Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD

Dirkje S Postma,1 Nicolas Roche,2 Gene Colice,3 Elliot Israel,4 Richard J Martin,5 Willem MC van Aalderen,6 Jonathan Grigg,7 Anne Burden,8 Elizabeth V Hillyer,8 Julie von Ziegenweidt,8 Gokul Gopalan,9 David Price8,10 1University of Groningen, Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 2Respiratory and Intensive Care Medicine, Cochin Hospital Group, APHP, Paris-Descartes University (EA2511), Paris, France; 3Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center and George Washington University School of Medicine, Washington DC, USA; 4Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, National Jewish Health, Denver, CO, USA; 6Dept of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital AMC, Amsterdam, the Netherlands; 7Blizard Institute, Queen Mary University London, London, UK; 8Research in Real Life, Ltd, Cambridge, UK; 9Respiratory, Global Scientific Affairs, Teva Pharmaceuticals, Frazer, PA, USA; 10Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2–4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD. Patients and methods: Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection. Results: Mean patient age was 67 years, 57%–60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32–4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 µg/day versus 436 µg/day for initiation, 438 µg/day versus 534 µg/day for step-up patients). Conclusion: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up. Keywords: COPD exacerbation, extrafine particle, matched cohort analysis, real life, small airway

Emission of photon echoes in a strongly scattering medium

We observe the two- and three-pulse photon echo emission from a scattering powder, obtained by grinding a Pr$^{3+}$:Y$_2$SiO$_5$ rare earth doped single crystal. We show that the collective emission is coherently constructed over several grains. A well defined atomic coherence can therefore be created between randomly placed particles. Observation of photon echo on powders as opposed to bulk materials opens the way to faster material development. More generally, time-domain resonant four-wave mixing offers an attractive approach to investigate coherent propagation in scattering media

Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

Asthma management guidelines recommend adding a long-acting β2-agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.Research in Real-Life ltd. Teva Pharmaceutical Industries

Spectroscopic investigations of a Ti:Tm:LiNbO3 waveguide for photon-echo quantum memory

We report the fabrication and characterization of a Ti$^{4+}$:Tm$^{3+}$:LiNbO$_3$ optical waveguide in view of photon-echo quantum memory applications. In particular, we investigated room- and cryogenic-temperature properties via absorption, spectral hole burning, photon echo, and Stark spectroscopy. We found radiative lifetimes of 82 $\mu$s and 2.4 ms for the $^3$H$_4$ and $^3$F$_4$ levels, respectively, and a 44% branching ratio from the $^3$H$_{4}$ to the $^3$F$_4$ level. We also measured an optical coherence time of 1.6 $\mu$s for the $^3$H$_6\leftrightarrow{}^3$H$_4$, 795 nm wavelength transition, and investigated the limitation of spectral diffusion to spectral hole burning. Upon application of magnetic fields of a few hundred Gauss, we observed persistent spectral holes with lifetimes up to seconds. Furthermore, we measured a linear Stark shift of 25 kHz$\cdot$cm/V. Our results are promising for integrated, electro-optical, waveguide quantum memory for photons.Comment: 11 pages, 14 figure

Let’s Get Naked: How to Amplify Student Voices in Vulnerable Conversations

Are you concerned that workshops about diversity and inclusion are not giving anything back to your students? We\u27ve been there. Come hear our story and learn about the evolution of our two-hour, interactive workshop for new underrepresented students at UNI. We\u27ve learned that to lead these conversations we have to be courageous, vulnerable, and committed to nurturing student voices. We invite you to bring your own stories and experiences in facilitating conversations about identity, self-awareness, and affinity group building

