Disinvestment in healthcare: An overview of HTA agencies and organizations activities at European level

Background: In an era of a growing economic pressure for all health systems, the interest for "disinvestment" in healthcare increased. In this context, evidence based approaches such as Health Technology Assessment (HTA) are needed both to invest and to disinvest in health technologies. In order to investigate the extent of application of HTA in this field, methodological projects/frameworks, case studies, dissemination initiatives on disinvestment released by HTA agencies and organizations located in Europe were searched. Methods: In July 2015, the websites of HTA agencies and organizations belonging to the European network for HTA (EUnetHTA) and the International Network of Agencies for HTA (INAHTA) were accessed and searched through the use of the term "disinvestment". Retrieved deliverables were considered eligible if they reported methodological projects/frameworks, case studies and dissemination initiatives focused on disinvestment in healthcare. Results: 62 HTA agencies/organizations were accessed and eight methodological projects/frameworks, one case study and one dissemination initiative were found starting from 2007. With respect to methodological projects/frameworks, two were delivered in Austria, one in Italy, two in Spain and three in U.K. As for the case study and the dissemination initiative, both came from U.K. The majority of deliverables were aimed at making an overview of existing disinvestment approaches and at identifying challenges in their introduction. Conclusions: Today, in a healthcare context characterized by resource scarcity and increasing service demand, "disinvestment" from low-value services and reinvestment in high-value ones is a key strategy that may be supported by HTA. The lack of evaluation of technologies in use, in particular at the end of their lifecycle, may be due to the scant availability of frameworks and guidelines for identification and assessment of obsolete technologies that was shown by our work. Although several projects were carried out in different countries, most remain constrained to the field of research. Disinvestment is a relatively new concept in HTA that could pose challenges also from a methodological point of view. To tackle these challenges, it is necessary to construct experiences at international level with the aim to develop new methodological approaches to produce and grow evidence on disinvestment policies and practices

LCAT cholesterol esterification is associated with the increase of ApoE/ApoA-I ratio during atherosclerosis progression in rabbit

Apolipoprotein A-I and Apolipoprotein E promote different steps of reverse cholesterol transport, including lecithin-cholesterol acyltransferase stimulation. Our aim was to study the changes in the levels of Apolipoprotein A-I, Apolipoprotein E, and lecithin-cholesterol acyltransferase activity during atherosclerosis progression in rabbits. Quantitative echocardiographic parameters were analyzed in order to evaluate, for the first time, whether atherosclerosis progression in rabbit is associated to apolipoproteins changes and alteration of indices of cardiac function, such as systolic strain and strain rate of the left ventricle. Atherosclerosis was induced by feeding rabbits for 8 weeks with 2 % cholesterol diet. The HDL levels of cholesterol and cholesteryl esters were measured by HPLC. The lecithin-cholesterol acyltransferase activity was evaluated both ex vivo, as cholesteryl esters/cholesterol molar ratio, and in vitro. Apolipoproteins levels were analyzed by ELISA. The HDL levels of cholesterol and cholesteryl esters increased, during treatment, up to 3.7- and 2.5-fold, respectively, compared to control animals. The lecithin-cholesterol acyltransferase activity in vitro was halved after 4 weeks. During cholesterol treatment, Apolipoprotein A-I level significantly decreased, whereas Apolipoprotein E concentration markedly increased. The molar ratio Apolipoprotein E/Apolipoprotein A-I was negatively correlated with the enzyme activity, and positively correlated with both increases in the intima-media thickness of common carotid wall and cardiac dysfunction signs, such as systolic strain and strain rate of the left ventricle. © 2012 University of Navarra

LCAT cholesterol esterification is associated with the increase of ApoE/ApoA-I ratio during atherosclerosis progression in rabbit

Apolipoprotein A-I and Apolipoprotein E promote different steps of reverse cholesterol transport, including lecithin-cholesterol acyltransferase stimulation. Our aim was to study the changes in the levels of Apolipoprotein A-I, Apolipoprotein E, and lecithin-cholesterol acyltransferase activity during atherosclerosis progression in rabbits. Quantitative echocardiographic parameters were analyzed in order to evaluate, for the first time, whether atherosclerosis progression in rabbit is associated to apolipoproteins changes and alteration of indices of cardiac function, such as systolic strain and strain rate of the left ventricle. Atherosclerosis was induced by feeding rabbits for 8 weeks with 2 % cholesterol diet. The HDL levels of cholesterol and cholesteryl esters were measured by HPLC. The lecithin-cholesterol acyltransferase activity was evaluated both ex vivo, as cholesteryl esters/cholesterol molar ratio, and in vitro. Apolipoproteins levels were analyzed by ELISA. The HDL levels of cholesterol and cholesteryl esters increased, during treatment, up to 3.7- and 2.5-fold, respectively, compared to control animals. The lecithin-cholesterol acyltransferase activity in vitro was halved after 4 weeks. During cholesterol treatment, Apolipoprotein A-I level significantly decreased, whereas Apolipoprotein E concentration markedly increased. The molar ratio Apolipoprotein E/Apolipoprotein A-I was negatively correlated with the enzyme activity, and positively correlated with both increases in the intima-media thickness of common carotid wall and cardiac dysfunction signs, such as systolic strain and strain rate of the left ventricle. © 2012 University of Navarra

