Antiepileptic drug treatment of generalized tonic-clonic seizures: An evaluation of regulatory data and five criteria for drug selection

BACKGROUND: A generalized tonic–clonic seizure (GTCS) is the most severe form of common epileptic seizure and carries the greatest risk of harm. The aim of this review is to provide an evidence-based guide for the selection of antiepileptic drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs (SGTCSs) and are considered in this paper. METHODS: Each AED is evaluated using five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2) adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of action (MOA). To ensure the inclusions of robust data, only efficacy data accepted by regulatory authorities were considered, and data related to adverse effects, interactions, adherence, and MOA were all extracted from UK Summaries of Product Characteristics (SPCs). RESULTS: (1a) There is class 1 evidence of the efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam, perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta-analyses supports the use of the four AEDs (levetiracetam, perampanel, topiramate, and with less robust data for lamotrigine). (2) AEDs are associated with different, but to some extent overlapping, common adverse effect profiles but have differing idiosyncratic adverse effects. (3) Pharmacokinetic interactions are seen with most, but not all, AEDs and are most common with carbamazepine and phenytoin. (4) Good adherence is important for seizure control and is influenced by frequency of dosing, among other factors. (5) Mechanism of action is also a consideration in rationalising AED selection when switching or combining AEDs. CONCLUSION: Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices

The editorial board

Introduction to the Symposium on Pig Biodiversity, which was held in the Spanish city of Córdoba during 7-9th November 2002

Observation of Weyl and Dirac fermions at smooth topological Volkov-Pankratov heterojunctions

Weyl and Dirac relativistic fermions are ubiquitous in topological matter. Their relativistic character enables high energy physics phenomena like the chiral anomaly to occur in solid state, which allows to experimentally probe and explore fundamental relativistic theories. Here we show that on smooth interfaces between a trivial and a topological material, massless Weyl and massive Dirac fermions intrinsically coexist. The emergence of the latter, known as Volkov-Pankratov states, is directly revealed by magneto-optical spectroscopy, evidencing that their energy spectrum is perfectly controlled by the smoothness of topological interface. Simultaneously, we reveal the optical absorption of the zero-energy chiral Weyl state, whose wavefunction is drastically transformed when the topological interface is smooth. Artificial engineering of the topology profile thus provides a novel textbook system to explore the rich relativistic energy spectra in condensed matter heterostructures.Comment: 21 pages 10 figure

Structure and relaxations in liquid and amorphous Selenium

We report a molecular dynamics simulation of selenium, described by a three-body interaction. The temperatures T_g and T_c and the structural properties are in agreement with experiment. The mean nearest neighbor coordination number is 2.1. A small pre-peak at about 1 AA^-1 can be explained in terms of void correlations. In the intermediate self-scattering function, i.e. the density fluctuation correlation, classical behavior, alpha- and beta-regimes, is found. We also observe the plateau in the beta-regime below T_g. In a second step, we investigated the heterogeneous and/or homogeneous behavior of the relaxations. At both short and long times the relaxations are homogeneous (or weakly heterogeneous). In the intermediate time scale, lowering the temperature increases the heterogeneity. We connect these different domains to the vibrational (ballistic), beta- and alpha-regimes. We have also shown that the increase in heterogeneity can be understood in terms of relaxations

Computing the first eigenpair of the p-Laplacian via inverse iteration of sublinear supersolutions

We introduce an iterative method for computing the first eigenpair $(\lambda_{p},e_{p})$ for the $p$-Laplacian operator with homogeneous Dirichlet data as the limit of $(\mu_{q,}u_{q})$ as $q\rightarrow p^{-}$, where $u_{q}$ is the positive solution of the sublinear Lane-Emden equation $-\Delta_{p}u_{q}=\mu_{q}u_{q}^{q-1}$ with same boundary data. The method is shown to work for any smooth, bounded domain. Solutions to the Lane-Emden problem are obtained through inverse iteration of a super-solution which is derived from the solution to the torsional creep problem. Convergence of $u_{q}$ to $e_{p}$ is in the $C^{1}$-norm and the rate of convergence of $\mu_{q}$ to $\lambda_{p}$ is at least $O(p-q)$. Numerical evidence is presented.Comment: Section 5 was rewritten. Jed Brown was added as autho

Low-temperature specific heat and thermal conductivity of glycerol

We have measured the thermal conductivity of glassy glycerol between 1.5 K and 100 K, as well as the specific heat of both glassy and crystalline phases of glycerol between 0.5 K and 25 K. We discuss both low-temperature properties of this typical molecular glass in terms of the soft-potential model. Our finding of an excellent agreement between its predictions and experimental data for these two independent measurements constitutes a robust proof of the capabilities of the soft-potential model to account for the low-temperature properties of glasses in a wide temperature range.Comment: 4 pages, 3 figures. To be published in Phys. Rev. B (2002