Home About us Contact
|
Home About us Contact | ||
|
|
||
Full Response (full + response)
Selected AbstractsCost-effectiveness of biological therapy for Crohn's disease: Markov cohort analyses incorporating United Kingdom patient-level cost dataALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009K. BODGER Summary Background, Anti-TNF-alpha agents for Crohn's disease (CD) have good clinical efficacy but high acquisition cost compared to rival drugs. Aim, To assess the cost-effectiveness of infliximab and adalimumab for Crohn's disease from the perspective of the UK NHS, incorporating recent trial and observational data. Methods, Lifetime Markov analyses constructed to simulate quality-adjusted life-years (QALYs) and costs. CD was represented by four health-states representing: Full response, partial response, nonresponse, surgery and death. The course of CD under standard care was based on the Olmsted county cohort. Systematic review identified ACCENT I (infliximab) and CHARM (adalimumab) as sources for efficacy data. We modelled an intention-to-treat strategy for biologics including surgical rates based on observational data, cost estimates from our UK dataset and utilities from an algorithm converting CDAI to EQ-5D utilities. Results, The incremental cost-effectiveness ratios (ICERs) compared to standard care for 1-year of treatment with infliximab or adalimumab were £19 050 and £7190 per QALY gained, respectively. Lifetime therapy was dominated by standard care. Analyses over shorter time horizons, matched to treatment duration, resulted in unfavourable ICERs. Conclusion, The model suggests acceptable ICERs for biological agents when considering a lifetime horizon with periods of up to 4 years continuous therapy. As with all economic evaluations, the results may not be generalizable beyond the perspective of analysis. [source] Glutamate drives the touch response through a rostral loop in the spinal cord of zebrafish embryosDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2009Thomas Pietri Abstract Characterizing connectivity in the spinal cord of zebrafish embryos is not only prerequisite to understanding the development of locomotion, but is also necessary for maximizing the potential of genetic studies of circuit formation in this model system. During their first day of development, zebrafish embryos show two simple motor behaviors. First, they coil their trunks spontaneously, and a few hours later they start responding to touch with contralateral coils. These behaviors are contemporaneous until spontaneous coils become infrequent by 30 h. Glutamatergic neurons are distributed throughout the embryonic spinal cord, but their contribution to these early motor behaviors in immature zebrafish is still unclear. We demonstrate that the kinetics of spontaneous coiling and touch-evoked responses show distinct developmental time courses and that the touch response is dependent on AMPA-type glutamate receptor activation. Transection experiments suggest that the circuits required for touch-evoked responses are confined to the spinal cord and that only the most rostral part of the spinal cord is sufficient for triggering the full response. This rostral sensory connection is presumably established via CoPA interneurons, as they project to the rostral spinal cord. Electrophysiological analysis demonstrates that these neurons receive short latency AMPA-type glutamatergic inputs in response to ipsilateral tactile stimuli. We conclude that touch responses in early embryonic zebrafish arise only after glutamatergic synapses connect sensory neurons and interneurons to the contralateral motor network via a rostral loop. This helps define an elementary circuit that is modified by the addition of sensory inputs, resulting in behavioral transformation. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast reveals a novel role for Gre2p as isovaleraldehyde reductaseFEMS YEAST RESEARCH, Issue 1 2007Michael Hauser Abstract A transcriptome analysis was performed of Saccharomyces cerevisiae undergoing isoamyl alcohol-induced filament formation. In the crucial first 5 h of this process, only four mRNA species displayed strong and statistically significant increases in their levels of more than 10-fold. Two of these (YEL071w/DLD3 and YOL151w/GRE2) appear to play important roles in filamentation. The biochemical activities ascribed to these two genes (d -lactate dehydrogenase and methylglyoxal reductase, respectively) displayed similarly timed increases to those of their respective mRNAs. Mutants carrying dld3 mutations displayed reduced filamentation in 0.5% isoamyl alcohol and needed a higher concentration of isoamyl alcohol to effect more complete filament formation. Hence, DLD3 seems to be required for a full response to isoamyl alcohol, but is not absolutely