751 results on '"Buxton M"'
Search Results
2. A Super-Eddington Compton-Thick Wind in GRO J1655-40?
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Neilsen, J., Rahoui, F., Homan, J., and Buxton, M.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
During its 2005 outburst, GRO J1655-40 was observed at high spectral resolution with the Chandra HETGS, revealing a spectrum rich with blueshifted absorption lines indicative of an accretion disk wind -- apparently too hot, too dense, and too close to the black hole to be driven by radiation pressure or thermal pressure (Miller et al.). But this exotic wind represents just one piece of the puzzle in this outburst, as its presence coincides with an extremely soft and curved X-ray continuum spectrum, remarkable X-ray variability (Uttley & Klein-Wolt), and a bright, unexpected optical/infrared blackbody component that varies on the orbital period. Focusing on the X-ray continuum and the optical/infrared/UV spectral energy distribution, we argue that the unusual features of this "hypersoft state" are natural consequences of a super-Eddington Compton-thick wind from the disk: the optical/infrared blackbody represents the cool photosphere of a dense, extended outflow, while the X-ray emission is explained as Compton scattering by the relatively cool, optically thick wind. This wind obscures the intrinsic luminosity of the inner disk, which we suggest may have been at or above the Eddington limit., Comment: 15 pages, 5 figures. To appear in ApJ, version resubmitted after final referee report. Comments welcome
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- 2016
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3. The SMARTS Multi-epoch Optical Spectroscopy Atlas (SAMOSA): Using Emission Line Variability to Probe the Location of the Blazar Gamma-emitting Region
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Isler, Jedidah C., Urry, C. M., Bailyn, C., Smith, P. S., Coppi, P., Brady, M., Macpherson, E., Hasan, I., and Buxton, M.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Astrophysics of Galaxies - Abstract
We present multi-epoch optical spectroscopy of seven southern Fermi-monitored blazars from 2008 - 2013 using the Small and Medium Aperture Research Telescope System (SMARTS), with supplemental spectroscopy and polarization data from the Steward Observatory. We find that the emission lines are much less variable than the continuum; 4 of 7 blazars had no detectable emission line variability over the 5 years. This is consistent with photoionization primarily by an accretion disk, allowing us to use the lines as a probe of disk activity. Comparing optical emission line flux with Fermi $\gamma$-ray flux and optical polarized flux, we investigate whether relativistic jet variability is related to the accretion flow. In general, we see no such dependence, suggesting the jet variability is likely caused by internal processes like turbulence or shock acceleration rather than a variable accretion rate. However, three sources showed statistically significant emission line flares in close temporal proximity to very large Fermi $\gamma$-ray flares. While we do not have sufficient emission line data to quantitatively assess their correlation with the $\gamma$-ray flux, it appears that in some cases, the jet might provide additional photoionizing flux to the broad line region, which implies some gamma-rays are produced within the broad line region, at least for these large flares., Comment: 15 pages, 15 figures, Accepted to the Astrophysical Journal
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- 2015
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4. Multi-Wavelength Coverage of State Transitions in the New Black Hole X-Ray Binary Swift J1910.2-0546
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Degenaar, N., Maitra, D., Cackett, E. M., Reynolds, M. T., Miller, J. M., Reis, R. C., King, A. L., Gultekin, K., Bailyn, C. D., Buxton, M. M., MacDonald, R. K. D., Fabian, A. C., Fox, D. B., and Rykoff, E. S.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
Understanding how black holes accrete and supply feedback to their environment is one of the outstanding challenges of modern astrophysics. Swift J1910.2-0546 is a candidate black hole low-mass X-ray binary that was discovered in 2012 when it entered an accretion outburst. To investigate the binary configuration and the accretion morphology we monitored the evolution of the outburst for ~3 months at X-ray, UV, optical (B,V,R,I), and near-infrared (J,H,K) wavelengths using Swift and SMARTS. The source evolved from a hard to a soft X-ray spectral state with a relatively cold accretion disk that peaked at ~0.5 keV. A Chandra/HETG spectrum obtained during this soft state did not reveal signatures of an ionized disk wind. Both the low disk temperature and the absence of a detectable wind could indicate that the system is viewed at relatively low inclination. The multi-wavelength light curves revealed two notable features that appear to be related to X-ray state changes. Firstly, a prominent flux decrease was observed in all wavebands ~1-2 weeks before the source entered the soft state. This dip occurred in (0.6-10 keV) X-rays ~6 days later than at longer wavelengths, which could possibly reflect the viscous time scale of the disk. Secondly, about two weeks after the source transitioned back into the hard state, the UV emission significantly increased while the X-rays steadily decayed. We discuss how these observations may reflect changes in the accretion flow morphology, perhaps related to the quenching/launch of a jet or the collapse/recovery of a hot flow., Comment: 8 pages, 5 figures, 1 table. To be published in ApJ
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- 2014
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5. Broadband monitoring tracing the evolution of the jet and disk in the black hole candidate X-ray binary MAXI J1659-152
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van der Horst, A. J., Curran, P. A., Miller-Jones, J. C. A., Linford, J. D., Gorosabel, J., Russell, D. M., Postigo, A. de Ugarte, Lundgren, A. A., Taylor, G. B., Maitra, D., Guziy, S., Belloni, T. M., Kouveliotou, C., Jonker, P. G., Kamble, A., Paragi, Z., Homan, J., Kuulkers, E., Granot, J., Altamirano, D., Buxton, M. M., Castro-Tirado, A., Fender, R. P., Garrett, M. A., Gehrels, N., Hartmann, D. H., Kennea, J. A., Krimm, H. A., Mangano, V., Ramirez-Ruiz, E., Romano, P., Wijers, R. A. M. J., Wijnands, R., and Yang, Y. J.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
MAXI J1659-152 was discovered on 2010 September 25 as a new X-ray transient, initially identified as a gamma-ray burst, but was later shown to be a new X-ray binary with a black hole as the most likely compact object. Dips in the X-ray light curves have revealed that MAXI J1659-152 is the shortest period black hole candidate identified to date. Here we present the results of a large observing campaign at radio, sub-millimeter, near-infrared (nIR), optical and ultraviolet (UV) wavelengths. We have combined this very rich data set with the available X-ray observations to compile a broadband picture of the evolution of this outburst. We have performed broadband spectral modeling, demonstrating the presence of a spectral break at radio frequencies and a relationship between the radio spectrum and X-ray states. Also, we have determined physical parameters of the accretion disk and put them into context with respect to the other parameters of the binary system. Finally, we have investigated the radio-X-ray and nIR/optical/UV-X-ray correlations up to ~3 years after the outburst onset to examine the link between the jet and the accretion disk, and found that there is no significant jet contribution to the nIR emission when the source is in the soft or intermediate X-ray spectral state, consistent with our detection of the jet break at radio frequencies during these states., Comment: 18 pages, 8 figures, 2 tables; accepted for publication in MNRAS after minor revisions
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- 2013
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6. Multiwavelength observations of the black hole transient XTE J1752-223 during its 2010 outburst decay
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Chun, Y. Y., Dinçer, T., Kalemci, E., Güver, T., Tomsick, J. A., Buxton, M. M., Brocksopp, C., Corbel, S., and Cabrera-Lavers, A.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
Galactic black hole transients show many interesting phenomena during outburst decays. We present simultaneous X-ray (RXTE, Swift, and INTEGRAL), and optical/near-infrared (O/NIR) observations (SMARTS) of the X-ray transient XTE J1752-223 during its outburst decay in 2010. The multiwavelength observations over 150 days in 2010 cover the transition from soft to hard spectral state. We discuss the evolution of radio emission is with respect to the O/NIR light curve which shows several flares. One of those flares is bright and long, starting about 60 days after the transition in X-ray timing properties. During this flare, the radio spectral index becomes harder. Other smaller flares occur along with the X-ray timing transition, and also right after the detection of the radio core. We discuss the significances of these flares. Furthermore, using the simultaneous broadband X-ray spectra including INTEGRAL, we find that a high energy cut-off with a folding energy near 250 keV is necessary around the time that the compact jet is forming. The broad band spectrum can be fitted equally well with a Comptonization model. In addition, using photoelectric absorption edges in the XMM-Newton RGS X-ray spectra and the extinction of red clump giants in the direction of the source, we find a lower limit on the distance of > 5 kpc., Comment: 14 pages, 15 figures
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- 2013
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7. Formation of the compact jets in the black hole GX 339-4
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Corbel, S., Aussel, H., Broderick, J. W., Chanial, P., Coriat, M., Maury, A. J., Buxton, M., Tzioumis, J. A. Tomsick A., Markoff, S., Rodriguez, J., Bailyn, C., Brocksopp, C., Fender, R., Petrucci, P. O., Cadolle-Bel, M., Calvelo, D., and Harvey-Smith, L.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
Galactic black hole binaries produce powerful outflows with emit over almost the entire electromagnetic spectrum. Here, we report the first detection with the Herschel observatory of a variable far-infrared source associated with the compact jets of the black hole transient GX 339-4 during the decay of its recent 2010-2011 outburst, after the transition to the hard state. We also outline the results of very sensitive radio observations conducted with the Australia Telescope Compact Array, along with a series of near-infrared, optical (OIR) and X-ray observations, allowing for the first time the re-ignition of the compact jets to be observed over a wide range of wavelengths. The compact jets first turn on at radio frequencies with an optically thin spectrum that later evolves to optically thick synchrotron emission. An OIR reflare is observed about ten days after the onset of radio and hard X-ray emission, likely reflecting the necessary time to build up enough density, as well as to have acceleration (e.g. through shocks) along an extended region in the jets. The Herschel measurements are consistent with an extrapolation of the radio inverted power-law spectrum, but they highlight a more complex radio to OIR spectral energy distribution for the jets., Comment: Accepted for publication in MNRAS Letter, 6 pages, 3 Figures + 1 online Table
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- 2013
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8. The Contrasting Nature of Gamma-Ray/Optical Variability in the Blazar PKS 0208-512 During Successive Outbursts
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Chatterjee, Ritaban, Fossati, G., Urry, C. M., Bailyn, C. D., Maraschi, L., Buxton, M., Bonning, E. W., Isler, J., and Coppi, P.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
The Yale/SMARTS optical-near-IR monitoring program has followed the variations in emission of the Fermi-LAT monitored blazars in the southern sky with closely spaced observations since 2008. We report the discovery of an optical-near-IR (OIR) outburst with no accompanying gamma-rays in the blazar PKS 0208-512, one of the targets of this program. While the source undergoes three outbursts of 1 mag or more at OIR wavelengths lasting for longer than 3 months during 2008-2011, only interval 1 and 3 have corresponding bright phases in GeV energies lasting longer than 1 month. The OIR outburst during interval 2 is comparable in brightness and temporal extent to the OIR flares during intervals 1 and 3 which do have gamma-ray counterparts. Gamma-ray and OIR variability are very well-correlated in most cases in the Fermi blazars and the lack of correlation in this case is anomalous. By analyzing the gamma-ray, OIR, and supporting multi-wavelength variability data in details, we speculate that the location of the outburst in the jet during interval 2 was closer to the black hole where the jet is more compact and the magnetic field strength is higher, and the bulk Lorentz factor of the material in the jet is smaller. These result in a much lower Compton dominance and no observable gamma-ray outburst during interval 2., Comment: 6 pages, 3 figures. 2012 Fermi Symposium proceedings - eConf C121028
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- 2013
9. Sensor Based Real-Time Resource Model Reconciliation for Improved Mine Production Control—A Conceptual Framework
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Benndorf, J., Buxton, M., Shishvan, M. S., and Dimitrakopoulos, Roussos, editor
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- 2018
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10. Cut-off Grade Based Sublevel Stope Mine Optimisation : Introduction and Evaluation of an Optimisation Approach and Method for Grade Risk Quantification
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Bootsma, M. T., Alford, C., Benndorf, J., Buxton, M. W. N., and Dimitrakopoulos, Roussos, editor
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- 2018
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11. An Optical-Near-Infrared Outburst with No Accompanying Gamma-Rays in the Blazar PKS 0208-512
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Chatterjee, Ritaban, Fossati, G., Urry, C. M., Bailyn, C. D., Maraschi, L., Buxton, M., Bonning, E. W., Isler, J., and Coppi, P.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
