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

HHV-8 transmission via saliva to soothe blood-sucking arthropod bites

The British Journal of Cance

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

A dominant mutation etiologic for human tricho-dento-osseous syndrome impairs the ability of DLX3 to downregulate ΔNp63α.

The homeodomain transcription factors play crucial roles in many developmental processes ranging from organization of the body plan to differentiation of individual tissues. The homeodomain protein Distal-less-3 (DLX3) has an essential role in epidermal stratification and development of ectodermal appendages, placenta and bones. A four-nucleotide deletion in the human DLX3 gene is etiologic for the human hereditary tricho-dento-osseous (TDO) ectodermal dysplasia, a dominant syndrome characterized by abnormalities in hair, nails, teeth, and bones. We have previously demonstrated that DLX3 gene expression induces degradation of ΔNp63α, a specific product of the TP63 gene, a master regulator of multi-layered epithelia. Here we show that the DLX3(TDO) mutant protein is unable to promote ΔNp63α protein degradation and impairs the expression of cell cycle regulatory proteins and skin differentiation markers. However, we found that in cell expressing equal amounts of mutant and wild-type DLX3, ΔNp63α protein level is efficiently regulated implying that genetic heterozygosity at the DLX3 locus protects TDO patients from developing severe p63-associated skin defects

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

Evaluation of acute cardiovascular effects of immediate-release methylphenidate in children and adolescents with attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder is a frequent condition in children and often extends into adulthood. Use of immediate-release methylphenidate (MPH) has raised concerns about potential cardiovascular adverse effects within a few hours after administration. This study was carried out to investigate acute effects of MPH on electrocardiogram (ECG) in a pediatric population. A total of 54 consecutive patients with attention-deficit hyperactivity disorder (51 males and 3 females; mean age =12.14±2.6 years, range 6–19 years), receiving a new prescription of MPH, underwent a standard ECG 2 hours before and after the administration of MPH 10 mg per os. Basal and posttreatment ECG parameters, including mean QT (QT interval when corrected for heart rate [QTc]), QTc dispersion (QTd) interval duration, T-peak to T-end (TpTe) intervals, and TpTe/QT ratio were compared. Significant modifications of both QTc and QTd values were not found after drug administration. QTd fluctuated slightly from 25.7±9.3 milliseconds to 25.1±8.4 milliseconds; QTc varied from 407.6±12.4 milliseconds to 409.8±12.7 milliseconds. A significant variation in blood pressure (systolic blood pressure 105.4±10.3 vs 109.6±11.5; P<0.05; diastolic blood pressure 59.2±7.1 vs 63.1±7.9; P<0.05) was observed, but all the data were within normal range. Heart rate moved from 80.5±15.5 bpm to 87.7±18.8 bpm. No change in TpTe values was found, but a statistically significant increase in TpTe/QTc intervals was found with respect to basal values (0.207±0.02 milliseconds vs 0.214±0.02 milliseconds; P<0.01). The findings of this study show no significant changes in ECG parameters. TpTe values can be an additional parameter to evaluate borderline cases

The VANDELS survey: A strong correlation between Lyα\alpha equivalent width and stellar metallicity at 3≤z≤5\mathbf{3\leq z \leq 5}

We present the results of a new study investigating the relationship between observed Ly$\alpha$ equivalent width ($W_{\lambda}$(Ly$\alpha$)) and the metallicity of the ionizing stellar population ($Z_{\star}$) for a sample of $768$ star-forming galaxies at $3 \leq z \leq 5$ drawn from the VANDELS survey. Dividing our sample into quartiles of rest-frame $W_{\lambda}$(Ly$\alpha$) across the range -58 \unicode{xC5} \lesssim $W_{\lambda}$(Ly$\alpha$) \lesssim 110 \unicode{xC5} we determine $Z_{\star}$ from full spectral fitting of composite far-ultraviolet (FUV) spectra and find a clear anti-correlation between $W_{\lambda}$(Ly$\alpha$) and $Z_{\star}$. Our results indicate that $Z_{\star}$ decreases by a factor $\gtrsim 3$ between the lowest $W_{\lambda}$(Ly$\alpha$) quartile ($\langle$$W_{\lambda}$(Ly$\alpha$)\rangle=-18\unicode{xC5}) and the highest $W_{\lambda}$(Ly$\alpha$) quartile ($\langle$$W_{\lambda}$(Ly$\alpha$)\rangle=24\unicode{xC5}). Similarly, galaxies typically defined as Lyman Alpha Emitters (LAEs; $W_{\lambda}$(Ly$\alpha$) >20\unicode{xC5}) are, on average, metal poor with respect to the non-LAE galaxy population ($W_{\lambda}$(Ly$\alpha$) \leq20\unicode{xC5}) with $Z_{\star}$$_{\rm{non-LAE}}\gtrsim 2 \times$ $Z_{\star}$$_{\rm{LAE}}$. Finally, based on the best-fitting stellar models, we estimate that the increasing strength of the stellar ionizing spectrum towards lower $Z_{\star}$ is responsible for $\simeq 15-25\%$ of the observed variation in $W_{\lambda}$(Ly$\alpha$) across our sample, with the remaining contribution ($\simeq 75-85\%$) being due to a decrease in the HI/dust covering fractions in low $Z_{\star}$ galaxies.Comment: 10 pages, 6 figures, MNRAS accepte

PP020—Effects of aripiprazole and risperidone on ventricular repolarization in children and adolescents

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