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European cooperation in Health Technology Assessment (HTA) requires joint assessments to be of high quality, providing findings transferable into national HTA report. To this aim, we piloted the combining of methodological guidance of EUnetHTA for Relative Effectiveness Assessment (REA), GRADE for selection/rating of outcomes and assessing quality of evidence, and Cochrane for Systematic Reviews, while carrying out a collaborative REA on Femtosecond Laser Assisted versus Standard Cataract Surgery.
While developing the collaborative REA, we used the three organizations’ handbooks, templates and tools for Scope, Project Plan (PP), Summary of Findings, Effectiveness (EFF) and Safety (SAF) domains. We structured the PP according to the EUnetHTA template and added detailed methods on EFF and SAF systematic reviews, as per Cochrane Handbook. For the Scope we convened a multidisciplinary panel for selection and rating of importance of outcomes and clinically significant difference, using the GRADEpro platform. We developed the complete report adopting the EUnetHTA REA Core Model. We used Cochrane's tool Revman to assess risk of bias of included studies for each outcome, and to carry out metanalyses. We applied the GRADE approach to assess quality of evidence for each outcome and to express level of certainty in the estimates. We used the Cochrane handbook's guidance for structuring a scientific abstract and a Plain Language Summary to integrate the Summary of Findings.
The PP resulted in a detailed scientific and operational protocol, receiving extensive and constructive internal and external peer review. Reporting of EFF and SAF domains followed EUnetHTA Assessment Elements while keeping the order of stakeholders' rating of outcomes’ importance. Graphic representation of risk of bias for each outcome contributed to immediacy of the data quality assessment and transparency of the judgement on certainty. The scientific abstract and the Plain Language Summary, facilitated the external dissemination of results.
Merging of the three most important methodological contributions in the field proved successful without altering the distinctive trait of the REA.
To present real-world evidence on the effects of switching from oral to long-acting injectable (LAI) antipsychotic maintenance treatment (AMT) in a sample of clinically stable patients with schizophrenia, with regard to subjective experience of treatment, attitude towards drug and quality of life.
50 clinically stable adult schizophrenic outpatients were recruited. At the time of enrolment (T0), all patients were under a stabilized therapy with a single oral second-generation antipsychotic (SGA) and were switched to the equivalent maintenance regimen with the long-acting formulation of the same antipsychotic. 43 patients completed the 24-month prospective, longitudinal, open-label, observational study. Participants were assessed at baseline (T0), after 12 (T1) and 24 months (T2), using psychometric scales (PANSS, YMRS and MDRS) and patient-reported outcome measures (SWN-K, DAI-10 and SF-36).
The switch to LAI-AMT was associated with a significant clinical improvement at T1 and T2 compared to baseline (T0). All of the psychometric indexes, as well as patients’ subjective experience of treatment (SWN-K), and quality of life (SF-36) showed a significant improvement after one year of LAI-AMT, with stable results after two years. Patients’ attitude towards drug (DAI-10) increased throughout the follow-up period, with a further improvement during the second year.
The switch to LAI-AMT may help to address the subjective core of an optimal recovery in stabilized schizophrenic patients. A sustained improvement in patients’ attitude towards drug may help to achieve patient’s compliance. The size of this study needs to be expanded to produce more solid and generalizable results.
Depression is an important risk factor for suicide. However, other dimensions may contribute to the suicidal risk and to the transition from ideas to acts. We aimed to test the relative involvement of hopelessness, temperament, childhood trauma, and aggression in suicide risk in a large sample of patients with mood disorders.
We assessed 306 patients with major depressive and bipolar disorders for clinical characteristics including hopelessness, temperament, childhood trauma, and aggression. We tested their associations with suicidal ideation and acts using standard univariate/bivariate methods, followed by multivariate logistic regression models.
In multivariate analyses, the loss of expectations subscore of the hopelessness scale was associated with lifetime suicidal ideation but not suicide attempt. Childhood emotional abuse, severity of current depression, and female gender were associated with lifetime suicide attempts, whereas hyperthymic temperament was protective. Only hyperthymic temperament differentiated patients with a history of suicidal ideas vs. those with a history of suicide attempt.
Findings support the association of hopelessness with suicidal ideation and point to considering in suicidal acts not only depression, but also childhood emotional abuse, hyperthymic temperament, and gender.
