The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study

Rupert Jones,1 Jessica Martin,2 Vicky Thomas,3 Derek Skinner,4 Jonathan Marshall,5 Martina Stagno d’Alcontres,2 David Price2,6 1Clinical Trials and Health Research, Institute of Translational and Stratified Medicine, Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK; 2Observational and Pragmatic Research Institute, Singapore; 3Cambridge Research Support, Cambridge, UK; 4Optimum Patient Care, Cambridge, UK; 5Mundipharma International Limited, Cambridge, UK; 6Centre for Academic Primary Care, University of Aberdeen, Aberdeen, UK Abstract: Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 µg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 µg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 µg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI. Keywords: COPD, inhaler type, exacerbations, pneumonia, diabetes, dose-response, inhaled steroid/LABA combination&nbsp

Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD

The Role of FeNO in Cough Management : A Randomised Controlled Trial

This abstract is funded by: Observational & Pragmatic Research Institute Pte Ltd, and Circassia Presented at thematic poster session: A34 ASTHMA CLINICAL STUDIES I Sunday 20th MayPeer reviewedPostprin

Accessory oral cavity associated with duplication of the tongue and the mandible in a newborn: A rare case of Diprosopus. Multi-row detector computed tomography diagnostic role

Craniofacial duplication is a very rare malformation. The phenotype comprises a wide spectrum, ranging from partial duplication of few facial structures to complete dicephalus. We report the case of a newborn with an accessory oral cavity associated to duplication of the tongue and the mandible diagnosed by multi-row detector Computed Tomography, few days after her birth. Our case of partial craniofacial duplication can be considered as Type II of Gorlin classification or as an intermediate form between Type I and Type II of Sun classification.Our experience demonstrates that CT scan, using appropriate reconstruction algorithms, permits a detailed evaluation of the different structures in an anatomical region. Multi-row CT scan is also the more accurate diagnostic procedure for the pre-surgical evaluation of craniofacial malformations. (C) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved

TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice.

The TPP1/ACD protein (hereafter TPP1) is a component of the shelterin complex at mammalian telomeres. Here we find that Tpp1-deficient mouse embryonic fibroblasts (MEFs) show increased chromosomal instability including sister chromatid fusions and chromosomes with multitelomeric signals related to telomere fragility. Tpp1 deletion decreases both TERT (the telomerase catalytic subunit) binding to telomeres in MEFs and telomerase function at chromosome ends in vivo. Abrogation of Tpp1 abolished net telomere elongation in the context of nuclear reprogramming of MEFs into induced pluripotent stem cells, whereas Tpp1 deletion in stratified epithelia of Tpp1(Delta/Delta)K5-Cre mice resulted in perinatal death, severe skin hyperpigmentation, and impaired hair follicle morphogenesis. p53 deficiency rescues skin hyperpigmentation and hair growth in these mice, indicating that p53 restricts proliferation of Tpp1-deficient cells. These results suggest a telomere-capping model where TPP1 protects telomere integrity and regulates telomerase recruitment to telomeres, thereby preventing early occurrence of degenerative pathologies