We report the discovery of an anomalous flare in a bright blazar, namely, PKS 0208-512, one of the targets of the Yale/SMARTS optical-near-infrared (OIR) monitoring program of Fermi blazars. We identify three intervals during which PKS 0208-512 undergoes outbursts at OIR wavelengths lasting for longer than 3 months. Its brightness increases and then decreases again by at least 1 magnitude in these intervals. In contrast, the source undergoes bright phases in GeV energies lasting for longer than 1 month during intervals 1 and 3 only. The OIR outburst during interval 2 is comparable in brightness and temporal extent to the OIR flares during intervals 1 and 3 which do have gamma-ray counterparts. By analyzing the gamma-ray, OIR, and supporting multi-wavelength variability data in details, we speculate that the OIR outburst during interval 2 was caused by a change in the magnetic field without any change in the total number of emitting electrons or Doppler factor of the emitting region. Alternatively, it is possible that the location of the outburst in the jet during interval 2 was closer to the black hole where the jet is more compact and the bulk Lorentz factor of the material in the jet is smaller. We also discuss the complex OIR spectral behavior during these three intervals., Comment: 7 pages, 4 figures, Accepted for publication in ApJ Letters
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- 2012
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12. The 'universal' radio/X-ray flux correlation : the case study of the black hole GX 339-4
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Corbel, S., Coriat, M., Brocksopp, C., Tzioumis, A. K., Fender, R. P., Tomsick, J. A., Buxton, M. M., and Bailyn, C. D.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
The existing radio and X-ray flux correlation for Galactic black holes in the hard and quiescent states relies on a sample which is mostly dominated by two sources (GX 339-4 and V404 Cyg) observed in a single outburst. In this paper, we report on a series of radio and X-ray observations of the recurrent black hole GX 339-4 with the Australia Telescope Compact Array, the Rossi X-ray Timing Explorer and the Swift satellites. With our new long term campaign, we now have a total of 88 quasi-simultaneous radio and X-ray observations of GX 339-4 during its hard state, covering a total of seven outbursts over a 15--year period. Our new measurements represent the largest sample for a stellar mass black hole, without any bias from distance uncertainties, over the largest flux variations and down to a level that could be close to quiescence, making GX 339-4 the reference source for comparison with other accreting sources (black holes, neutrons stars, white dwarfs and active galactic nuclei). Our results demonstrate a very strong and stable coupling between radio and X-ray emission, despite several outbursts of different nature and separated by a period of quiescence. The radio and X-ray luminosity correlation of the form L_X ~L_Rad^0.62 +/-0.01 confirms the non-linear coupling between the jet and the inner accretion flow powers and better defines the standard correlation track in the radio-X-ray diagram for stellar mass black holes. We further note epochs of deviations from the fit that significantly exceed the measurement uncertainties, especially during the formation and destruction of the compact jets ...[abridged]. We incorporated our new data in a more global study of black hole candidates strongly supporting a scale invariance in the jet-accretion coupling of accreting black holes, and confirms the existence of two populations of sources in the radio/X-ray diagram., Comment: Paper accepted in MNRAS. 18 pages, 9 figures
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- 2012
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13. SMARTS optical and infrared monitoring of 12 gamma-ray bright blazars
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Bonning, E. W., Urry, C. M., Bailyn, C., Buxton, M., Chatterjee, R., Coppi, P., Fossati, G., Isler, J., and Maraschi, L.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We present multiwavelength data for twelve blazars observed from 2008-2010 as part of an ongoing optical-infrared photometric monitoring project. Sources were selected to be bright, southern (dec < 20 deg) blazars observed by the Fermi Gamma-Ray Space Telescope, with daily and weekly gamma-ray fluxes made available from the start of the Fermi mission. Light curves are presented for the twelve blazars in BVRJK at near-daily cadence. We find that optical and infrared fluxes are well correlated in all sources. Gamma-ray bright flat spectrum radio quasars (FSRQs) in our sample have optical/infrared emission correlated with gamma-rays consistent with inverse Compton-scattering models for GeV emission. In FSRQs, the variability amplitude decreases towards optical/IR wavelengths, consistent with the presence of a thermal emission component from the accretion disk varying on significantly longer timescales than the jet synchrotron emission. In BL Lac objects, variability is mainly constant across wavelengths, consistent with a weak or radiatively inefficient disk. FSRQs have redder optical-infrared colors when they are brighter, while BL Lac objects show no such trend. Several objects show complicated color-magnitude behavior: AO 0235+164 appears in two different states depending on whether it is gamma-ray bright or not. OJ 287 and 3C 279 show some hysteresis tracks in their color-magnitude diagrams. Individual flares may be achromatic or otherwise depart from the trend, suggesting different jet components becoming important at different times. We present a time-dependent spectral energy distribution of the bright FSRQ 3C 454.3 during its December 2009 flare, which is well fit by an external Compton model in the bright state, although day to day changes pose challenges to a simple one-zone model. All data from the SMARTS monitoring program are publicly available on our website., Comment: 71 pages, submitted to ApJ
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- 2012
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14. Overview of an Extensive Multi-wavelength Study of GX 339-4 during the 2010 Outburst
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Bel, M. Cadolle, Rodriguez, J., D'Avanzo, P., Russell, D. M., Tomsick, J., Corbel, S., Lewis, F., Rahoui, F., Buxton, M., Goldoni, P., and Kuulkers, E.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
The microquasar GX 339-4 experienced a new outburst in 2010: it was observed simultaneously at various wavelengths from radio up to soft gamma-rays. We focused on observations that are quasi-simultaneous with those made with the INTEGRAL and RXTE satellites: these were collected in 2010 March-April during our INTEGRAL Target of Opportunity program, and during some of the other INTEGRAL observing programs with GX 339-4 in the field-of-view. X-ray transients are extreme systems that often harbour a black hole, and are known to emit throughout the whole electromagnetic spectrum when in outburst. The goals of our program are to understand the evolution of the physical processes close to the black hole and to study the connections between the accretion and ejection. We analysed radio, NIR, optical, UV, X-ray and soft gamma-ray observations. We studied the source evolution in detail by producing light curves, hardness-intensity diagrams and spectra. We fitted the broadband data with phenomenological, then physical, models to study the emission coming from the distinct components. Based on the energy spectra, the source evolved from the canonical hard state to the canonical soft state. The source showed X-ray spectral variations that were correlated with changes in radio, NIR and optical emission. The bolometric flux increased from 0.8 to 2.9*10^{-8} erg cm^{-2} s^{-1} while the relative flux and contribution of the hot medium globally decreased. Reprocessing in the disc was likely to be strong at the end of our observations. The source showed a behaviour similar to that of previous outbursts, with some small deviations in the hard X-rays parameters' evolution. The radio, NIR and optical emission from jets was detected, and seen to fade as the source softened. The results are discussed within the context of disc and jet models., Comment: 13 pages, 10 figures, 4 tables. Accepted by A&A
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- 2011
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15. Similarity of the Optical-IR and Gamma-Ray Time Variability of Fermi Blazars
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Chatterjee, Ritaban, Bailyn, C., Bonning, E. W., Buxton, M., Coppi, P., Fossati, G., Isler, J., Maraschi, L., and Urry, C. M.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We present the time variability properties of a sample of six blazars, AO 0235+164, 3C 273, 3C 279, PKS 1510-089, PKS 2155-304, and 3C 454.3, at optical-IR as well as gamma-ray energies. These observations were carried out as a part of the Yale/SMARTS program during 2008-2010 that has followed the variations in emission of the bright Fermi-LAT-monitored blazars in the southern sky with closely-spaced observations at BVRJK bands. We find the optical/IR time variability properties of these blazars to be remarkably similar to those at the gamma-ray energies. The power spectral density (PSD) functions of the R-band variability of all six blazars are fit well by simple power-law functions with negative slope such that there is higher amplitude variability on longer timescales. No clear break is identified in the PSD of any of the sources. The average slope of the PSD of R-band variability of these blazars is similar to what was found by the Fermi team for the gamma-ray variability of a larger sample of bright blazars. This is consistent with leptonic models where the optical-IR and gamma-ray emission is generated by the same population of electrons through synchrotron and inverse-Compton processes, respectively. The prominent flares present in the optical-IR as well as the gamma-ray light curves of these blazars are predominantly symmetric, i.e., have similar rise and decay timescales, indicating that the long-term variability is dominated by the crossing time of radiation or a disturbance through the emission region rather than by the acceleration or energy-loss timescales of the radiating electrons. In the blazar 3C 454.3, which has the highest-quality light curves, the location of a large gamma-ray outburst during 2009 December is consistent with being in the jet at ~18 pc from the central engine. This poses strong constraints on the models of high energy emission in the jets of blazars., Comment: Accepted for publication in ApJ. 15 pages (ApJ format), 6 tables, 11 figures. More discussion, explanation of analysis, and references have been added. Major conclusions remain unchanged
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- 2011
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16. Multiwavelength monitoring of the enigmatic Narrow-Line Seyfert 1 PMN J0948+0022 in March-July 2009
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Collaboration, Fermi/LAT, Angelakis, E., Bailyn, C., Bignall, H., Blanchard, J., Bonning, E. W., Buxton, M., Canterna, R., Carraminana, A., Carrasco, L., Colomer, F., Doi, A., Ghisellini, G., Hauser, M., Hong, X., Isler, J., Kino, M., Kovalev, Y. Y., Kovalev, Yu. A., Krichbaum, T. P., Kutyrev, A., Lahteenmaki, A., van Langevelde, H. J., Lister, M. L., Macomb, D., Maraschi, L., Marchili, N., Nagai, H., Paragi, Z., Phillips, C., Pushkarev, A. B., Recillas, E., Roming, P., Sekido, M., Stark, M. A., Szomoru, A., Tammi, J., Tavecchio, F., Tornikoski, M., Tzioumis, A. K., Urry, C. M., and Wagner, S.
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Cosmology and Extragalactic Astrophysics - Abstract
Following the recent discovery of gamma rays from the radio-loud narrow-line Seyfert 1 galaxy PMN J0948+0022 (z=0.5846), we started a multiwavelength campaign from radio to gamma rays, which was carried out between the end of March and the beginning of July 2009. The source displayed activity at all the observed wavelengths: a general decreasing trend from optical to gamma-ray frequencies was followed by an increase of radio emission after less than two months from the peak of the gamma-ray emission. The largest flux change, about a factor of about 4, occurred in the X-ray band. The smallest was at ultraviolet and near-infrared frequencies, where the rate of the detected photons dropped by a factor 1.6-1.9. At optical wavelengths, where the sampling rate was the highest, it was possible to observe day-scale variability, with flux variations up to a factor of about 3. The behavior of PMN J0948+0022 observed in this campaign and the calculated power carried out by its jet in the form of protons, electrons, radiation and magnetic field are quite similar to that of blazars, specifically of flat-spectrum radio quasars. These results confirm the idea that radio-loud narrow-line Seyfert 1 galaxies host relativistic jets with power similar to that of average blazars., Comment: 39 pages, 12 figures. Accepted for publication on ApJ Main Journal. Corresponding author: Luigi Foschini
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- 2009
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17. The infrared/X-ray correlation of GX 339-4: Probing hard X-ray emission in accreting black holes
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Coriat, M., Corbel, S., Buxton, M. M., Bailyn, C. D., Tomsick, J. A., Koerding, E., and Kalemci, E.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
GX 339-4 has been one of the key sources for unravelling the accretion ejection coupling in accreting stellar mass black holes. After a long period of quiescence between 1999 and 2002, GX 339-4 underwent a series of 4 outbursts that have been intensively observed by many ground based observatories [radio, infrared(IR), optical] and satellites (X-rays). Here, we present results of these broad-band observational campaigns, focusing on the optical-IR (OIR)/X-ray flux correlations over the four outbursts. We found tight OIR/X-ray correlations over four decades with the presence of a break in the IR/X-ray correlation in the hard state. This correlation is the same for all four outbursts. This can be interpreted in a consistent way by considering a synchrotron self-Compton origin of the X-rays in which the break frequency varies between the optically thick and thin regime of the jet spectrum. We also highlight the similarities and differences between optical/X-ray and IR/X-ray correlations which suggest a jet origin of the near-IR emission in the hard state while the optical is more likely dominated by the blackbody emission of the accretion disc in both hard and soft state. However we find a non negligible contribution of 40 per cent of the jet emission in the V-band during the hard state. We finally concentrate on a soft-to-hard state transition during the decay of the 2004 outburst by comparing the radio, IR, optical and hard X-rays light curves. It appears that unusual delays between the peak of emission in the different energy domains may provide some important constraints on jet formation scenario., Comment: Accepted for publication in MNRAS, 12 pages, 8 figures
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- 2009
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18. Correlated variability in the blazar 3C 454.3
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Bonning, E. W., Bailyn, C., Urry, C. M., Buxton, M., Fossati, G., Maraschi, L., Coppi, P., Scalzo, R., Isler, J., and Kaptur, A.