Health professionals often advocate and request innovative health technologies, perceiving Health Technology Assessment (HTA) as a delay or counterargument to their requests. To facilitate engagement of professionals and decision makers in the HTA process and endorsement of process outputs, a system for technology requests submission, based on the European Network for HTA (EUnetHTA) Submission Template, was established and subsequently piloted in a cancer research institute.
The “EUnetHTA medical devices evidence submission template” for companies (1) was adapted for use by professionals proposing a health technology for acquisition. Adaptation consisted mainly in: re-arrangement of chapters order with emphasis on the health problem, unmet needs, claimed additional benefits of the technology and potential for research; inclusion of information on costs/financial resources; and inclusion of a summary with a pre-defined set of brief statements to inform appraisal. The headings for the nine one-paragraph statements were: relevance of the health problem; degree of innovativeness of the technology; potential clinical impact; potential research relevance; comparative safety and effectiveness; economic impact; organizational impact; availability/quality of scientific literature; and degree of diffusion. Decision makers discussed the appraisal's statements with the proponents before reaching a conclusion.
From January 2016 technology requests were examined only if presented through the submission template. Results from submissions of three innovative technologies for prostate cancer treatment, endovascular procedures and cataract surgery will be discussed. Acceptability of the submission template was high and professionals — supported by experts available in their institution (clinical engineers, epidemiologists and others) — were successful in completing the dossier. Decision-makers appraisal proved facilitated and transparent. Concerted decisions were taken within a few weeks from submission.
The EUnetHTA tool proved flexible and valuable to initiate an HTA-based decision-making process. Appraisal was cooperative and proponents were involved in the decisions, through a process requiring a mean total time of 6 months. Participants’ misgivings were overcome by transparency and objectivity of the process.
In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age for cervical cancer (CC) screening from 2017. According to the National Prevention Plan 2014–18, HPV-based screening must be implemented for women ≥30 years old, following the Italian Health Technology Assessment (HTA) report recommendations (1). The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention.
The National Screening Monitoring Centre and the Italian Group for Cervical Screening, following a commitment by the Italian the Ministry of Health (MoH), identified the consensus conference as the most suitable method for addressing this topic. The objective was defining the best screening methods in girls vaccinated against HPV and the knowledge needs for defining evidence-based screening strategies. During the consensus celebration (24 November 2015) a jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews (2).
The jury considered changing the screening protocols for girls vaccinated in their 12th year as appropriate. Tailored screening protocols based on vaccination status could be replaced by “one size fits all” protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with the HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5 years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their 15th year or later, the current protocol should be kept.
As further action, in 2016 the Ministry of Health funded a Health Technology Assessment program of the new screening protocol proposed by the consensus conference and a cohort study for determining a safe interval in vaccinated women.
This chapter focuses on the usage of wireless sensor and actuator networks to provide data connectivity in smart grids. In particular, we discuss the configuration adopted for the implementation of the sensor network test-bed deployed at the Information Engineering Department of the University of Padova, Italy. The test-bed has been designed to reproduce typical deployment scenarios in an urban network by mimicking diverse contexts such as dense building networks, sparse environmental scenarios, and linear deployments along streets.
The test-bed software has been realized taking full advantage of the most advanced solutions provided by the academic community and the standardization bodies by implementing a completely IP interoperable communication framework. Moreover, the latest solutions for the Internet of things  have been used to develop a lightweight modular architecture offering services and data sources through simple and efficient web services. All of this facilitates the integration of the test-bed functionalities into flexible web applications, capable of performing the needed monitoring and managing routines in the entire network as well as on single nodes.
The Internet-like approach, coupled with a variety of network configurations, has been used to verify the advantages brought by the usage of constrained wireless communication for smart grids. In particular, we have been able to quantify useful performance metrics, such as maximum throughput, delivery delay, and transmission reliability, in typical smart grid network scenarios. Specifically, these performance metrics were determined for linearly shaped multihop configurations, to address networks deployed along streets, such as those controlling the street lights, as well as for dense single- and multihop configurations to address small-to-medium-sized building deployments.
