Cost-effectiveness analysis of Vaborem in Carbapenem-resistant Enterobacterales (CRE) -Klebsiella pneumoniae infections in Italy

Background: Vaborem is a fixed dose combination of vaborbactam and meropenem with potent activity against target Carbapenem-resistant Enterobacterales (CRE) pathogens, optimally developed for Klebsiella pneumoniae carbapenemase (KPC). The study aims to evaluate the cost-effectiveness of Vaborem versus best available therapy (BAT) for the treatment of patients with CRE-KPC associated infections in the Italian setting. Methods: A cost-effectiveness analysis was conducted based on a decision tree model that simulates the clinical pathway followed by physicians treating patients with a confirmed CRE-KPC infection in a 5-year time horizon. The Italian National Health System perspective was adopted with a 3% discount rate. The clinical inputs were mostly sourced from the phase 3, randomised, clinical trial (TANGO II). Unit costs were retrieved from the Italian official drug pricing list and legislation, while patient resource use was validated by a national expert. Model outcomes included life years (LYs) and quality adjusted life years (QALYs) gained, incremental costs, incremental cost- effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Deterministic and probabilistic sensitivity analyses were also performed. Results: Vaborem is expected to decrease the burden associated with treatment failure and reduce the need for chronic renal replacement therapy while costs related to drug acquisition and long-term care (due to higher survival) may increase. Treatment with Vaborem versus BAT leads to a gain of 0.475 LYs, 0.384 QALYs, and incremental costs of €3549, resulting in an ICER and ICUR of €7473/LY and €9246/QALY, respectively. Sensitivity analyses proved the robustness of the model and also revealed that the probability of Vaborem being cost-effective reaches 90% when willingness to pay is €15,850/QALY. Conclusions: In the Italian setting, the introduction of Vaborem will lead to a substantial increase in the quality of life together with a minimal cost impact, therefore Vaborem is expected to be a cost-effective strategy compared to BAT

Toxoplasmosis en animales de granja en la provincia de San Luis, Argentina

La toxoplasmosis es una enfermedad producida por un parásito protozoario unicelular eucariota, llamado Toxoplasma gondii, que puede afectar a todos los animales de sangre caliente inclusive al ser humano y es de distribución mundial. Entre los animales de importancia epidemiológica todos los de consumo habitual (cerdo, ovino, bovino, caprinos etc.) y los no tradicionales (como la liebre, vizcacha, etc.), también las aves y los insectos (moscas, cucarachas, etc.) pueden ser vectores y diseminadores del parásito. Los felinos son los únicos animales donde el parásito produce ooquistes, por esto se llaman hospedadores definitivos; en el resto de los animales el parásito no produce ooquistes y actúan como hospedadores intermediarios. El objetivo del presente trabajo fue estimar la prevalencia de la Toxoplasmosis en las poblaciones animales domésticas que conviven con el hombre en la zona rural del Departamento La Capital de la Provincia de San Luis.Facultad de Ciencias Veterinaria

Estudio exploratorio de la toxoplasmosis y leptospirosis en pequeños rumiantes y animales de granja en el Departamento La Capital, San Luis.

La Toxoplasmosis y la Leptospirosis como enfermedades zoonóticas afectan a animales y seres humanos, por lo que el conocimiento de factores causales y consecuencias de su existencia en una localidad o región implica el trabajo interdisciplinario. La toxoplasmosis es una enfermedad producida por un parásito protozoario unicelular eucariota, llamado Toxoplasma gondii, que puede afectar a todos los animales de sangre caliente inclusive al ser humano y es de distribución mundial

Estudio exploratorio de la toxoplasmosis y leptospirosis en pequeños rumiantes y animales de granja en el departamento La Capital, San Luis

La Toxoplasmosis y la Leptospirosis como enfermedades zoonóticas afectan a animales y seres humanos, por lo que el conocimiento de factores causales y consecuencias de su existencia en una localidad o región implica el trabajo interdisciplinario. La toxoplasmosis es una enfermedad producida por un parásito protozoario unicelular eucariota, llamado Toxoplasma gondii, que puede afectar a todos los animales de sangre caliente inclusive al ser humano y es de distribución mundial. Entre los animales de importancia epidemiológica todos los de consumo habitual (cerdo, ovino, bovino, caprinos etc.) y los no tradicionales (como la liebre, vizcacha, etc.), también las aves y los insectos (moscas, cucarachas, etc.) pueden ser vectores y diseminadores del parásito. Los felinos son los únicos animales donde el parásito produce ooquistes, por esto se llaman hospedadores definitivos; en el resto de los animales el parásito no produce ooquistes y actúan como hospedadores intermediarios. La leptospirosis es una antigua enfermedad producida por Leptospira interrogans, espiroqueta ampliamente distribuida en la naturaleza y que afecta al hombre y a varias especies animales. Se presume que es la zoonosis de mayor difusión en el mundo. La orina de animales infectados es la fuente de infección más común. Los reservorios son los animales, con especial importancia en roedores y mamíferos domésticos. El hombre es un hospedador accidental ya que la transmisión interhumana carece de importancia epidemiológica. El objetivo de este trabajo es estimar la Prevalencia de enfermedades Toxoplasmosis y Leptospirosis en las poblaciones animales domésticas que conviven con el hombre en la zona rural del Departamento La Capital de la Provincia de San Luis.Facultad de Ciencias Veterinaria

