Quality of spirometry and related diagnosis in primary care with a focus on clinical use

Contains fulltext : 220998.pdf (publisher's version ) (Open Access

Three-Nucleon Force Effects in Nucleon Induced Deuteron Breakup: Comparison to Data (II)

Selected Nd breakup data over a wide energy range are compared to solutions of Faddeev equations based on modern high precision NN interactions alone and adding current three-nucleon force models. Unfortunately currently available data probe phase space regions for the final three nucleon momenta which are rather insensitive to 3NF effects as predicted by current models. Overall there is good to fair agreement between present day theory and experiment but also some cases exist with striking discrepancies. Regions in the phase space are suggested where large 3NF effects can be expected.Comment: 33 pages, 24 ps figures, 9 gif figure

Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells

Voltage-gated Cav1.2 calcium channels couple membrane depolarization to cAMP response-element-binding protein (CREB)-dependent transcriptional activation. To investigate the spatial and temporal organization of CREB-dependent transcriptional nuclear microdomains, we combined perforated patch-clamp technique and FRET microscopy for monitoring CREB and CREB-binding protein interaction in the nuclei of live cells. The experimental approach to the quantitative assessment of CREB-dependent transcriptional signaling evoked by cAMP- and Cav1.2-dependent mechanisms was devised in COS1 cells expressing recombinant Cav1.2 calcium channels. Using continuous 2-dimensional wavelet transform and time series analyses, we found that nuclear CREB-dependent transcriptional signaling is organized differentially in spatially and temporally separated microdomains of 4 distinct types. In rat neonatal cardiomyocytes, CREB-dependent transcription is mediated by the cAMP-initiated CaMKII-sensitive and Cav1.2-initiated CaMKII-insensitive mechanisms. The latter microdomains show a tendency to exhibit periodic behavior correlated with spontaneous contraction of myocytes suggestive of frequency-dependent CREB-dependent transcriptional regulation in the heart.—Kobrinsky, E., Duong, S.Q., Sheydina, A., Soldatov, N. M. Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells

The demographics, clinical characteristics and quality of life of patients with chronic cough from the Isala Cough Clinic in the Netherlands

Introduction Chronic cough affects ∼10% of the population and adversely impacts quality of life. This retrospective observational cohort study aimed to identify the demographics, clinical characteristics and quality of life of the chronic cough population in a Dutch chronic cough clinic, at baseline and following treatment at 6 months. Patients were categorised based on the underlying phenotype and response to treatment. Methods Retrospective data on 2397 patients who were diagnosed according to standard guidelines of the American College of Chest Physicians were analysed. Quality of life was captured via the Leicester Cough Questionnaire, the Cough Numeric Rating Scale and the Hospital Anxiety and Depression Scale. Results Mean patient age was 59 years; 62.5% of the patients were female; and 69.1% had at least one underlying phenotype associated with chronic cough. Of the latter, 52.1% had bronchial hyperresponsiveness/airflow limitation, 33.3% had airway reflux and 20.1% had upper airway cough syndrome. 46% of patients with a phenotype, and 51% without, experienced no improvement in their quality of life or still had significant cough remaining after 6 months. Of patients with available quality-of-life data, 37.5% were categorised as having refractory chronic cough, and 9.5% were categorised as unexplained chronic cough. Discussion This study highlights the poor quality-of-life outcomes in patients with chronic cough, despite interventions to treat underlying conditions, and indicates a need to manage chronic cough irrespective of phenotype

Anti-IL-5/5Ra biologics improve work productivity and activity in severe asthma:a RAPSODI registry-based cohort study

Introduction: Severe asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment. Aims and objectives: This study aims to relate treatment with biologics targeting IL-5/5Ra to work productivity and activity in the long term in a real-world context. Material and methods: This is a registry-based multi-center cohort study evaluating data from adults with severe eosinophilic asthma included in the Dutch Register of Adult Patients with Severe Asthma for Optimal DIsease management (RAPSODI). Patients that started with anti-IL-5/5Ra biologics and completed the work productivity and activity improvement questionnaire, were included. Study and patient characteristics were compared between the employed and unemployed patients. Work productivity and activity impairment are related to accompanying improvements in clinical outcomes. Results: At baseline, 91 of 137 patients (66%) were employed which remained stable throughout the follow-up period. Patients in the working age category were younger and had significantly better asthma control (p = 0.02). Mean overall work impairment due to health decreased significantly from 25.5% (SD2.6) to 17.6% (SD 2.8) during 12 months anti-IL-5/5Ra biologics treatment (P = 0.010). There was a significant association between ACQ6 and overall work improvement after targeted therapy (β = 8.7, CI 2.1–15.4, P = 0.01). The improvement of asthma control of 0.5 points on the asthma Control Questionnaire was associated with an overall work impairment of −9%. Conclusions: Work productivity and activity in severe eosinophilic asthma improved after starting anti-IL-5/5Ra biologics. Clinically relevant improvement in asthma control was associated with an overall work impairment score of −9% in this study.</p