essential for it. Mutants carrying gre2 mutations were derepressed for filament formation and formed large, invasive filaments even in the absence of isoamyl alcohol. These results indicate a previously unsuspected and novel role for the GRE2 gene product as a suppressor of filamentation by virtue of encoding isovaleraldehyde reductase activity. [source] Eicosanoids mediate the laminarin-induced nodulation response in larvae of the flesh fly, Neobellieria bullataARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2005Vanessa Franssens Abstract Insects have a highly developed innate immune system, including humoral and cellular components. The cellular immune responses refer to hemocyte-mediated processes such as phagocytosis, nodulation, and encapsulation. Nodulation is considered the predominant defense reaction to infection in insects. Treating third instar larvae of the grey flesh fly, Neobellieria bullata, with laminarin (,-1,3-glucan, a typical component of fungal cell walls) induced nodulation in a dose-dependent manner. This reaction was initiated very soon after injection and reached its maximal response level after 4 h. The nodules were not randomly distributed in the hemocoel, but were concentrated around the crop. The possible role of eicosanoids in this nodulation process was determined by treating larvae with the phospholipase A2 inhibitor, dexamethasone, the cyclooxygenase inhibitor, naproxen, and the lipoxygenase inhibitor, esculetin. Both dexamethasone and naproxen significantly impaired the ability of N. bullata larvae to form nodules in response to laminarin. Supplying dexamethasone-treated larvae with the eicosanoid precursor, arachidonic acid, restored the full response. On the other hand, treating larvae with esculetin did not influence the formation of nodules in response to laminarin. This is the first study that demonstrates the occurrence of a laminarin-induced nodulation response in Diptera. Phospholipase A2 and cyclooxygenase activities, both involved in prostaglandin biosynthesis, appear to play an important role in the regulation of this process. Arch. Insect Biochem. Physiol. 59:32,41, 2005. © 2005 Wiley-Liss, Inc. [source] Addressing an Idiosyncrasy in Estimating Survival Curves Using Double Sampling in the Presence of Self-Selected Right CensoringBIOMETRICS, Issue 2 2001Constantine E. Frangakis Summary. We investigate the use of follow-up samples of individuals to estimate survival curves from studies that are subject to right censoring from two sources: (i) early termination of the study, namely, administrative censoring, or (ii) censoring due to lost data prior to administrative censoring, so-called dropout. We assume that, for the full cohort of individuals, administrative censoring times are independent of the subjects' inherent characteristics, including survival time. To address the loss to censoring due to dropout, which we allow to be possibly selective, we consider an intensive second phase of the study where a representative sample of the originally lost subjects is subsequently followed and their data recorded. As with double-sampling designs in survey methodology, the objective is to provide data on a representative subset of the dropouts. Despite assumed full response from the follow-up sample, we show that, in general in our setting, administrative censoring times are not independent of survival times within the two subgroups, nondropouts and sampled dropouts. As a result, the stratified Kaplan,Meier estimator is not appropriate for the cohort survival curve. Moreover, using the concept of potential outcomes, as opposed to observed outcomes, and thereby explicitly formulating the problem as a missing data problem, reveals and addresses these complications. We present an estimation method based on the likelihood of an easily observed subset of the data and study its properties analytically for large samples. We evaluate our method in a realistic situation by simulating data that match published margins on survival and dropout from an actual hip-replacement study. Limitations and extensions of our design and analytic method are discussed. [source] Supply of inpatient geriatric medical services in AustraliaINTERNAL MEDICINE JOURNAL, Issue 4 2007L. Gray Abstract This study summarizes the findings of a national survey of inpatient geriatric services in Australia conducted in 2001. These data are unique as there are no uniform administrative data systems available to provide this information. Eight hundred and eighty-eight hospitals were surveyed and full responses were received from 690, representing 78% of hospitals and 85% of all hospital beds. The results illustrated wide variation in the style and level of provision of services among hospitals and across regional and state jurisdictions. [source] | |||||||||||||