BackgroundPersistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes.MethodsA systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted.ResultsSeventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0–1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities.ConclusionsLAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rare, heterogeneous, life-threatening, autoimmune condition. This study aimed to evaluate the cost-utility of avacopan in combination with rituximab or cyclophosphamide compared with glucocorticoids (GC) and cyclophosphamide or rituximab for the treatment of severe, active AAV from the Spanish National Health System perspective.

Treprostinil is a prostacyclin analogue indicated for the treatment of pulmonary arterial hypertension (PAH). A recent retrospective study analyzed the drug safety events of treprostinil and showed that higher doses were associated with lower hospitalization rates compared to lower doses. This analysis aims to estimate annual PAH-related hospitalization costs in patients treated with low, medium and high treprostinil doses in nine European countries (Belgium, France, Germany, Italy, Poland, Portugal, Spain, the Netherlands and the United Kingdom).

The aim. The aim of this work was to conduct a microscopic and phytochemical study of the seeds of chia (Salvia hispanica L.).
 Materials and methods. Chia seeds were examined macroscopically and microscopically. To study the qualitative composition of the main groups of biologically active substances, histochemical, microchemical and chemical reactions were used. Hydroxycinnamic acids were identified by paper chromatography. To obtain a lipophilic extract, a Soxhlet apparatus and an exhaustive chloroform extraction method were used. The study of the quantitative content of fatty acids was carried out by gas chromatography. The content of polysaccharides in the raw material was determined by the gravimetric method. According to the SPhU method, the raw material swelling index was determined.
 Results. The main macro- and microscopic features of chia seeds have been established. Histochemical reactions, microchemical reactions made it possible to establish the presence of mucus and fatty oils in chia seeds. With the help of chemical reactions, the presence of flavonoids in the raw material was established. The quantitative content of fatty oils is 24.0±1.2 %. The content of water-soluble polysaccharides in the whole raw material was 4.01±0.07 %, in the crushed raw material - 5.04 ± 0.05 %. As a result of determining the swelling index, it was found that this indicator for the whole chia seeds was 20, and for the crushed ones – 17. The content of hydroxycinnamic acids in the chia seeds was 1.07±0.03 %. 9 fatty acids have been identified, among which linoleic acid predominates in terms of content.
 Conclusions. The presence and quantitative content of mucus, fatty oils, water-soluble polysaccharides, flavonoids, hydroxycinnamic acids, fatty acids was confirmed in the seeds of chia (Salvia hispanica L.). The obtained data can be used to develop regulatory documentation for chia seeds in order to use this raw material in pharmacy and medicine

In the present study, Organosandwich structures consisting of a folded polypropylene (PP) honeycomb core and glass-fiber reinforced PP cross-ply face sheets are investigated with the aim of developing a valid method for structural simulation of Organosandwich structures. On the one hand, effective material properties are gained from a mesoscopic model on the basis of a representative volume element (RVE) and compared with data from experimental characterization. The morphology of the folded honeycomb structure was investigated via X-Ray computed tomography and 3d image analysis. On the other hand, the differences between experimental and effective core properties are shown, and the correlation between the mesoscopic honeycomb core structure and the entire sandwich behavior is validated by bending tests and a corresponding finite element model. A comparison shows that results can be achieved with the RVE model as well as with the homogenized core FE model with good agreement with the experimental data.

The 11th Global CRO Council Closed Forum was held in Universal City, CA, USA on 3 April 2017. Representatives from international CRO members offering bioanalytical services were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The second CRO-Pharma Scientific Interchange Meeting was held on 7 April 2017, which included Pharma representatives' sharing perspectives on the topics discussed earlier in the week with the CRO members. The issues discussed at the meetings included cumulative stability evaluations, matrix stability evaluations, the 2016 US FDA Immunogenicity Guidance and recent and unexpected FDA Form 483s on immunogenicity assays, the bioanalytical laboratory's role in writing PK sample collection instructions, biosimilars, CRO perspectives on the use of chiral versus achiral methods, hybrid LBA/LCMS assays, applications of fit-for-purpose validation and, at the Global CRO Council Closed Forum only, the status and trend of current regulated bioanalytical practice in China under CFDA's new BMV policy. Conclusions from discussions of these topics at both meetings are included in this report.

The 10th Global CRO Council (GCC) Closed Forum was held in Orlando, FL, USA on 18 April 2016. In attendance were decision makers from international CRO member companies offering bioanalytical services. The objective of this meeting was for GCC members to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at this closed forum included reporting data from failed method validation runs, GCP for clinical sample bioanalysis, extracted sample stability, biomarker assay validation, processed batch acceptance criteria, electronic laboratory notebooks and data integrity, Health Canada's Notice regarding replicates in matrix stability evaluations, critical reagents and regulatory approaches to counteract fraud. In order to obtain the pharma perspectives on some of these topics, the first joint CRO-Pharma Scientific Interchange Meeting was held on 12 November 2016, in Denver, Colorado, USA. The five topics discussed at this Interchange meeting were reporting data from failed method validation runs, GCP for clinical sample bioanalysis, extracted sample stability, processed batch acceptance criteria and electronic laboratory notebooks and data integrity. The conclusions from the discussions of these topics at both meetings are included in this report.

The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this year's closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industry's best practices and the conclusions from the discussion of these topics is included in this meeting report.

AimsThis bioequivalence study was conducted to assess the bioequivalence of two formulations, test and reference, of pregabalin 300 mg hard capsules, under fasting conditions.MethodsThis was a single-center, randomized, single-dose, open-label, laboratory-blinded, two-way crossover study, with a minimum washout period of 7 days. Plasma samples were collected prior to and up to 36 h after dosing. Pregabalin plasma concentrations were determined, using a validated method, by reversed phase high performance liquid chromatography coupled to a tandem mass spectrometry detector (LC–MS–MS). Pharmacokinetic metrics used for bioequivalence assessment were the AUC(0–t) (area under the plasma concentration–time curve from time zero to time of last observed non-zero plasma concentration) and the Cmax (maximum observed plasma concentration). These parameters were determined from the pregabalin plasma concentration data using noncompartmental analysis.ResultsForty healthy subjects, age ranging from 18 to 43 years old, were enrolled and randomized, of whom 39 completed the study. The ratio of geometric least square means for Cmax was 99.29 % (90 % confidence interval [CI] 93.29–105.67). The ratio of geometric least square means for AUC(0–t) was 101.54 % (90 % CI 100.13–102.98). The 90 % CIs were within the predefined range (80.00–125.00).ConclusionsBioequivalence between test and reference formulations, under fasting conditions, was concluded both in terms of rate and extent of absorption.