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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]

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]

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]

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]

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]

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]

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]

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]

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]