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Astrophysics - Abstract
The blazar 3C 454.3 was revealed by the Fermi Gamma-ray Space Telescope to be in an exceptionally high flux state in July 2008. Accordingly, we performed a multi-wavelength monitoring campaign on this blazar using IR and optical observations from the SMARTS telescopes, optical, UV and X-ray data from the Swift satellite, and public-release gamma-ray data from Fermi. We find an excellent correlation between the IR, optical, UV and gamma-ray light curves, with a time lag of less than one day. The amplitude of the infrared variability is comparable to that in gamma-rays, and larger than at optical or UV wavelengths. The X-ray flux is not strongly correlated with either the gamma-rays or longer wavelength data. These variability characteristics find a natural explanation in the external Compton model, in which electrons with Lorentz factor gamma~10^(3-4) radiate synchrotron emission in the infrared-optical and also scatter accretion disk or emission line photons to gamma-ray energies, while much cooler electrons (gamma~10^(1-2)) produce X-rays by scattering synchrotron or other ambient photons., Comment: 7 pages, 3 figures, submitted to ApJ Letters
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- 2008
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19. Tracing the jet contribution to the mid-IR over the 2005 outburst of GRO J1655-40 via broadband spectral modeling
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Migliari, S., Tomsick, J. A., Markoff, S., Kalemci, E., Bailyn, C. D., Buxton, M., Corbel, S., Fender, R. P., and Kaaret, P.
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Astrophysics - Abstract
We present new results from a multi-wavelength (radio/infrared/optical/X-ray) study of the black hole X-ray binary GRO J1655-40 during its 2005 outburst. We detected, for the first time, mid-infrared emission at 24 um from the compact jet of a black hole X-ray binary during its hard state, when the source shows emission from a radio compact jet as well as a strong non-thermal hard X-ray component. These detections strongly constrain the optically thick part of the synchrotron spectrum of the compact jet, which is consistent with being flat over four orders of magnitude in frequency. Moreover, using this unprecedented coverage, and especially thanks to the new Spitzer observations, we can test broadband disk and jet models during the hard state. Two of the hard state broadband spectra are reasonably well fitted using a jet model with parameters overall similar to those previously found for Cyg X-1 and GX 339-4. Differences are also present; most notably, the jet power in GRO J1655-40 appears to be a factor of at least ~3-5 higher (depending on the distance) than that of Cyg X-1 and GX 339-4 at comparable disk luminosities. Furthermore, a few discrepancies between the model and the data, previously not found for the other two black hole systems for which there was no mid-IR/IR and optical coverage, are evident, and will help to constrain and refine theoretical models., Comment: accepted for publication in ApJ
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- 2007
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20. Global optical/infrared - X-ray correlations in X-ray binaries: quantifying disc and jet contributions
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Russell, D. M., Fender, R. P., Hynes, R. I., Brocksopp, C., Homan, J., Jonker, P. G., and Buxton, M. M.
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Astrophysics - Abstract
The optical/near-infrared (OIR) region of the spectra of low-mass X-ray binaries appears to lie at the intersection of a variety of different emission processes. In this paper we present quasi-simultaneous OIR - X-ray observations of 33 XBs in an attempt to estimate the contributions of various emission processes in these sources, as a function of X-ray state and luminosity. A global correlation is found between OIR and X-ray luminosity for low-mass black hole candidate XBs (BHXBs) in the hard X-ray state, of the form L_OIR is proportional to Lx^0.6. This correlation holds over 8 orders of magnitude in Lx and includes data from BHXBs in quiescence and at large distances (LMC and M31). A similar correlation is found in low-mass neutron star XBs (NSXBs) in the hard state. For BHXBs in the soft state, all the near-infrared (NIR) and some of the optical emission is suppressed below the correlation, a behaviour indicative of the jet switching off/on in transition to/from the soft state. We compare these relations to theoretical models of a number of emission processes. We find that X-ray reprocessing in the disc and emission from the jets both predict a slope close to 0.6 for BHXBs, and both contribute to the OIR in BHXBs in the hard state, the jets producing ~90 percent of the NIR emission at high luminosities. X-ray reprocessing dominates the OIR in NSXBs in the hard state, with possible contributions from the jets (only at high luminosity) and the viscously heated disc. We also show that the optically thick jet spectrum of BHXBs extends to near the K-band. (abridged), Comment: Accepted for publication in MNRAS; 19 pages, 7 figures
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- 2006
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21. Multi-wavelength observations of the Galactic black hole transient 4U1543-47 during outburst decay: state transitions and jet contribution
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Kalemci, E., Tomsick, J. A., Buxton, M. M., Rothschild, R. E., Pottschmidt, K., Corbel, S., Brocksopp, C., and Kaaret, P.
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Astrophysics - Abstract
Multiwavelength observations of Galactic black hole (GBH) transients during the state transitions and in the low/hard state may provide detailed information on the accretion structure of these systems. 4U1543-47 is a GBH transient that was covered exceptionally well in X-ray and infrared (daily observations) and reasonably well in optical and radio during its outburst decay in 2002. When all the available information is gathered in the intermediate and the low/hard state, 4U1543-47 makes an important contribution to our understanding of state transitions and the role of outflows on the high energy emission properties of black hole binaries. The evolution of the X-ray spectral and temporal properties and the IR light curve place strong constraints on different models for explaining the overall emission from accreting black holes. The overall spectral energy distribution is consistent with synchrotron origin for the optical and infrared emission, however, the X-ray flux is above the power-law continuation of the optical and infrared flux. The infrared light curve, the HEXTE light curve and the evolution of the X-ray photon index indicate that the major source of hard X-rays cannot be direct synchrotron radiation from an acceleration region in a jet for most of the outburst decay., Comment: 11 pages, 8 figures, revised version accepted by the Astrophysical Journal
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- 2004
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22. The 2002 Outburst of the Black-Hole X-ray Binary 4U 1543-47: Optical and Infrared Light Curves
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Buxton, M. M. and Bailyn, C. D.
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Astrophysics - Abstract
We have obtained simultaneous optical and near infrared observations of 4U 1543-47 during its 2002 outburst. The most striking feature of the outburst light curve is the secondary maximum which appears after the object transitions into the low-hard state. This secondary maximum is much stronger in the infrared bands than optical. We suggest that the origin of the secondary maximum flux may be synchrotron radiation associated with a jet. Close infrared monitoring may lead to reliable triggers for simultaneous multiwavelength campaigns to study jet formation processes., Comment: Accepted for publication in ApJ
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- 2004
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23. Optical and X-ray observations of the neutron star soft X-ray transient XTE J1709-267
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Jonker, P. G., Galloway, D. K., McClintock, J. E., Buxton, M., Garcia, M., and Murray, S.
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Astrophysics - Abstract
We report on the discovery of the optical counterpart to the neutron star soft X-ray transient (SXT) XTE J1709-267 in outburst and quiescence. We further report the detection of type I bursts in RXTE data obtained during an outburst of the source in 2002. These bursts show a precursor event before the onset of the main burst event, reminiscent of photospheric radius expansion bursts. Sifting through the archival RXTE data for the burster 4U 1636-53 we found a nearly identical burst with precursor in 4U 1636-53. A comparison of this burst to true photospheric radius expansion bursts in 4U 1636-53 leads us to conclude that these bursts-with-precursor do not reach the Eddington limit. We further report on the analysis of a 22.4 ksec observation of XTE J1709-267 obtained with the Chandra satellite when the source was in quiescence. We found that the source has a soft quiescent spectrum which can be fit well by an absorbed black body or neutron star atmosphere model. A power law contributes less than 10 per cent to the 0.5-10 keV unabsorbed flux of (1.0+-0.3)x10^-13 erg cm^-2 s^-1. This flux is the same within the errors as the flux measured right after the outburst in 2002, indicating that the quiescent flux was reached within a few weeks after the outburst. Finally, we compared the power-law fractional contribution to the unabsorbed 0.5-10 keV luminosity for neutron star SXTs in quiescence for which the distance is well-known. We find that the power-law contribution is low only when the source quiescent luminosity is close to \~1-2x10^33 erg s^-1. Both at higher and lower values the power-law contribution to the 0.5-10 keV luminosity increases. We discuss how models for the quiescent X-ray emission can explain these trends.(Abridged), Comment: 10 pages, 5 Figures, 1 color Fig, accepted for publication by MNRAS, added Globular Cluster sources to Figure 5
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- 2004
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24. Discovery of a supernova associated with GRB 031203: SMARTS Optical-Infrared Lightcurves from 0.2 to 92 days
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Cobb, B. E., Bailyn, C. D., van Dokkum, P. G., Buxton, M. M., and Bloom, J. S.
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Astrophysics - Abstract
Optical and infrared monitoring of the afterglow site of gamma-ray burst (GRB) 031203 has revealed a brightening source embedded in the host galaxy, which we attribute to the presence of a supernova (SN) related to the GRB ("SN 031203"). We present details of the discovery and evolution of SN 031203 from 0.2 to 92 days after the GRB, derived from SMARTS consortium photometry in I and J bands. A template type Ic lightcurve, constructed from SN 1998bw photometry, is consistent with the peak brightness of SN 031203 although the lightcurves are not identical. Differential astrometry reveals that the SN, and hence the GRB, occurred less than 300 h_71^-1 pc (3-sigma) from the apparent galaxy center. The peak of the supernova is brighter than the optical afterglow suggesting that this source is intermediate between a strong GRB and a supernova., Comment: 11 pages, 3 figures, submitted to ApJ Letters
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- 2004
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25. The detailed optical light curve of GRB 030329
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Lipkin, Y. M., Ofek, E. O., Gal-Yam, A., Leibowitz, E. M., Poznanski, D., Kaspi, S., Polishook, D., Kulkarni, S. R., Fox, D. W., Berger, E., Mirabal, N., Halpern, J., Bureau, M., Fathi, K., Price, P. A., Peterson, B. A., Frebel, A., Schmidt, B., Orosz, J. A., Fitzgerald, J. B., Bloom, J. S., van Dokkum, P. G., Bailyn, C. D., Buxton, M. M., and Barsony, M.
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Astrophysics - Abstract
(Abridged) We present densely sampled BVRI light curves of the optical transient associated with the gamma-ray burst GRB 030329, the result of a coordinated observing campaign conducted at five observatories. Augmented with published observations of this GRB, the compiled optical dataset contains 2687 photometric measurements, obtained between 78 minutes and 79 days after the burst. We show that the underlying supernova 2003dh evolved faster than, and was probably somewhat fainter than the type Ic SN 1998bw, associated with GRB 980425. We find that our data can be described by a broken power-law decay perturbed by a complex variable component. The early- and late-time decay slopes are determined to be ~1.1 and ~2, respectively. Assuming this single power-law model, we constrain the break to lie between ~3 and ~8 days after the burst. This simple, singly-broken power-law model, derived only from the analysis of our optical observations, may also account for available multi-band data, provided that the break happened ~8 days after the burst. The more complex double-jet model of Berger et al. provides a comparable fit to the optical, X-ray, mm and radio observations of this event. We detect a significant change in optical colors during the first day. Our color analysis is consistent with a cooling break frequency sweeping through the optical band during the first day. The light curves of GRB 030329 reveal a rich array of variations, superposed over the mean power-law decay. We find that the early variations are asymmetric, with a steep rise followed by a relatively slower (by a factor of about two) decline. The variations maintain a similar time scale during the first four days, and then get significantly longer., Comment: 14 pages, 12 figures, accepted for publication in ApJ with minor changes. See the GRB030329 Data Treasury at http://wise-obs.tau.ac.il/GRB030329/
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- 2003
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26. Possible Optical/Infrared Jet Emission in 4U 1543-47
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Buxton, M. and Bailyn, C.