Septal ablation versus surgical myomectomy for hypertrophic obstructive cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) who have left ventricular outflow tract obstruction (LVOTO) often experience severe symptoms and functional limitation. Relief of LVOTO can be achieved by two invasive interventions, i.e., surgery myectomy and alcohol septal ablation (ASA), leading in experienced hands to a dramatic improvement in clinical status. Despite extensive research, however, the choice of the best option in individual patients remains challenging and poses numerous clinical dilemmas

Identifying Ly{\alpha} emitter candidates with Random Forest: learning from galaxies in CANDELS survey

The physical processes which make a galaxy a Lyman Alpha Emitter have been extensively studied for the past 25 years. However, the correlations between physical and morphological properties of galaxies and the strength of the Ly$\alpha$ emission line are still highly debated. Therefore, we investigate the correlations between the rest-frame Ly$\alpha$ equivalent width and stellar mass, star formation rate, dust reddening, metallicity, age, half-light semi-major axis, S\'ersic index and projected axis ratio in a sample of 1578 galaxies in the redshift range $2 \leq z \leq 7.9$ from the GOODS-S, UDS and COSMOS fields. From the large sample of Ly$\alpha$ emitters (LAEs) in the dataset we find that LAEs are typically common main sequence star forming galaxies which show stellar mass $\leq 10^9 \text{M}_{\odot}$, star formation rate $\leq 10^{0.5} \text{M}_{\odot}/\text{yr}$, $E(B-V) \leq 0.2$ and half-light semi-major axis $\leq 1 \text{kpc}$. Building on these findings we develop a new method based on Random Forest (i.e. a Machine Learning classifier) in order to select galaxies which have the highest probability of being Ly$\alpha$ emitters. When applied to a population in the redshift range $z \in [2.5, 4.5]$, our classifier holds a $(80 \pm 2)\%$ accuracy and $(73 \pm 4)\%$ precision. At higher redshifts ($z \in [4.5, 6]$), we obtain a $73\%$ accuracy and a $80\%$ precision. These results highlight it is possible to overcome the current limitations in assembling large samples of LAEs by making informed predictions that can be used for planning future large scale spectroscopic surveys.Comment: Accepted for publication in the 4. Extragalactic astronomy section of Astronomy & Astrophysics, 13 pages, 13 figure

Lipid-lowering treatment and LDL-C goal attainment in high and very high cardiovascular risk patients: Evidence from the SANTORINI study-The Italian experience

The SANTORINI study is an observational study that enrolled 9602 adult individuals at high or very high cardiovascular (CV) risk across Europe, aimed at providing information on the current status of the management of dyslipidaemias, in light of the most recent 2019 EAS/ESC guidelines. Italy participated in the study with 1977 patients, 1531 (77.4%) of whom were classified at very high CV risk and 446 (22.6%) at high CV risk. Overall, in the Italian population, 79.31% of the patients had a history of atherosclerotic cardiovascular disease (ASCVD). At enrolment, the mean level of LDL-C in the total population was 98.4 mg/dL. LDL-C levels were lower in the very high-risk group (94.6 mg/dL) than in the high-risk group (111.4 mg/dL). Considering the therapeutic goals recommended by the most recent 2019 ESC/EAS guidelines (LDL-C <55 mg/dL or <70 mg/dL respectively in very high or high-risk patients, respectively), only 20.3% of the overall study population achieved such goals (19.9% of very high-risk patients and 21.8% of high-risk patients). About one-third of the patients included in the study (32.6%) were not prescribed any therapy, one-third received statin monotherapy (34.4%), and only one-third (33%) were taking combination therapy; these percentages were comparable in the two risk subgroups. Based on the most recent 2019 ESC/EAS guidelines, the use of cholesterol-lowering therapies is not always optimal to achieve the therapeutic goals even in patients with very high CV risk. This means that about 80% of patients are far from the recommended therapeutic goals for their risk category

Usefulness of Low-Dose Statin Plus Ezetimibe and/or Nutraceuticals in Patients With Coronary Artery Disease Intolerant to High-Dose Statin Treatment.

