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

Erythrocyte's aging in microgravity highlights how environmental stimuli shape metabolism and morphology

The determination of the function of cells in zero-gravity conditions is a subject of interest in many different research fields. Due to their metabolic unicity, the characterization of the behaviour of erythrocytes maintained in prolonged microgravity conditions is of particular importance. Here, we used a 3D-clinostat to assess the microgravity-induced modifications of the structure and function of these cells, by investigating how they translate these peculiar mechanical stimuli into modifications, with potential clinical interest, of the biochemical pathways and the aging processes. We compared the erythrocyte's structural parameters and selected metabolic indicators that are characteristic of the aging in microgravity and standard static incubation conditions. The results suggest that, at first, human erythrocytes react to external stimuli by adapting their metabolic patterns and the rate of consumption of the cell resources. On longer timeframes, the cells translate even small differences in the environment mechanical solicitations into structural and morphologic features, leading to distinctive morphological patterns of agin

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

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

Transient spectroscopy of the reaction of cyanide with ferrous myoglobin: Effect of distal side residues

The reaction of cyanide metmyoglobin with dithionite conforms to a two-step sequential mechanism with formation of an unstable intermediate, identified as cyanide bound ferrous myoglobin. This reaction was investigated by stopped-flow time resolved spectroscopy using different myoglobins, i.e. those from horse heart, Aplysia limacina buccal muscle, and three recombinant derivatives of sperm whale skeletal muscle myoglobin (Mb) (the wild type and two mutants). The myoglobins from horse and sperm whale (wild type) have in the distal position (E7) a histidyl residue, which is missing in A. limacina Mb as well as the two sperm whale mutants (E7 His----Gly and E7 His----Val). All these proteins in the reduced form display an extremely low affinity for cyanide at pH less than 10. The differences in spectroscopy and kinetics of the ferrous cyanide complex of these myoglobins indicate a role of the distal pocket on the properties of the complex. The two mutants of sperm whale Mb are characterized by a rate constant for the decay of the unstable intermediate much faster than that of the wild type, at all pH values explored. Therefore, we envisage a specific role of the distal His (E7) in controlling the rate of cyanide dissociation and also find that this effect depends on the protonation of a single ionizable group, with pK = 7.2, attributed to the E7 imidazole ring. The results on A. limacina Mb, which displays the slowest rate of cyanide dissociation, suggests that a considerable stabilizing effect can be exerted by Arg E10 which, according to Bolognesi et al. (Bolognesi, M., Coda, A., Frigerio, F., Gatti, C., Ascenzi, P., and Brunori, M. (1990) J. Mol. Biol. 213, 621-625), interacts inside the pocket with fluoride bound to the ferric heme iron. A mechanism of control for the rate of dissociation of cyanide from ferrous myoglobin, involving protonation of the bound anion, is discussed

Detecting delirium superimposed on dementia: diagnostic accuracy of a simple combined arousal and attention testing procedure

Detecting delirium superimposed on dementia (DSD) can be challenging because assessment partly relies on cognitive tests that may be abnormal in both conditions. We hypothesized that a combined arousal and attention testing procedure would accurately detect DSD. Patients aged ≥70 years were recruited from five hospitals across Europe. Delirium was diagnosed by physicians using DSM-5 criteria using information from nurses, carers, and medical records. Dementia was ascertained by the Informant Questionnaire on Cognitive Decline in the Elderly. Arousal was measured using the Observational Scale of Level of Arousal (OSLA), which assesses eye opening, eye contact, posture, movement, and communication. Attention was measured by participants signaling each time an “A” was heard when “S-A-V-E-A-H-A-A-R-T” was read out. The sample included 114 persons (mean age 82 years (SD 7); 54% women). Dementia alone was present in 25% (n = 28), delirium alone in 18% (n = 21), DSD in 27% (n = 31), and neither in 30% (n = 34). Arousal and attention was assessed in n = 109 (96%). Using OSLA, 83% participants were correctly identified as having delirium (sensitivity 85%, specificity 82%, AUROC 0.92). The attention task correctly classified 76% of participants with delirium (sensitivity 90%, specificity 64%, AUROC 0.80). Combining scores correctly classified 91% of participants with delirium (sensitivity 84%, specificity 92%, AUROC 0.94). Diagnostic accuracy remained high in the subgroup with dementia (93% correctly classified, sensitivity 94%, specificity 92%, AUROC 0.98). This combined arousal–attention assessment to detect DSD was brief yet had high diagnostic accuracy. Such an approach could have clinical utility for diagnosing DSD