Cluster protocols in SCIT: enough evidence for practical use?
ABSTRACT The review provides a comprehensive evaluation of Cluster schedules in subcutaneous-specific immunotherapy (SCIT) in terms of the safety profile and onset of clinical and immunological effects.
Recent major clinical studies could clearly reveal that Cluster schedules with both (semi-)depot-allergen preparations and chemically modified allergen preparations ('allergoids') are well tolerated therapeutic options in SCIT comparable to the safety profile of conventional build-up schedules. Moreover, preliminary data indicate that these accelerated protocols result in a more rapid achievement of clinical and immunological effects.
Conventional schedules in SCIT have the disadvantage of both a high expenditure of time and the need for a high patient compliance. In accelerated cluster schedules two to three injections are administered sequentially per treatment day (with an interval of 30 min between the injections) in weekly intervals aimed to reach the maintenance dose of SCIT in a short time interval. Recent studies indicate that these accelerated SCIT protocols result in a more rapid achievement of clinical and immunological effects than conventional schedules. Moreover, the safety profile is comparable between conventional and cluster SCIT.
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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: Several years ago, omalizumab became commercially available for the treatment of severe asthma. It remains the only monoclonal antibody to be marketed for this purpose. Since then, many studies have been published endorsing its efficacy and effectiveness. Concomitantly, evidence of an overlap between atopic and non-atopic severe asthma has emerged. However, there also appears to be some disagreement regarding the value of omalizumab in the management of non-atopic disease, as some studies have failed to show any benefit in these patients. The recent literature has also sought to identify appropriate prognostic biomarkers for the use of omalizumab, other than immunoglobulin (IgE) levels. This article briefly summarizes the evolution of asthma treatment, the pathophysiology of the condition, and the method of action of omalizumab. The author describes the controlled and uncontrolled studies (also named "real-life studies") published in adult and pediatric populations in different countries and expresses his view on the current place of the drug in the management of severe allergic asthma. He offers a personal perspective on the recent evidence for the use of omalizumab in non-atopic patients, highlighting the implications for current clinical practice and the gaps in our knowledge. The author justifies his belief that omalizumab is not only an IgE-blocking drug and should be considered as a disease-modifying therapy because of its multiple effects on different biologic pathways. Finally, some areas for future research are indicated.Drugs 04/2014; 74(5). DOI:10.1007/s40265-014-0203-y · 4.13 Impact Factor