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Astrophysics - Abstract
We have taken optical and infrared observations during the 2002 outburst of the soft X-ray transient, 4U 1543-47. A secondary maximum occurs in the lightcurves during the outburst decline. This feature is much stronger at infrared wavelengths than optical. We have applied single blackbody, multicolor blackbody and broken-power law models to the optical/infrared spectral energy distribution of the secondary maximum and find that the broken power-law provides the best fit. We therefore conclude that the secondary maximum emission originates from a jet. We also show the most recent lightcurves of the 2002/2003 outburst of GX 339-4 in which a secondary maximum appears. This leads us to the conclusion that secondary maxima may be a common occurrence in soft X-ray transients during outburst decline which appear after the object transitions into the low-hard state. Infrared observations of such phenomena will give reliable triggers for multiwavelength observations, allowing us to greatly improve our knowledge of jet formation and behavior, and how this relates to the accretion geometry., Comment: 4 pages, to appear in ``X-Ray Timing 2003: Rossi and Beyond'' conference proceedings, references now visible
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- 2003
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27. Imaging X-ray, Optical, and Infrared Observations of the Transient Anomalous X-ray Pulsar XTE J1810-197
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Gotthelf, E. V., Halpern, J. P., Buxton, M., and Bailyn, C.
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Astrophysics - Abstract
We report X-ray imaging, timing, and spectral studies of XTE J1810-197, a 5.54s pulsar discovered by Ibrahim et al. (2003) in recent RXTE observations. In a set of short exposures with the Chandra HRC camera we detect a strongly modulated signal (55+/-4% pulsed fraction) with the expected period located at (J2000) 18:09:51.08, -19:43:51.7, with a uncertainty radius of 0.6 arcsec (90% C.L.). Spectra obtained with XMM-Newton are well fitted by a two-component model that typically describes anomalous X-ray pulsars (AXPs), an absorbed blackbody plus power law with parameters kT = 0.67+/-0.01 keV, Gamma=3.7+/-0.2, N_H=(1.05+/-0.05)E22 cm^-2, and Fx(0.5-10 keV) = 3.98E-11 ergs/cm2/s. Alternatively, a 2T blackbody fit is just as acceptable. The location of CXOU J180951.1-194351 is consistent with a point source seen in archival Einstein, Rosat, & ASCA images, when its flux was nearly two orders-of-magnitude fainter, and from which no pulsations are found. The spectrum changed dramatically between the "quiescent" and "active" states, the former can be modeled as a softer blackbody. Using XMM timing data, we place an upper limit of 0.03 lt-s on any orbital motion in the period range 10m-8hr. Optical and infrared images obtained on the SMARTS 1.3m telescope at CTIO show no object in the Chandra error circle to limits V=22.5, I=21.3, J=18.9, & K=17.5. Together, these results argue that CXOU J180951.1-194351 is an isolated neutron star, one most similar to the transient AXP AX J1844.8-0256. Continuing study of XTE J1810-197 in various states of luminosity is important for understanding and possibly unifying a growing class of isolated, young neutron stars that are not powered by rotation., Comment: 12 pages, 7 figures, AAS LaTex, uses emulateapj5.sty. Updated to include additional archival data and a new HRC observation. To appear in The Astrophysical Journal
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- 2003
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28. Optical-Infrared ANDICAM Observations of the Transient Associated with GRB 030329
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Bloom, J. S., van Dokkum, P. G., Bailyn, C. D., Buxton, M. M., Kulkarni, S. R., and Schmidt, B. P.
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Astrophysics - Abstract
We present photometry of the transient associated with GRB 030329 obtained with the CTIO 1.3--meter telescope and the ANDICAM instrument, a dual optical/infrared imager with a dichroic centered at one micron. Without the need for light curve interpolation to produce snapshot broadband spectra, we show that the transient spectrum remained statistically achromatic from day 2.7 to day 5.6, during a re-brightening episode. Associating the light in these early epochs with the GRB afterglow, we infer a modest level of extinction due to the host galaxy in the line--of--sight toward the GRB: A_V(host) = 0.30 +/- 0.03 mag for beta = -0.5 and A_V(host) < 0.4 mag (3 sigma) for any physically plausible value of beta (with flux f_nu ~ lambda^-beta). We conclude that the spectral slope of the afterglow component was more than beta = -0.8 between day 2.7-5.6 after the GRB, excluding the possibility that the synchrotron cooling break passed through the optical/IR bandpass over that period. Taking extinction into account, a decomposition of the light curve into an afterglow and supernova component requires the presence of a supernova similar to that of SN 1998bw, an afterglow that shows some evidence for a second break around day 8-10, and a fifth re-brightening event around day 15. Assuming an SN 1988bw-like evolution and a contemporaneous GRB and SN event, the peak SN brightness was M_V = -19.8 +/- 0.4 - 5 log h_65 mag., Comment: Published in the Astronomical Journal, January 2004: see http://adsabs.harvard.edu/cgi-bin/nph-bib_query?bibcode=2004AJ....127..252B
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- 2003
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29. Ore–Waste Discrimination in Epithermal Deposits Using Near-Infrared to Short-Wavelength Infrared (NIR-SWIR) Hyperspectral Imagery
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Dalm, M., Buxton, M. W. N., and van Ruitenbeek, F. J. A.
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- 2019
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30. Chemometric Analysis of Mid-Wave Infrared Spectral Reflectance Data for Sulphide Ore Discrimination
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Desta, F. S. and Buxton, M. W. N.
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- 2019
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31. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.
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Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Webb, S.A., Lawler, P.R., Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Webb, S.A., and Lawler, P.R.
- Abstract
Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06
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- 2023
32. Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.
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Lawler, P.R., Derde, L.P.G., Veerdonk, F.L. van de, McVerry, B.J., Huang, D.T., Berry, L.R., Lorenzi, E., Kimmenade, R.R.J. van, Gommans, F., Vaduganathan, M., Leaf, D.E., Baron, R.M., Kim, E.Y., Frankfurter, C., Epelman, S., Kwan, Y., Grieve, R., O'Neill, S., Sadique, Z., Puskarich, M., Marshall, J.C., Higgins, A.M., Mouncey, P.R., Rowan, K.M., Al-Beidh, F., Annane, D., Arabi, Y.M., Au, C., Beane, A., Bentum-Puijk, W. van, Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Cecconi, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Ezekowitz, J., Fitzgerald, M., Gattas, D., Godoy, L.C., Goossens, H., Haniffa, R., Harrison, D.A., Hills, T., Horvat, C.M., Ichihara, N., Lamontagne, F., Linstrum, K.M., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McQuilten, Z., Murthy, S., Nichol, A.D., Owen, D.R.J., Parke, R.L., Parker, J.C., Pollock, K.M., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Singh, V., Turgeon, A.F., Turner, A.M., Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., Berry, S., Gordon, A.C., McArthur, C.J., Webb, S.A., Lawler, P.R., Derde, L.P.G., Veerdonk, F.L. van de, McVerry, B.J., Huang, D.T., Berry, L.R., Lorenzi, E., Kimmenade, R.R.J. van, Gommans, F., Vaduganathan, M., Leaf, D.E., Baron, R.M., Kim, E.Y., Frankfurter, C., Epelman, S., Kwan, Y., Grieve, R., O'Neill, S., Sadique, Z., Puskarich, M., Marshall, J.C., Higgins, A.M., Mouncey, P.R., Rowan, K.M., Al-Beidh, F., Annane, D., Arabi, Y.M., Au, C., Beane, A., Bentum-Puijk, W. van, Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Cecconi, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Ezekowitz, J., Fitzgerald, M., Gattas, D., Godoy, L.C., Goossens, H., Haniffa, R., Harrison, D.A., Hills, T., Horvat, C.M., Ichihara, N., Lamontagne, F., Linstrum, K.M., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McQuilten, Z., Murthy, S., Nichol, A.D., Owen, D.R.J., Parke, R.L., Parker, J.C., Pollock, K.M., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Singh, V., Turgeon, A.F., Turner, A.M., Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., Berry, S., Gordon, A.C., McArthur, C.J., and Webb, S.A.
- Abstract
Item does not contain fulltext, IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital surv
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- 2023
33. Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support–free days in patients hospitalized with COVID-19
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Writing Committee for the REMAP-CAP Investigators, Lawler, PR, Derde, LPG, Van de Veerdonk, FL, McVerry, BJ, Huang, DT, Berry, LR, Lorenzi, E, Van Kimmenade, R, Gommans, F, Vaduganathan, M, Leaf, DE, Baron, RM, Kim, EY, Frankfurter, C, Epelman, S, Kwan, Y, Grieve, R, O'Neill, S, Sadique, Z, Puskarich, M, Marshall, JC, Higgins, AM, Mouncey, PR, Rowan, KM, Al-Beidh, F, Annane, D, Arabi, YM, Au, C, Beane, A, Van Bentum-Puijk, W, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Burrell, A, Buzgau, A, Buxton, M, Cecconi, M, Cheng, AC, Cove, M, Detry, MA, Estcourt, LJ, Ezekowitz, J, Fitzgerald, M, Gattas, D, Godoy, LC, Goossens, H, Haniffa, R, Harrison, DA, Hills, T, Horvat, CM, Ichihara, N, Lamontagne, F, Linstrum, KM, McAuley, DF, McGlothlin, A, McGuinness, SP, McQuilten, Z, Murthy, S, Nichol, AD, Owen, DRJ, Parke, RL, Parker, JC, Pollock, KM, Reyes, LF, Saito, H, Santos, MS, Saunders, CT, Seymour, CW, Shankar-Hari, M, Singh, V, Turgeon, AF, Turner, AM, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, Berry, S, Gordon, AC, McArthur, CJ, and Webb, SA
