Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA.Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis.Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 +/- 13.5 (p < 0.001) for DAPSA and 1.21 +/- 0.97 (p < 0.001) for ASDAS-CRP. thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naive to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24.conclusions this is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months

The 2009 december gamma-ray flare of 3C 454.3: The multifrequency campaign

During the month of 2009 December, the blazar 3C 454.3 became the brightest gamma-ray source in the sky, reaching a peak flux F 2000 × 10 -8 photons cm-2 s-1 for E > 100 MeV. Starting in 2009 November intensive multifrequency campaigns monitored the 3C 454 gamma-ray outburst. Here, we report on the results of a two-month campaign involving AGILE, INTEGRAL, Swift/XRT, Swift/BAT, and Rossi XTE for the high-energy observations and Swift/UVOT, KANATA, Goddard Robotic Telescope, and REM for the near-IR/optical/UV data. GASP/WEBT provided radio and additional optical data. We detected a long-term active emission phase lasting 1 month at all wavelengths: in the gamma-ray band, peak emission was reached on 2009 December 2-3. Remarkably, this gamma-ray super-flare was not accompanied by correspondingly intense emission in the optical/UV band that reached a level substantially lower than the previous observations in 2007-2008. The lack of strong simultaneous optical brightening during the super-flare and the determination of the broadband spectral evolution severely constrain the theoretical modeling. We find that the pre- and post-flare broadband behavior can be explained by a one-zone model involving synchrotron self-Compton plus external Compton emission from an accretion disk and a broad-line region. However, the spectra of the 2009 December 2-3 super-flare and of the secondary peak emission on 2009 December 9 cannot be satisfactorily modeled by a simple one-zone model. An additional particle component is most likely active during these states. © 2010. The American Astronomical Society. All rights reserved

AGILE detection of extreme γ -ray activity from the blazar PKS 1510-089 during March 2009: Multifrequency analysis

We report on the extreme gamma-ray activity from the FSRQ PKS 1510-089 observed by AGILE in March 2009. In the same period a radio-to-optical monitoring of the source was provided by the GASP-WEBT and REM. Moreover, several Swift ToO observations were triggered, adding important information on the source behaviour from optical/UV to hard X-rays. We paid particular attention to the calibration of the Swift/UVOT data to make it suitable to the blazars spectra. Simultaneous observations from radio to gamma rays allowed us to study in detail the correlation among the emission variability at different frequencies and to investigate the mechanisms at work. In the period 9-30 March 2009, AGILE detected an average gamma-ray flux of (311+/-21)x10^-8 ph cm^-2 s^-1 for E>100 MeV, and a peak level of (702+/-131)x10^-8 ph cm^-2 s^-1 on daily integration. The gamma-ray activity occurred during a period of increasing activity from near-IR to UV, with a flaring episode detected on 26-27 March 2009, suggesting that a single mechanism is responsible for the flux enhancement observed from near-IR to UV. By contrast, Swift/XRT observations seem to show no clear correlation of the X-ray fluxes with the optical and gamma-ray ones. However, the X-ray observations show a harder photon index (1.3-1.6) with respect to most FSRQs and a hint of harder-when-brighter behaviour, indicating the possible presence of a second emission component at soft X-ray energies. Moreover, the broad band spectrum from radio-to-UV confirmed the evidence of thermal features in the optical/UV spectrum of PKS 1510-089 also during high gamma-ray state. On the other hand, during 25-26 March 2009 a flat spectrum in the optical/UV energy band was observed, suggesting an important contribution of the synchrotron emission in this part of the spectrum during the brightest gamma-ray flare, therefore a significant shift of the synchrotron peak

Multiwavelength observations of 3C 454.3. III. Eighteen months of agile monitoring of the "crazy diamond"

We report on 18 months of multiwavelength observations of the blazar 3C 454.3 (Crazy Diamond) carried out in the period 2007 July-2009 January. In particular, we show the results of the AGILE campaigns which took place on 2008 May-June, 2008 July-August, and 2008 October-2009 January. During the 2008 May-2009 January period, the source average flux was highly variable, with a clear fading trend toward the end of the period, from an average γ-ray flux F E>100 MeV ≳ 200 × 10-8photonscm -2s-1 in 2008 May-June, to F E>100 MeV 80 × 10-8photonscm-2s-1 in 2008 October-2009 January. The average γ-ray spectrum between 100 MeV and 1 GeV can be fit by a simple power law, showing a moderate softening (from ΓGRID ∼ 2.0 to ΓGRID ∼ 2.2) toward the end of the observing campaign. Only 3σ upper limits can be derived in the 20-60 keV energy band with Super-AGILE, because the source was considerably off-axis during the whole time period. In 2007 July-August and 2008 May-June, 3C 454.3 was monitored by Rossi X-ray Timing Explorer (RXTE). The RXTE/Proportional Counter Array (PCA) light curve in the 3-20 keV energy band shows variability correlated with the γ-ray one. The RXTE/PCA average flux during the two time periods is F 3-20 keV = 8.4 × 10-11ergcm-2s -1, and F 3-20 keV = 4.5 × 10 -11ergcm-2s-1, respectively, while the spectrum (a power law with photon index ΓPCA = 1.65 0.02) does not show any significant variability. Consistent results are obtained with the analysis of the RXTE/High-Energy X-Ray Timing Experiment quasi-simultaneous data. We also carried out simultaneous Swift observations during all AGILE campaigns. Swift/XRT detected 3C 454.3 with an observed flux in the 2-10 keV energy band in the range (0.9-7.5) × 10-11ergcm-2s-1 and a photon index in the range ΓXRT = 1.33-2.04. In the 15-150 keV energy band, when detected, the source has an average flux of about 5mCrab. GASP-WEBT monitored 3C 454.3 during the whole 2007-2008 period in the radio, millimeter, near-IR, and optical bands. The observations show an extremely variable behavior at all frequencies, with flux peaks almost simultaneous with those at higher energies. A correlation analysis between the optical and the γ-ray fluxes shows that the γ-optical correlation occurs with a time lag of τ = -0.4+0.6-0.8 days, consistent with previous findings for this source. An analysis of 15 GHz and 43 GHz VLBI core radio flux observations in the period 2007 July-2009 February shows an increasing trend of the core radio flux, anti-correlated with the higher frequency data, allowing us to derive the value of the source magnetic field. Finally, the modeling of the broadband spectral energy distributions for the still unpublished data, and the behavior of the long-term light curves in different energy bands, allow us to compare the jet properties during different emission states, and to study the geometrical properties of the jet on a time-span longer than one year. © 2010. The American Astronomical Society. All rights reserved

Public-Private Partnerships and Public Healthcare Sustainability: The Contribution of Governance and Digitalization

The chapter, starting from the Sustainable Development Goal n. 17, aims to investigate – from a managerial perspective – public-private partnership (PPP) in the public healthcare sector for the sustainability implementation. In particular, applying the case study methodology, the research discusses the role of the gover nance of PPP and of the digitalization for the sustainability of healthcare services. The chapter contributes to the managerial literature on these aspects by concluding that (1) PPPs require a structure in charge of overseeing the main governance aspects and governance can be considered as a preparatory factor for sustainability and (2) digitalization contributes to sustainability by reducing time and costs. In addition, the research also makes it possible to highlight some criticalities related to governance and digitalization

Additional file 1 of Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Additional file 1: Additional Table 1a. Characteristics of the UPREAL-PsA study patients subgroups at baseline. Additional Table 1b. Characteristics of the UPREAL-PsA study patients subgroups at baseline. Additional Table 2. List of the comorbidities considered as Other in patients of the UPREAL-PsA study. Additional Table 3. List of the previous bDMARDs used in bio-failure patients. Additional Table 4. DAPSA responses in patients’ subgroups of the UPREAL-PsA study. Additional Table 5. ASDAS-CRP responses in patients’ subgroups of the UPREAL-PsA study. Additional Table 6. List of all the adverse events observed in patients of the UPREAL-PsA study

Gamma-Light: High-Energy Astrophysics above 10 MeV

High-energy phenomena in the cosmos, and in particular processes leading to the emission of gamma- rays in the energy range 10 MeV - 100 GeV, play a very special role in the understanding of our Universe. This energy range is indeed associated with non-thermal phenomena and challenging particle acceleration processes. The technology involved in detecting gamma-rays is challenging and drives our ability to develop improved instruments for a large variety of applications. GAMMA-LIGHT is a Small Mission which aims at an unprecedented advance of our knowledge in many sectors of astrophysical and Earth studies research. The Mission will open a new observational window in the low-energy gamma-ray range 10-50 MeV, and is configured to make substantial advances compared with the previous and current gamma-ray experiments (AGILE and Fermi). The improvement is based on an exquisite angular resolution achieved by GAMMA-LIGHT using state-of-the-art Silicon technology with innovative data acquisition. GAMMA-LIGHT will address all astrophysics issues left open by the current generation of instruments. In particular, the breakthrough angular resolution in the energy range 100 MeV - 1 GeV is crucial to resolve patchy and complex features of diffuse sources in the Galaxy as well as increasing the point source sensitivity. This proposal addresses scientific topics of great interest to the community, with particular emphasis on multifrequency correlation studies involving radio, optical, IR, X-ray, soft gamma-ray and TeV emission. At the end of this decade several new observatories will be operational including LOFAR, SKA, ALMA, HAWK, CTA. GAMMA-LIGHT will "fill the vacuum" in the 10 MeV-10 GeV band, and will provide invaluable data for the understanding of cosmic and terrestrial high-energy sources.Comment: 6 pages, 8 figure

Temporal properties of GX 301-2 over a year-long observation with SuperAGILE

We present the long-term monitoring of the high-mass X-ray binary GX 301-2 performed with the SuperAGILE (SA) instrument on-board the Astro-rivelatore Gamma ad Immagini LEggero (AGILE) mission. The source was monitored in the 20-60 keV energy band during the first year of the mission from 2007 July 17 to 2008 August 31, covering about one whole orbital period and three more pre-periastron (PP) passages for a total net observation time of about 3.7 Ms. The SA data set represents one of the most continuous and complete monitoring at hard X-ray energies of the 41.5 days long binary period available to date. The source behavior was characterized at all orbital phases in terms of hard X-ray flux, spectral hardness, spin-period history, pulsed fraction, and pulse shape profile. We also complemented the SA observations with the soft X-ray data of the Rossi X-Ray Timing Explorer/All-Sky Monitor. Our analysis shows a clear orbital modulation of the spectral hardness, with peaks in correspondence with the PP flare and near phase 0.25. The hardness peaks, we found, could be related with the wind-plus-stream accretion model proposed in order to explain the orbital light-curve modulation of GX 301-2. Timing analysis of the pulsar spin period shows that the secular trend of the similar to 680 s pulse period is consistent with the previous observations, although there is evidence of a slight decrease in the spin-down rate. The analysis of the hard X-ray-pulsed emission also showed a variable pulse shape profile as a function of the orbital phase, with substructures detected near the passage at the periastron, and a clear modulation of the pulsed fraction, which appears in turn strongly anticorrelated with the source intensity