A 69-year-old man presented with Cotard's delusions, insomnia, profound depression, amnesia, difficulty concentrating, and cognitive deficit after two different surgical interventions. Brain imaging showed frontotemporal-subcortical atrophy and lateral ventricular enlargement. He responded poorly to a combination of sertraline, amisulpride and mirtazapine, with modest benefit on insomnia, and developed hypotension. After 18 days he was switched to olanzapine and venlafaxine, but his cognition worsened. He underwent bilateral electroconvulsive therapy (ECT). His mood improved, cognitive performance increased and anxiety symptoms remitted. This improvement persisted through the one-month post-discharge follow-up and depression eventually remitted.
Epitaxial diamond films were deposited on polished single crystal Ib type HPHT diamond plates of (100) orientation by microwave CVD. The epilayers were used for the fabrication of surface channel MESFET structures having sub-micrometer gate length in the range 200-800 nm. Realized devices show maximum drain current and trasconductance values of about 190 mA/mm and 80 mS/mm, respectively, for MESFETs having 200 nm gate length. RF performance evaluation gave cut off frequency of about 14 GHz and maximum oscillation frequency of more than 26 GHz for the same device geometry.
Large-signal radiofrequency performances of surface channel diamond MESFET fabricated on hydrogenated polycrystalline diamond are investigated. The adopted device structure is a typical coplanar two-finger gate layout, characterized in DC by an accumulation-like behavior with threshold voltage Vt ∼ 0-0.5 V and maximum DC drain current of 120 mA/mm. The best radiofrequency performances (in terms of fT and fmax) were obtained close to the threshold voltage. Realized devices are analyzed in standard class A operation, at an operating frequency of 2 GHz. The MESFET devices show a linear power gain of 8 dB and approximately 0.2 Wmm RF output power with 22% power added efficiency. An output power density of about 0.8 W/mm can be then extrapolated at 1 GHz, showing the potential of surface channel MESFET technology on polycrystalline diamond for microwave power devices.
Negli ultimi anni il modello categoriale della psicosi e della schizofrenia in particolare, è stato riconsiderato a favore di una visione dimensionale. Questa assume che I sintomi psicotici differiscono in modo quantitativo dalle normali esperienze psichiche distribuendosi lungo un continuum che va dalla popolazione clinica affetta da schizofrenia ad individui con disturbo di personalità, fino alla popolazione generale che può mostrare esperienze simil psicotiche (Hanssen et al., 2003; Johns & Phil, 2005). Tale continuità fenomenologica è suggerita da studi che mostrano che le dimensioni del fenotipo della psicosi subclinica sono molto simili a quelle identificate nei disturbi clinici (Van Os et al. 2000; Van Os & Tamminga, 2007; Rossler et al., 2007). Sono state infatti riportate dimensioni positive e negative sia in ambito clinico che subclinico, mentre più incerta appare la presenza della dimensione disorganizzazione (Vollema & Hoijtink, 2000; van Os et al., 2002). Vari studi hanno riportato che i fenotipi clinico e non clinico condividono fattori di rischio, meccanismi psicologici ed i pattern epidemiologici (Sharpley & Peters,1999; Johns & van Os, 2001; van Os et al., 2001), fornendo un'ulteriore prova che l'espressione clinica e subclinica delle psicosi fanno parte dello stesso continuum.
Aim and Method – The paper is a selective review of the literature on strategies and methods of cognitive remediation in schizophrenic disorders. It has been focused on the remediation of executive functions and the present hypotheses about the possibility of an improvement of the neurocognitive deficit through specific interventions. Results and Conclusions –People with Schizophrenic Disorders have some degree of cognitive deficit that often precede the clinical onset not secondary to the pathology characteristics persisting even when the positive symptoms have been resolved. The possibility that the neurocognitive deficits could be modified by psychological remediation with effects not exclusively confined to the cognitive domain has been nowadays accepted and numerous studies demonstrate that these interventions are effective and durable with a positive impact on social and working abilities, symptomatology and self-esteem.
Declaration of Interest
the authors declare that no economical support was obtained for this paper and no other kind of conflict of interest is present.