High-dose statin (HDS) therapy is recommended to reduce low-density lipoprotein cholesterol (LDL-C); however, some patients are unable to tolerate the associated side effects. Nutraceuticals have shown efficacy in lowering LDL-C. The aim of this study was to evaluate whether the combination of low-dose statin (LDS) plus ezetimibe (EZE) or LDS plus nutraceutical (Armolipid Plus [ALP] containing red yeast rice, policosanol, and berberine) can lead to a higher proportion of high-risk patients achieving target LDL-C. A secondary objective was to assess the efficacy of triple combination LDS + EZE + ALP in resistant patients (LDL-C >70 mg/dl). A randomized, prospective, parallel-group, single-blind study was conducted in patients with coronary artery disease (n = 100) who had undergone percutaneous coronary intervention in the preceding 12 months, were HDS-intolerant, and were not at LDL-C target (<70 mg/dl) with LDS alone. Patients received either LDS + EZE or LDS + ALP. Of the 100 patients, 33 patients (66%) treated with LDS + EZE and 31 patients (62%) treated with LDS + ALP achieved target LDL-C after 3 months, which was maintained at 6 months. Patients who did not achieve the therapeutic goal received a triple combination of LDS + EZE + ALP for a further 3 months. At 6 months, 28 of 36 patients (78%) achieved LDL-C target. Overall, 92% of patients enrolled in this study were at target LDL-C at 6 months. No patients in any group experienced major side effects. In conclusion, in HDS-intolerant coronary artery disease patients, the combination of LDS plus EZE and/or ALP represents a valuable therapeutic option allowing most patients to reach target LDL-C within 3 to 6 months

Transitional hemodynamics in infants of diabetic mothers by targeted neonatal echocardiography, electrocardiography and peripheral flow study

Objective: Metabolic alterations of intrauterine environment in diabetes mellitus (DM) lead to fetal cardiac dysfunctions that can persist after birth. The aim of the study was to assess the cardiovascular adaptation in infants born to diabetic mothers (IDM) with different degrees of glycometabolic control, in relation to revised guidelines for diagnosis of DM and quality improvements in neonatal care. Materials and methods: An observational case-control study was conducted on IDM with gestational, type 1 and type 2\ue2\u80\u89DM. Relevant maternal and neonatal anamnestic, clinical and laboratory data were analyzed. Electrocardiographic and echocardiographic analyses, including structural and systo-diastolic evaluation, were performed. Results: In 68 IDM enrolled, we observed a lower incidence of negative perinatal outcome than expected. Comparing to non-IDM, they presented larger fetal shunts, higher pulmonary pressures, early and atrial wave velocities. At 72\ue2\u80\u89hours, kinesis and heart rate variability remained low. Cerebral blood flow velocities were higher. The most serious impairment of transition was in pregestational IDM. Conclusion: Maternal DM impaired neonatal transitional hemodynamics also in asymptomatic IDM with good glycometabolic control. These results confirm the need for an early cardiologic and cerebrovascular evaluation, to identify IDM with delayed maturation at risk of worse long-term metabolic, cardiovascular, and neurodevelopmental outcome

Exploring a New Paradigm for Accelerators and Large Experimental Apparatus Control Systems

International audienceThe integration of web technologies and web services has been, in the recent years, one of the major trends in upgrading and developing control systems for accelerators and large experimental apparatuses. Usually, web technologies have been introduced to complement the control systems with smart add-ons and user friendly services or, for instance, to safely allow access to the control system to users from remote sites. In spite of this still narrow spectrum of employment, some software technologies developed for high performance web services, although originally intended and optimized for these particular applications, deserve some features that would allow their deeper integration in a control system and, eventually, use them to develop some of the control system's core components. In this paper we present the conclusion of the preliminary investigations of a new paradigm for an accelerator control system and associated machine data acquisition system (DAQ), based on a synergic combination of network distributed cache memory and a non-relational key/value database. We investigated these technologies with particular interest on performances, namely speed of data storage and retrieve for the network memory, data throughput and queries execution time for the database and, especially, how much this performances can benefit from their inherent scalability. The work has been developed in a collaboration between INFN-LNF and INFN-Roma Tor Vergata

High current and low q95 scenario studies for FAST in the view of ITER and DEMO

The Fusion Advanced Study Torus (FAST) has been proposed as a possible European satellite, in view of ITER and DEMO, in order to: a) explore plasma wall interaction in reactor relevant conditions b) test tools and scenarios for safe and reliable tokamak operation up to the border of stability c) address fusion plasmas with a significant population of fast particles. A new FAST scenario has been designed focusing on low-q operation, at plasma current IP=10 MA, toroidal field BT=8.5T, with a q95=2.3 that would correspond to IP=20 MA in ITER. The flat-top of the discharge can last a couple of seconds (i.e. half the diffusive resistive time and twice the energy confinement time), and is limited by the heating of the toroidal field coils. A preliminary evaluation of the end-of-pulse temperatures and of the electromagnetic forces acting on the central solenoid pack and poloidal field coils has been performed. Moreover, a VDE plasma disruption has been simulated and the maximum total vertical force applied on the vacuum vessel has been estimated