Analysis of the cost-effectiveness of surfactant treatment (Curosurf®) in respiratory distress syndrome therapy in preterm infants: early treatment compared to late treatment

BACKGROUND: The best criteria for surfactant treatment in the perinatal period are unknown and this makes it of interest to consider the possible economic implications of lessening the use of more restrictive criteria. OBJECTIVE: The objective of this study is the evaluation of the costs of respiratory care for preterm infants with Respiratory Distress Syndrome (RDS) treated with "early rescue" surfactant compared to a "late rescue" strategy. METHODS: The study was carried out applying the costs of materials used, of staff and pharmacological therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian hospital to the Verder et al. study (Pediatrics 1999) clinical data. RESULTS: The cost for patients treated with early strategy was slightly lower than for patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro 311.74), but this was compensated by the greater cost of treatment with Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro 259.25). CONCLUSIONS: The cost-effectiveness analysis performed in this study shows how early treatment with surfactant in preterm infants with RDS, as well as being clinically more effective, is associated with a slightly lower cost

Cost minimization analysis of BoNT-As in the treatment of upper limb spasticity and cervical dystonia

Botulinum toxin type A (BoNT-A) injections are recommended for the management of upper limb spasticity (ULS) and cervical dystonia (CD). The main aim of this cost minimization analysis (CMA) was to compare the annual cost per patient for three BoNT-As (Botox®, Dysport® and Xeomin®) in the treatment of ULS or CD in Italy. A budget impact analysis (BIA) was also conducted. Methods The CMA was conducted from the perspective of the Italian National Health Service. Only direct medical costs (BoNT-A and standard therapy) were considered. By using a Delphi panel of twelve Italian Experts in the treatment of ULS and CD, data was collected about BoNT-As (dose, number of administrations and acquisition price) and standard therapy (concomitant medications, visits, Day-Hospital, hospitalizations, etc.). Costs were assessed in Euros 2014. The BIA was conducted to evaluate the pharmaceutical expenditure for the three BoNT-As on a five-year time horizon. A sensitivity analysis was conducted. Results The mean annual cost per patient with ULS was €1,840.20 with Dysport®, €2,067.12 with Botox® and €2,171.05 with Xeomin®. The mean annual cost per patient with CD was €1,353.79 with Dysport®, €1,433.12 with Botox® and €1,503.60 with Xeomin®. In the time horizon considered, the substitution process of Botox® and Xeomin® by Dysport® would result in a total saving of €620,000 when treating ULS and a total saving of €481,000 in the case of CD. Sensitivity and probabilistic analyses showed the robustness of results. Conclusions From the Italian National Health Service's perspective, Dysport® appears to be the cost-saving therapeutic option compared with Botox® and Xeomin® in the treatment of ULS or CD

Spectral index-flux relation for investigating the origins of steep decay in γ\gamma-ray bursts

$\gamma$-ray bursts (GRBs) are short-lived transients releasing a large amount of energy ($10^{51}-10^{53}$ erg) in the keV-MeV energy range. GRBs are thought to originate from internal dissipation of the energy carried by ultra-relativistic jets launched by the remnant of a massive star's death or a compact binary coalescence. While thousands of GRBs have been observed over the last thirty years, we still have an incomplete understanding of where and how the radiation is generated in the jet. Here we show a relation between the spectral index and the flux found by investigating the X-ray tails of bright GRB pulses via time-resolved spectral analysis. This relation is incompatible with the long standing scenario which invokes the delayed arrival of photons from high-latitude parts of the jet. While the alternative scenarios cannot be firmly excluded, the adiabatic cooling of the emitting particles is the most plausible explanation for the discovered relation, suggesting a proton-synchrotron origin of the GRB emission.Comment: Published in Nature Communication

Budget impact analysis of dabigatran compared with rivaroxaban in the prevention of the thromboembolic risk in patients with non-valvular atrial fibrillation

BACKGROUND: Dabigatran 150 mg BID (D150) and rivaroxaban 20 mg (R20) are indicated for the prevention of thromboembolic events in patients with Non-Valvular Atrial Fibrillation (NVAF). Outcomes from observational study demonstrated that D150 and R20 reduced the rate of thromboembolic events.OBJECTIVE: This analysis estimated the budget impact of the use of D150 and R20 for the treatment of NAFV patients in Italy.METHODS: A budget-impact model (BIM) was developed to estimate the direct costs up to 12 months from an Italian NHS perspective. The resource utilization (drugs and intracranial hemorrhage or major extracranial bleeding event) was derived from an observational study. Only direct medical costs were considered. Ex-factory prices and National Tariffs were considered to estimate the costs of drugs and medical resource used, respectively. The BIM showed the difference of expenditure and clinical events (intracranial hemorrhage or major extracranial bleeding) generated by the base case calculated for current prescription volumes (D150 30%, R20 100%), and for different prescription volume scenarios (D150 at 70% and 100%). Key variables were tested in the sensitivity analysis.RESULTS: D150 was associated with a medical cost offset driven by fewer intracranial hemorrhage and major extracranial bleeding event, these offset the incremental drug cost and results in an annual saving per patient treated (D150: € 1,052.78; R20: € 1,161.23). The present scenario determines an annual cost of € 262,543,583. The impact of total annual costs for the Italian NHS would be lower if D150 prescription volumes would be higher. The total cost is predicted to decrease by 3.8% if the D150 prescription increase to 70% and it is predicted to decrease by 6.7% if the D150 prescription increase to 100%.CONCLUSION: The use of D150, as an alternative to R20 to prevent events in patients with NVAF, could represent a cost-saving option for the Italian NHS

Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling

Class 2: Transcripts that are less abundant in the phr1Δ mutant than in the wild type. (XLSX 39 kb

Spectral index-flux relation for investigating the origins of steep decay in γ-ray bursts

γ-ray bursts (GRBs) are short-lived transients releasing a large amount of energy (10 − 10 erg) in the keV-MeV energy range. GRBs are thought to originate from internal dissipation of the energy carried by ultra-relativistic jets launched by the remnant of a massive star’s death or a compact binary coalescence. While thousands of GRBs have been observed over the last thirty years, we still have an incomplete understanding of where and how the radiation is generated in the jet. Here we show a relation between the spectral index and the flux found by investigating the X-ray tails of bright GRB pulses via time-resolved spectral analysis. This relation is incompatible with the long standing scenario which invokes the delayed arrival of photons from high-latitude parts of the jet. While the alternative scenarios cannot be firmly excluded, the adiabatic cooling of the emitting particles is the most plausible explanation for the discovered relation, suggesting a proton-synchrotron origin of the GRB emission.The research leading to these results has received funding from the European Union’s Horizon 2020 Programme under the AHEAD2020 project (Grant agreement n. 871158). G. Ghir. acknowledges the support from the ASI-Nustar Grant (1.05.04.95). M.B., P.D., and G.G. acknowledge support from PRIN-MIUR 2017 (Grant 20179ZF5KS). G.O. acknowledges financial contribution from the agreement ASI-INAF n.2017-14-H.0. S.A. acknowledges the PRIN-INAF “Towards the SKA and CTA era: discovery, localization, and physics of transient sources” and the ERC Consolidator Grant “MAGNESIA” (nr. 817661). M.G.B. and P.D. acknowledge ASI Grant I/004/11/3. O.S.S. acknowledges the INAF-Prin 2017 (1.05.01.88.06) and the Italian Ministry for University and Research Grant “FIGARO” (1.05.06.13) for support. G.O. and S.R. are thankful to INAF—Osservatorio Astronomico di Brera for kind hospitality during the completion of this work. This work made use of data supplied by the UK Swift Science Data Centre at the University of Leicester

Probing the extragalactic fast transient sky at minute timescales with DECam

Searches for optical transients are usually performed with a cadence of days to weeks, optimised for supernova discovery. The optical fast transient sky is still largely unexplored, with only a few surveys to date having placed meaningful constraints on the detection of extragalactic transients evolving at sub-hour timescales. Here, we present the results of deep searches for dim, minute-timescale extragalactic fast transients using the Dark Energy Camera, a core facility of our all-wavelength and all-messenger Deeper, Wider, Faster programme. We used continuous 20s exposures to systematically probe timescales down to 1.17 minutes at magnitude limits $g > 23$ (AB), detecting hundreds of transient and variable sources. Nine candidates passed our strict criteria on duration and non-stellarity, all of which could be classified as flare stars based on deep multi-band imaging. Searches for fast radio burst and gamma-ray counterparts during simultaneous multi-facility observations yielded no counterparts to the optical transients. Also, no long-term variability was detected with pre-imaging and follow-up observations using the SkyMapper optical telescope. We place upper limits for minute-timescale fast optical transient rates for a range of depths and timescales. Finally, we demonstrate that optical $g$-band light curve behaviour alone cannot discriminate between confirmed extragalactic fast transients such as prompt GRB flashes and Galactic stellar flares.Comment: Published in MNRA

A bright megaelectronvolt emission line in γ\gamma-ray burst GRB 221009A

The highly variable and energetic pulsed emission of a long gamma-ray burst (GRB) is thought to originate from local, rapid dissipation of kinetic or magnetic energy within an ultra-relativistic jet launched by a newborn compact object, formed during the collapse of a massive star. The spectra of GRB pulses are best modelled by power-law segments, indicating the dominance of non-thermal radiation processes. Spectral lines in the X-ray and soft $\gamma$-ray regime for the afterglow have been searched for intensively, but never confirmed. No line features ever been identified in the high energy prompt emission. Here we report the discovery of a highly significant ($> 6 \sigma$) narrow emission feature at around $10$ MeV in the brightest ever GRB 221009A. By modelling its profile with a Gaussian, we find a roughly constant width $\sigma \sim 1$ MeV and temporal evolution both in energy ($\sim 12$ MeV to $\sim 6$ MeV) and luminosity ($\sim 10^{50}$ erg/s to $\sim 2 \times 10^{49}$ erg/s) over 80 seconds. We interpret this feature as a blue-shifted annihilation line of relatively cold ($k_\mathrm{B}T\ll m_\mathrm{e}c^2$) electron-positron pairs, which could have formed within the jet region where the brightest pulses of the GRB were produced. A detailed understanding of the conditions that can give rise to such a feature could shed light on the so far poorly understood GRB jet properties and energy dissipation mechanism.Comment: Submitte