- Abstract
IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
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- 2023
34. Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19
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Goligher, EC, Lawler, PR, Jensen, TP, Talisa, V, Berry, LR, Lorenzi, E, McVerry, BJ, Chang, C-CH, Leifer, E, Bradbury, C, Berger, J, Hunt, BJ, Castellucci, LA, Kornblith, LZ, Gordon, AC, McArthur, C, Webb, S, Hochman, J, Neal, MD, Zarychanski, R, Berry, S, Angus, DC, Aday, A, Ahuja, T, Al-Beidh, F, Annane, D, Arabi, YM, Aryal, D, Baumann Kreuziger, L, Beane, A, Berger, JS, Berry, SM, Bhimani, Z, Bihari, S, Billett, HH, Bond, L, Bonten, M, Bradbury, CA, Brooks, MM, Brunkhorst, F, Buxton, M, Buzgau, A, Carrier, M, Castelucci, LA, Chekuri, S, Chen, J-T, Cheng, AC, Chkhikvadze, T, Coiffard, B, Contreras, A, Costantini, TW, Cushman, M, De Brouwer, S, Derde, LPG, Detry, MA, Duggal, A, Džavík, V, Effron, MB, Eng, HF, Escobedo, J, Estcourt, LJ, Everett, BM, Farkough, ME, Fergusson, DA, Fitzgerald, M, Fowler, RA, Froess, JD, Fu, Z, Galanaud, J-P, Galen, BT, Gandotra, S, Girard, TD, Godoy, LD, Gong, MN, Goodman, AL, Goossens, H, Green, C, Greenstein, YY, Gross, PL, Guerrero, RM, Hamburg, N, Haniffa, R, Hanna, G, Hanna, N, Hedge, SM, Hendrickson, CM, Higgins, AM, Hindenburg, AA, Hite, RD, Hochman, JS, Hope, AA, Horowitz, JM, Horvat, CM, Houston, BL, Huang, DT, Hudock, K, Husain, M, Hyzy, RC, Iyer, V, Jacobson, JR, Jayakumar, D, Kahn, SR, Keller, NM, Khan, A, Kim, Y, Kim, KS, Kindzelski, A, King, AJ, Kirwan, B-A, Knudson, MM, Kornblith, AE, Krishnan, V, Kumar, A, Kutcher, ME, Laffan, MA, Lamontagne, F, Le Gal, G, Leeper, CM, Leifer, ES, Lewis, RJ, Lim, G, Lima, FG, Linstrum, K, Litton, E, Lopez-Sendon, J, Lopez-Sendon Moreno, JL, Lother, SA, Madrona, SG, Malhotra, S, Marcos Martin, M, Marshall, JC, Marten, N, Martinez, AS, Martinez, M, Mateos Garcia, E, Matthay, MA, Mavromichalis, S, McArthur, CJ, McAuley, DF, McDonald, EG, McGlothlin, A, McGuinness, SP, McQuilten, ZK, Middeldorp, S, Montgomery, SK, Moore, SC, Mouncey, PR, Murthy, S, Nair, GB, Nair, R, Nichol, AD, Nicolau, JC, Nunez-Garcia, B, Pandey, A, Park, JJ, Park, PK, Parke, RL, Parker, JC, Parnia, S, Paul, JD, Pompilio, M, Prekker, M, Quigley, JG, Reynolds, HR, Rosenson, RS, Rost, NS, Rowan, K, Santos, MO, Santos, FO, Santos, M, Satterwhite, L, Saunders, CT, Schreiber, J, Schutgens, REG, Seymour, CW, Shankar Hari, M, Sheehan, JP, Siegal, DM, Silva Jr., DG, Singhal, AB, Slutsky, AS, Solvason, D, Stanworth, SJ, Tritschler, T, Turgeon, AF, Turner, AM, Van Bentum-Puijk, W, Van de Veerdonk, FL, Van Diepen, S, Vazquez Grande, G, Wahid, L, Wareham, V, Webb, SA, Wells, B, Widmer, RJ, Wilson, JG, Yuriditsky, E, Zampieri, F, and Zhong, Y
- Abstract
Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR
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- 2023
35. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
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Florescu, S, Stanciu, D, Zaharia, M, Kosa, A, Codreanu, D, Kidwai, A, Masood, S, Kaye, C, Coutts, A, MacKay, L, Summers, C, Polgarova, P, Farahi, N, Fox, E, McWilliam, S, Hawcutt, D, Rad, L, O’Malley, L, Whitbread, J, Jones, D, Dore, R, Saunderson, P, Kelsall, O, Cowley, N, Wild, L, Thrush, J, Wood, H, Austin, K, Bélteczki, J, Magyar, I, Fazekas, Á, Kovács, S, Szőke, V, Donnelly, A, Kelly, M, Smyth, N, O’Kane, S, McClintock, D, Warnock, M, Campbell, R, McCallion, E, Azaiz, A, Charron, C, Godement, M, Geri, G, Vieillard-Baron, A, Johnson, P, McKenna, S, Hanley, J, Currie, A, Allen, B, McGoldrick, C, McMaster, M, Mani, A, Mathew, M, Kandeepan, R, Vignesh, C, TV, B, Ramakrishnan, N, James, A, Elvira, E, Jayakumar, D, Pratheema, R, Babu, S, Ebenezer, R, Krishnaoorthy, S, Ranganathan, L, Ganesan, M, Shree, M, Guilder, E, Butler, M, Cowdrey, K-A, Robertson, M, Ali, F, McMahon, E, Duffy, E, Chen, Y, Simmonds, C, McConnochie, R, O’Connor, C, El-Khawas, K, Richardson, A, Hill, D, Commons, R, Abdelkharim, H, Saxena, M, Muteithia, M, Dobell-Brown, K, Jha, R, Kalogirou, M, Ellis, C, Krishnamurthy, V, O’Connor, A, Thurairatnam, S, Mukherjee, D, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Maloney, G, Kittridge, L, Solesbury, A, Ramos, A, Collins, D, Brickell, K, Reid, L, Smyth, M, Breen, P, Spain, S, Curley, G, McEvoy, N, Geoghegan, P, Clarke, J, Silversides, J, McGuigan, P, Ward, K, O’Neill, A, Finn, S, Wright, C, Green, J, Collins, É, Knott, C, Smith, J, Boschert, C, Slieker, K, Ewalds, E, Sanders, A, Wittenberg, W, Geurts, H, Poojara, L, Sara, T, Nand, K, Reeve, B, Dechert, W, Phillips, B, Oritz-Ruiz de Gordoa, L, Affleck, J, Shaikh, A, Murray, A, Ramanan, M, Frakking, T, Pinnell, J, Robinson, M, Gledhill, L, Wood, T, Sanghavi, R, Bhonagiri, D, Ford, M, Parikh, HG, Avard, B, Nourse, M, McDonald, B, Edmunds, N, Hoiting, O, Peters, M, Rengers, E, Evers, M, Prinssen, A, Morgan, M, Cole, J, Hill, H, Davies, M, Williams, A, Thomas, E, Davies, R, Wise, M, Grimm, P, Soukup, J, Wetzold, R, Löbel, M, Starke, L, Lellouche, F, Lizotte, P, Declerq, P, Antoine, M, Stephanie, G, Jean-Pierre, E, François, B, Marion, B, Philippe, R, Pourcine, F, Monchi, M, Luis, D, Mercier, R, Sagnier, A, Verrier, N, Caplin, C, Richecoeu, J, Combaux, D, Siami, S, Aparicio, C, Vautier, S, Jeblaoui, A, Lemaire-Brunel, D, D'Aragon, F, Carbonneau, E, Leblond, J, Plantefeve, G, Leparco, C, Contou, D, Fartoukh, M, Courtin, L, Labbe, V, Voiriot, G, Salhi, S, Chassé, M, Carrier, F, Boumahni, D, Benettaib, F, Ghamraoui, A, Sement, A, Gachet, A, Hanisch, A, Haffiane, A, Boivin, A-H, Barreau, A, Guerineau, E, Poupblanc, S, Egreteau, P, Lefevre, M, Bocher, S, Le Loup, G, Le Guen, L, Carn, V, Bertel, M, Antcliffe, D, Templeton, M, Rojo, R, Coghlan, P, Smee, J, Barker, G, Finn, A, Kreb, G, Hoff, U, Hinrichs, C, Nee, J, Mackay, E, Cort, J, Whileman, A, Spencer, T, Spittle, N, Beavis, S, Padmakumar, A, Dale, K, Hawes, J, Moakes, E, Gascoyne, R, Pritchard, K, Stevenson, L, Cooke, J, Nemeth-Roszpopa, K, Gauli, B, Bastola, S, Muller, G, Nay, M-A, Kamel, T, Benzekri, D, Jacquier, S, Runge, I, Mathonnet, A, Barbier, F, Bretagnol, A, Carter, J, Van Der Heyden, K, Mehrtens, J, Morris, A, Morgan, S, Burke, T, Mercier, E, Chartier, D, Salmon, C, Dequin, P-F, Garot, D, Bellemare, D, Cloutier, È, Daher, R, Costerousse, O, Boulanger, M-C, Couillard-Chénard, É, Lauzier, F, Francoeur, C, Francois, B, Gay, A, Anne-Laure, F, Ramali, M, HC, O, Ghosh, A, Osagie, R, Arachchige, M, Hartley, M, Cheung, W, Wong, H, Seigne, P, Eustace, J, O'Callaghan, A-M, O'Brien, F, Bamford, P, Reid, A, Cawley, K, Faulkner, M, Pickering, C, Raj, A, Tsinaslanidis, G, Khade, R, Agha, G, Sekiwala, R, Smith, T, Brewer, C, Gregory, J, Limb, J, Cowton, A, O’Brien, J, Postlethwaite, K, Malakouti, S, Music, E, Ricketts, D, King, A, Clermont, G, Bart, R, Mayr, F, Schoenling, A, Andreae, M, Shetty, V, Brant, E, Malley, B, Donadee, C, Sackrowitz, R, Weissman, A, Yealy, D, Barton, D, Talia, N, Nikitas, N, Wells, C, Lankester, L, McMillan, H, Van den Oever, H, Kruisdijk-Gerritsen, A, Haidar, G, Bain, W, Barbash, I, Fitzpatrick, M, Franz, C, Kitsios, G, Moghbeli, K, Rosborough, B, Shah, F, Suber, T, Pulletz, M, Williams, P, Birch, J, Wiseman, S, Horton, S, Alegria, A, Turki, S, Elsefi, T, Crisp, N, Allen, L, Truman, N, Smith, M, Chukkambotla, S, Goddard, W, Duberley, S, Khan, M, Kazi, A, Simpson, J, Duke, G, Chan, P, Carter, B, Hunter, S, Voigt, I, Schueler, R, Blank, E, Hüning, V, Steffen, M, Goralski, P, Litton, E, Regli, A, Pellicano, S, Palermo, A, Eroglu, E, Bihari, S, Laver, RD, Jin, X, Brown, J, McIntyre, J, French, C, Bates, S, Towns, M, Yang, Y, McGain, F, McCullagh, I, Cairns, T, Hanson, H, Patel, B, Clement, I, Evetts, G, Touma, O, Holland, S, Hodge, C, Taylor, H, Alderman, M, Barnes, N, Da Rocha, J, Smith, C, Brooks, N, Weerasinghe, T, Sinclair, J-A, Abusamra, Y, Doherty, R, Cudlipp, J, Singh, R, Yu, H, Daebis, A, Ng, C, Kendrick, S, Saran, A, Makky, A, Greener, D, Rowe-Leete, L, Edwards, A, Bland, Y, Dolman, R, Foster, T, Laffey, J, McNicholas, B, Scully, M, Casey, S, Kernan, M, Brennan, A, Rangan, R, Tully, R, Corbett, S, McCarthy, A, Duffy, O, Burke, D, Linnett, V, Sanderson, A, Ritzema, J, Wild, H, Lucas, R, Marriott, Y, Andric, Z, Cviljevic, S, Br, R, Zapalac, M, Mirković, G, Khare, D, Pinder, M, Gopinath, A, Kannan, T, Dean, S, Vanmali, P, Depuydt, P, De Waele, J, De Bus, L, Fierens, J, Bracke, S, Vermassen, J, Vermeiren, D, Pugh, R, Lean, R, Qiu, X, Scanlan, J, Evans, A, Davies, G, Lewis, J, Plesnikova, Y, Khoud, A, Coetzee, S, Puxty, K, Cathcart, S, Rimmer, D, Bagot, C, Scott, K, Martin, L, Yusuff, H, Isgro, G, Brightling, C, Bourne, M, Craner, M, Boyles, R, Alexander, B, Roberts, T, Nelli, A, Rosenstein-Sisson, R, Speyer, R, Pech, Y, McCullough, J, Tallott, M, Vazquez-Grande, G, Marten, N, Liu, T, Siddiqui, A, Khanal, S, Amatya, S, Szakmany, T, Cherian, S, Williams, G, James, C, Waters, A, Prout, R, Stedman, R, Davies, L, Pegler, S, Kyeremeh, L, Moorhouse, L, Arbane, G, Marotti, M, Bociek, A, Campos, S, Van Nieuwkoop, K, Ottens, T, Visser, Y, Van den Berg, L, Van der