Objective – Aim of the study was to investigate the psychometric properties of the Italian version of the Drug Attitude Inventory (DAI) by exploring its construct validity. Setting – 90 voluntary admitted patients with DSM III-R Schizophrenic (n.72) and Schizoaffective (n.18) disorders, age range between 18 and 50 years, treated with typical antipsychotics, able to participate in the study, were selected. Design – Exploratory factor analyses with alpha factoring and maximum–likelihood methods with Varimax Rotation were used to analyse DAI scores. Results – Extraction methods found 7 factors which explained 62.5% of the total variance. The first 2 factors could be labelled as “subjective response to treatment” construct and factors 3 to 7 as “attitude to medication” contruct. Conclusion – Although preliminarily, the Italian version of the DAI seems to maintain the original psychometric properties and it can be used easily to get a valid measurement of the patients' attitude to neuroleptic medication.
We report here that in vitro exposure of monomeric
actin to hydrogen peroxide leads to a conversion of 6 of
the 16 methionine residues to methionine sulfoxide residues.
Although the initial effect of H2O2
on actin is the oxidation of Cys374, we have found that
Met44, Met47, Met176, Met190, Met269, and Met355 are the
other sites of the oxidative modification. Met44 and Met47
are the methionyl sites first oxidized. The methionine
residues that are oxidized are not simply related to their
accessibility to the external medium and are found in all
four subdomains of actin. The conformations of subdomain
1, a region critical for the functional binding of different
actin-binding proteins, and subdomain 2, which plays important
roles in the polymerization process and stabilization of
the actin filament, are changed upon oxidation. The conformational
changes are deduced from the increased exposure of hydrophobic
residues, which correlates with methionine sulfoxide formation,
from the perturbations in tryptophan fluorescence, and
from the decreased susceptibility to limited proteolysis
of oxidized actin.
PbZrO3 undergoes a phase transition to a paraelectric phase at 230°C. During this phase transition the unit cell changes from orthorhombic to cubic. Structural changes of PbZrO3 have been monitored using solid state NMR by measuring the variation in the 207Pb chemical shielding tensor as a function of temperature. The two distinct lead sites show rather different behavior as a function of temperature. The less shielded lead maintains an almost constant asymmetry parameter η = 0.2 from 0°C to 200°C while the more shielded lead resonance becomes more axially symmetric as the temperature is raised going from η = 0.24 at 0°C to [.eta] = 0.08 at 200°C. Powder pattern singularities become less distinct near the phase transitions, but the temperature dependence of the chemical shift tensor principal values remains continuous, and there is no evidence of an intervening higher-symmetry phase. At the phase transition, both resonances collapse into a single narrow line characteristic of a nucleus at a high-symmetry site. Results of a preliminary study of the PbZr1−xTixO3 solid solutions by 207Pb solid state NMR are also presented.
The crystal-chemical relationships occurring within a single grain of monazite-(Ce) from Vetralla, Vico Volcanic Complex, north of Rome, are outlined. The sample is from a miarolitic cavity in a holocrystalline ejectum consisting of K-feldspar plus minor plagioclase, mica and Fe-oxides, collected from a pyroclastic explosive level. The Gandolfi film (Cu-Kα radiation) can be indexed in space group P21/n with a = 6.816(4); b = 6.976(4); c = 6.471(3) Å; β = 103.63(3)°; V = 299.0(6) Å3. Electron-probe microanalyses plot within the field of monazite along the huttonite-monazite edge of the huttonite-monazite-brabantite triangle. Despite patchy and irregular zoning, the grain shows a clear enrichment towards pure monazite at the outer rim. A constant Th:Si ratio of 1:1 indicates the existence of a simple solid-solution between huttonite and monazite. The substitution can be written as Th4+ + Si4+ → REE3+ + P5+ without requiring any electrostatic compensation by divalent cations, or by anionic groups. The REE distribution pattern is compatible with that of monazites from syenitic rocks.
When we pronounce the word science many things come to our minds: the theories and the experiments, the laboratories and places of research, the scientific communities and congresses, the journals and the manuals, the academies and scientific societies, the institutions and the languages of science.
Sometimes, when we speak of science in reference to Bacon or Mersenne or Galilei we are drawn to forget that that which we call science (in the form in which we know it) did not exist in the first half of the seventeenth century. The two great historic processes which gave life to our science, and which the sociologists have called institutionalization and professionalization of science, took place between the middle of the seventeenth and the middle of the nineteenth centuries. The question that the historians of philosophical and scientific thought ask themselves (must ask themselves) is the following: what idea or what image of science made those processes possible? On what terrain were they born?