Potential Cost Savings by Switching from Subcutaneous to Intralymphatic Insect Venom Immunotherapy

Introduction: IgE-mediated bee venom allergy can be treated with allergen-specific immunotherapy (AIT). Subcutaneous immunotherapy (SCIT) is time and cost intensive due to the repeated consultations, but the costs are justified by the high risk of potentially life-threatening allergic reactions, including anaphylaxis. However, intralymphatic immunotherapy (ILIT) offers potential to reduce treatment costs due to a significant reduction in injections and a shorter duration of therapy. Therefore, we calculated the cost savings that arise when switching from SCIT to ILIT. Methods: Treatment protocols for ILIT were based on previous ILIT studies. Treatment protocols for SCIT were based on routine treatment at the University Hospital Zurich (USZ). The treatment costs were calculated based on the internal hospital information system (KISIM). Results: The calculations revealed a potential two-fold reduction in treatment costs if ILIT is used instead of SCIT in patients with bee venom allergy. The costs could be reduced from EUR 11,612.59 with SCIT to EUR 5,942.15 with ILIT over 5 years. Conclusions: This study shows that bee venom ILIT has a cost-benefit potential for health insurances and patients, which should encourage further ILIT studies and which should be taken into account when considering future implementation of ILIT in the standard care of venom allergy

Intralymphatic Immunotherapy (ILIT) With Bee Venom Allergens: A Clinical Proof-of-Concept Study and the Very First ILIT in Humans

BackgroundSubcutaneous venom immunotherapy (VIT) represents an effective treatment against bee venom allergy. However, it involves long treatment times, high costs, and the risk of adverse events (AEs). Shorter, safer, and cheaper treatment options are therefore pursued.ObjectiveTo determine the safety, immunogenicity, and efficacy of bee venom intralymphatic immunotherapy (ILIT).MethodsIn an open pilot study, 12 patients received bee venom ILIT in three sessions with 14-day intervals: 0.1–5 μg/dose. Ultrasound imaging was applied to guide an injection and to document the lymph node structure. In a second study, 67 patients from 15 centers in Europe and Australia were randomized to receive four doses of either 10- or 20-μg bee venom ILIT with 28-day intervals. Clinical endpoints included specific IgE and IgG and protection after a bee sting challenge. These studies were performed in the years 2000–2003.ResultsIn a proof-of-concept study, no serious AEs were observed. An increase in allergen-specific IgG1 but no IgG4 and IgE was observed. ILIT induced the protection against a bee sting challenge in 7 out of 8 challenged patients. In a multicenter study, an increase in allergen-specific IgG and IgE was observed, with the highest increase in patients receiving a higher ILIT dose. The study was terminated due to several serious AEs upon the sting challenge provocation after the completion of treatment. However, out of 45 patients challenged, 15 (65%) and 18 (82%) patients in the 10- and 20-μg group, respectively, showed an improvement of two grades or more. No correlation was observed between antibody levels and sting protection.ConclusionsWhile a pilot study suggested the safety and efficacy of bee venom ILIT, a high number of AEs seen after the sting challenge following a randomized study indicate that the immunology protection offered by bee venom ILIT is insufficient. Of note, the bee venom allergen extract used in the two studies were from the two different providers. While the first study used a formulation approved for use in subcutaneous VIT, the second study used a nonapproved formulation never tested in humans. Further studies on approved formulations should be performed to generate conclusive results regarding the safety and efficacy of bee venom ILIT

A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor

A monoclonal anti-CD160 antibody inhibits the growth of new vessels in pathological ocular and tumor neoangiogenesis but not in healthy tissues

Bacteria-inducing legume nodules involved in the improvement of plant growth, health and nutrition

