Blood-sampling collection prior to surgery may have a significant influence upon biomarker concentrations measured

Abstract Background Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and disease progression. The validation of biomarkers is a cumbersome process involving many steps. Serum samples from lung cancer patients were collected in the framework of a larger study for evaluation of biomarkers for early detection of lung cancer. The analysis of biomarker levels measured revealed a noticeable difference in certain biomarker values that exhibited a dependence of the time point and setting of the sampling. Biomarker concentrations differed significantly if taken before or after the induction of anesthesia and if sampled via venipuncture or arterial catheter. Methods To investigate this observation, blood samples from 13 patients were drawn 1–2 days prior to surgery (T1), on the same day by venipuncture (T2) and after induction of anesthesia via arterial catheter (T3). The biomarkers Squamous Cell Carcinoma antigen (CanAG SCC EIA, Fujirebio Diagnostics, Malvern, USA), Carcinoembrionic Antigen (CEA), and CYFRA 21-1 (Roche Diagnostics GmbH, Mannheim, Germany) were analyzed. Results SCC showed a very strong effect in relation to the sampling time and procedure. While the first two points in time (T1; T2) were highly comparable (median fold-change: 0.84; p = 0.7354; correlation ρ = 0.883), patients showed a significant increase (median fold-change: 4.96; p = 0.0017; correlation ρ = -0.036) in concentration when comparing T1 with the sample time subsequent to anesthesia induction (T3). A much weaker increase was found for CYFRA 21-1 at T3 (median fold-change: 1.40; p = 0.0479). The concentration of CEA showed a very small, but systematic decrease (median fold-change: 0.72; p = 0.0039). Conclusions In this study we show the unexpectedly marked influence of blood withdrawal timing (before vs. after anesthesia) and procedure (venous versus arterial vessel puncture) has on the concentration of the protein biomarker SCC and to a less extent upon CYFRA21-1. The potential causes for these effects remain to be elucidated in subsequent studies, however these findings highlight the importance of a standardized, controlled blood collection protocol for biomarker detection

Medical physics challenges in clinical MR-guided radiotherapy

The integration of magnetic resonance imaging (MRI) for guidance in external beam radiotherapy has faced significant research and development efforts in recent years. The current availability of linear accelerators with an embedded MRI unit, providing volumetric imaging at excellent soft tissue contrast, is expected to provide novel possibilities in the implementation of image-guided adaptive radiotherapy (IGART) protocols. This study reviews open medical physics issues in MR-guided radiotherapy (MRgRT) implementation, with a focus on current approaches and on the potential for innovation in IGART.Daily imaging in MRgRT provides the ability to visualize the static anatomy, to capture internal tumor motion and to extract quantitative image features for treatment verification and monitoring. Those capabilities enable the use of treatment adaptation, with potential benefits in terms of personalized medicine. The use of online MRI requires dedicated efforts to perform accurate dose measurements and calculations, due to the presence of magnetic fields. Likewise, MRgRT requires dedicated quality assurance (QA) protocols for safe clinical implementation.Reaction to anatomical changes in MRgRT, as visualized on daily images, demands for treatment adaptation concepts, with stringent requirements in terms of fast and accurate validation before the treatment fraction can be delivered. This entails specific challenges in terms of treatment workflow optimization, QA, and verification of the expected delivered dose while the patient is in treatment position. Those challenges require specialized medical physics developments towards the aim of fully exploiting MRI capabilities. Conversely, the use of MRgRT allows for higher confidence in tumor targeting and organs-at-risk (OAR) sparing.The systematic use of MRgRT brings the possibility of leveraging IGART methods for the optimization of tumor targeting and quantitative treatment verification. Although several challenges exist, the intrinsic benefits of MRgRT will provide a deeper understanding of dose delivery effects on an individual basis, with the potential for further treatment personalization

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

FUNDING Regeneron Pharmaceuticals NCT0213402; NCT02528214 Sanofi NCT0213402; NCT02528214Peer reviewedPublisher PD

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic

Framework for ReSTful Web Services in OSGi

Ensemble ReST is a software system that eases the development, deployment, and maintenance of server-side application programs to perform functions that would otherwise be performed by client software. Ensemble ReST takes advantage of the proven disciplines of ReST (Representational State Transfer. ReST leverages the standardized HTTP protocol to enable developers to offer services to a diverse variety of clients: from shell scripts to sophisticated Java application suite

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 o

Dupilumab reduces OCS use and improves lung function in patients with severe OCS-dependent asthma

Peer reviewedPostprin

Sustained Improvement in Clinical Efficacy, Asthma Control, and Quality of Life in Patients With Severe, Oral Corticosteroid (OCS)-Dependent Asthma Treated With Dupilumab : LIBERTY ASTHMA TRAVERSE Study

Acknowledgments and funding sources Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02528214 (VENTURE)/NCT02134028 (TRAVERSE). Medical writing/editorial assistance was provided by Nevena Krstić, PhD, of Excerpta Medica, and was funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline.Peer reviewedPostprin

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease

Abstract Background Long-acting muscarinic antagonist/long-acting β 2 -agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI). Methods This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD (NCT01085045). Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV 1 AUC 0–12 ) on Day 7 relative to baseline FEV 1 . Secondary endpoints included pharmacokinetics and safety. Results GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV 1 AUC 0–12 after 7 days’ treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002). GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators. Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful. GFF MDI was well tolerated. Conclusions GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD. Trial registration ClinicalTrials.gov NCT01085045. Registered 9 March 2010