Observation of the TeV gamma-ray source MGRO J1908+06 with ARGO-YBJ

The extended gamma ray source MGRO J1908+06, discovered by the Milagro air shower detector in 2007, has been observed for about 4 years by the ARGO-YBJ experiment at TeV energies, with a statistical significance of 6.2 standard deviations. The peak of the signal is found at a position consistent with the pulsar PSR J1907+0602. Parametrizing the source shape with a two-dimensional Gauss function we estimate an extension \sigma = 0.49 \pm 0.22 degrees, consistent with a previous measurement by the Cherenkov Array H.E.S.S.. The observed energy spectrum is dN/dE = 6.1 \pm 1.4 \times 10^-13 (E/4 TeV)^{-2.54 \pm 0.36} photons cm^-2 s^-1 TeV^-1, in the energy range 1-20 TeV. The measured gamma ray flux is consistent with the results of the Milagro detector, but is 2-3 times larger than the flux previously derived by H.E.S.S. at energies of a few TeV. The continuity of the Milagro and ARGO-YBJ observations and the stable excess rate observed by ARGO-YBJ along 4 years of data taking support the identification of MGRO J1908+06 as the steady powerful TeV pulsar wind nebula of PSR J1907+0602, with an integrated luminosity above 1 TeV about 1.8 times the Crab Nebula luminosity.Comment: 6 pages, accepted for pubblication by ApJ. Replaced to correct the author lis

Pain and Frailty in Hospitalized Older Adults

Introduction: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods: In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people

Long-term Monitoring on Mrk 501 for Its VHE gamma Emission and a Flare in October 2011

As one of the brightest active blazars in both X-ray and very high energy $\gamma$-ray bands, Mrk 501 is very useful for physics associated with jets from AGNs. The ARGO-YBJ experiment is monitoring it for $\gamma$-rays above 0.3 TeV since November 2007. Starting from October 2011 the largest flare since 2005 is observed, which lasts to about April 2012. In this paper, a detailed analysis is reported. During the brightest $\gamma$-rays flaring episodes from October 17 to November 22, 2011, an excess of the event rate over 6 $\sigma$ is detected by ARGO-YBJ in the direction of Mrk 501, corresponding to an increase of the $\gamma$-ray flux above 1 TeV by a factor of 6.6$\pm$2.2 from its steady emission. In particular, the $\gamma$-ray flux above 8 TeV is detected with a significance better than 4 $\sigma$. Based on time-dependent synchrotron self-Compton (SSC) processes, the broad-band energy spectrum is interpreted as the emission from an electron energy distribution parameterized with a single power-law function with an exponential cutoff at its high energy end. The average spectral energy distribution for the steady emission is well described by this simple one-zone SSC model. However, the detection of $\gamma$-rays above 8 TeV during the flare challenges this model due to the hardness of the spectra. Correlations between X-rays and $\gamma$-rays are also investigated.Comment: have been accepted for publication at Ap

Electromechanical impedance method to assess the stability of dental implants

In this paper we illustrate the application of the electromechanical impedance (EMI) technique, popular in structural health monitoring, to assess the stability of dental implants. The technique consists of bonding a piezoelectric transducer to the element to be monitored. When subjected to an electric field, the transducer induces low to high frequency structural excitations which, in turn, affect the transducer's electrical admittance. As the structural vibrations depend on the mechanical impedance of the host structure (in this case the implant secured to the jaw), the measurement of the PZT's admittance can infer the progress of the osseointegration process. In the study presented in this article we created a 3D finite element model to mimic a transducer bonded to the abutment of a dental implant placed in a host bone site. We simulated the healing that occurs after surgery by changing the Young's modulus of the bone-implant interface. The results show that as the Young's modulus of the interface increases, i.e. as the mechanical interlock of the implant within the bone is achieved, the electromechanical characteristic of the transducer changes. The model and the findings of this numerical study may be used in the future to predict and interpret experimental data, and to develop a robust and cost-effective method for the assessment of primary and secondary dental implant stability

Hyperbolic Graph Codebooks

This work proposes codebook encodings for graph networks that operate on hyperbolic manifolds. Where graph networks commonly learn node representations in Euclidean space, recent work has provided a generalization to Riemannian manifolds, with a particular focus on the hyperbolic space. Expressive node representations are obtained by repeatedly performing a logarithmic map, followed by message passing in the tangent space and an exponential map back to the manifold at hand. Where current hyperbolic graph approaches predominantly focus on node representation, we propose a way to aggregate over nodes for graph-level inference. We introduce Hyperbolic Graph Codebooks, a family of graph encodings where a shared codebook is learned and used to aggregate over nodes. The resulting representations are permutation invariant and fixed-size, yet expressive. We show how to obtain zeroth-order codebook encodings through soft assignments over hyperbolic distances, first-order encodings with anchored logarithmic mappings, and second-order encodings by computing variance information in the tangent space. Empirically, we highlight the effectiveness of our approach, especially when few examples and embedding dimensions are available

Granular chains for the assessment of thermal stress in slender structures

Slender beams subjected to compressive stress are common in civil and mechanical engineering. The rapid in-situ measurement of this stress may prevent structural anomalies. In this paper, we describe the coupling mechanism between highly nonlinear solitary waves (HNSWs) propagating along an L-shaped granular system and a beam in contact with the granular medium. We evaluate the use of HNSWs as a tool to measure stress in thermally loaded structures and to estimate the neutral temperature, i.e. the temperature at which this stress is null. We investigated numerically and experimentally one and two L-shaped chains of spherical particles in contact with a prismatic beam subjected to heat. We found that certain features of the solitary waves are affected by the beam's stress. In the future, these findings may help developing a novel sensing system for the nondestructive prediction of neutral temperature and thermal buckling