Kraan-Donker, A, Brett, S, Arias, S, Hall, R, Paneru, H, Koirala, S, Paudel, P, Wilson, M, Vaara, S, Pettilä, L, Heinonen, J, Pettilä, V, Jain, S, Gupta, A, Holbrook, C, Antoine, P, Meziani, F, Allam, H, Cattelan, J, Clere-Jehl, R, Helms, J, Kummerlen, C, Merdji, H, Monnier, A, Rahmani, H, Studer, A, Schneider, F, Castelain, V, Morel, G, L’Hotellier, S, Ochin, E, Vanjak, C, Rouge, P, Bendjemar, L, Albert, M, Serri, K, Cavayas, A, Duplaix, M, Williams, V, Catorze, NJTADS, Pereira, TNAL, Ferreira, RMC, Bastos, JMPS, Batista, TMO, Badie, J, Berdaguer, F, Malfroy, S, Mezher, C, Bourgoin, C, Moneger, G, Bouvier, E, Muñoz-Bermúdez, R, Marin-Corral, J, Degracia, A, Gómez, F, López, M, Aceto, R, Aghemo, A, Badalamenti, S, Brunetta, E, Cecconi, M, Ciccarelli, M, Constantini, E, Greco, M, Folci, M, Selmi, C, Voza, A, Henning, J, Bonner, S, Hugill, K, Cirstea, E, Wilkinson, D, Jones, J, Altomy, M, Karlikowski, M, Sutherland, H, Wilhelmsen, E, Woods, J, North, J, Pletz, M, Hagel, S, Ankert, J, Kolanos, S, Bloos, F, Simons, K, Van Zuylen, T, Bouman, A, Kumar, N, Panwar, R, Poulter, A-L, Sunkara, K, Szigligeti, G, Leszkoven, J, Rochwerg, B, Karachi, T, Oczkowski, S, Centofanti, J, Millen, T, Sundaran, D, Hollos, L, Turns, M, Walsh, J, Al Qasim, E, Alswaidan, L, Hegazy, M, Arishi, H, Al Amri, A, AlQahtani, S, Naidu, B, Tlayjeh, H, Hussain, S, Al Enezi, F, Abdukahil, SA, Hopkins, P, Noble, H, O’Reilly, K, Mehta, R, Wong, O, Makanju, E, Rao, D, Sikondari, N, Saha, S, Corcoran, E, Pappa, E, Cockrell, M, Donegan, C, Balaie, M, Nickoleit-Bitzenberger, D, Schaaf, B, Meermeier, W, Prebeg, K, Azzaui, H, Hower, M, Brieger, K-G, Elender, C, Sabelhaus, T, Riepe, A, Akamp, C, Kremling, J, Klein, D, Landsiedel-Mechenbier, E, Laha, S, Verlander, M, Jha, A, Megarbane, B, Voicu, S, Deye, N, Malissin, I, Sutterlin, L, Mrad, A, Lehalleur, A, Naim, G, Nguyen, P, Ekhérian, J-M, Boué, Y, Sidéris, G, Vodovar, D, Guérin, E, Grant, C, Brain, M, Mineall, S, Paramasivam, E, Wilby, E, Ogg, B, Howcroft, C, Aspinwall, A, Charlton, S, Gould, R, Mistry, D, Awan, S, Bedford, C, Carr-Wilkinson, J, Hall, A, Gardiner-Hill, C, Maloney, C, Brunskill, N, Watchorn, O, Hardy, C, Qureshi, H, Flint, N, Nicholson, S, Southin, S, Ghattaoraya, A, Harding, D, O’Halloran, S, Collins, A, Smith, E, Trues, E, Borgatta, B, Turner-Bone, I, Reddy, A, Wilding, L, Wilson, C, Surti, Z, Aneman, A, Miller, J, White, H, Estensen, K, Morrison, L, Sutton, J, Cooper, M, Warnapura, L, Agno, R, Sathianathan, P, Shaw, D, Ijaz, N, Spong, A, Sabaretnam, S, Burns, D, Lang, E, Tate, M, Fischer, R, Biradar, V, Soar, N, Golden, D, Davey, M, Seaman, R, Osborne, A, Bannard-Smith, J, Clark, R, Birchall, K, Henry, J, Pomeroy, F, Quayle, R, Wylie, K, Sukuraman, A, John, M, Sibin, S, Leditschke, A, Finnis, M, Jongebloed, K, Khwaja, K, Campisi, J, Van Vonderen, M, Pietersma, M, Vrolijk, L, Kampschreur, L, Van Gulik, L, Makowski, A, Misztal, B, Haider, S, Liao, A, Squires, R, Oborska, A, Kayani, A, Kalchko-Veyssal, S, Prabakaran, R, Hadebe, B, KalchkoVeyssal, S, Williams, T, Song, R, Morpeth, S, Lai, V, Habraken, H, Stewart, R, Mwaura, E, Mew, L, Wren, L, Willams, F, Sutherland, S-B, Rebello, R, Shehabi, Y, Al-Bassam, W, Hulley, A, Kadam, U, Sathianathan, K, Innes, R, Doble, P, Graham, L, Shovelton, C, Dean, T, Salahuddin, N, Aryal, D, Koirala, K, Rai, N, Luitel, S, Seppelt, I, Whitehead, C, Lowrey, J, Gresham, R, Masters, K, Hamlyn, V, Hawkins, N, Roynon-Reed, A, Cutler, S, Lewis, S, Lazaro, J, Newman, T, Aravindan, L, Asghar, A, Bartholomew, J, Bayne, M, Beddows, S, Birch, C, Brend, M, Byrne, R, Campbell, D, Campbell, H, Chambers, E, Clinton, A, Collins, J, Crawshaw, S, Dawson, LA, Donaldson, K, Drake, C, Dyas, S, Ellis, Y, Gilmour, K, Goodwin, J, Halden, S, Hall, AS, Hanson, J, Harper, H, Harrison, S, Hayes, A, Hodgson, H, Hurford, S-A, Jackson, S, Levett, C, Lock, S, Lockett, T, Logan, M, Lomme, K, Luo, J, Marsh, E, Mguni, N, Monaghan, H, Murphy, S, Muzengi, N, Naz, M, O'Kell, E, Oliver, A, O'Reilly, J, Pearson, K, Porter, D, Potter, A, Rook, C, Rounds, C, Sheffield, J, Shirley, K, Siewersk, C, Skinner, T, Speight, H, Sutu, M, Unsworth, A, Van’t Hoff, W, Walker, S, Williams, H, Williamson, D, Williamson, JD, Duan, E, Tsang, J, Patterson, L, Austin, P, Chapman, S, Cabrelli, L, Fletcher, S, Nortje, J, Fottrell-Gould, D, Randell, G, Stammers, K, Healey, G, Pinto, M, Borrill, Z, Duncan, T, Ustianowski, A, Uriel, A, Eltayeb, A, Alfonso, J, Hey, S, Shaw, J, Fox, C, Lindergard, G, Charles, B, Blackledge, B, Connolly, K, Harris, J, Cuesta, J, Xavier, K, Purohit, D, Elhassan, M, Haldeos, A, Vincent, R, Abdelrazik, M, Jenkins, S, Ganesan, A, Kumar, R, Carter, D, Bakthavatsalam, D, Frater, A, Saleem, M, Everitt, R, Hacking, D, Zaman, M, Elmahi, E, Jones, A, Hall, K, Phillips, M, Terrill, L, Mills, G, Raithatha, A, Bauchmuller, K, Ryalls, K, Harrington, K, Bowler, H, Sall, J, 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McIntyre, L, Brady, K, Vale, C, Shekar, K, Lavana, J, Parmar, D, Peake, S, Kurenda, C, Hormis, A, Walker, R, Collier, D, Kimpton, S, Oakley, S, Bhagani, S, De Neef, M, Garcia, S, Maharajh, A, Nandani, A, Dobson, J, Fernando, G, Eastgate, C, Gomez, K, Abdi, Z, Tatham, K, Jhanji, S, Black, E, Dela Rosa, A, Howle, R, Baikady, R, Drummond, A, Dearden, J, Philbin, J, Munt, S, Gopal, S, Pooni, J-S, Ganguly, S, Smallwood, A, Metherell, S, Naeem, A, Fagan, L, Ryan, E, Mariappa, V, Foulds, A, Revill, A, Bhattarai, B, De Jonge, E, Wigbers, J, Del Prado, M, Cremer, O, Mulier, J, Peters, A, Romberg, B, Schutgens, R, Troeman, D, Van Opdorp, M, Besten, H, Brakké, K, Barber, R, Hilldrith, A, Kluge, S, Nierhaus, A, Jarczak, D, Roedl, K, Kochanek, M, Rueß-Paterno, G, Mc-Kenzie, J, Eichenauer, D, Shimabukuro-Vornhagen, A, Wilcox, E, Del Sorbo, L, Abdelhady, H, Romagnuolo, T, Simpson, S, Maiden, M, Horton, M, Trickey, J, Krajinovic, V, Kutleša, M, Kotarski, V, Brohi, F, Jagannathan, V, Clark, M, Purvis, S, Wetherill, B, Brajković, A, Babel, J, Sever, H, Dragija, L, Kušan, I, Dushianthan, A, Cusack, R, De Courcy-Golder, K, Salmon, K, Burnish, R, Smith, S, Ruiz, W, Duke, Z, Johns, M, Male, M, Gladas, K, Virdee, S, Swabe, J, Tomlinson, H, Rohde, G, Grünewaldt, A, Bojunga, J, Petros, S, Kunz, K, Schütze, B, Weismann, D, Frey, A, Drayss, M, Goebeler, ME, Flor, T, Fragner, G, Wahl, N, Totzke, J, Sayehli, C, Hakak, S, Altaf, W, O'Sullivan, M, Murphy, A, Walsh, L, Rega La Valle, A, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Wyatt, R, Morgan, K, Varghese, S, Willis, J, Stratton, E, Kyle, L, Putensen, D, Drury, K, Skorko, A, Bremmer, P, Ward, G, Bassford, C, Sligl, W, Baig, N, Rewa, O, Bagshaw, S, Basile, K, Stavor, D, Burbee, D, McNamara, A, Wunderley, R, Bensen, N, Adams, P, Vita, T, Buhay, M, Scholl, D, Gilliam, M, Winters, J, Doherty, K, Berryman, E, Ghaffari, M, Marroquin, O, Quinn, K, Garrard, W, Kalchthaler, K, Beard, G, Skrtich, A, Bagavathy, K, Drapola, D, Bryan-Morris, K, Arnold, J, Reynolds, B, Hussain, M, Dunsavage, J, Saiyed, S, Hernandez, E, Goldman, J, Brown, C, Comp, S, Raczek, J, Morris, J, Vargas Jr., J, Weiss, D, Hensley, J, Kochert, E, Wnuk, C, Nemeth, C, Mowery, B, Hutchinson, C, Winters, L, McAdams, D, Walker, G, Minnier, T, Wisniewski, M, Mayak, K, McCreary, E, Bariola, R, Viehman, A, Daley, J, Lopus, A, Schmidhofer, M, Ambrosino, R, Keen, S, Toffalo, S, Stambaugh, M, Trimmer, K, Perri, R, Casali, S, Medva, R, Massar, B, Beyerl, A, Burkey, J, Keeler, S, Lowery, M, Oncea, L, Daugherty, J, Sevilla, C, Woelke, A, Dice, J, Weber, L, Roth, J, Ferringer, C, Beer, D, Fesz, J, Carpio, L, Colin, G, Zinzoni, V, Maquigneau, N, Henri-Lagarrigue, M, Pouplet, C, Reill, L, Distler, M, Maselli, A, Martynoga, R, Trask, K, Butler, A, Attwood, B, Parsons, P, Campbell, B, Smith, A, Page, V, Zhao, X, Oza, D, Abrahamson, G, Sheath, B, Young, P, Young, C, Lesona, E, Navarra, L, Cruz, R, Delaney, K, Aguilar-Dano, A, Gojanovic, M, Rhodes, J, Anderson, T, Morris, S, Nayyar, V, Bowen, D, Kong, J, Joy, J, Fuchs, R, Lambert, B, Tai, C, Thomas, A, Keen, A, Tierney, C, Omer, N, Bacon, G, Tridente, A, Shuker, K, Anders, J, Greer, S, Scott, P, Millington, A, Buchanan, P, Binnie, A, Powell, E, McMillan, A, Luk, T, Aref, N, Denmade, C, Sadera, G, Jacob, R, Hughes, D, Sterba, M, Geng, W, Digby, S, Southern, D, Reddy, H, Hulse, S, Campbell, A, Garton, M, Watkins, C, Smuts, S, Quinn, A, Simpson, B, McMillan, C, Finch, C, Hill, C, Cooper, J, Budd, J, Small, C, O’Leary, R, Collins, E, Holland, A, Alexander, P, Felton, T, Ferguson, S, Sellers, K, Ward, L, Yates, D, Birkinshaw, I, Kell, K, Scott, Z, Pearson, H, Hashmi, M, Hassan, N, Panjwani, A, Umrani, Z, Shaikh, M, Ain, Q, Kanwal, D, Van Bree, S, Bouw-Ruiter, M, Osinga, M, Van Zanten, A, McEldrew, R, Rashan, S, Singh, V, Azergui, N, Bari, S, Beltran, M, Brugman, C, Groeneveld, E, Jafarzadeh, M, Keijzer-Timmers, N, Kester, E, Koelink, M, Kwakkenbos-Craanen, M, Okundaye, C, Parker, L, Peters, S, Post, S, Rietveld, I, Scheepstra-Beukers, I, Schreuder, G, Smit, A, Brillinger, N, Markgraf, R, Eichinger, F, Doran, P, Anjum, A, Best-Lane, J, Barton, F, Miller, L, Richards-Belle, A, Saull, M, Sprinckmoller, S, Wiley, D, Darnell, R, Au, C, Lindstrum, K, Cheng, A, Forbes, A, Heritier, S, Trapani, T, Cuthbertson, B, Manoharan, V, Dondrop, A, Tolppa, T, Ehrmann, S, Hullegie, S, Povoa, P, Beasley, R, Daneman, N, McGloughlin, S, Paterson, D, Venkatesh, B, De Jong, M, Uyeki, T, Baillie, K, Netea, M, Orr, K, Patanwala, A, Tong, S, Cooper, N, Galea, J, Leavis, H, Ogungbenro, K, Patawala, A, Rademaker, E, Youngstein, T, Carrier, M, Fergusson, D, Hunt, B, Kumar, A, Laffan, M, Lother, S, Middeldorp, S, Stanworth, S, De Man, A, Masse, M-H, Abraham, J, Arnold, D, Begin, P, Charlewood, R, Chasse, M, Coyne, M, Daly, J, Gosbell, I, Harvala-Simmonds, H, MacLennan, S, McDyer, J, Menon, D, Pridee, N, Roberts, D, Thomas, H, Tinmouth, A, Triulzi, D, Walsh, T, Wood, E, Calfee, C, O’Kane, C, Shyamsundar, M, Sinha, P, Thompson, T, Young, I, Burrell, A, Ferguson, N, Hodgson, C, Orford, N, Phua, J, Baron, R, Epelman, S, Frankfurter, C, Gommans, F, Kim, E, Leaf, D, Vaduganathan, M, Van Kimmenade, R, Sanil, A, Van Beurden, M, Effelaar, E, Schotsman, J, Boyd, C, Harland, C, Shearer, A, Wren, J, Attanayaka, U, Darshana, S, Ishani, P, Udayanga, I, Higgins, AM, Berry, LR, Lorenzi, E, Murthy, S, McQuilten, Z, Mouncey, PR, Al-Beidh, F, Annane, D, Arabi, YM, Beane, A, Van