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

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&

GRB 190114C: from prompt to afterglow?

GRB 190114C is the first gamma-ray burst detected at Very High Energies (VHE, i.e. >300 GeV) by the MAGIC Cherenkov telescope. The analysis of the emission detected by the Fermi satellite at lower energies, in the 10 keV -- 100 GeV energy range, up to ~ 50 seconds (i.e. before the MAGIC detection) can hold valuable information. We analyze the spectral evolution of the emission of GRB 190114C as detected by the Fermi Gamma-Ray Burst Monitor (GBM) in the 10 keV -- 40 MeV energy range up to ~60 sec. The first 4 s of the burst feature a typical prompt emission spectrum, which can be fit by a smoothly broken power-law function with typical parameters. Starting on ~4 s post-trigger, we find an additional nonthermal component, which can be fit by a power law. This component rises and decays quickly. The 10 keV -- 40 MeV flux of the power-law component peaks at ~ 6 s; it reaches a value of 1.7e-5 erg cm-2 s-1. The time of the peak coincides with the emission peak detected by the Large Area Telescope (LAT) on board Fermi. The power-law spectral slope that we find in the GBM data is remarkably similar to that of the LAT spectrum, and the GBM+LAT spectral energy distribution seems to be consistent with a single component. This suggests that the LAT emission and the power-law component that we find in the GBM data belong to the same emission component, which we interpret as due to the afterglow of the burst. The onset time allows us to estimate the initial jet bulk Lorentz factor Gamma_0 is about 500, depending on the assumed circum-burst density.Comment: 7 pages, 2 figures, in press, accepted for publication in A&

Application of hyaluronic acid in the healing of non-experimental open wounds : A pilot study on 12 wounds in 10 client-owned dogs

Aim: Veterinarians have frequently to deal with wounds to the skin, subcutis, and underlying muscle. The aim was to explore the application of hyaluronic acid (HA)-containing dressing on open skin wounds in dogs. The progress of healing was assessed by wound area reduction and two scoring scales applied in human medicine. Materials and Methods: Ten client-owned dogs with 12 cutaneous open wounds healed by the second intention were included. All wounds were treated using available in commerce HA-containing wound dressing from admission to complete re-epithelialization. At every clinical examination, wound area and scale scoring assessments were performed. Results: After debridement, an increased wound size was obtained while an improvement was determined by both grading systems. The median numbers of return to the clinic for bandage change were 5 times. The median time to complete wound healing was 34.5 days. The mean wound area at day 7, 14, 21, and 28 were, respectively, 90.4%, 47.7%, 22.4%, and 14.8% of the original size (for linear measurement) and 95.5%, 54.4%, 23.10%, and 14.8% of the original size (for software measurement). Regarding wound healing assessment tools, the agreement between two operators was considered high for both scales. Conclusions: HA-containing dressing may be a possible wound treatment for cutaneous open wounds in dogs. The assessment of wound quality using scale scoring system could be useful especially in the 1st week and to direct clinical decision-making process