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11.
Harold M. Hudson Serigne N. Lô R. John Simes Andrew M. Tonkin Stephane Heritier 《Statistics in medicine》2014,33(10):1621-1645
Transform methods have proved effective for networks describing a progression of events. In semi‐Markov networks, we calculated the transform of time to a terminating event from corresponding transforms of intermediate steps. Saddlepoint inversion then provided survival and hazard functions, which integrated, and fully utilised, the network data. However, the presence of censored data introduces significant difficulties for these methods. Many participants in controlled trials commonly remain event‐free at study completion, a consequence of the limited period of follow‐up specified in the trial design. Transforms are not estimable using nonparametric methods in states with survival truncated by end‐of‐study censoring. We propose the use of parametric models specifying residual survival to next event. As a simple approach to extrapolation with competing alternative states, we imposed a proportional incidence (constant relative hazard) assumption beyond the range of study data. No proportional hazards assumptions are necessary for inferences concerning time to endpoint; indeed, estimation of survival and hazard functions can proceed in a single study arm. We demonstrate feasibility and efficiency of transform inversion in a large randomised controlled trial of cholesterol‐lowering therapy, the Long‐Term Intervention with Pravastatin in Ischaemic Disease study. Transform inversion integrates information available in components of multistate models: estimates of transition probabilities and empirical survival distributions. As a by‐product, it provides some ability to forecast survival and hazard functions forward, beyond the time horizon of available follow‐up. Functionals of survival and hazard functions provide inference, which proves sharper than that of log‐rank and related methods for survival comparisons ignoring intermediate events. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
12.
A. P. Bel’nik R. U. Ostrovskaya I. I. Poletaeva 《Neuroscience and behavioral physiology》2009,39(1):81-86
Male C57BL/6J, BALB/c, and DBA/2J mice showed differences in their abilities to perform two cognitive tests. C57BL/6J mice
had good learning ability and memory trace retention (at 10 days) in a simplified Morris maze, while BALB/c mice had low levels
of memory trace retention and DBA/2J mice had low learning ability in this test. I.p. administration of the nootropic agent
Noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) at a dose of 0.5 mg/kg 15 min before the start of the test induced
significant improvements in long-term memory in this test in BALB/c mice but no further improvement in C57BL/6J mice, and
had no effect in DBA/2J mice. On testing the ability to extrapolate the direction of movement of a stimulus, administration
of Noopept increased the proportion of correct responses in C57BL/6J and BALB/c mice, but had no effect in DBA/2J mice.
Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 57, No. 6, pp. 721–728, November–December,
2007. 相似文献
13.
利用信号外推实现磁共振快速成像 总被引:1,自引:0,他引:1
本文提出了一种广义的频域紧支集信号外推的新方法 ,并将之应用于提高核磁共振成像速度。计算机仿真和实验结果表明了文中的理论和方法是有效的和可应用的。 相似文献
14.
BACKGROUND: The purpose of this report was to review issues associated with the introduction of alternative versions of biosimilars used in the oncology setting. DESIGN: Data were obtained by searches of MEDLINE, PubMed, references from relevant English-language articles, and guidelines from the European Medicines Agency. RESULTS: When biosimilars are approved in EU, they will be considered 'comparable' to the reference product, but this does not ensure therapeutic equivalence. Inherent differences between biosimilars may produce dissimilarities in clinical efficacy, safety, and immunogenicity. Switching biosimilars should be considered a change in clinical management. Regulatory guidelines have been established for some biosimilar categories but, because of the limited clinical experience with biosimilars at approval, pharmacovigilance programs will be important to establish clinical databases. Guidelines also provide a mechanism for the extrapolation of clinical indications (approved indications for which the biosimilar has not been studied). This may be of concern where differences in biological activity can result in adverse outcomes or when safety is paramount (e.g. stem cell mobilization in healthy donors). These issues should be addressed in biosimilar labeling. CONCLUSIONS: Biosimilars should provide cost savings and greater accessibility to biopharmaceuticals. A thorough knowledge surrounding biosimilars will ensure the appropriate use of biopharmaceuticals. 相似文献
15.
Michael Wilhelm Sabine Bergmann Hermann H. Dieter 《International journal of hygiene and environmental health》2010,213(3):224-232
After detection of perfluorooctanoate (PFOA) in drinking water at concentrations up to 0.64 μg/l in Arnsberg, Sauerland, Germany, the German Drinking Water Commission (TWK) assessed perfluorinated compounds (PFCs) in drinking water and set for the first time worldwide in June 2006 a health-based guide value for safe lifelong exposure at 0.3 μg/l (sum of PFOA and perfluorooctanesulfonate, PFOS). PFOA and PFOS can be effectively removed from drinking water by percolation over granular activated carbon. Additionally, recent EU-regulations require phasing out use of PFOS and ask to voluntarily reduce the one of PFOA. New and shorter-chained PFCs (C4–C7) and their mixtures are being introduced as replacements. We assume that some of these “new” compounds could be main contributors to total PFC levels in drinking water in future, especially since short-chained PFCs are difficult to remove from drinking water by common treatment techniques and also by filtration over activated carbon. The aims of the study were to summarize the data from the regularly measured PFC levels in drinking water and in the drinking water resources in North Rhine-Westphalia (NRW) for the sampling period 2008–2009, to give an overview on the general approach to assess PFC mixtures and to assess short-chained PFCs by using toxicokinetic instead of (sub)chronic data. No general increase of substitutes for PFOS and PFOA in wastewater and surface water was detected. Present findings of short-chained PFC in drinking waters in NRW were due to extended analysis and caused by other impacts. Additionally, several PFC contamination incidents in drinking water resources (groundwater and rivers) have been reported in NRW. The new approach to assess short-chained PFCs is based on a ranking of their estimated half-lives for elimination from the human body. Accordingly, we consider the following provisional health-related indication values (HRIV) as safe in drinking water for lifelong exposure: perfluorobutanoate (PFBA) 7 μg/l, perfluoropentanoate (PFPA) 3 μg/l, perfluorohexanoate (PFHxA) 1 μg/l, perfluoroheptanoate (PFHpA) 0.3 μg/l, perfluorobutanesulfonate (PFBS) 3 μg/l, perfluoropentanesulfonate (PFPS) 1 μg/l, perfluorohexanesulfonate (PFHxS) 0.3 μg/l and perfluoroheptanesulfonate (PFHpS) 0.3 μg/l. For all PFCs the long-term lowest maximal quality goal (general precautionary value, PVg) in drinking water is set to −0.1 μg/l. 相似文献
16.