Bentum-Puijk, W, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buzgau, A, Buxton, M, Charles, WN, Cove, M, Detry, MA, Estcourt, LJ, Fagbodun, EO, Fitzgerald, M, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Hills, T, Horvat, CM, Huang, DT, Ichihara, N, Lamontagne, F, Marshall, JC, McAuley, DF, McGlothlin, A, McGuinness, SP, McVerry, BJ, Neal, MD, Nichol, AD, Parke, RL, Parker, JC, Parry-Billings, K, Peters, SEC, Reyes, LF, Rowan, KM, Saito, H, Santos, MS, Saunders, CT, Serpa-Neto, A, Seymour, CW, Shankar-Hari, M, Stronach, LM, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, McArthur, CJ, Berry, S, Derde, LPG, Gordon, AC, Webb, SA, Lawler, PR, Comm REMAP-CAP Investigators, Apollo - University of Cambridge Repository, Intensive Care Medicine, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pittsburgh Foundation, PF, Amgen, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, Heart and Stroke Foundation of Canada, HSF, National Institute for Health and Care Research, NIHR, European Commission, EC, National Health and Medical Research Council, NHMRC: 1101719, APP194811, CS-2016-16-011, GNT2008447, RP-2015-06-18, Office of Health and Medical Research, OHMR, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support : The Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (#602525), the Rapid European COVID-19 Emergency Research response (RECOVER) consortium by the European Union’s Horizon 2020 research and innovation programme (#101003589), the Australian National Health and Medical Research Council (#APP1101719), the Australian Medical Research Future Fund (#APP2002132), the Health Research Council of New Zealand (#16/631), the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant (#158584) and the Canadian Institute of Health Research COVID-19 Rapid Research Funding (#447335), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Wellcome Trust Innovations Project (215522), the Minderoo Foundation, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the Translational Breast Cancer Research Consortium, the NSW Office of Health and Medical Research, Amgen, Eisai, and the Pittsburgh Foundation. Dr Higgins is funded by an NHMRC Emerging Leadership Fellowship (GNT2008447). Dr McQuilten is funded by an NHMRC Emerging Leadership Fellowship (APP194811). Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18) and Dr Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011). Dr Turgeon is the Chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. Dr Lawler is supported by a career award from the Heart and Stroke Foundation of Canada., and European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014)
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Adult ,Male ,corticosteroid ,[SDV]Life Sciences [q-bio] ,Critical Illness ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,antiplatelet ,Lopinavir ,Adaptive platform trial randomized controlled trial intensive care, pneumonia COVID-19 antiplatelet immunoglobulin antiviral corticosteroid immune modulation anticoagulation ,All institutes and research themes of the Radboud University Medical Center ,Adrenal Cortex Hormones ,Humans ,anticoagulation ,intensive care, pneumonia ,COVID-19 Serotherapy ,Original Investigation ,Medicine(all) ,immune modulation ,Ritonavir ,SARS-CoV-2 ,COVID-19 ,Anticoagulants ,Bayes Theorem ,General Medicine ,Middle Aged ,antiviral ,Receptors, Interleukin-6 ,Adaptive platform trial ,randomized controlled trial ,Female ,Human medicine ,immunoglobulin ,Follow-Up Studies ,Hydroxychloroquine - Abstract
ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
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- 2023
36. A spatial framework to support scenario planning for Melbourne's Peri-Urban region - planning options for water security and climate change adaption
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Practical Responses to Climate Change (2nd : 2012 : Canberra, A.C.T.), Buxton, M, Butt, A, Farrell, S, Pelikan, M, Alvarez, A, Densley, L, and O'Neill, D
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- 2012
37. P11.65.B GBM AGILE: A global, phase 2/3 adaptive platform trial to evaluate multiple treatment regimens in newly diagnosed and recurrent glioblastoma
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Weller, M, primary, Ellingson, B, additional, Alexander, B, additional, Wen, P, additional, Sulman, E, additional, Colman, H, additional, Berry, D, additional, Tanner, K, additional, Khasraw, M, additional, Lim, M, additional, Perry, J, additional, Lassman, A, additional, Cloughesy, T, additional, Yung, W K A, additional, Lee, E Q, additional, Mellinghoff, I, additional, Gordon, G, additional, de Groot, J, additional, Mikkelsen, T, additional, Cavenee, W, additional, Nelli, A, additional, Buxton, M, additional, and Li, W, additional
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- 2022
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38. 500TiP Update on GBM AGILE: A global, phase II/III adaptive platform trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma
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Weller, M., Berry, D.A., Blondin, N., Buxton, M., Colman, H., de Groot, J.F., Fuente, M. de la, Ducray, F., Ellingson, B., Gordon, G., Lassman, A.B., Lee, E., Lim, M., Mellinghoff, I., Perry, J., Sulman, E., Yung, W-K.A., Wen, P., Wick, A., and Cloughesy, T.
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- 2024
- Full Text
- View/download PDF
39. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.
- Author
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Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., Van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., Van De Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., Gordon A.C., Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., Van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., Van De Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., and Gordon A.C.
- Abstract
Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective(s): To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Intervention(s): Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from-1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Result(s): The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespe
- Published
- 2022
40. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial
- Author
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Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Berry, L.R., Lorenzi, E., Zarychanski, R., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bihari, S., Bonten, M.J.M., Brunkhorst, F.M., Buzgau, A., Buxton, M., Carrier, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Huang, D.T., Horvat, C.M., Hunt, B.J., Ichihara, N., Lamontagne, F., Leavis, H.L., Linstrum, K.M., Litton, E., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., Middeldorp, S., Montgomery, S.K., Morpeth, S.C., Murthy, S., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Singh, V., Tolppa, T., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Pickkers, P., Schouten, J.A., Webb, S.A., Gordon, A.C., Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Berry, L.R., Lorenzi, E., Zarychanski, R., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bihari, S., Bonten, M.J.M., Brunkhorst, F.M., Buzgau, A., Buxton, M., Carrier, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Huang, D.T., Horvat, C.M., Hunt, B.J., Ichihara, N., Lamontagne, F., Leavis, H.L., Linstrum, K.M., Litton, E., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., Middeldorp, S., Montgomery, S.K., Morpeth, S.C., Murthy, S., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Singh, V., Tolppa, T., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Pickkers, P., Schouten, J.A., Webb, S.A., and Gordon, A.C.
- Abstract
Item does not contain fulltext, IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified c
- Published
- 2022
41. Meta‐analysis of individual‐patient data from EVAR‐1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years
- Author
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Powell, J. T., Sweeting, M. J., Ulug, P., Blankensteijn, J. D., Lederle, F. A., Becquemin, J.‐P., Greenhalgh, R. M., Greenhalgh, R. M., Beard, J. D., Buxton, M. J., Brown, L. C., Harris, P. L., Powell, J. T., Rose, J. D. G., Russell, I. T., Sculpher, M. J., Thompson, S. G., Lilford, R.J., Bell, P. R. F., Greenhalgh, R. M., Whitaker, S.C., Poole‐Wilson, the late P.A., Ruckley, C. V., Campbell, W. B., Dean, M. R. E., Ruttley, M. S. T., Coles, E. C., Powell, J. T., Halliday, A., Gibbs, S. J., Brown, L. C., Epstein, D., Sculpher, M. J., Thompson, S. G., Hannon, R. J., Johnston, L., Bradbury, A. W., Henderson, M. J., Parvin, S. D., Shepherd, D. F. C., Greenhalgh, R. M., Mitchell, A. W., Edwards, P. R., Abbott, G. T., Higman, D. J., Vohra, A., Ashley, S., Robottom, C., Wyatt, M. G., Rose, J. D. G., Byrne, D., Edwards, R., Leiberman, D. P., McCarter, D. H., Taylor, P. R., Reidy, J. F., Wilkinson, A. R., Ettles, D. F., Clason, A. E., Leen, G. L. S., Wilson, N. V., Downes, M., Walker, S. R., Lavelle, J. M., Gough, M. J., McPherson, S., Scott, D. J. A., Kessell, D. O., Naylor, R., Sayers, R., Fishwick, N. G., Harris, P. L., Gould, D. A., Walker, M. G., Chalmers, N. C., Garnham, A., Collins, M. A., Beard, J. D., Gaines, P. A., Ashour, M. Y., Uberoi, R., Braithwaite, B., Whitaker, S. C., Davies, J. N., Travis, S., Hamilton, G., Platts, A., Shandall, A., Sullivan, B. A., Sobeh, M., Matson, M., Fox, A. D., Orme, R., Yusef, W., Doyle, T., Horrocks, M., Hardman, J., Blair, P. H. B., Ellis, P. K., Morris, G., Odurny, A., Vohra, R., Duddy, M., Thompson, M., Loosemore, T. M. L., Belli, A. M., Morgan, R., Adiseshiah, M., Brookes, J. A. S., McCollum, C. N., Ashleigh, R., Aukett, M., Baker, S., Barbe, E., Batson, N., Bell, J., Blundell, J., Boardley, D., Boyes, S., Brown, O., Bryce, J., Carmichael, M., Chance, T., Coleman, J., Cosgrove, C., Curran, G., Dennison, T., Devine, C., Dewhirst, N., Errington, B., Farrell, H., Fisher, C., Fulford, P., Gough, M., Graham, C., Hooper, R., Horne, G., Horrocks, L., Hughes, B., Hutchings, T., Ireland, M., Judge, C., Kelly, L., Kemp, J., Kite, A., Kivela, M., Lapworth, M., Lee, C., Linekar, L., Mahmood, A., March, L., Martin, J., Matharu, N., McGuigen, K., Morris‐Vincent, P., Murray, S., Murtagh, A., Owen, G., Ramoutar, V., Rippin, C., Rowley, J., Sinclair, J., Spencer, S., Taylor, V., Tomlinson, C., Ward, S., Wealleans, V., West, J., White, K., Williams, J., Wilson, L., Grobbee, D. E., Blankensteijn, J. D., Bak, A. A. A., Buth, J., Pattynama, P. M., Verhoeven, E. L. G., van