Subcutaneous allergen immunotherapy for allergic disease: examining efficacy, safety and cost-effectiveness of current and novel formulations.
ABSTRACT Subcutaneous immunotherapy (SCIT) is a unique therapy for allergic disease because it provides symptomatic relief while modifying the allergic disease by targeting the underlying immunological mechanism. Its efficacy and safety have been established in the treatment of asthma, allergic rhinitis/rhinoconjunctivitis and stinging insect hypersensitivity in numerous controlled clinical trials. This review evaluates a spectrum of clinical factors, ranging from efficacy to cost-effectiveness, which should be considered in evaluating SCIT. The evidence for SCIT safety and efficacy for these conditions is reviewed in an evaluation of the systematic reviews and meta-analyses. The evidence for the persistent and preventive effects of SCIT is also examined. An overview of the SCIT outcomes measures utilized in clinical trials is presented. The cost-effectiveness of SCIT compared with conventional medication treatment, novel indications and formulations for SCIT are also explored in this review.
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ABSTRACT: Background Cluster immunotherapy represents an interesting alternative to conventional up-dosing schedules because it allows achieving the maintenance dose within a shorter time interval. In this study, the efficacy and safety of cluster immunotherapy with a highly polymerized allergen extract of a grass/rye pollen mixture has been evaluated in a randomized, double-blind, placebo-controlled, multicenter study.Methods In total, 121 patients with allergic rhinoconjunctivitis due to grass pollen were randomized 1:1 to verum or placebo group. A short cluster-up-dosing-schedule of only 1 week was applied to achieve the maintenance dose which was administered monthly during the study period of one year. Total combined symptom and medication score (TCS) was defined as primary outcome parameter. Secondary outcome parameters were individual symptom and medication scores, “well days”, global improvement as well as immunological effects and nasal allergen challenge. The safety profile was evaluated based on the EAACI grading system.ResultsSignificant reduction in the verum compared to the placebo group (ITT-population, verum: n= 55; placebo: n= 47) was found regarding TCS (p=0.005), rhinoconjunctivitis total symptom score (RTSS, p=0.006) and total rescue medication score (TRMS, p=0.002). Additionally, secondary outcomes like “well days”, nasal challenge results and increase of specific IgG4 were in favor of the active treatment. All systemic adverse reactions (0.8% of all injections in the verum group) were of mild intensity. No severe reactions related to the study medication were observed.Conclusion Cluster immunotherapy with highly polymerized grass pollen extracts resulted in significant clinical efficacy and has been shown to be a safe treatment for grass pollen allergic patients.This article is protected by copyright. All rights reserved.Allergy 08/2014; DOI:10.1111/all.12513 · 6.00 Impact Factor
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ABSTRACT: In nand Flash memory, all pages have the same storage capacity and hence accommodate the same amount of redundancy in support of error correction. In current practice, user data in all the pages are protected by the same error correction code. However, different types of pages in multibit per cell memory have largely different bit error rates, for which appropriate unequal error correction can achieve a better utilization of memory redundancy and hence improve program/erase (P/E) cycling endurance. Nevertheless, a straightforward realization of unequal error correction suffers from severe memory read latency penalty. This brief presents a design strategy to implement unequal error correction through concatenated coding, which can well match the unequal error rates among different types of pages at minimal memory read latency penalty. Based on measurement results from commercial sub-22-nm 2 bits/cell nand Flash memory chips, we carried out simulations from both the coding and storage system perspectives, and the results show that this design strategy can improve the P/E cycling endurance by 20% and only incur less than 7% increase of storage system read response time at the end of Flash memory lifetime with the P/E cycling of around 1800.Circuits and Systems II: Express Briefs, IEEE Transactions on 05/2014; 61(5):354-358. DOI:10.1109/TCSII.2014.2312640 · 1.19 Impact Factor
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ABSTRACT: Allergen immunotherapy (AIT) is the only available causal treatment for allergic respiratory diseases; however, data demonstrate a high discontinuation rate for both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). The complex mechanism of action of allergen immunotherapy (AIT) includes an interaction of innate and adaptive immune processes, resulting in immune tolerance, as illustrated by a decrease in specific immunoglobulin (Ig)-E, an increase in specific IgG1 and IgG4, and inhibition of inflammation involving mast cells, basophils, and eosinophils. This induction of immune tolerance leads to a significant improvement in symptoms and decreased medication scores. A 3- to 5-year course of AIT is required to obtain this disease-modifying effect, which substantially differentiates AIT frompharmacologic treatment. A carry-over effect can persist for up to 12 years. Furthermore, AIT may prevent the onset of asthma in patients with allergic rhinitis, as well as decreasing the onset of new sensitizations to inhalant allergens. Several meta-analyses and controlled studies, involving adult and pediatric subjects, have indicated that both sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) are relatively safe, effective, and well tolerated. AIT may also have a positive impact on the cost to the healthcare system, as evidence indicates the cost–benefit of such treatment. Adherence to AIT is crucial for a positive clinical outcome and non-adherence represents a major drawback for such therapy. It actually concerns not only AIT but also various pharmacologic treatments for allergic respiratory diseases, as well as for other chronic illnesses. The issue of non-adherence is an emerging and worldwide problem for chronic diseases and could be an important factor responsible for an overall decrease in treatment efficacy and increased rates of hospitalization, morbidity, and mortality. This review provides an overview of the different reasons that may account for the low adherence rate for AIT. Some of these reasons can be related to the patient’s age when they begin such therapy, the allergic disease being treated, and questions about the efficacy, costs, inconvenience, and safety of AIT. Well-structured educational programs,especially by healthcare professionals, the print media, and the Internet, are needed to improve adherence to AIT.12/2014; 2(1). DOI:10.1007/s40521-014-0037-6