A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely

Closed-Form Bayesian Inferences for the Logit Model via Polynomial Expansions

Articles in Marketing and choice literatures have demonstrated the need for incorporating person-level heterogeneity into behavioral models (e.g., logit models for multiple binary outcomes as studied here). However, the logit likelihood extended with a population distribution of heterogeneity doesn't yield closed-form inferences, and therefore numerical integration techniques are relied upon (e.g., MCMC methods). We present here an alternative, closed-form Bayesian inferences for the logit model, which we obtain by approximating the logit likelihood via a polynomial expansion, and then positing a distribution of heterogeneity from a flexible family that is now conjugate and integrable. For problems where the response coefficients are independent, choosing the Gamma distribution leads to rapidly convergent closed-form expansions; if there are correlations among the coefficients one can still obtain rapidly convergent closed-form expansions by positing a distribution of heterogeneity from a Multivariate Gamma distribution. The solution then comes from the moment generating function of the Multivariate Gamma distribution or in general from the multivariate heterogeneity distribution assumed. Closed-form Bayesian inferences, derivatives (useful for elasticity calculations), population distribution parameter estimates (useful for summarization) and starting values (useful for complicated algorithms) are hence directly available. Two simulation studies demonstrate the efficacy of our approach.Comment: 30 pages, 2 figures, corrected some typos. Appears in Quantitative Marketing and Economics vol 4 (2006), no. 2, 173--20

Sustainability of the chemical manufacturing industry - Towards a new paradigm?

This paper describes the current situation of the chemicalmanufacturingindustry, with special reference to Europe and looks to the future sustainability demands on the sector, and the implications of these demands for chemical engineering education. These implications include definitions of sustainability criteria for the sector and the need for transparent reporting under the Triple Bottom Line approach. The response of the education system to the sustainability agenda over the years and a number of strategies to incorporate it into courses are described. The important role of chemical (or more generally, process) engineers in delivering sustainable solutions is emphasised but this also suggests that anew way of thinking about the discipline is required. Indeed, this paper argues that the demand for a sustainable chemicalmanufacturing sector could bring about the next paradigm shift in the discipline which has been predicted for some time

Reproducibility of the computational fluid dynamic analysis of a cerebral aneurysm monitored over a decade

Computational fluid dynamics (CFD) simulations are increasingly utilised to evaluate intracranial aneurysm (IA) haemodynamics to aid in the prediction of morphological changes and rupture risk. However, these models vary and differences in published results warrant the investigation of IA-CFD reproducibility. This study aims to explore sources of intra-team variability and determine its impact on the aneurysm morphology and CFD parameters. A team of four operators were given six sets of magnetic resonance angiography data spanning a decade from one patient with a middle cerebral aneurysm. All operators were given the same protocol and software for model reconstruction and numerical analysis. The morphology and haemodynamics of the operator models were then compared. The segmentation, smoothing factor, inlet and outflow branch lengths were found to cause intra-team variability. There was 80% reproducibility in the time-averaged wall shear stress distribution among operators with the major difference attributed to the level of smoothing. Based on these findings, it was concluded that the clinical applicability of CFD simulations may be feasible if a standardised segmentation protocol is developed. Moreover, when analysing the aneurysm shape change over a decade, it was noted that the co-existence of positive and negative values of the wall shear stress divergence (WSSD) contributed to the growth of a daughter sac

Sequential Sampling Models of Choice: Some Recent Advances

Choice models in marketing and economics are generally derived without specifying the underlying cognitive process of decision making. This approach has been successfully used to predict choice behavior. However, it has not much to say about such aspects of decision making as deliberation, attention, conflict, and cognitive limitations and how these influence choices. In contrast, sequential sampling models developed in cognitive psychology explain observed choices based on assumptions about cognitive processes that return the observed choice as the terminal state. We illustrate three advantages of this perspective. First, making explicit assumptions about underlying cognitive processes results in measures of deliberation, attention, conflict, and cognitive limitation. Second, the mathematical representations of underlying cognitive processes imply well documented departures from Luce’s Choice Axiom such as the similarity, compromise, and attraction effects. Third, the process perspective predicts response time and thus allows for inference based on observed choices and response times. Finally, we briefly discuss the relationship between these cognitive models and rules for statistically optimal decisions in sequential designs