487 research outputs found
La valutazione economica del trattamento farmacologico con antipsicotici nella schizofrenia: una revisione sistematica della letteratura
Schizophrenia is a chronic, severe, and disabling brain disease. Approximately 1 percent of the population develops schizophrenia during their lifetime. Available treatments can relieve many symptoms, but most people with schizophrenia continue to suffer some symptoms throughout their lives; it has been estimated that no more than one in five individuals recovers completely. The introduction of second-generation antipsychotics, also defined as atypicals, has increased the therapeutic options available for individuals with schizophrenia. Potential benefits of these agents include a more favourable profile in terms of positive and negative symptoms, less adverse effects and better cognitive functioning than first-generation antipsychotics. It is uncertain whether atypical antipsychotic agents, as prescribed in ordinary practice, are a cost-effective alternative to conventional agents. This study examined the financial and clinical implications of using atypical antipsychotics in the treatment of schizophrenia, considering both related costs and consequences. To elaborate the paper, we reviewed 8 economical studies regarding the comparison between atypical and typical antipsychotics, published in the years 1998-2004. In 5 studies atypical antipsychotics were cost-saving compared to typical, in 2 studies they were cost-neutral and in one study they resulted cost-effective. Consequently typical antipsychotics were cost-saving just in one study
Cost-effectiveness analysis of alectinib versus crizotinib in first-line treatment of anaplastic lymphoma kinase-positive advanced non-small cell lung cancer:
In the randomized, active-controlled, multicenter Phase III open-label ALEX trial, alectinib showed superior efficacy and lower toxicity compared with crizotinib in the primary treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK-positive NSCLC). The aim of this economic evaluation was to assess the cost-utility of alectinib versus crizotinib from the perspective of the Italian National Health Service (INHS). A partitioned survival model with three health states (progression-free, post-progression, and death) was used. The clinical data (progression-free survival, overall survival and time to progression) was based on the ALEX trial. Utility values were derived from EQ-5D scores evaluated in the ALEX trial and literature. Costs included drug treatments, progression-free, post-progression and supportive care. Direct medical costs and benefits (quality-adjusted life-years, QALYs) were discounted at a 3.0% annual rate. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Treatment with alectinib versus crizotinib led to a gain of 2.82 life-years, 1.86 QALYs, and incremental costs of €58,276, resulting in an incremental cost-utility ratio of €31,353 per QALY. The deterministic analysis showed that the most critical parameters in the model were the cost of post-progression and utility scores. From the probabilistic sensitivity analysis, alectinib had a 64.5% probability of being cost-effective at a willingness-to-pay threshold of €40,000 per QALY. Compared with crizotinib, alectinib increased the length of the progression-free state and the QALYs. The incremental overall cost increase was reflective of longer treatment durations in the progression-free state. Compared with crizotinib, alectinib can be considered a valid cost-utility option in the treatment of naive patients with ALK-positive NSCLC
In silico identification of new putative pathogenic variants in the NEU1 sialidase gene affecting enzyme function and subcellular localization
The NEU1 gene is the first identified member of the human sialidases, glycohydrolitic enzymes that remove the terminal sialic acid from oligosaccharide chains. Mutations in NEU1 gene are causative of sialidosis (MIM 256550), a severe lysosomal storage disorder showing autosomal recessive mode of inheritance. Sialidosis has been classified into two subtypes: sialidosis type I, a normomorphic, late-onset form, and sialidosis type II, a more severe neonatal or early-onset form. A total of 50 causative mutations are reported in HGMD database, most of which are missense variants. To further characterize the NEU1 gene and identify new functionally relevant protein isoforms, we decided to study its genetic variability in the human population using the data generated by two large sequencing projects: the 1000 Genomes Project (1000G) and the NHLBI GO Exome Sequencing Project (ESP). Together these two datasets comprise a cohort of 7595 sequenced individuals, making it possible to identify rare variants and dissect population