominal aortic aneurysm expansion?

BACKGROUND: Although there is evidence demonstrating an association between chronic obstructive pulmonary disease (COPD) and abdominal aortic aneurysm (AAA), it is not clear whether COPD predicts greater rates of expansion of established aneurysms. We sought such an association in a cohort of men with aneurysms detected in a population-based study of screening for aneurysms. METHODS: In addition to regular aortic ultrasound scans, 179 men with AAA underwent full lung function testing in order to identify the presence of COPD and its subgroups, emphysema and other obstructive ventilatory defects (OVD). The rate of expansion of each aneurysm was calculated and the men were divided into 'rapid expanders' (3 mm or more per year) and 'slow expanders' (less than 3 mm per year). Any association with the presence of COPD or smoking was tested using a multivariate model. RESULTS: Over a median follow-up period of 36 months the mean rate of aortic expansion for the cohort of 179 men was 2.1 mm/year. There was no significant difference in prevalence of COPD (68% overall) or having ever been a smoker (87% overall) between the rapid expanders and the slow expanders. CONCLUSIONS: Although there was a high prevalence of COPD among men with an AAA, there was no association between the rate of expansion of AAA and the presence of any form of this disease.

A day in the life of a volunteer incident commander: errors, pressures and mitigating strategies.

To meet an identified gap in the literature this paper investigates the tasks that a volunteer incident commander needs to carry out during an incident, the errors that can be made and the way that errors are managed. In addition, pressure from goal seduction and situation aversion were also examined. Volunteer incident commanders participated in a two-part interview consisting of a critical decision method interview and discussions about a hierarchical task analysis constructed by the authors. A SHERPA analysis was conducted to further identify potential errors. The results identified the key tasks, errors with extreme risk, pressures from strong situations and mitigating strategies for errors and pressures. The errors and pressures provide a basic set of issues that need to be managed by both volunteer incident commanders and fire agencies. The mitigating strategies identified here suggest some ways that this can be done.

Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion.

BACKGROUND: Patients with malignant pleural effusion (MPE) have limited prognoses. They require long-lasting symptom relief with minimal hospitalization. Indwelling pleural catheters (IPCs) and talc pleurodesis are approved treatments for MPE. Establishing the implications of IPC and talc pleurodesis on subsequent hospital stay will influence patient choice of treatment. Therefore, our objective was to compare patients with MPE treated with IPC vs pleurodesis in terms of hospital bed days (from procedure to death or end of follow-up) and safety. METHODS: In this prospective, 12-month, multicenter study, patients with MPE were treated with IPC or talc pleurodesis, based on patient choice. Key end points were hospital bed days from procedure to death (total and effusion-related). Complications, including infection and protein depletion, were monitored longitudinally. RESULTS: One hundred sixty patients with MPE were recruited, and 65 required definitive fluid control; 34 chose IPCs and 31 pleurodesis. Total hospital bed days (from any causes) were significantly fewer in patients with IPCs (median, 6.5 days; interquartile range [IQR] = 3.75-13.0 vs pleurodesis, mean, 18.0; IQR, 8.0-26.0; P = .002). Effusion-related hospital bed days were significantly fewer with IPCs (median, 3.0 days; IQR, 1.8-8.3 vs pleurodesis, median, 10.0 days; IQR, 6.0-18.0; P < .001). Patients with IPCs spent significantly fewer of their remaining days of life in hospital (8.0% vs 11.2%, P < .001, χ(2) = 28.25). Fewer patients with IPCs required further pleural procedures (13.5% vs 32.3% in pleurodesis group). There was no difference in rates of pleural infection (P = .68) and protein (P = .65) or albumin loss (P = .22). More patients treated with IPC reported immediate (within 7 days) improvements in quality of life and dyspnea. CONCLUSIONS: Patients treated with IPCs required significantly fewer days in hospital and fewer additional pleural procedures than those who received pleurodesis. Safety profiles and symptom control were comparable.

Zoonotic tuberculosis: on the decline.

Mycobacterium bovis is a zoonotic member of the Mycobacterium tuberculosis complex responsible for a clinical syndrome indistinguishable from that due to M. tuberculosis. In Australia, infection with M. bovis has historically been associated with employment in the livestock industry or immigration from countries in which animal disease is endemic. It currently accounts for 0.2% of all human cases of tuberculosis within Australia. This paper describes a case of pulmonary M. bovis in a butcher and reviews factors responsible for the declining incidence of this disease in Australia.