Bacteria-inducing legume nodules are known as rhizobia and belong to the class Alphaproteobacteria and Betaproteobacteria. They promote the growth and nutrition of their respective legume hosts through atmospheric nitrogen fixation which takes place in the nodules induced in their roots or stems. In addition, rhizobia have other plant growth-promoting mechanisms, mainly solubilization of phosphate and production of indoleacetic acid, ACC deaminase and siderophores. Some of these mechanisms have been reported for strains of rhizobia which are also able to promote the growth of several nonlegumes, such as cereals, oilseeds and vegetables. Less studied are the mechanisms that have the rhizobia to promote the plant health; however, these bacteria are able to exert biocontrol of some phytopathogens and to induce the plant resistance. In this chapter, we revised the available data about the ability of the legume nodule-inducing bacteria for improving the plant growth, health and nutrition of both legumes and nonlegumes. These data showed that rhizobia meet all the requirements of sustainable agriculture to be used as bio-inoculants allowing the total or partial replacement of chemicals used for fertilization or protection of crops

Interface debonding behaviour: Chapter III of the State-of-the-Art Report of RILEM Technical Committee 241-MCD Series

International audienceThe performance and durability of multi-layered pavements strongly depend on interlayer bonding between layers, especially for pavements with a thin or ultra-thin surface course. These pavements, comprised of several differing material layers, are often subjected to premature distresses (corrugation, peeling, slippage or fatigue cracking, etc.) caused by poor interface bonding. This chapter summarizes the different bond characterization tests available around the world (mostly in the laboratory) available to characterize the bond between pavement layers. Many of the tests can be performed on specimens prepared in the laboratory or on cores or slabs obtained from the pavement. Mostly, 'pure' fracture mode test methods (opening mode I or in-plane, shear mode II or out-of-plane, shear mode III) are currently used worldwide for determining the interlayer bond of pavement layers. Most of the mixed-mode test methods (mainly for the combination of Modes I and II) were developed by a few research teams and there are therefore no standard tests. Although tack coat type and content are the main parameters studied by researchers and engineers, surface roughness, moisture, freezing, and presence of dust or debris on the interface are additional parameters that may decrease bonding performance

Recommendation of RILEM TC 241-MCD on Interface Debonding Testing in Pavements

International audienceThe following recommendations are based on the chapter III of a State of the Art review conducted by the Task Group 2 of the RILEM Technical Committee 241-MCD 'Mechanisms of cracking and debonding in asphalt and composite pavements' (Petit et al in Mechanisms of cracking and debonding in asphalt and composite pavements. Chapter III of the State-of-the-Art report of the RILEM technical committee 241-MCD series, vol 28. Springer, New York, pp 103-154. ISBN 978-3-319-76848-9 2018). The recommendations mostly concern 'pure' fracture mode test methods that are currently used worldwide and even standardized, while mixed mode test methods developed by few research teams have not received full attention. This paper intends to give guidance for the application and characterization of interlayer bond testing, looking at the appropriate test methods and the importance of influencing parameters

Feeding ecology and predation impact of the recently established amphipod, Themisto libellula, in the St. Lawrence marine system, Canada

Themisto libellula was virtually absent from the St. Lawrence marine system (SLMS) before 1990. Since then, it has become an abundant, full-time resident of this system. Hyperiid amphipods of the genus Themisto are principally carnivorous and represent an essential link in the trophic pathway from secondary production to higher trophic levels. Sampling of T. libellula was carried out in the lower St. Lawrence Estuary (LSLE) and the northwest Gulf of St. Lawrence (NWGSL) in the fall of 1998, 2003 and 2004 to study the feeding dynamics and predation impact of this species on mesozooplankton and macrozooplankton communities. Our results showed that T. libellula was an opportunistic predator with a circadian feeding cycle; activity was higher during the second part of the night and the sunrise period. Stomach content analyses showed that these amphipods consumed chiefly copepods, in particular, the copepodite stages CIV and CV of Calanus finmarchicus. Euphausiids, chaetognaths, amphipods and mysids constituted other important prey. Digestion time was estimated at 13 h. The daily ingestion rate of T. libellula was estimated using 2 approaches: (1) stomach fullness index and (2) mean number of prey removed per unit of time and converted to prey biomass using the stage-species dry masses of each prey item. We found that the daily ingestion rate of T. libellula ranged from 6.32 to 16.82% of body dry mass per day in both study areas (LSLE and NWGSL). Concerning predation impact, T. libellula consumed between 0.14 and 1.79% of the combined mesozooplankton and macrozooplankton standing stock per day and between 0.43 and 2.48% of the C. finmarchicus standing stock. Themisto libellula may thus exert a significant control on the mesozooplankton and macrozooplankton communities in the SLMS through direct predation. -- Keywords : Hyperiid amphipod ; Themisto libellula ; Feeding ecology ; Ingestion rate ; Digestion time ; Predation impact ; Gulf of St. Lawrence