specific ones. By integrating this approach with biochemical and cellular studies, we were able to identify new rare missense and frameshift alleles in NEU1 gene. Among the 9 candidate variants tested, only two resulted in significantly lower levels of sialidase activity (pC and c.700G>A. These two mutations give rise to the amino acid substitutions p.V217A and p.D234N, respectively. NEU1 variants including either of these two amino acid changes have 44% and 25% residual sialidase activity when compared to the wild-type enzyme, reduced protein levels and altered subcellular localization. Thus they may represent new, putative pathological mutations resulting in sialidosis type I. The in silico approach used in this study has enabled the identification of previously unknown NEU1 functional alleles that are widespread in the population and could be tested in future functional studies
Decaying shock studies of phase transitions in MgOSiO2 systems: implications for the Super-Earths interiors
We report an experimental study of the phase diagrams of periclase (MgO),
enstatite (MgSiO3) and forsterite (Mg2SiO4) at high pressures. We investigated
with laser driven decaying shocks the pressure/temperature curves of MgO,
MgSiO3 and Mg2SiO4 between 0.2-1.2 TPa, 0.12-0.5 TPa and 0.2-0.85 TPa
respectively. A melting signature has been observed in MgO at 0.47 TPa and 9860
K, while no phase changes were observed neither in MgSiO3 nor in Mg2SiO4. An
increasing of reflectivity of MgO, MgSiO3 and Mg2SiO4 liquids have been
detected at 0.55 TPa -12 760 K, 0.15 TPa - 7540 K, 0.2 TPa - 5800 K,
respectively. In contrast to SiO2, melting and metallization of these compounds
do not coincide implying the presence of poor electrically conducting liquids
close to the melting lines. This has important implications for the generation
of dynamos in Super-earths mantles
Wide band X-ray and optical observations of the BL Lac object 1ES 1959+650 in high state
The blazar 1ES 1959+650 was observed twice by BeppoSAX in September 2001
simultaneously with optical observations. We report here the X-ray data
together with the optical, R_C magnitude, light curve since August 1995. The
BeppoSAX observations were triggered by an active X-ray status of the source.
The X-ray spectra are brighter than the previously published X-ray
observations, although the source was in an even higher state a few months
later, as monitored by the ASM onboard RossiXTE, when it was also detected to
flare in the TeV band. Our X-ray spectra are well represented by a continuosly
curved model up to 45 keV and are interpreted as synchrotron emission, with the
peak moving to higher energies. This is also confirmed by the slope of the
X-ray spectrum which is harder than in previous observations. Based on our
optical and X-ray data, the synchrotron peak turns out to be in the range
0.1-0.7 keV. We compare our data with non simultaneous radio to TeV data and
model the spectral energy distribution with a homogeneous, one-zone synchrotron
inverse Compton model. We derive physical parameters that are typical of low
power High Energy peaked Blazar, characterised by a relatively large beaming
factor, low luminosity and absence of external seed photons.Comment: 12 pages, 6 figures, accepted by A&
The BL Lac objects OQ 530 and S5 0716+714. Simultaneous observations in the X-rays, radio, optical and TeV bands
We present the results of the BeppoSAX observations of two BL Lacs, OQ 530
and S5 0716+714, as part of a ToO program for the simultaneous observation at
radio, optical, X-ray and TeV energies. Both sources are detected in the LECS
and MECS, with S5 0716+714 visible also in the PDS band, up to about 60 keV.
The X-ray spectra of both sources are better fitted by a double power-law
model, with a steep soft X-ray component flattening at harder energies, with
breaks at 0.3 and 1.5 keV, respectively. The concave shape of the spectra in
both objects is consistent with soft X-rays being produced by the synchrotron
and harder X-rays by the inverse Compton processes. Also the X-ray variability
properties confirm this scenario, in particular for S5 0716+714 our observation
shows variations by about a factor 3 over one hour below 3 keV and no
variability above. Their simultaneous broad band energy spectral distributions
can be successfully interpreted within the frame of a homogeneous synchrotron
and inverse Compton model, including a possible contribution from an external
source of seed photons with the different spectral states of S5 0716+714 being
reproduced by changing the injected power. The resulting parameters are fully
consistent with the two sources being intermediate objects within the
"sequence" scenario proposed for blazars.Comment: 10 pages, 8 figures, accepted by A&
- …