Les médicaments génériques: quels sont les problèmes et d'où viennent-ils ?

L'un des moyens utilisés par les pouvoirs publics afin de mieux contrôler l'augmentation des coûts de la santé est la promotion des médicaments génériques. Sur le plan de l'assurance et de la sécurité thérapeutique, la principale contrainte à respecter pour enregistrer un médicament générique est de démontrer une bioéquivalence entre le produit générique et le produit original sur un groupe restreint de sujets sains. Chez certains patients, l'utilisation de ces produits génériques entraîne des échecs thérapeutiques mais aussi des effets secondaires qui n'étaient pas apparus lors du traitement avec le produit original. Cet article analyse, au travers de la littérature, les différentes causes de ces problèmes dans des catégories variées avant de se concentrer sur les antidépresseurs. Les exigences légales actuelles pour la mise sur le marché de tels produits ne sont apparemment pas suffisantes si l'on veut assurer que les produits génériques ont le même effet thérapeutique que le médicament original breveté. Les coûts supplémentaires engendrés par ces problèmes mettent en question les gains potentiels de tels produits génériques en plus des risques qu'ils font encourir aux patients. [Auteurs]]]> Drugs, Generic oai:serval.unil.ch:BIB_E417FD772CDE 2022-05-07T01:28:56Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_E417FD772CDE Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus. info:doi:10.1016/j.jcrs.2009.07.008 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jcrs.2009.07.008 info:eu-repo/semantics/altIdentifier/pmid/19969212 Coskunseven, E. Jankov, M.R. Hafezi, F. Atun, S. Arslan, E. Kymionis, G.D. info:eu-repo/semantics/article article 2009-12 Journal of cataract and refractive surgery, vol. 35, no. 12, pp. 2084-2091 info:eu-repo/semantics/altIdentifier/eissn/1873-4502 urn:issn:0886-3350 <![CDATA[To compare 2 sequences of combined intrastromal corneal ring segment (ICRS) implantation and ultraviolet/riboflavin-mediated corneal collagen crosslinking (CXL) in progressive keratoconus. Dunya Eye Hospital, Istanbul, Turkey. In this prospective comparative randomized consecutive study, CXL was followed by ICRS implantation (Group 1) or ICRS implantation was followed by CXL (Group 2). Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, spherical equivalent (SE), manifest cylinder (cylinder), and mean keratometry (K) were compared preoperatively and postoperatively. The mean interval between treatments was 7 months +/- 2 (SD) (mean follow-up, 13 +/- 1 months). The mean UDVA and CDVA improved in both groups (UDVA: 0.07 +/- 0.09 to 0.25 +/- 0.12, Group 1, and 0.11 +/- 0.09 to 0.32 +/- 0.21, Group 2; CDVA: 0.24 +/- 0.11 to 0.41 +/- 0.20 and 0.22 +/- 0.16 to 0.55 +/- 0.2, respectively). The mean SE, cylinder, and mean K values decreased in both groups (SE: -7.13 +/- 3.34 D to -2.98 +/- 2.33 D, Group 1, and -7.05 +/- 5.54 D to -2.81 +/- 4.08 D, Group 2; cylinder: -4.38 +/- 2.03 D to -2.62 +/- 1.93 D and -4.68 +/- 2.60 D to -2.20 +/- 1.67 D, respectively; mean K: 52.47 +/- 4.01 D to 48.31 +/- 3.65 D and 52.06 +/- 4.93 D to 48.08 +/- 4.13 D, respectively). Overall, there was more improvement in CDVA, SE, and mean K in Group 2 than in Group 1. Implantation of ICRS followed by CXL resulted in greater improvement of keratoconus

The Quest for Stability: the macro view

On September 3-4, 2009 SUERF and Utrecht University School of Economicsorganized the Colloquium "The Quest for Stability" in Utrecht, the Netherlands. The papers included in this SUERF Study are based on contributions to the Colloquium.asset prices, bubbles, financial institutions, global recession, interest rates, liquidity, monetary policy, regulation, stability, supervision.

