The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK

Susan C Edwards,1 Sian E Fairbrother,2 Anna Scowcroft,3 Gavin Chiu,4 Andrew Ternouth,3 Brian J Lipworth5 1Department of Market Access Pricing & Outcomes Research, 2Department of Medical Affairs - Respiratory, 3Department of Market Access, 4Department of Prescription Medicine - Respiratory, Boehringer Ingelheim, Bracknell, UK; 5Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK Background: This study characterized a cohort of chronic obstructive pulmonary disease (COPD) patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization.Methods: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013) or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of face-to-face interactions with a health care professional (HCP), COPD-related exacerbations, hospitalizations, and referrals.Results: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B) on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on maintenance bronchodilator monotherapy was 2 years. The median number of prescriptions was 14. On average, patients had 15 HCP interactions per year, and one in ten patients experienced a COPD exacerbation (N=8,811). One in 50 patients were hospitalized for COPD per year (n=4,848).Conclusion: The average monotherapy-treated patient had a higher than average HCP interaction rate. We also identified a large cohort of patients who were stepped up to triple therapy despite a low rate of exacerbations. The use of the new class of long-acting muscarinic antagonist/long-acting β2-adrenergic agonist fixed-dose combinations may provide a useful step-up treatment option in such monotherapy patients, before the use of inhaled corticosteroids. Keywords: COPD, UK primary care setting, bronchodilators, prescribing patterns, monotherap

Development of a Methodology for Large-Scale Production of Prions for Biological and Structural Studies

Prion diseases are a group of infectious neurodegenerative diseases produced by the conversion of the normal prion protein (PrPC) into the disease-associated form (PrPSc). Extensive evidence indicate that the main or sole component of the infectious agent is PrPSc, which can replicate in affected individuals in the absence of nucleic acids. However, the mechanism of PrPC-to-PrPSc conversion remains elusive, which has been attributed to the lack of sufficient structural information of infectious PrPSc and a reliable system to study prion replication in vitro. In this article we adapted the Protein Misfolding Cyclic Amplification (PMCA) technology for rapid and efficient generation of highly infectious prions in large-scale. Murine prions of the RML strain were efficiently propagated in volumes up to 1,000-fold larger than conventional PMCA. The large-scale PMCA (LS-PMCA) procedure enabled to produce highly infectious prions, which maintain the strain properties of the seed used to begin the reaction. LS-PMCA was shown to work with various species and strains of prions, including mouse RML and 301C strains, hamster Hyper prion, cervid CWD prions, including a rare Norwegian CWD prion, and human CJD prions. We further improved the LS-PMCA into a bioreactor format that can operate under industry-mimicking conditions for continuous and unlimited production of PrPSc without the need to keep adding brain-derived prions. In our estimation, this bioreactor can produce in 1d an amount of prions equivalent to that present in 25 infected animals at the terminal stage of the disease. Our LS-PMCA technology may provide a valuable tool to produce large quantities of well-defined and homogeneous infectious prions for biological and structural studies

The Carnegie Hubble Program: The Infrared Leavitt Law in IC 1613

We have observed the dwarf galaxy IC 1613, at multiple epochs in the mid-infrared using Spitzer and contemporaneously in the near-infrared using the new FourStar near-infrared camera on Magellan. We have constructed Cepheid period–luminosity relations in the J, H, K_s, [3.6] and [4.5] bands and have used the run of their apparent distance moduli as a function of wavelength to derive the line-of-sight reddening and distance to IC 1613. Using a nine-band fit, we find E(B − V) = 0.05 ± 0.01 mag and an extinction-corrected distance modulus of μ_0 = 24.29 ± 0.03_(statistical) ± 0.03_(systematic) mag. By comparing our multi-band and [3.6] distance moduli to results from the tip of the red giant branch and red clump distance indicators, we find that metallicity has no measurable effect on Cepheid distances at 3.6 μm in the metallicity range −1.0 ≤ [Fe/H] ≤ 0.2, hence derivations of the Hubble constant at this wavelength require no correction for metallicity

Erratum: The Carnegie Hubble Program: The Leavitt Law at 3.6 micron and 4.5 micron in the Large Magellanic Cloud (2011, APJ, 743, 76)

Due to an error at the publisher, an incorrect version of Table 3 appeared in the published article. The updated version of Table 3 is given

Standard Galactic Field RR Lyrae. I. Optical to Mid-infrared Phased Photometry

We present a multi-wavelength compilation of new and previously published photometry for 55 Galactic field RR Lyrae variables. Individual studies, spanning a time baseline of up to 30 years, are self-consistently phased to produce light curves in 10 photometric bands covering the wavelength range from 0.4 to 4.5 microns. Data smoothing via the GLOESS technique is described and applied to generate high-fidelity light curves, from which mean magnitudes, amplitudes, rise times, and times of minimum and maximum light are derived. 60,000 observations were acquired using the new robotic Three-hundred MilliMeter Telescope (TMMT), which was first deployed at the Carnegie Observatories in Pasadena, CA, and is now permanently installed and operating at Las Campanas Observatory in Chile. We provide a full description of the TMMT hardware, software, and data reduction pipeline. Archival photometry contributed approximately 31,000 observations. Photometric data are given in the standard Johnson UBV, Kron–Cousins ${R}_{C}{I}_{C}$, 2MASS JHK, and Spitzer [3.6] and [4.5] bandpasses

Biomass distribution among tropical tree species grown under\ud differing regional climates

In the Neotropics, there is a growing interest in establishing plantations of native tree species for commerce, local consumption, and to replant on abandoned agricultural lands. Although numerous trial plantations have been established, comparative information on the performance of native trees under different regional environments is generally lacking. In this study, we evaluated the accumulation and partitioning of above-ground biomass in 16 native and two exotic tree species growing in replicated species selection trials in Panama under humid and dry regional environments. Seven of the 18 species accumulated greater total biomass at the humid site than at the dry site over a two-year period. Species specific biomass partitioning among leaves, branches and trunks was observed. However, awide range of total biomass found among species (from 1.06 kg for Dipteryx panamensis to 29.84 kg for Acacia mangium at Soberania) justified the used of an Aitchison log ratio transformation to adjust for size. When biomass partitioning was adjusted for size, a majority of these differences proved to be a result of the ability of the tree to support biomass components rather than the result of differences in the regional environments at the two sites. These findings were confirmed by comparative ANCOVAs on Aitchison-transformed and non-Aitchison-transformed variables. In these comparisons, basal diameter, height and diameter at breast height were robust predictors of biomass for the pooled data from both sites, but Aitchison-transformed\ud variables had little predictive power