Prediction of response to biological treatment with monoclonal antibodies in severe asthma

In recent years, major developments have occurred in severe asthma management. Different asthma phenotypes and subgroups have been identified and new treatment options have become available. A total of five monoclonal antibodies are currently approved in severe asthma treatment: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. These drugs have been shown to reduce exacerbations and to have an oral corticosteroid-sparing effect in many severe asthma patients. However, biological treatment is not successful in all patients and should be discontinued in non-responsive patients. Treating the right patient with the right biologic, and therefore biologic response prediction, has become a major point of interest in severe asthma management. A variety of response outcomes is utilized in the different clinical trials, as well as a huge range of potential predicting factors. Also, regarding the timing of the response evaluation, there are considerable differences between studies. This review summarizes the results from studies on predicting responses and responders to biological treatment in severe asthma, taking into account clinical, functional and inflammatory parameters assessed prior to the start of treatment as well as following a few months of therapy. In addition, future perspectives are discussed, highlighting the need for more research to improve patient identification and treatment responses in the field of biological treatment in severe asthma

The perceived waning of biologics in severe asthma

BACKGROUND: Biologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown.OBJECTIVE: To explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration.METHODS: Severe asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files.RESULTS: 65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5-7.5) on a 0-10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p &lt; 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval.CONCLUSION: Two-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.</p

Seismic and geochemical evidence for large-scale mantle upwelling beneath the eastern Atlantic and western and central Europe

Seismic tomography and the isotope geochemistry of Cenozoic volcanic rocks suggest the existence of a large, sheet-like region of upwelling in the upper mantle which extends from the eastern Atlantic Ocean to central Europe and the western Mediterranean. A belt of extension and rifting in the latter two areas appears to lie above the intersection of the centre of the upwelling region with the base of the lithosphere. Lead, strontium and neodymium isotope data for all three regions converge on a restricted composition, inferred to be that of the upwelling mantle

Time-to-pregnancy and pregnancy outcomes in a South African population

<p>Abstract</p> <p>Background</p> <p>Time-to-pregnancy (TTP) has never been studied in an African setting and there are no data on the rates of adverse pregnancy outcomes in South Africa. The study objectives were to measure TTP and the rates of adverse pregnancy outcomes in South Africa, and to determine the reliability of the questionnaire tool.</p> <p>Methods</p> <p>The study was cross-sectional and applied systematic stratified sampling to obtain a representative sample of reproductive age women for a South African population. Data on socio-demographic, work, health and reproductive variables were collected on 1121 women using a standardized questionnaire. A small number (n = 73) of randomly selected questionnaires was repeated to determine reliability of the questionnaire. Data was described using simple summary statistics while Kappa and intra-class correlation statistics were calculated for reliability.</p> <p>Results</p> <p>Of the 1121 women, 47 (4.2%) had never been pregnant. Mean gravidity was 2.3 while mean parity was 2.0 There were a total of 2467 pregnancies; most (87%) resulted in live births, 9.5% in spontaneous abortion and 2.2% in still births. The proportion of planned pregnancies was 39% and the median TTP was 6 months. The reliability of the questionnaire for TTP data was good; 63% for all participants and 97% when censored at 14 months. Overall reliability of reporting adverse pregnancy outcomes was very high, ranging from 90 - 98% for most outcomes.</p> <p>Conclusion</p> <p>This is the first comprehensive population-based reproductive health study in South Africa, to describe the biologic fertility of the population, and provides rates for planned pregnancies and adverse pregnancy outcomes. The reliability of the study questionnaire was substantial, with most outcomes within 70 - 100% reliability index. The study provides important public information for health practitioners and researchers in reproductive health. It also highlights the need for public health intervention programmes and epidemiological research on biologic fertility and adverse pregnancy outcomes in the population.</p

Development of microspheres for biomedical applications: a review

An overview of microspheres manufactured for use in biomedical applications based on recent literature is presented in this review. Different types of glasses (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres (both natural and synthetic) in the form of porous , non-porous and hollow structures that are either already in use or are currently being investigated within the biomedical area are discussed. The advantages of using microspheres in applications such as drug delivery, bone tissue engineering and regeneration, absorption and desorption of substances, kinetic release of the loaded drug components are also presented. This review also reports on the preparation and characterisation methodologies used for the manufacture of these microspheres. Finally, a brief summary of the existing challenges associated with processing these microspheres which requires further research and development are presented

Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward