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Introduction: Primary immune thrombocytopenia is a rare autoimmune disease characterised by a decreased platelet count resulting in an increased risk of bleeding events and even lifethreatening haemorrhages. Thrombopoietin receptor agonists (TPO-RAs) are the standard of care second-line therapy for adult patients with chronic immune thrombocytopenia. The first TPO-RAs approved and reimbursed in Italy, eltrombopag and romiplostim, while effective, pose some issues in terms of safety (e.g., hepatotoxicity) or general management (e.g., dietary restrictions). Avatrombopag, an effective and well-tolerated TPO-RA, was recently granted reimbursement. Methods: A 3-year (2023-2025) budget impact analysis (BIA) was conducted to estimate its impact on the Italian National Health Service (NHS). Two scenarios were compared, of which one represents the current situation, without avatrombopag, and the other provides for an increasing market share of avatrombopag (up to 26.6%). Results: BIA shows that the increase in the use of avatrombopag correlates with savings for NHS: in the first year, saving would be €1,300,564, increasing to €2,774,210 in the third year, for a total of €6,083,231 over the 3-year period. The sensitivity analysis confirmed these savings in the scenario with avatrombopag. Conclusions: Based on this BIA, the introduction and reimbursement of avatrombopag is an efficient and advantageous choice for the Italian NHS. [ABSTRACT FROM AUTHOR]

Due to the increasing mass mortality of Pinna nobilis, mainly caused by the protozoan Haplosporidium pinnae along the Mediterranean Sea, it is necessary to develop rapid and effective methods to detect the pathogen. The present study describes the development and validation of a species-specific assay based on hydrolysis probe chemistry to detect H. pinnae DNA from faeces and pseudofaeces of P. nobilis. During a study campaign in the Gulf of Trieste (Italy) in the spring and summer of 2022, 18 samples (10 faeces and 8 pseudofaeces) were collected. DNA was isolated from all samples and the presence of H. pinnae was tested by amplifying a small portion of 18S rDNA using qPCR. The newly developed assay detected positive H. pinnae in the faeces of the fan mussel in the spring, while no evidence of an outbreak of H. pinnae was found in the summer. In addition, the method proved to be noninvasive and can be used to monitor suspected H. pinnae infections in the early stages when bivalves are still vital. Furthermore, fecal analysis allows the monitoring of P. nobilis without dissecting tissues. The presented assay can also be used to routinely monitor the progress of mass mortalities caused by H. pinnae and to screen for the pathogen in live fan mussels and other environmental matrices, such as water, sediment, and faeces from other species that can host the protozoan. [ABSTRACT FROM AUTHOR]

The helicity representation of the linear momentum density of a light wave is well understood for monochromatic optical fields in both paraxial and non-paraxial regimes of propagation. In this note we generalize such representation to nonmonochromatic optical fields. We find that, differently from the monochromatic case, the linear momentum density, aka the Poynting vector divided by c 2, does not separate into the sum of right-handed and left-handed terms, even when the so-called electricâ€"magnetic democracy in enforced by averaging the electric and magnetic contributions. However, for quasimonochromatic light, such a separation is approximately restored after time-averaging. This paper is dedicated to Sir Michael Berry on the occasion of his 80th birthday. [ABSTRACT FROM AUTHOR]

Haemophilia B (HB) is a rare disease which may lead to chronic disabling arthropathy, resulting in a significant clinical, social and economic impact. In recent years, new extended half-life (EHL) factor IX concentrates produced by recombinant technology (rFIX) have been developed. They have shown significantly prolonged half-life as compared to other rFIX products and improved bleeding control when used as prophylaxis. To date, EHL rFIX products reimbursed in Italy are a recombinant coagulation factor IX produced with Fc technology (rFIXFc) and a recombinant fusion protein containing rFIX fused with recombinant albumin (rIX-FP). The results of extension studies with injection intervals with a median of almost every 14 days for the complete individualized interval prophylaxis (IP) group on rFIXFc and 21 days for a selected subgroup of patients on rIX-FP have recently been published. The aim of this analysis was to estimate the cost of prophylactic treatment with rFIXFc and rIX-FP in adult pa- tients, in the light of new clinical evidence and current average prices in Italy. The cost of therapy was estimated on the basis of the results of extension studies, the average prices reported in regional drug tenders and assuming an average patient weight of 70 kg. The analysis estimated a cost per patient/year between €224,407 and €230,355 for rFIXFc and between €242,259 and €368,587 for rIX-FP. The sensitivity analysis confirmed the robustness of the results. The use of rFIXFc over rIX-FP proves to be the least expensive choice for the treatment of HB in Italy. [ABSTRACT FROM AUTHOR]

Purpose Erythropoiesis‐stimulating agents (ESAs), are used for treating chronic kidney disease (CKD)‐related anemia, contributing to CKD costs. The study was aimed at investigating direct healthcare costs of CKD patients treated with ESAs and the potential savings achievable by increasing the use of biosimilars and preventing inappropriate ESA use. Methods: A multi‐center, cohort study was conducted using claims databases of five large Italian geographic areas. Yearly mean direct healthcare costs per patient were estimated, stratifying by CKD stage. The total yearly cost and potential savings related to ESA use were estimated: (a) considering 25/50/75% of originator ESA substitution with biosimilars; (b) eliminating inappropriate ESA dispensing. Results: During the study period, the ESA‐related yearly mean cost represented 17% of total yearly costs in stage I‐III, decreasing to 13% in stage IV‐V and 6% in dialysis. Among originator users, assuming a 25% of biosimilar uptake, the annual cost‐savings of ESA treatment would represent 10.5% of total ESA costs in CKD stage I‐V and 7.7% in dialysis. Among incident ESA users for which hemoglobin levels were available, 9% started inappropriately ESA treatment, increasing to 62.0% during the first year of maintenance therapy. Hypothesizing prevention of the first inappropriate ESA dispensing, the total yearly cost‐savings would amount to €35 772, increasing to €167 641 eliminating the inappropriate dispensing during maintenance therapy. Conclusions: Higher use of lowest cost ESA, prevention of inappropriate ESA use as well as other strategies aimed at slowing down the progressive renal impairment are essential for minimizing clinical and economic burden of CKD. [ABSTRACT FROM AUTHOR]

Introduction: Clear cell Renal Cell Carcinoma (RCC), particularly when diagnosed at an advanced stage (aRCC), is associated with poor prognosis. The Italian Medical Oncology Association strongly recommends cabozantinib, sunitinib and pazopanib for first line of therapy. The aim of this study was to compare the cost-effectiveness of cabozantinib with sunitinib and pazopanib for treatment of adult patients with aRCC as first line therapy in Italy. Methods: A partitioned, three-state (progression-free, post-progression, death) survival model with a 20-year time horizon was used to estimate the proportion of patients in each state and the total costs associated with each treatment. Efficacy outcomes were retrieved from a recently published meta-analysis; model inputs included overall survival, progression free survival, time to treatment discontinuation and treatment-emergent adverse events. Utility values were based on published studies. Prices were based on published Italian hospital tenders and NHS Reference Costs. Results: Treatment with cabozantinib appears to be more costly and more effective than both sunitinib and pazopanib. In the reference case, treatment with cabozantinib results in an incremental +0.594 quality-adjusted life years (QALY), with an incremental cost-effectiveness ratio (ICER) of 29,126 €/QALY vs sunitinib and +0.608 QALY with ICER 30,794 €/QALY vs pazopanib. Results were confirmed by univariate and probabilistic sensitivity analyses. Conclusion: Cabozantinib represents a cost-effective option in first line treatment of aRCC in Italy. [ABSTRACT FROM AUTHOR]

Introduction: Prophylaxis with factor IX (FIX) concentrates, produced by recombinant DNA technology (rFIX) or human plasma-derived concentrates, is the treatment of choice for haemophilia B (HB); rFIX covalently fused to the Fc domain of human immunoglobulin G1 (rFIXFc) allows for prophylaxis/treatment with one infusion every 7-14 days. The purpose of this study is to quantify the financial impact of prophylaxis with rFIXFc vs. other approved rFIX and reimbursed for treatment of HB in Italy. Methods: The number of patients was estimated according to Italian epidemiological data and use of rFIX. Dose and frequency of administration used for weekly prophylaxis were those recommended in the Summary of Product Characteristics (SPC), while clinical trials and literature data were used to calculate bleeding rates and management. Drug costs were calculated using regional ex-factory net prices. In the model, a reference scenario (Reference) vs. an alternative scenario (Alternative) were created to account for introduction of rFIXFc, estimating an increasing trend of the market share of rFIXFc in a 3-year timeframe. The analysis was developed in the perspective of the National Health Service and included healthcare costs related to rFIX for prophylaxis and resolu- tion of bleeding events. Results: The model estimated an overall cumulative expenditure (years 1-3) of €209,453,646 for the Reference and €207,465,568 for Alternative scenarios, with calculated cumulative savings of €1,988,068. Conclusions: The increasing use of rFIXFc as a substitute for other rFIX concentrates in the treatment of HB can represent a financially viable choice for the Italian National Health Service while ensuring effective control of bleeding. [ABSTRACT FROM AUTHOR]

In paediatric coeliac disease (CD), symptoms may not be a reliable factor in the diagnosis of coeliac disease as described by Rosen et al,1 and thus, recommendations for reviewing CD screening criteria were suggested.2 Apart from the costs, an important limiting factor in paediatric population mass screening using conventional immunoglobulin (Ig) A tissue transglutaminase (tTGIgA) may be the low compliance of asymptomatic children to be referred for testing. In the first one, a cost of + 20% for POCT was used, while in the second one, to compare POCT screening strategy vs CF, a cost for each FP visit of €15.44 was added to every patient in the CF. For this reason, we suggest that paediatricians utilise POCT in asymptomatic children only and refer children with clinical suspicion of CD for undergoing conventional serology; otherwise, testing for CD might be slowed down by a negative POCT. [Extracted from the article]

Biofiltration systems are a promising retrofit option for site-constrained urban areas due to the vertical arrangement of treatment stages that leads to a relatively compact footprint. Existing knowledge about the influence of their design and configuration on hydrological, stormwater pollutant removal and long-term performance is limited and this has been identified as a barrier to their widespread uptake. Long-term simulations of lined and unlined biofiltration systems in four contrasting UK climatic regimes were used to assess the influence of climate, ponding depth, biofilter to drainage area ratio and infiltration rate on hydrological performance. The results showed that local differences in climate have a significant impact on performance and that infiltration rates as low as 0·36 mm/h are not suitable for locations in the UK with high rainfall unless the biofilter to drainage area ratio is greater than 10%. However, with higher infiltration rates (72 mm/h) a biofilter occupying only 3% of the impermeable catchment area would be capable of infiltrating 97% of annual rainfall in central England. Preliminary results of adsorption and column tests to assess the effectiveness of media amendments, specifically zeolite and granular activated carbon, for dissolved copper and phosphate removal are presented in this paper. [ABSTRACT FROM AUTHOR]

Teleportation describes the transmission of information without transport of neither matter nor energy. For many years, however, it has been implicitly assumed that this scheme is of inherently nonlocal nature, and therefore exclusive to quantum systems. Here, we experimentally demonstrate that the concept of teleportation can be readily generalized beyond the quantum realm. We present an optical implementation of the teleportation protocol solely based on classical entanglement between spatial and modal degrees of freedom, entirely independent of nonlocality. Our findings could enable novel methods for distributing information between different transmission channels and may provide the means to leverage the advantages of both quantum and classical systems to create a robust hybrid communication infrastructure. [ABSTRACT FROM AUTHOR]

We address the question of whether there exists a hidden relationship between the near-field distribution generated by an oscillating electric dipole and the so-called cross-polarization of a collimated beam of light. We find that the answer is affirmative by showing that the complex field distributions occurring in both cases have a common physical origin: the requirement that the electromagnetic fields must be transverse. [ABSTRACT FROM AUTHOR]

The spin Hall effect of light (SHEL) is the photonic analogue of the spin Hall effect occurring for charge carriers in solid-state systems. This intriguing phenomenon manifests itself when a light beam refracts at an air-glass interface (conventional SHEL) or when it is projected onto an oblique plane, the latter effect being known as the geometric SHEL. It amounts to a polarization-dependent displacement perpendicular to the plane of incidence. In this work, we experimentally investigate the geometric SHEL for a light beam transmitted across an oblique polarizer. We find that the spatial intensity distribution of the transmitted beam depends on the incident state of polarization and its centroid undergoes a positional displacement exceeding one wavelength. This novel phenomenon is virtually independent from the material properties of the polarizer and, thus, reveals universal features of spin-orbit coupling. [ABSTRACT FROM AUTHOR]

Numerical evolutions of whispering gallery modes of both isotropic and anisotropic spheroidal resonators are presented and are used to build analytical approximations of these modes. Such approximations are carried out mainly to have the possibility to have manageable analytic formulas for the eigenmodes and eigenfrequencies of anisotropic resonators. A qualitative analysis of ellipsoidal anisotropic modes in terms of superposition of spherical modes is also presented. [ABSTRACT FROM AUTHOR]

We study the classical optics effects known as Goos–Hänchen and Imbert–Fedorov shifts, occurring when reflecting a bounded light beam from a planar surface, by using a quantum-mechanical formalism. This new approach allows us to naturally separate the spatial shift into two parts, one independent on orbital angular momentum (OAM) and the other one showing OAM-induced spatial-versus-angular shift mixing. In addition, within this quantum-mechanical-like formalism, it becomes apparent that the angular shift is proportional to the beams angular spread, namely to the variance of the transverse components of the wave vector. Moreover, we extend our treatment to the enhancement of beam shifts via weak measurements and relate our results to the recent experiments. [ABSTRACT FROM AUTHOR]

The ABCD matrix formalism describing paraxial propagation of optical beams across linear systems is generalized to arbitrary beam trajectories. As a by-product of this study, a one-to-one correspondence between the extended ABCD matrix formalism presented here and the quantum mechanical translation operator is established. [ABSTRACT FROM AUTHOR]

A beam of light, reflected at a planar interface, does not follow perfectly the ray optics prediction. Diffractive corrections lead to beam shifts; the reflected beam is displaced (spatial Goos-Hänchen type shifts) and/or travels in a different direction (angular Imbert-Fedorov type shifts), as compared to geometric optics. How does the degree of spatial coherence of light influence these shifts? We investigate this issue first experimentally and find that the degree of spatial coherence influences the angular beam shifts, while the spatial beam shifts are unaffected. [ABSTRACT FROM AUTHOR]

We investigate how the orbital angular momentum of a paraxial light beam is affected upon reflection at a planar interface. Theoretically, the unavoidable angular spread of the beam leads to orbital angular momentum sidebands, which are found to be already significant for a modest beam spread (0.05). In analogy to the polarization Fresnel coefficients, we develop an analytical theory based upon spatial Fresnel coefficients; this allows a straightforward prediction of the strength of the sidebands. We confirm this by experiment and numerical simulation. [ABSTRACT FROM AUTHOR]

Two photons are said to be identical if they are prepared in the same quantum state. Given the latter, there is a unique way to achieve this. Conversely, there are many different ways of preparing two non-identical photons: they may differ in frequency, polarization, amplitude, etc. Therefore, photon distinguishability depends upon the specific degree of freedom being varied. By means of a careful analysis of the coincidence probability distribution in a Hong-Ou-Mandel experiment, we can show that photon distinguishability can be actually quantified by the rate of distinguishability of photons, an experimentally measurable parameter that crucially depends on both the photon quantum state and the degree of freedom under control [ABSTRACT FROM AUTHOR]

We present a graphical example of the interaction picture-time evolution. Our aim is to help students understand in a didactic manner the simplicity that this picture provides. Visualizing the interaction picture unveils its advantages, which are hidden behind the involved mathematics. Specifically, we show that the time evolution of a driven harmonic oscillator in the interaction picture corresponds to a local transformation of a phase space-reference frame into the one that is co-rotating with the Wigner function. [ABSTRACT FROM AUTHOR]

When a beam of light is reflected by a smooth surface its behavior deviates from geometrical optics predictions. Such deviations are quantified by the so-called spatial and angular Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts of the reflected beam. These shifts depend upon the shape of the incident beam, its polarization and on the material composition of the reflecting surface. In this paper we suggest a novel approach that allows one to unambiguously isolate the beam-shape dependent aspects of GH and IF shifts.We show that this separation is possible as a result of some universal features of shifted distribution functions which are presented and discussed. [ABSTRACT FROM AUTHOR]

An analytic solution for a uniaxial spherical resonator is presented using the method of Debye potentials. This serves as a starting point for the calculation of whispering gallery modes (WGMs) in such a resonator. Suitable approximations for the radial functions are discussed in order to best characterize WGMs. The characteristic equation and its asymptotic expansion for the anisotropic case is also discussed, and an analytic formula with a precision of the order O[v-1] is also given. Our careful treatment of both boundary conditions and asymptotic expansions makes the present work a particularly suitable platform for a quantum theory of whispering gallery resonators. [ABSTRACT FROM AUTHOR]

Biomarkers, especially CRP, have demonstrated their relevance to differentiate viral from bacterial infection, even though a reliable threshold is far to being found. In low- and middle-income countries, affordable and user-friendly rapid diagnostic tests based on biomarkers can be widely adopted to help health workers in the management of non-malarial fever. The primary objective of this study is to assess the best CRP cut-off to distinguish viral from bacterial infections. Other biomarkers were evaluated for the same purpose, alone or in combination with CRP. We retrospectively collected data from two referral hospital departments for infectious and tropical diseases in Italy. Areas under the ROC curve (AUC) were calculated and then compared using the DeLong test. Overall, we included 1193 febrile cases (viral 20.74% vs. bacterial 79.25%). We also collected malaria (n = 202) and intestinal parasite (n = 186) cases to establish their impact on biomarkers. CRP had the best accuracy in differentiating viral from bacterial infections. The best performance of CRP was a cut-off of 11 mg/L. All other biomarkers studied had significantly lower accuracy. Median CRP values were within the normal ranges in parasitic infections, while they were higher in malaria. None of the combinations of CRP with other biomarkers significantly increased the accuracy of CRP alone. [ABSTRACT FROM AUTHOR]

We derive a well-defined renormalized version of mutual information that allows us to estimate the dependence between continuous random variables in the important case when one is deterministically dependent on the other. This is the situation relevant for feature extraction, where the goal is to produce a low-dimensional effective description of a high-dimensional system. Our approach enables the discovery of collective variables in physical systems, thus adding to the toolbox of artificial scientific discovery, while also aiding the analysis of information flow in artificial neural networks. [ABSTRACT FROM AUTHOR]

The Schrödinger equation admits smooth and finite solutions that spontaneously evolve into a singularity, even for a free particle. This blowup is generally ascribed to the intrinsic dispersive character of the associated time evolution. We resort to the notion of quantum Bohmian trajectories to relate this singular behavior to local phase variations, which generate an underlying velocity field responsible for driving the quantum flux toward the singular region. • The dispersive blowup of the Schrödinger equation is investigated. • Local phase variations undergone by the wave function generate an underlying velocity field responsible for driving the quantum flux toward singular regions. • Bohmian trajectories are used to relate the wave function singular behavior to local phase variations. [ABSTRACT FROM AUTHOR]

Background and Objective: Ibrutinib has recently been approved in Europe for Waldenström Macroglobulinemia (WM) in symptomatic patients who have received at least one prior therapy, or in first-line treatment for patients unsuitable for chemo-immunotherapy. The aim of the study is to estimate the incremental cost-effectiveness ratio (ICER) of ibrutinib in relapse/refractory WM, compared with the Italian current therapeutic pathways (CTP). Methods: A Markov model was adapted for Italy considering the National Health System perspective. Input data from literature as well as global trials were used. The percentage use of therapies, and healthcare resources consumption were estimated according to expert panel advice. Drugs ex-factory prices and national tariffs were used for estimating costs. The model had a 15-year time horizon, with a 3.0% discount rate for both clinical and economic data. Deterministic and probabilistic sensitivity analyses were performed to test the results strength. Results: Ibrutinib resulted in increased Life Years Gained (LYGs) and increased costs compared to CTP, with an ICER of €52,698/LYG. Sensitivity analyses confirmed the results of the BaseCase. Specifically, in the probabilistic analysis, at a willingness to pay threshold of €60,000/LYG ibrutinib was cost-effective in 84% of simulations. Conclusions: Ibrutinib has demonstrated a positive cost-effectiveness profile in Italy. [ABSTRACT FROM AUTHOR]

Objective:To evaluate the cost-effectiveness of bedaquiline plus background drug regimens (BR) for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in Italy. Methods: A Markov model was adapted to the Italian setting to estimate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR in the treatment of MDR-TB and XDR-TB over 10 years, from both the National Health Service (NHS) and societal perspective. Cost-effectiveness was evaluated in terms of life-years gained (LYG). Clinical data were sourced from trials; resource consumption for compared treatments was modelled according to advice from an expert clinicians panel. NHS tariffs for inpatient and outpatient resource consumption were retrieved from published Italian sources. Drug costs were provided by reference centres for disease treatment in Italy. A 3% annual discount was applied to both cost and effectiveness. Deterministic and probabilistic sensitivity analyses were conducted. Results: Over 10 years, BBR vs. BR alone is cost-effective, with ICERs of €16,639/LYG and €4081/LYG for the NHS and society, respectively. The sensitivity analyses confirmed the robustness of the results from both considered perspectives. Conclusion: In Italy, BBR vs. BR alone has proven to be cost-effective in the treatment of MDR-TB and XDR-TB under a range of scenarios. [ABSTRACT FROM PUBLISHER]

Quantum approaches relying on entangled photons have been recently proposed to increase the efficiency of optical measurements. We demonstrate here that, surprisingly, the use of classical light with entangled degrees of freedom can also bring outstanding advantages over conventional measurements in polarization metrology. Specifically, we show that radially polarized beams of light allow to perform real-time single-shot Mueller matrix polarimetry. Our results also indicate that quantum optical procedures requiring entanglement without nonlocality can be actually achieved in the classical optics regime. [ABSTRACT FROM AUTHOR]

The generation of high-quality single-photon states with controllable narrow spectral bandwidths and central frequencies is key to facilitate efficient coupling of any atomic system to non-classical light fields. Such an interaction is essential in numerous experiments for fundamental science and applications in quantum communication and information processing, as well as in quantum metrology. Here we implement a fully tunable, narrow-band and efficient single-photon source based on a whispering gallery mode resonator. Our disk-shaped, monolithic and intrinsically stable resonator is made of lithium niobate and supports a cavity-assisted spontaneous parametric down-conversion process. The generated photon pairs are emitted into two highly tunable resonator modes. We verify wavelength tuning over 100?nm of both modes with controllable bandwidth between 7.2 and 13?MHz. Heralding of single photons yields anti-bunching with g(2)(0)<0.2. [ABSTRACT FROM AUTHOR]

We present precise expressions for the spatial and angular Goos–Hänchen and Imbert–Fedorov shifts experienced by a longitudinally and transversally limited beam of light (wavepacket) upon reflection from a dielectric interface, as opposed to the well-known case of a monochromatic beam which is bounded in transverse directions but infinitely extended along the direction of propagation. This is done under the assumption that the detector time is longer than the temporal length of the wavepacket (wavepacket regime). Our results will be applied to the case of a Gaussian wavepacket and show that, at the leading order in the Taylor expansion of reflected field amplitudes, the results are the same as in the monochromatic case. [ABSTRACT FROM AUTHOR]

We investigate how beams with orbital angular momentum (OAM) behave under total internal reflection. This is studied in two complementary experiments: in the first experiment, we study geometric shifts of OAM beams upon total internal reflection (Goos–Hänchen and Imbert–Fedorov shifts, for each the spatial and angular variant), and in the second experiment we determine changes in the OAM mode spectrum of a beam, again upon total internal reflection. As a result we find that, in the first case, the shifts are independent of OAM and beam focusing, while in the second case, modifications in the OAM spectrum occur which depend on the input OAM mode as well as on the beam focusing. This is investigated by experiment and theory. We also show how the two methods, beam shifts on the one hand, and OAM spectrum changes on the other, are related theoretically. [ABSTRACT FROM AUTHOR]