The social cost of rheumatoid arthritis in Italy: the results of an estimation exercise.

The objective of this study is to estimate the mean annual social cost per adult person and the total social cost of rheumatoid arthritis (RA) in Italy. A literature review was performed by searching primary economic studies on adults in order to collect cost data of RA in Italy in the last decade. The review results were merged with data of institutional sources for estimating - following the methodological steps of the cost of illness analysis - the social cost of RA in Italy. The mean annual social cost of RA was € 13,595 per adult patient in Italy. Affecting 259,795 persons, RA determines a social cost of € 3.5 billions in Italy. Non-medical direct cost and indirect cost represent the main cost items (48% and 31%) of the total social cost of RA in Italy. Based on these results, it appears evident that the assessment of the economic burden of RA solely based on direct medical costs evaluation gives a limited view of the phenomenon

Systematic review of the scientific literature on the economic evaluation of cochlear implants in adult patients

A systematic review of the economic literature of cochlear implants (CI) was conducted with the aim of summarizing the results of studies on the cost effectiveness of monolateral and bilateral (sequential/simultaneous) CI in adult patients affected by severe to profound prelingual and postlingual hearing impairment. The literature search was performed using “PubMed MEDLINE” and the Centre for Reviews and Dissemination search engines. Inclusion criteria related to economic evaluation included primary studies published in English language from January 2000 to May 2010 and aimed to quantify costs of CI and compare monolateral CI vs. acoustic prosthesis and bilateral (sequential/ simultaneous) CI vs. monolateral CI in terms of cost per unit of effectiveness. Four articles were identified. The mean direct medical cost of the monolateral CI varied from € 30,026 to € 45,770 in postlingually deafened patients, and the cost of device represented the main cost component. Additional median costs of simultaneous and sequential bilateral CI were, respectively, € 21,831 and € 25,459. The mean direct medical cost of monolateral CI was € 31,942 in prelingually deafened patients. The monolateral CI in postlingually deafened patients represented a cost effective intervention as compared with no implant (€ /QALY varied from € 7,930, € 24,983 to € 33,094). Monolateral CI were not a cost effective intervention for traditional patients with more than 40 years of hearing impairment (€ 64,604/QALY ) or for patients with marginal benefits from using acoustic prosthesis with more than 30 years of hearing impairment (€ 106,267/QALY ). The cost effectiveness of monolateral CI worsened with increasing age (€ /QALY from € 23,439 for patients < 30 years old to € 55,369 for patients > 70 years). Bilateral CI in postlingually deafened patients were less cost effective than monolateral CI (from € 91,943/QALY to € 102,640/QALY ). Monolateral CI were cost effective in prelingually deafened patients (€ /QALY : € 8,096). Given the few economic evaluation studies in literature, future researches are needed to support the cost effectiveness results of CI in adults and to evaluate the cost effectiveness of bilateral CI, as well as to estimate the non-medical direct and indirect cost components

Systematic review of the scientific literature on the economic evaluation of cochlear implants in paediatric patients

The aim of the study consists in a systematic review concerning the economic evaluation of cochlear implant (CI) in children by searching the main international clinical and economic electronic databases. All primary studies published in English from January 2000 to May 2010 were included. The types of studies selected concerned partial economic evaluation, including direct and indirect costs of cochlear implantation; complete economic evaluation, including minimization of costs, cost-effectiveness analysis (CEA), cost-utility analysis (CUA) and cost-benefit analysis (CBA) performed through observational and experimental studies. A total of 68 articles were obtained from the database research. Of these, 54 did not meet the inclusion criteria and were eliminated. After reading the abstracts of the 14 articles selected, 11 were considered eligible. The articles were then read in full text. Furthermore, 5 articles identified by bibliography research were added manually. After reading 16 of the selected articles, 9 were included in the review. With regard to the studies included, countries examined, objectives, study design, methodology, prospect of analysis adopted, temporal horizon, the cost categories analyzed strongly differ from one study to another. Cost analysis, cost-effectiveness analysis and an analysis of educational costs associated with cochlear implants were performed. Regarding the cost analysis, only two articles reported both direct cost and indirect costs. The direct cost ranged between € 39,507 and € 68,235 (2011 values). The studies related to cost-effectiveness analysis were not easily comparable: one study reported a cost per QALY ranging between $5197 and$ 9209; another referred a cost of $2154 for QALY if benefits were not discounted, and$ 16,546 if discounted. Educational costs are significant, and increase with the level of hearing loss and type of school attended. This systematic review shows that the healthcare costs are high, but savings in terms of indirect and quality of life costs are also significant. Cochlear implantation in a paediatric age is cost-effective. The exiguity and heterogeneity of studies did not allow detailed comparative analysis of the studies included in the review

Ligand binding to a hemoprotein lacking the distal histidine. The myoglobin from aplysia limacina (Val(E7)).