4f-spin dynamics in La(2-x-y)Sr(x)Nd(y)CuO(4)

We have performed inelastic magnetic neutron scattering experiments on La(2-x-y)Sr(x)Nd(y)CuO(4) in order to study the Nd 4f-spin dynamics at low energies. In all samples we find at high temperatures a quasielastic line (Lorentzian) with a line width which decreases on lowering the temperature. The temperature dependence of the quasielastic line width Gamma/2(T) can be explained with an Orbach-process, i.e. a relaxation via the coupling between crystal field excitations and phonons. At low temperatures the Nd-4f magnetic response S(Q,omega) correlates with the electronic properties of the CuO(2)-layers. In the insulator La(2-y)Nd(y)CuO(4) the quasielastic line vanishes below 80 K and an inelastic excitation occurs. This directly indicates the splitting of the Nd3+ ground state Kramers doublet due to the static antiferromagnetic order of the Cu moments. In La(1.7-x)Sr(x)Nd(0.3)CuO(4) with x = 0.12, 0.15 and La(1.4-x)Sr(x)Nd(0.6)CuO(4) with x = 0.1, 0.12, 0.15, 0.18 superconductivity is strongly suppressed. In these compounds we observe a temperature independent broad quasielastic line of Gaussian shape below T about 30 K. This suggests a distribution of various internal fields on different Nd sites and is interpreted in the frame of the stripe model. In La(1.8-y)Sr(0.2)Nd(y)CuO(4) (y = 0.3, 0.6) such a quasielastic broadening is not observed even at lowest temperature.Comment: 8 pages, 10 figures included, to appear in Phys. Rev.

Self-trapping transition for nonlinear impurities embedded in a Cayley tree

The self-trapping transition due to a single and a dimer nonlinear impurity embedded in a Cayley tree is studied. In particular, the effect of a perfectly nonlinear Cayley tree is considered. A sharp self-trapping transition is observed in each case. It is also observed that the transition is much sharper compared to the case of one-dimensional lattices. For each system, the critical values of $\chi$ for the self-trapping transitions are found to obey a power-law behavior as a function of the connectivity $K$ of the Cayley tree.Comment: 6 pages, 7 fig

Default Mode Network in the Effects of ¿9-Tetrahydrocannabinol (THC) on Human Executive Function

Evidence is increasing for involvement of the endocannabinoid system in cognitive functions including attention and executive function, as well as in psychiatric disorders characterized by cognitive deficits, such as schizophrenia. Executive function appears to be associated with both modulation of active networks and inhibition of activity in the default mode network. In the present study, we examined the role of the endocannabinoid system in executive function, focusing on both the associated brain network and the default mode network. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist ¿9-tetrahydrocannabinol (THC) on executive function in 20 healthy volunteers, using a continuous performance task with identical pairs. Task performance was impaired after THC administration, reflected in both an increase in false alarms and a reduction in detected targets. This was associated with reduced deactivation in a set of brain regions linked to the default mode network, including posterior cingulate cortex and angular gyrus. Less deactivation was significantly correlated with lower performance after THC. Regions that were activated by the continuous performance task, notably bilateral prefrontal and parietal cortex, did not show effects of THC. These findings suggest an important role for the endocannabinoid system in both default mode modulation and executive function. This may be relevant for psychiatric disorders associated with executive function deficits, such as schizophrenia and ADH

Exact solution of a 2D interacting fermion model

We study an exactly solvable quantum field theory (QFT) model describing interacting fermions in 2+1 dimensions. This model is motivated by physical arguments suggesting that it provides an effective description of spinless fermions on a square lattice with local hopping and density-density interactions if, close to half filling, the system develops a partial energy gap. The necessary regularization of the QFT model is based on this proposed relation to lattice fermions. We use bosonization methods to diagonalize the Hamiltonian and to compute all correlation functions. We also discuss how, after appropriate multiplicative renormalizations, all short- and long distance cutoffs can be removed. In particular, we prove that the renormalized two-point functions have algebraic decay with non-trivial exponents depending on the interaction strengths, which is a hallmark of Luttinger-liquid behavior.Comment: 59 pages, 3 figures, v2: further references added; additional subsections elaborating mathematical details; additional appendix with details on the relation to lattice fermion

