Choosing the optimal dose in sublingual immunotherapy: Rationale for the 300 index of reactivity dose

Sublingual immunotherapy (SLIT) is an effective and well-tolerated method of treating allergic respiratory diseases associated with seasonal and perennial allergens. In contrast to the subcutaneous route, SLIT requires a much greater amount of antigen to achieve a clinical effect. Many studies have shown that SLIT involves a dose-response relationship, and therefore it is important to use a proven clinically effective dose from the onset of treatment, because low doses are ineffective and very high doses may increase the risk of side effects. A well-defined standardization of allergen content is also crucial to ensure consistent quality, potency and appropriate immunomodulatory action of the SLIT product. Several methods of measuring antigenicity are used by manufacturers of SLIT products, including the index of reactivity (IR), standardized quality tablet unit, and bioequivalent allergy unit. A large body of evidence has established the 300 IR dose of SLIT as offering optimal efficacy and tolerability for allergic rhinitis due to grass and birch pollen and HDM, and HDM-induced moderate, persistent allergic asthma. The 300 IR dose also offers consistency of dosing across a variety of different allergens, and is associated with higher rates of adherence and patient satisfaction. Studies in patients with grass pollen allergies showed that the 300 IR dose has a rapid onset of action, is effective in both adults and children in the short term and, when administered pre-coseasonally in the long term, and maintains the clinical benefit, even after cessation of treatment. In patients with HDM-associated AR and/or asthma, the 300 IR dose also demonstrated significant improvements in symptoms and quality of life, and significantly decreased use of symptomatic medication. The 300 IR dose is well tolerated, with adverse events generally being of mild or moderate severity, declining in frequency and severity over time and in the subsequent courses. We discuss herein the most important factors that affect the selection of the optimal dose of SLIT with natural allergens, and review the rationale and evidence supporting the use of the 300 IR dose

Management of the polyallergic patient with allergy immunotherapy: A practice-based approach

Background: The great majority (60-80 %) of patients consulting specialist physicians for allergic respiratory disease are polysensitized and thus may be potentially clinically polyallergic. However, management approaches to allergen immunotherapy (AIT) in polysensitized and polyallergic patients are not standardized. Methods: An international group of clinicians with in-depth expertise in AIT product development, clinical trials and clinical practice met to generate up-to-date, unambiguous, pragmatic guidance on AIT in polysensitized and polyallergic patients. The guidance was developed after reviewing (1) the current stance of regulatory bodies and learned societies, (2) the literature data on single- and multi-AIT and (3) the members' confirmed clinical experience with polysensitized patients. Results: AIT is safe and effective in polysensitized and polyallergic patients, and should always be based on the identification of one or more clinically relevant allergens (based on the type and severity of symptoms, the duration of induced symptoms, the impact on quality of life and how difficult an allergen is to avoid). Single-AIT is recommended in polyallergic patients in whom one of the relevant allergens is nevertheless clearly responsible for the most intense and/or bothersome symptoms. Parallel 2-allergen immunotherapy or mixed 2-allergen immunotherapy is indicated in polyallergic patients in whom two causal relevant allergens have a marked clinical and QoL impact. In parallel 2-allergen immunotherapy (whether subcutaneous or sublingual), high-quality, standardized, single-allergen formulations must be administered with an interval of 30 min. Mixing of allergen extracts may be considered, as long as (1) the mixture is technically feasible, (2) the mixture is allowed from a regulatory standpoint, (3) the allergen doses are reduced in proportion to the number of components but are still at concentrations with demonstrated efficacy. Conclusions: Physicians can prescribe AIT (preferably with high-quality, standardized, single-allergen formulations) with confidence in polysensitized and polyallergic patients by focusing on clinical/QoL relevance and safety

A DRIVING SIMULATION STUDY ON THE EFFECTS OF DIFFERENT WINE TYPES ON THE PERFORMANCE OF YOUNG DRIVERS

Background. Alcohol consumption is responsible for a significant number of road fatalities. To contrast this phenomenon, a more responsible attitude to the wine consumption, especially among young, inexperienced drivers prone to risky behaviour on the road must be promoted. Method. This is a simplified single-blind, placebo-controlled experiment aimed at evaluating 44 young drivers monitored during a driving simulation following the consumption of natural and conventional wines, with a reference blood alcohol concentration (BAC) of 0.5 g/l. Two hypotheses are tested: (1) the legal consumption of wine has no significant impact on young drivers’ performance in both ordinary and unusual road events; (2) natural and conventional wines are expected to produce negligible and acceptable impairments in young drivers the same BAC. Two reference groups (BAC = 0 g/l), one a placebo controlled group with drivers treated with a dealcoholized wine, were included. Results and Conclusions. Significant differences between the groups in terms of perception and reaction times (PRT) to visual and auditory stimuli, and to speeding were observed, with young drivers treated with conventional wine displaying more aggressive behaviours. In contrast, participants treated with natural wine showed PRT which were not significantly different from those belonging to control groups. The gaze attention levels of wine treated drivers were found to be dose dependant, with young drivers of the two control groups and those of the treated ones with BAC < 0.3 g/l able to focus on wider area ahead and, thereby, collect more information from the road environment

Turbocompound power unit modelling for a supercapacitor-based series hybrid vehicle application

In this paper, starting from the measurements available for a 2000 cm3 turbocharged diesel engine, an analytical model of the turbocharger is proposed and validated. The model is then used to extrapolate the efficiency of a power unit with a diesel engine combined with a turbocompound system. The obtained efficiency map is used to evaluate the fuel economy of a supercapacitor-based series hybrid vehicle equipped with the turbocompound power unit. The turbocompound model, in accordance with the studies available in the technical literature, shows that the advantages (in terms of efficiency increase) are significant at high loads. For this reason, turbocompound introduction allows a significant efficiency improvement in a series hybrid vehicle, where the engine always works at high-load. The fuel economy of the proposed vehicle is compared with other hybrid and conventional vehicle configurations

Multiplex Networks: A Framework for Studying Multiprocess Multiscale Connectivity Via Coupled-Network Theory With an Application to River Deltas

Transport of water, nutrients, or energy fluxes in many natural or coupled human natural systems occurs along different pathways that often have a wide range of transport timescales and might exchange fluxes with each other dynamically. Although network approaches have been proposed for studying connectivity and transport properties on single-layer networks, theories considering interacting networks are lacking. We present a general framework for transport on multiscale coupled-connectivity systems, via multilayer networks which conceptualize the system as a set of interacting networks, each arranged in a separate layer, and with interactions across layers acknowledged by interlayer links. We illustrate this framework by examining transport in river deltas as a dynamic interaction of flow within river channels and overland flow on the islands, when controlled by the flooding level. We show the potential of the framework to answer quantitative questions related to the characteristic timescale of response in the system