Lin JH 《Pharmaceutical research》2006,23(6):1089-1116
Cytochrome P450 (CYP) induction-mediated interaction is one of the major concerns in clinical practice and for the pharmaceutical
industry. There are two major issues associated with CYP induction: a reduction in therapeutic efficacy of comedications and
an induction in reactive metabolite-induced toxicity. Because CYP induction is a metabolic liability in drug therapy, it is
highly desirable to develop new drug candidates that are not potent CYP inducer to avoid the potential of CYP induction-mediated
drug interactions. For this reason, today, many drug companies routinely include the assessment of CYP induction at the stage
of drug discovery as part of the selection processes of new drug candidates for further clinical development. The purpose
of this article is to review the molecular mechanisms of CYP induction and the clinical implications, including pharmacokinetic
and pharmacodynamic consequences. In addition, factors that affect the degree of CYP induction and extrapolation of in vitro CYP induction data to in vivo situations will also be discussed. Finally, assessment of the potential of CYP induction at the drug discovery and development
stage will be discussed. 相似文献
17.
To analyze the in vitro release profiles of mitomycin C from albumin microspheres prepared by chemical denaturation in a multiparticulate system, a method to calculate the total cumulative amount of mitomycin C released from a batch of microspheres was developed. Mitomycin C-loaded albumin macrospheres (diameter in mm range) were prepared, and the in vitro release kinetics of mitomycin C from individual macrospheres were determined. Then the relationship between the kinetic parameters and the physical parameters (e.g., diameter, weight) was investigated under the assumption that macrospheres and microspheres behave identically. Further, the size distribution of microspheres was measured, and the total cumulative amount of mitomycin C released from albumin microspheres was calculated. The release profiles of mitomycin C from individual macrospheres fitted first-order release kinetics better than spherical matrix kinetics. The calculated initial mitomycin C contents and first-order release rate constants for individual macrospheres were correlated with the weight and reciprocal of surface area of the macrospheres, respectively. The observed in vitro release profile for the microspheres agreed with the calculated values. These results suggest that this method is valid for calculating drug release from albumin microspheres. 相似文献
18.
G. Jonderko K. Jonderko A. Końca M. Gałaszek W. Koterla Z. Gałaszek 《European journal of applied physiology》1991,63(2):135-139
Summary The purpose of this study was to determine the validity and practicality of exponential vs linear backward extrapolation of the O2 recovery curve for prediction of exercise oxygen consumption (VO2). Eight men and women, age 20.1, 0.9 years, body mass 66.0, 2.5 kg (mean, SEM), completed seven bouts of cycle ergometer exercise at submaximal power outputs ranging from 50 to 175 W. Respiratory gases were collected from each subject during exercise and recovery. The monoexponential extrapolation of five recovery samples (r
2=0.85) and linear extrapolation of one recovery sample taken during the first 20-s of recovery (r
2=0.83) accounted for similar amounts of variance in predicting exercise VO2. The linear regression equation was the most practical predictor, as only one recovery gas sample was necessary and it did not require the complicated mathematical techniques used in exponential regression. 相似文献
19.
Wojciech Jurczak Monika Długosz Danecka Christian Buske 《Expert opinion on biological therapy》2019,19(10):1045-1056
ABSTRACTIntroduction: The approval of rituximab, a monoclonal antibody targeting CD20, revolutionized the treatment of B-cell non-Hodgkin lymphomas and became an undisputed standard of care. However, as with all biologic medicines, the complex development and manufacturing process for rituximab have meant that the medicine attracts high treatment costs. Approved rituximab biosimilars have been comprehensively demonstrated to match the reference medicine. With the potential to increase access to biologic therapy, they have a key role in helping to improve patient outcomes in lymphoma care.Areas covered: In this review, we discuss the role of rituximab in the treatment of lymphoma. We explore development and regulatory requirements for biosimilar development and the potential impact of these medicines on access and sustainability. Focusing on biosimilars of rituximab, we examine in detail the evidence for biosimilarity for the two rituximab biosimilars that are approved in Europe and provide an overview of rituximab biosimilars currently in development.Expert opinion: We foresee a wider uptake of biosimilar medicines for lymphoma treatment over the next 5 years. The associated cost savings should be invested in broadening patient access to biological therapies, enabling wider use of more expensive treatment strategies and driving innovation in cancer care. 相似文献
20.
Extrapolation from a source to a target, eg, from adults to children, is a promising approach to utilize external information when data are sparse. In the context of meta-analyses, one is commonly faced with a small number of studies, whereas potentially relevant additional information may also be available. Here, we describe a simple extrapolation strategy using heavy-tailed mixture priors for effect estimation in meta-analysis, which effectively results in a model-averaging technique. The described method is robust in the sense that a potential prior-data conflict, ie, a discrepancy between source and target data, is explicitly anticipated. The aim of this paper is to develop a solution for this particular application to showcase the ease of implementation by providing R code, and to demonstrate the robustness of the general approach in simulations. 相似文献