Wiselib: A Generic Algorithm Library for Heterogeneous Sensor Networks

One unfortunate consequence of the success story of wireless sensor networks (WSNs) in separate research communities is an ever-growing gap between theory and practice. Even though there is a increasing number of algorithmic methods for WSNs, the vast majority has never been tried in practice; conversely, many practical challenges are still awaiting efficient algorithmic solutions. The main cause for this discrepancy is the fact that programming sensor nodes still happens at a very technical level. We remedy the situation by introducing Wiselib, our algorithm library that allows for simple implementations of algorithms onto a large variety of hardware and software. This is achieved by employing advanced C++ techniques such as templates and inline functions, allowing to write generic code that is resolved and bound at compile time, resulting in virtually no memory or computation overhead at run time. The Wiselib runs on different host operating systems, such as Contiki, iSense OS, and ScatterWeb. Furthermore, it runs on virtual nodes simulated by Shawn. For any algorithm, the Wiselib provides data structures that suit the specific properties of the target platform. Algorithm code does not contain any platform-specific specializations, allowing a single implementation to run natively on heterogeneous networks. In this paper, we describe the building blocks of the Wiselib, and analyze the overhead. We demonstrate the effectiveness of our approach by showing how routing algorithms can be implemented. We also report on results from experiments with real sensor-node hardware.Comment: 16 pages, 1 figure, 7 tables. Appears in European Conference on Wireless Sensor Networks (EWSN 2010

Is the Sun Embedded in a Typical Interstellar Cloud?

The physical properties and kinematics of the partially ionized interstellar material near the Sun are typical of warm diffuse clouds in the solar vicinity. The interstellar magnetic field at the heliosphere and the kinematics of nearby clouds are naturally explained in terms of the S1 superbubble shell. The interstellar radiation field at the Sun appears to be harder than the field ionizing ambient diffuse gas, which may be a consequence of the low opacity of the tiny cloud surrounding the heliosphere. The spatial context of the Local Bubble is consistent with our location in the Orion spur.Comment: "From the Outer Heliosphere to the Local Bubble", held at International Space Sciences Institute, October 200

Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors

Altres ajuts: This work has also been supported by a "Marató TV3" grant (20141210 to J.F. and 044412 to R.B.).Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological function by ill-defined mechanisms. Here we report a large metabolomics study of plasma and cerebrospinal fluid, showing in independent cohorts that people with DS produce elevated levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent immunosuppressive and neurotoxic properties, respectively. Immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. Furthermore, the levels of IFN-inducible cytokines positively correlate with KP dysregulation. Using metabolic tracing assays, we show that overexpression of IFN receptors encoded on chromosome 21 contribute to enhanced IFN stimulation, thereby causing IDO1 overexpression and kynurenine overproduction in cells with T21. Finally, a mouse model of DS carrying triplication of IFN receptors exhibits KP dysregulation. Together, our results reveal a mechanism by which T21 could drive immunosuppression and neurotoxicity in DS

HI in the Outskirts of Nearby Galaxies

The HI in disk galaxies frequently extends beyond the optical image, and can trace the dark matter there. I briefly highlight the history of high spatial resolution HI imaging, the contribution it made to the dark matter problem, and the current tension between several dynamical methods to break the disk-halo degeneracy. I then turn to the flaring problem, which could in principle probe the shape of the dark halo. Instead, however, a lot of attention is now devoted to understanding the role of gas accretion via galactic fountains. The current $\rm \Lambda$ cold dark matter theory has problems on galactic scales, such as the core-cusp problem, which can be addressed with HI observations of dwarf galaxies. For a similar range in rotation velocities, galaxies of type Sd have thin disks, while those of type Im are much thicker. After a few comments on modified Newtonian dynamics and on irregular galaxies, I close with statistics on the HI extent of galaxies.Comment: 38 pages, 17 figures, invited review, book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres