Costs and effects of on-demand treatment of hereditary angioedema in Italy : a prospective cohort study of 167 patients

Objectives To explore treatment behaviours in a cohort of Italian patients with hereditary angioedema due to complement C1-inhibitor deficiency (C1-INH-HAE), and to estimate how effects and costs of treating attacks in routine practice differed across available on-demand treatments. Design Cost analyses and survival analyses using attack-level data collected prospectively for 1 year. Setting National reference centre for C1-INH-HAE. Participants 167 patients with proved diagnosis of C1-INH-HAE, who reported data on angioedema attacks, including severity, localisation and duration, treatment received, and use of other healthcare services. Interventions Attacks were treated with either icatibant, plasma-derived C1-INH (pdC1-INH) or just supportive care. Main outcome measures Treatment efficacy in reducing attack duration and the direct costs of acute attacks. Results Overall, 133 of 167 patients (79.6%) reported 1508 attacks during the study period, with mean incidence of 11 attacks per patient per year. Only 78.9% of attacks were treated in contrast to current guidelines. Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment (median times from onset 7, 10 and 47 hours, respectively), but remission rates with icatibant were 31% faster compared with pdC1-INH (HR 1.31, 95% CI 1.14 to 1.51). However, observed treatment behaviours suggest patterns of suboptimal dosing for pdC1-INH. The average cost per attack was \u20ac1183 (SD \u20ac789) resulting in \u20ac1.58 million healthcare costs during the observation period (\u20ac11 912 per patient per year). Icatibant was 54% more expensive than pdC1-INH, whereas age, sex and prophylactic treatment were not associated to higher or lower costs. Conclusions Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment, however, icatibant was more effective but also more expensive. Treatment behaviours and suboptimal dosing of pdC1-INH may account for the differences, but further research is needed to define their role

Comparison of multiple techniques for endobronchial ultrasound-transbronchial needle aspiration specimen preparation in a single institution experience.

The optimal method for specimen preparation of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is still controversial. This study aims to compare several techniques available for EBUS-TBNA specimen acquisition and processing, in order to identify the best performing technique. We retrospectively reviewed the data of 199 consecutive patients [male, 73%; median age, 64 years (IQR: 52-74 years)] undergoing EBUS-TBNA at our institution from 2012 through 2014 for diagnosis of hilar-mediastinal lymph node enlargement suspect of neoplastic (n=139) or granulomatous (n=60) disease. All procedures were performed by two experienced bronchoscopists, under conscious sedation and local anaesthesia, using 21/22-Gauge (G) needle, without rapid on-site evaluation (ROSE). Five specimen-processing techniques were used: cytology slides in 42 cases (21%); cell-block in 25 (13%); core-tissue in 60 (30%); combination of cytology slides and core-tissue in 51 (26%); combination of cytology slides and cell-block in 21 (10%). To assess the diagnostic accuracy of each tissue-processing technique we compared the EBUS-TBNA results to those obtained with surgical lymphadenectomy, or 1-year follow-up in non-operated patients. Diagnostic yield, accuracy and area under the curve (AUC) were as follows. Cytology slides: 81%, 80%, 0.90; cell-block: 48%, 33%, 0.67; core-tissue: 87%, 99%, 0.96; cytology slides + core-tissue: 80%, 100%, 1.00; cytology slides + cell-block: 86%, 100%, 1.00. Cytology slides and core-tissue method showed non-significantly different diagnostic yield (P=0.435) and AUC (P=0.152). In our single-institution experience, cytology slides and core-tissue preparations demonstrated high and similar diagnostic performance. Cytology slides combination with core-tissue or cell-block showed the highest performance, however these combination methods were more resource-consuming

Parallaxes of southern extremely cool objects III : 118 L and T dwarfs

We present new results from the Parallaxes of Southern Extremely Cool dwarfs program to measure parallaxes, proper motions and multiepoch photometry of L and early T dwarfs. The observations were made on 108 nights over the course of 8 yr using the Wide Field Imager on the ESO 2.2m telescope. We present 118 new parallaxes of L and T dwarfs of which 52 have no published values and 24 of the 66 published values are preliminary estimates from this program. The parallax precision varies from 1.0 to 15.5mas with a median of 3.8mas. We find evidence for two objects with long term photometric variation and 24 new moving group candidates. We cross-match our sample to published photometric catalogues and find standard magnitudes in up to 16 pass-bands from which we build spectral energy distributions and H-R diagrams. This allows us to confirm the theoretically anticipated minimum in radius between stars and brown dwarfs across the hydrogen burning minimum mass. We find the minimum occurs between L2 and L6 and verify the predicted steep dependence of radius in the hydrogen burning regime and the gentle rise into the degenerate brown dwarf regime. We find a relatively young age of ~2 Gyr from the kinematics of our sample.Peer reviewedFinal Accepted Versio

Use of thermographic imaging in clinical diagnosis of small animal: preliminary note

Introduction. The authors, after a description of the physics of infrared thermographic technique (IRT), analyze the reading of images and the main applications in the veterinary field, compared to the existing literature on the subject and to their experimental researches. IRT lends itself to countless applications in biology, thanks to its characteristics of versatility, lack of invasiveness and high sensitivity. Probably the major limitation to its application in the animal lies in the ease of use and in its extreme sensitivity. Materials and methods. From September 2009 to October 2010, the experimental investigation with the thermo camera took into consideration 110 animals (92 dogs and 18 cats), without any selection criteria. All patients were brought to the Faculty of Veterinary Medicine in Milan University by the owner, to be examined by a specialist, or to undergo one of the following diagnostic procedures: X-rays, computed tomography, or ultrasound examinations; finally some patients were brought in for surgical procedures. With the consent of the owner, 1 to 10 thermographic images were recorded from each clinical case. Results. In this first experimental investigation, thermography has shown a high sensitivity (100%), but a low specificity (44%). This figure excludes the use of thermal imaging technology to replace other imaging techniques such as radiography, computed tomography and magnetic resonance imaging. Furthermore, it does not show any ability to recognize the etiology of the disease, but only the thermal alteration, and this is restricting its use. However, this experimental study has demonstrated that thermography can be used in veterinary medicine, and specifically in dogs and cats. It is hoped that in the field of targeted diseases this technique will become an important tool for diagnostic purposes by using working protocols validated and repeatable

Phenomenology of the Lense-Thirring effect in the Solar System

Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study

BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19

Community action: value or instrument? An ethics and planning critical review

The community concept has maintained a constant and growing interest in urban studies and many related fields. The origin of this continuing interest seems to derive from the importance of the concept of community within diverse forms of political language and interpretations within different planning practices. In this contribution, through the analysis of different ethical and planning theories, we want to provide an update framework on community action. According to this objective, the argumentation will proceed through a literature review on four ethics theories and three key aspects related to spatial planning, as well as matching this theoretical analysis with exemplifying practices. The final objective is to provide an original analysis on drivers and outcomesof different forms of community, raising general issues that refer to spatial planning, social organization and regulation