Examining E-Loyalty in a Sexual Health Website: Cross-Sectional Study

Background: Web-based sexual health resources are typically evaluated in terms of their efficacy. Information is lacking about how sexual health promotion websites are perceived and used. It is essential to understand website use to address challenges with adherence and attrition to Web-based health interventions. An existing theoretical framework for examining loyalty to electronic health (eHealth) interventions has been not yet been applied in the context of sexual health promotion nor has the association between e-loyalty and intended intervention efficacy outcomes been investigated. Objective: The objectives of this study were to investigate users’ loyalty toward a sexual health website (ie, e-loyalty), measure user perceptions of the website, and measure the association between e-loyalty and perceived knowledge increase and intent to change behavior. Methods: Over 4 months, website users (clients and health care providers) participated in an open, online, cross-sectional survey about their user experiences that measured e-loyalty, user perceptions, and intended website efficacy outcomes. Relationships between user perceptions and e-loyalty were investigated using structural equation modeling (SEM). Associations between e-loyalty and website efficacy outcomes were tested using Spearman rank correlation. Results: A total of 173 participants completed user perception questions and were included in the analysis. E-loyalty was high for both clients and providers and was significantly correlated with clients’ perceived knowledge increase (ρ(171)=.30, P<.001), their intent to have safer sex (ρ(171)=.24, P=.01), and their intent to get tested for sexually transmitted infections (ρ(171)=.37, P<.001). The SEM showed that trustworthiness, overall experience, active trust, and effectiveness were directly related to e-loyalty. Finding the website “easy to understand” was significantly related to active trust (ie, participants’ willingness to act upon information presented on the website). Conclusions: E-loyalty may be related to the efficacy of the selected website in improving one’s sexual health and was significantly associated with all three intended knowledge and behavioral outcomes. To increase e-loyalty, trustworthiness and active trust are important user perceptions to deliberately engender. Our findings indicate that understanding a website contributes to active trust, thereby highlighting the importance of considering eHealth literacy in designing health promotion websites. Our study confirms the relevance of e-loyalty as an outcome for evaluating the antecedents of the use and efficacy of online public health interventions across disciplines by adapting and validating an existing e-loyalty framework to the field of sexual health promotion. Our findings suggest that e-loyalty is positively associated with measures of website efficacy, including increased knowledge and intent to change behavior. Longitudinal research with larger samples could further investigate the relationships between e-loyalty, website understandability, and outcomes of online health interventions to determine how the manipulation of website characteristics may impact user perceptions and e-loyalty

The Role of Lateral Tension in Calcium-Induced DPPS Vesicle Rupture

We assess the role of lateral tension in rupturing anionic dipalmitoylphosphatidyserine (DPPS), neutral dipalmitoylphosphatidylcholine (DPPC), and mixed DPPS–DPPC vesicles. Binding of Ca²⁺ is known to have a significant impact on the effective size of DPPS lipids and little effect on the size of DPPC lipids in bilayer structures. In the present work we utilized laser transmission spectroscopy (LTS) to assess the effect of Ca²⁺-induced stress on the stability of the DPPS and DPPC vesicles. The high sensitivity and resolution of LTS has permitted the determination of the size and shape of liposomes in solution. The results indicate a critical size after which DPPS single shell vesicles are no longer stable. Our measurements indicate Ca²⁺ promotes bilayer fusion up to a maximum diameter of ca. 320 nm. These observations are consistent with a straightforward free-energy-based model of vesicle rupture involving lateral tension between lipids regulated by the binding of Ca²⁺. Our results support a critical role of lateral interactions within lipid bilayers for controlling such processes as the formation of supported bilayer membranes and pore formation in vesicle fusion. Using this free energy model we are able to infer a lower bound for the area dilation modulus for DPPS (252 pN/nm) and demonstrate a substantial free energy increase associated with vesicle rupture