An economic evaluation of aripiprazole vs olanzapine adapted to the Italian setting using outcomes of metabolic syndrome and risk for diabetes in patients with schizophrenia

Objective

To evaluate the cost-effectiveness of aripiprazole and olanzapine in patients with schizophrenia.

Methods

Data from a double-blind, randomized study demonstrating the efficacy of aripiprazole and olanzapine were used to observe new incidence of metabolic syndrome (26-week therapy) and to model the risk of developing diabetes over 5 years of therapy. Cumulative incidence of metabolic syndrome was compared using Kaplan–Meier estimates; diabetes risk was estimated using a validated, general population risk-prediction model. Economic assessment was conducted from the third-party payer perspective by evaluating pharmacotherapy costs of treating schizophrenia and medical costs associated with treating adverse metabolic effects in a hypothetical cohort of 1000 patients. Resource utilization and costs were derived from the underlying study and published data, using a 3% rate to discount costs and benefits.

Results

For the patients switched from olanzapine to aripiprazole, treatment with aripiprazole was a dominant cost-saving strategy. Use of aripiprazole avoided 184 events of metabolic syndrome over 26 weeks of treatment, contributing to a real-world (RW) cost savings of €2.53 per patient and a total savings of approximately €465.52 over a 5-year period. For the same cohort, the risk-prediction model indicated that 34 occurrences of diabetes could be avoided over 5 years, corresponding to a RW cost savings of €56.86 per patient and a total saving of approximately €1,933.24. These savings reflect avoided costs in treating adverse metabolic events and comparable costs in the acquisition of aripiprazole.

Conclusions

Maintenance aripiprazole therapy offers medical and economic benefits over olanzapine, reflected by reduced incidence of metabolic syndrome and diabetes and associated lower costs.     

Further evidence of genetic heterogeneity in familial essential tremor

Familial essential tremor (FET) is a common hereditary movement disorder with phenotypic variability and genetic heterogeneity. To date, linkage analyses revealed three loci associated to essential tremor (ET) (ETM1 on 3q13, ETM2 on 2p22-25, and a locus on 6p23). We performed a genetic analysis of these candidate chromosomal regions in a fifth-generation Italian kindred with autosomal-dominant ET. Of the 22 clinically evaluated family members, nine were affected by ET. The genetic study indicates that the ET in this family is not associated to any of the known ET loci. These findings support evidence of further genetic heterogeneity for such disease.     

Benign adult familial myoclonic epilepsy (BAFME): evidence of an extended founder haplotype on chromosome 2p11.1-q12.2 in five Italian families

Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype-phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1 software assuming an autosomal dominant trait with 0.99 penetrance and frequency of 0.001. Significant linkage was found on chromosome 2p11.1-q12.2 and a maximum cumulative lod score of 18.5 was found for markers D2S2161 and D2S388. The haplotype "5332" of adjacent markers D2S388, D2S2216, D2S113, and D2S2175 segregates with the disease in all families indicating that the same mutation inherited from a common ancestor segregates in these families. Preliminary genotype-phenotype showed that patients carrying the disease haplotype show minor clinical differences, suggesting that expressivity of the founder mutation is not markedly influenced by other factors. The identification of causative mutations in BAFME requires an extensive and collaborative screening effort.     

Myasthenia gravis during pregnancy

Myasthenia gravis (MG) affects women in the second and third decades of life, overlapping with the childbearing years. During pregnancy, the course of this disease is unpredictable; worsening of symptoms occurs more likely during the first half of pregnancy and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies. Cesarean section is recommended only for obstetric reasons; epidural anesthesia is advised to reduce physical and emotional stress. Anticholinesterase drugs are the mainstay of treatment, when MG symptoms are not satisfactorily controlled, corticosteroids, azathioprine and in some cases cyclosporin A may be used. Life-threatening conditions (e.g., respiratory insufficiency) may occur during pregnancy; therefore, intensive check-ups by a gynecologist and a neurologist are necessary.     

