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

Vibrational properties of sulfoselenide solid solutions

In this work, Raman spectroscopy and X-ray diffraction were applied together to evaluate the crystal structure and the phonon modes of photovoltaic grade Cu 2ZnSn(SxSe1−x)4 thin films, leading to a complete characterization of their structural and vibrational properties. Vibrational characterization has been based on Raman scattering measurements performed with different excitation wavelengths and polarization configurations. Analysis of the experimental spectra has permitted identification of 19 peaks, which positions are in good accord with theoretical predictions. Besides, the observation of Cu 2ZnSnS4-like A symmetry peaks related to S vibrations and Cu 2ZnSnSe4-like A symmetry peaks related to Se vibrations, additional Raman peaks, characteristic of the solid solution and previously not reported, are observed, and are attributed to vibrations involving both S and Se anions

Candidate Screening of the TRPC3 Gene in Cerebellar Ataxia

The hereditary cerebellar ataxias are a diverse group of neurodegenerative disorders primarily characterised by loss of balance and coordination due to dysfunction of the cerebellum and its associated pathways. Although many genetic mutations causing inherited cerebellar ataxia have been identified, a significant percentage of patients remain whose cause is unknown. The transient receptor potential (TRP) family member TRPC3 is a non-selective cation channel linked to key signalling pathways that are affected in cerebellar ataxia. Furthermore, genetic mouse models of TRPC3 dysfunction display cerebellar ataxia, making the TRPC3 gene an excellent candidate for screening ataxic patients with unknown genetic aetiology. Here, we report a genetic screen for TRPC3 mutations in a cohort of 98 patients with genetically undefined late-onset cerebellar ataxia and further ten patients with undefined episodic ataxia. We identified a number of variants but no causative mutations in TRPC3. Our findings suggest that mutations in TRPC3 do not significantly contribute to the cause of late-onset and episodic human cerebellar ataxias

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Multidisciplinary systematic review of the relationships between poverty and stress, low level anxiety and depression across the life course

This multi-disciplinary systematic evidence review considers the main ways in which poverty and stress, low level anxiety and depression are linked in order to answer two key questions: • Does poverty cause stress, low level anxiety and depression? • Do stress, low level anxiety and depression cause poverty