The time course of ligand recombination to the myoglobin from Aplysia limacina, which has Val(E7), was measured following photolysis by flashes of 35 ps to 300 ns with a time resolution of 10 ps or 1 ns. CO shows only biomolecular recombination. O2 has a small geminate reaction with a half-time of tens of picoseconds, but no nanosecond geminate reaction. NO has two picosecond relaxations with half-times of 70 ps (15%) and 1 ns (80%) and one nanosecond relaxation with a half-time of 4.6 ns. The biomolecular rates for O2 and NO are the same: 2 x 10(7) M-1 s-1. Methyl and ethyl isonitriles have a geminate reaction with a half-time of 35 ps. Ethyl isonitrile has, in addition, a nanosecond relaxation (25%) with a half-time of 100 ns. t-Butyl isonitrile has four geminate relaxations (10 ps, 35 ps, 1 ns, and 1 microseconds). Analysis of the results suggests much easier movement of ligand between the heme pocket and the exterior than in sperm whale myoglobin (His(E7]. The reactivity of the heme is little different, placing the effect of the differences from sperm whale myoglobin on the distal side of the heme

Systematic review of the literature on the clinical effectiveness of the cochlear implant procedure in paediatric patients

The aim of this systematic review of the literature was to summarize the results of scientific publications on the clinical effectiveness of the cochlear implant (CI) procedure in children. The members of the Working Group first examined existing national and international literature and the principal international guidelines on the procedure. They considered as universally-accepted the usefulness/effectiveness of unilateral cochlear implantation in severely-profoundly deaf children. Accordingly, they focused attention on systematic reviews addressing clinical effectiveness and cost/efficacy of the CI procedure, with particular regard to the most controversial issues for which international consensus is lacking. The following aspects were evaluated: post-CI outcomes linked to precocity of CI; bilateral (simultaneous/ sequential) CI vs. unilateral CI and vs. bimodal stimulation; benefits derived from CI in deaf children with associated disabilities. With regard to the outcomes after implantation linked to precocity of intervention, there are few studies comparing post-CI outcomes in children implanted within the first year of life with those of children implanted in the second year. The selected studies suggest that children implanted within the first year of life present hearing and communicative outcomes that are better than those of children implanted after 12 months of age. Concerning children implanted after the first year of life, all studies confirm an advantage with respect to implant precocity, and many document an advantage in children who received cochlear implants under 18 months of age compared to those implanted at a later stage. With regard to bilateral CI, the studies demonstrate that compared to unilateral CI, bilateral CI offers advantages in terms of hearing in noise, sound localization and during hearing in a silent environment. There is, however, a wide range of variability. The studies also document the advantages after sequential bilateral CI. In these cases, a short interval between interventions, precocity of the first CI and precocity of the second CI are considered positive prognostic factors. In deaf children with associated disabilities, the studies analyzed evidence that the CI procedure is also suitable for children with disabilities associated with deafness, and that even these children may benefit from the procedure, even if these may be slower and inferior to those in children with isolated deafness, especially in terms of high communicative and perceptive skills

Innovation in rehabilitation technology: technological opportunities and socio-economic implications

Innovation in stroke rehabilitation technology is discussed that, based on published epidemiological and economic data, represents an urgent case to deal with adopting a multidisciplinary perspective. A theoretical model is proposed for the evaluation of socioeconomic implications related to an early diagnosis and early and timely adjustments in the stroke treatment strategy. The model is applied to the case of a new rehabilitation technology: the ALLADIN diagnostic device. The model compares a traditional approach – ‘trial and error strategy’ – to the innovative one – ‘in progress evaluation’, considering the diagnostic and rehabilitative steps of the patient’s assistive route and assessing social and economic benefits of the innovative device. The new technology allows a precise initial assessment of both the severity of stroke and the level of lost functionality, as long as an evaluation of the expected return from different potential therapies. Moreover, supposing that higher severity of stroke implies higher level of disabilities and social costs, and that the negative impact increases as the level of disability increases, the use of innovative rehabilitation technologies would be more effective in the case of patients with severe and very severe stroke

Fragment-based discovery of a regulatory site in thioredoxin glutathione reductase acting as "doorstop" for NADPH entry

Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases are difficult to inhibit in a selective manner with off target inhibition reducing usefulness of identified compounds. Thioredoxin glutathione reductase (TGR), a high molecular weight thioredoxin reductase-like enzyme, has emerged as a promising drug target for the treatment of schistosomiasis, a parasitosis afflicting more than 200 million people. Taking advantage of small molecules selected from a high-throughput screen and using X-ray crystallography, functional assays, and docking studies, we identify a critical secondary site of the enzyme. Compounds binding at this site interfere with well-known and conserved conformational changes associated with NADPH reduction, acting as a doorstop for cofactor entry. They selectivity inhibit TGR from Schistosoma mansoni and are active against parasites in culture. Since many members of the FAD/NAD-linked reductase family have similar catalytic mechanisms the unique mechanism of inhibition identified in this study for TGR broadly opens new routes to selectively inhibit homologous enzymes of central importance in numerous diseases