The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI Identifiers

This paper describes the NIF LinkOut Broker (NLB) that has been built as part of the Neuroscience Information Framework (NIF) project. The NLB is designed to coordinate the assembly of links to neuroscience information items (e.g., experimental data, knowledge bases, and software tools) that are (1) accessible via the Web, and (2) related to entries in the National Center for Biotechnology Information’s (NCBI’s) Entrez system. The NLB collects these links from each resource and passes them to the NCBI which incorporates them into its Entrez LinkOut service. In this way, an Entrez user looking at a specific Entrez entry can LinkOut directly to related neuroscience information. The information stored in the NLB can also be utilized in other ways. A second approach, which is operational on a pilot basis, is for the NLB Web server to create dynamically its own Web page of LinkOut links for each NCBI identifier in the NLB database. This approach can allow other resources (in addition to the NCBI Entrez) to LinkOut to related neuroscience information. The paper describes the current NLB system and discusses certain design issues that arose during its implementation.     

Point Analysis in Java Applied to Histological Images of the Perforant Pathway: A User’s Account

The freeware Java tool Point Analysis in Java (PAJ), created to perform 3D point analysis, was tested in an independent laboratory setting. The input data consisted of images of the hippocampal perforant pathway from serial immunocytochemical localizations of the rat brain in multiple views at different resolutions. The low magnification set (×2 objective) comprised the entire perforant pathway, while the high magnification set (×100 objective) allowed the identification of individual fibers. A preliminary stereological study revealed a striking linear relationship between the fiber count at high magnification and the optical density at low magnification. PAJ enabled fast analysis for down-sampled data sets and a friendly interface with automated plot drawings. Noted strengths included the multi-platform support as well as the free availability of the source code, conducive to a broad user base and maximum flexibility for ad hoc requirements. PAJ has great potential to extend its usability by (a) improving its graphical user interface, (b) increasing its input size limit, (c) improving response time for large data sets, and (d) potentially being integrated with other Java graphical tools such as ImageJ.     

Efficient delivery of human single fiber-derived muscle precursor cells via biocompatible scaffold

The success of cell therapy for skeletal muscle disorders depends upon two main factors: the cell source and the method of delivery. In this work we have explored the therapeutic potential of human muscle precursor cells (hMPCs), obtained from single human muscle fibers, implanted in vivo via micropatterned scaffolds. hMPCs were initially expanded and characterized in vitro by immunostaining and flow cytometric analysis. For in vivo studies, hMPCs were seeded onto micropatterned poly-lactic-glycolic acid 3D-scaffolds fabricated using soft-lithography and thermal membrane lamination. Seeded scaffolds were then implanted in predamaged tibialis anterior muscles of CD1 nude mice; hMPCs were also directly injected in contralateral limbs as controls. Similarly to what we previously described with mouse precursors cells, we found that hMPCs were able to participate in muscle regeneration and scaffold-implanted muscles contained a greater number of human nuclei, as revealed by immunostaining and Western blot analyses. These results indicate that hMPCs derived from single fibers could be a good and reliable cell source for the design of therapeutic protocols and that implantation of cellularized scaffolds is superior to direct injection for the delivery of myogenic cells into regenerating skeletal muscle.     

Influence of weight loss on outcomes in patients with head and neck cancer undergoing concomitant chemoradiotherapy

BACKGROUND: The purpose of this study was to determine the influence of weight loss on outcome in patients with head and neck cancer undergoing concomitant chemoradiotherapy (CCRT): treatment interruption, infections, mortality, and hospital readmission rate. METHODS: Forty patients with head and neck cancer were enrolled. All patients were counseled to follow a nutritional program during CCRT. Body weight was evaluated at baseline, at the end, and 30 days after radiochemotherapy. RESULTS: Ninety percent of compliant patients with nutritional program maintained body weight (mean, 1 +/- 2.4 kg) and 100% of noncompliant patients continued to lose weight (mean, -9 +/- 4 kg; p < .001). A reduction greater than 20% of prediagnosis weight significantly correlated with treatment interruption (p = .003), infections (p = .002), early mortality (p = .011), hospital readmission rate (p = .001), and survival (log-rank test: z = -2.722, p = .006). CONCLUSION: In patients with head and neck cancer undergoing CCRT, the early nutritional management reduces weight loss and improve outcome.