Tiotropium in asthma: A systematic review

Introduction: The objective of this paper is to systematically review the existing evidence of the effectiveness and safety profile of a long-acting inhaled muscarinic antagonist as add-on therapy in patients with asthma that is uncontrolled despite inhaled corticosteroid (ICS) use. Methods: With the assistance of two experienced research librarians, we searched Ovid MEDLINE/PubMed (1946 to September 12, 2013), the Cochrane Library review, and the TRIP database. The key search terms were “tiotropium and asthma.” The search was limited to human data published in English. Included in the systematic review were all randomized controlled trials that evaluated the efficacy of tiotropium in patients with asthma. The clinical trials had to be at least 4 weeks in duration and to provide adequate information on clinically appropriate end points in asthma care (eg, change in lung function, exacerbation rates, and/or ICS dosing). Data on patient characteristics, study design, outcome measures, concomitant asthma medication, and adverse events were extracted from the full text of each included individual study. Marked heterogeneity of study design precluded statistical pooling of results for a meta-analysis. Consequently, only descriptive summaries of outcomes are provided. Results: Our database search retrieved 149 citations. We found five randomized controlled trials in humans that met our criteria for inclusion in the systematic review. We also found two open-label uncontrolled trials that were considered in the discussion. Each of the five included studies met the Consolidated Standards of Reporting Trials criteria for a well-designed randomized trial. Discussion: The five clinical studies included in this systematic review focused on evaluating the efficacy of tiotropium as add-on therapy to ICS or ICS in combination with a long-acting inhaled β2-agonist (LABA) in patients with uncontrolled moderate to severe persistent asthma. Tiotropium maintained lung function when ICSs were tapered and when an LABA was discontinued. Tiotropium improved lung function when added to ICS alone or ICS–LABA combination therapy. In the only trial to have compared the addition of tiotropium with doubling the dose of ICS, tiotropium provided significantly superior results. In trials in which the addition of tiotropium was compared with salmeterol, the beneficial effects of these two bronchodilators were similar. No safety concerns were found with use of tiotropium as add-on therapy. Conclusion: Tiotropium may have a beneficial role in moderate to severe persistent asthma despite use of an ICS or ICS and LABA. Use of tiotropium as add-on therapy poses no safety concerns

Cost-effectiveness of initiating extrafine- or standard size-particle inhaled corticosteroid for asthma in two health-care systems: a retrospective matched cohort study

Data acquisition and analyses were funded by Teva Pharmaceuticals

Physiological characteristics of dysphagia following thermal burn injury

The study aim was to document the acute physiological characteristics of swallowing impairment following thermal burn injury. A series of 19 participants admitted to a specialised burn centre with thermal burn injury were identified with suspected aspiration risk by a clinical swallow examination (CSE) conducted by a speech-language pathologist and referred to the study. Once medically stable, each then underwent more detailed assessment using both a CSE and fiberoptic evaluation of swallowing (FEES). FEES confirmed six individuals (32%) had no aspiration risk and were excluded from further analyses. Of the remaining 13, CSE confirmed that two had specific oral-phase deficits due to orofacial scarring and contractures, and all 13 had generalised oromotor weakness. FEES revealed numerous pharyngeal-phase deficits, with the major findings evident in greater than 50% being impaired secretion management, laryngotracheal edema, delayed swallow initiation, impaired sensation, inadequate movement of structures within the hypopharynx and larynx, and diffuse pharyngeal residue. Penetration and/or aspiration occurred in 83% (n = 10/12) of thin fluids trials, with a lack of response to the penetration/aspiration noted in 50% (n = 6/12 penetration aspiration events) of the cases. Most events occurred post swallow. Findings support the fact that individuals with dysphagia post thermal burn present with multiple risk factors for aspiration that appear predominantly related to generalised weakness and inefficiency and further impacted by edema and sensory impairments. Generalised oromotor weakness and orofacial contractures (when present) impact oral-stage swallow function. This study has identified a range of factors that may contribute to both oral- and pharyngeal-stage dysfunction in this clinical population and has highlighted the importance of using a combination of clinical and instrumental assessments to fully understand the influence of burn injury on oral intake and swallowing

Acute cough: a diagnostic and therapeutic challenge

Abstract Background Acute cough is one of the most common complaints prompting patient visits to healthcare professionals. Despite the broad repercussions of acute cough on patient quality of life, school and work productivity, and public health resources, research on this condition is minimal, as are the available treatment options. Many patients use over-the-counter medicines, which are often ineffective for symptom relief. Some therapies may achieve antitussive activity, but at the expense of unpleasant or intolerable side effects. Unmet needs When considering the treatments currently available for the management of acute cough, the multiple limitations of such treatments are quite apparent. Most of these treatments lack clinically proven efficacy and reliability to support their use. This reinforces the need for the generation of quality scientific data from well-performed clinical trials. Hopefully, the result will be the development of safer, more effective and more reliable therapeutic options in the management of acute cough. Cough assessment and management Acute cough can be due to a variety of causes, and it is worthwhile to consider these pathogenic factors in some detail. It is also important to be familiar with the effects that acute cough has on patients' quality of life, work productivity, and the healthcare system; proper awareness of these effects may contribute to better understanding of the social impact of cough. In reference to the available treatments for the management of acute cough, adequate knowledge of the type of over-the-counter and prescription products in the market, as well as their mode of action and advantages/disadvantages, may provide expanded pharmacotherapeutic opportunities and facilitate better clinical decisions. However, due to the drawbacks of current treatment options, ideas for future cough management and newer products need to be considered and tested. Conclusion In view of the socio-economic impact of acute cough and the limitations of available treatments, a renewed interest in the management of acute cough needs to be encouraged. The current strategies for acute cough management need to be reassessed, with a focus on developing new, reliable products and formulations with proven efficacy and safety