Voorthuisen, A. E., Blankensteijn, J. D., Balm, R., Buth, J., Cuypers, P. W. M., Grobbee, D. E., Prinssen, M., van Sambeek, M. R. H. M., Verhoeven, E. L. G., Baas, A. F., Hunink, M. G., van Engelshoven, J. M., Jacobs, M. J. H. M., de Mol, B. A. J. M., van Bockel, J. H., Balm, R., Reekers, J., Tielbeek, X., Verhoeven, E. L. G., Wisselink, W., Boekema, N., Heuveling, L. M., Sikking, I., Prinssen, M., Balm, R., Blankensteijn, J. D., Buth, J., Cuypers, P. W. M., van Sambeek, M. R. H. M., Verhoeven, E. L. G., de Bruin, J. L., Baas, A. F., Blankensteijn, J. D., Prinssen, M., Buth, J., Tielbeek, A.V., Blankensteijn, J. D., Balm, R., Reekers, J. A., van Sambeek, M. R. H. M., Pattynama, P., Verhoeven, E. L. G., Prins, T., van der Ham, A. C., van der Velden, J. J. I. M., van Sterkenburg, S. M. M., ten Haken, G. B., Bruijninckx, C. M. A., van Overhagen, H., Tutein Nolthenius, R. P., Hendriksz, T. R., Teijink, J. A. W., Odink, H. F., de Smet, A. A. E. A., Vroegindeweij, D., van Loenhout, R. M. M., Rutten, M. J., Hamming, J. F., Lampmann, L. E. H., Bender, M. H. M., Pasmans, H., Vahl, A. C., de Vries, C., Mackaay, A. J. C., van Dortmont, L. M. C., van der Vliet, A. J., Schultze Kool, L. J., Boomsma, J. H. B., van Dop, H. R., de Mol van Otterloo, J. C. A., de Rooij, T. P. W., Smits, T. M., Yilmaz, E. N., Wisselink, W., van den Berg, F. G., Visser, M. J. T., van der Linden, E., Schurink, G. W. H., de Haan, M., Smeets, H. J., Stabel, P., van Elst, F., Poniewierski, J., Vermassen, F. E. G., Lederle, F. A., Freischlag, J. A., Kohler, T. R., Latts, E., Matsumura, J., Padberg, F. T., Jr, Kyriakides, T. C., Swanson, K. M., Guarino, P., Peduzzi, P., Antonelli, M., Cushing, C., Davis, E., Durant, L., Joyner, S., Kossack, the late A., Kyriakides, T. C., LeGwin, Mary, McBride, V., OʼConnor, T., Poulton, J., Stratton, the late S., Zellner, S., Snodgrass, A. J., Thornton, J., Swanson, K. M., Haakenson, C. M., Stroupe, K.T., Jonk, Y., Hallett, J. W., Hertzer, N., Towne, J., Katz, D. A., Karrison, T., Matts, J. P., Marottoli, R., Kasl, S., Mehta, R., Feldman, R., Farrell, W., Allore, H., Perry, E., Niederman, J., Randall, F., Zeman, M., Beckwith, the late D., OʼLeary, T. J., Huang, G. D., Latts, E., Bader, M., Ketteler, E. R., Kingsley, D. D., Marek, J. M., Massen, R. J., Matteson, B. D., Pitcher, J. D., Langsfeld, M., Corson, J. D., Goff, J. M., Jr, Kasirajan, K., Paap, C., Robertson, D. C., Salam, A., Veeraswamy, R., Milner, R., Kasirajan, K., Guidot, J., Lal, B. K., Busuttil, S. J., Lilly, M. P., Braganza, M., Ellis, K., Patterson, M. A., Jordan, W. D., Whitley, D., Taylor, S., Passman, M., Kerns, D., Inman, C., Poirier, J., Ebaugh, J., Raffetto, J., Chew, D., Lathi, S., Owens, C., Hickson, K., Dosluoglu, H. H., Eschberger, K., Kibbe, M. R., Baraniewski, H. M., Matsumura, J., Endo, M., Busman, A., Meadows, W., Evans, M., Giglia, J. S., El Sayed, H., Reed, A. B., Ruf, M., Ross, S., Jean‐Claude, J. M., Pinault, G., Kang, P., White, N., Eiseman, M., Jones, the late R., Timaran, C. H., Modrall, J. G., Welborn, M. B., III, Lopez, J., Nguyen, T., Chacko, J. K. Y., Granke, K., Vouyouka, A. G., Olgren, E., Chand, P., Allende, B., Ranella, M., Yales, C., Whitehill, T. A., Krupski, the late W. C., Nehler, M. R., Johnson, S. P., Jones, D. N., Strecker, P., Bhola, M. A., Shortell, C. K., Gray, J. L., Lawson, J. H., McCann, R., Sebastian, M.W., Kistler Tetterton, J., Blackwell, C., Prinzo, P. A., Lee, N., Padberg, F. T., Jr, Cerveira, J. J., Lal, B. K., Zickler, R. W., Hauck, K. A., Berceli, S. A., Lee, W. A., Ozaki, C. K., Nelson, P. R., Irwin, A. S., Baum, R., Aulivola, B., Rodriguez, H., Littooy, F. N., Greisler, H., OʼSullivan, M. T., Kougias, P., Lin, P. H., Bush, R. L., Guinn, G., Bechara, C., Cagiannos, C., Pisimisis, G., Barshes, N., Pillack, S., Guillory, B., Cikrit, D., Lalka, S. G., Lemmon, G., Nachreiner, R., Rusomaroff, M., OʼBrien, E., Cullen, J. J., Hoballah, J., Sharp, W. J., McCandless, J. L., Beach, V., Minion, D., Schwarcz, T. H., Kimbrough, J., Ashe, L., Rockich, A., Warner‐Carpenter, J., Moursi, M., Eidt, J. F., Brock, S., Bianchi, C., Bishop, V., Gordon, I. L., Fujitani, R., Kubaska, S. M., III, Behdad, M., Azadegan, R., Ma Agas, C., Zalecki, K., Hoch, J. R., Carr, S. C., Acher, C., Schwarze, M., Tefera, G., Mell, M., Dunlap, B., Rieder, J., Stuart, J. M., Weiman, D. S., Abul‐Khoudoud, O., Garrett, H. E., Walsh, S. M., Wilson, K. L., Seabrook, G. R., Cambria, R. A., Brown, K. R., Lewis, B. D., Framberg, S., Kallio, C., Barke, R. A., Santilli, S. M., dʼAudiffret, A. C., Oberle, N., Proebstle, C., Johnson, L. L., Jacobowitz, G. R., Cayne, N., Rockman, C., Adelman, M., Gagne, P., Nalbandian, M., Caropolo, L. J., Pipinos, I. I., Johanning, J., Lynch, T., DeSpiegelaere, H., Purviance, G., Zhou, W., Dalman, R., Lee, J. T., Safadi, B., Coogan, S. M., Wren, S. M., Bahmani, D. D., Maples, D., Thunen, S., Golden, M. A., Mitchell, M. E., Fairman, R., Reinhardt, S., Wilson, M. A., Tzeng, E., Muluk, S., Peterson, N. M., Foster, M., Edwards, J., Moneta, G. L., Landry, G., Taylor, L., Yeager, R., Cannady, E., Treiman, G., Hatton‐Ward, S., Salabsky, the late B., Kansal, N., Owens, E., Estes, M., Forbes, B. A., Sobotta, C., Rapp, J. H., Reilly, L. M., Perez, S. L., Yan, K., Sarkar, R., Dwyer, S. S., Perez, S., Chong, K., Kohler, T. R., Hatsukami, T. S., Glickerman, D. G., Sobel, M., Burdick, T. S., Pedersen, K., Cleary, P., Back, M., Bandyk, D., Johnson, B., Shames, M., Reinhard, R. L., Thomas, S. C., Hunter, G. C., Leon, L. R., Jr, Westerband, A., Guerra, R. J., Riveros, M., Mills, J. L., Sr, Hughes, J. D., Escalante, A. M., Psalms, S. B., Day, N. N., Macsata, R., Sidawy, A., Weiswasser, J., Arora, S., Jasper, B. J., Dardik, A., Gahtan, V., Muhs, B. E., Sumpio, B. E., Gusberg, R. J., Spector, M., Pollak, J., Aruny, J., Kelly, E. L., Wong, J., Vasilas, P., Joncas, C., Gelabert, H. A., DeVirgillio, C., Rigberg, D. A., Cole, L., Becquemin, J.‐P., Marzelle, J., Becquemin, J.‐P., Sapoval, M., Becquemin, J.‐P., Favre, J.‐P., Watelet, J., Lermusiaux, P., Sapoval, M., Lepage, E., Hemery, F., Dolbeau, G., Hawajry, N., Cunin, P., Harris, P., Stockx, L., Chatellier, G., Mialhe, C., Fiessinger, J.‐N., Pagny, L., Kobeiter, H., Boissier, C., Lacroix, P., Ledru, F., Pinot, J.‐J., Deux, J.‐F., Tzvetkov, B., Duvaldestin, P., Watelet, J., Jourdain, C., David, V., Enouf, D., Ady, N., Krimi, A., Boudjema, N., Jousset, Y., Enon, B., Blin, V., Picquet, J., LʼHoste, P., Thouveny, F., Borie, H., Kowarski, S., Pernes, J.‐M., Auguste, M., Becquemin, J.‐P., Desgranges, P., Allaire, E., Marzelle, J., Kobeiter, H., Meaulle, P.‐Y., Chaix, D., Juliae, P., Fabiani, J. N., Chevalier, P., Combes, M., Seguin, A., Belhomme, D., Sapoval, M., Baque, J., Pellerin, O., Favre, J. P., Barral, X., Veyret, C., Watelet, J., Peillon, C., Plissonier, D., Thomas, P., Clavier, E., Lermusiaux, P., Martinez, R., Bleuet, F., C, Dupreix, Verhoye, J. P., Langanay, T., Heautot, J. F., Koussa, M., Haulon, S., Halna, P., Destrieux, L., Lions, C., Wiloteaux, S., Beregi, J. P., Bergeron, P., Pinot, J.‐J., Patra, P., Costargent, A., Chaillou, P., DʼAlicourt, A., Goueffic, Y., Cheysson, E., Parrot, A., Garance, P., Demon, A., Tyazi, A., Pillet, J.‐C., Lescalie, F., Tilly, G., Steinmetz, E., Favier, C., Brenot, R., Krause, D., Cercueil, J. P., Vahdat, O., Sauer, M., Soula, P., Querian, A., Garcia, O., Levade, M., Colombier, D., Cardon, J.‐M., Joyeux, A., Borrelly, P., Dogas, G., Magnan, P.‐É., Branchereau, A., Bartoli, J.‐M., Hassen‐Khodja, R., Batt, M., Planchard, P.‐F., Bouillanne, P.‐J., Haudebourg, P., Bayne, J., Gouny, P., Badra, A., Braesco, J., Nonent, M., Lucas, A., Cardon, A., Kerdiles, Y., Rolland, Y., Kassab, M., Brillu, C., Goubault, F., Tailboux, L., Darrieux, H., Briand, O., Maillard, J.‐C., Varty, K., and Cousins, C.
- Published
- 2017
- Full Text
- View/download PDF
42. Cost Effectiveness of Clinically Appropriate Decisions on Alternative Treatments for Angina Pectoris: Prospective Observational Study
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Griffin, S. C., Barber, J. A., Manca, A., Sculpher, M. J., Thompson, S. G., Buxton, M. J., and Hemingway, H.
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- 2007
- Full Text
- View/download PDF
43. Evaluation of PACS at Hammersmith Hospital: Baseline Assessment of Costs and other Resource-use Parameters within the Radiology Department
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Bryan, S., Weatherburn, G., Keen, J., Buxton, M., Lemke, Heinz U., editor, Inamura, Kiyonari, editor, Jaffe, C. Carl, editor, and Felix, Roland, editor
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- 1993
- Full Text
- View/download PDF
44. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial
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Estcourt, L.J., Turgeon, A.F., McQuilten, Z.K., McVerry, B.J., Al-Beidh, F., Annane, D., Arabi, Y.M., Arnold, D.M., Beane, A., Bégin, P., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Birchall, J.E., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Callum, J.L., Chassé, M., Cheng, A.C., Cove, M.E., Daly, J., Derde, L., Detry, M.A., Jong, Menno de, Evans, A., Fergusson, D.A., Fish, M., Fitzgerald, M., Foley, C., Goossens, H., Gordon, A.C., Gosbell, I.B., Green, C., Haniffa, R., Harvala, H., Higgins, A.M., Hills, T.E., Hoad, V.C., Horvat, C., Huang, D.T., Hudson, C.L., Ichihara, N., Laing, E., Lamikanra, A.A., Lamontagne, F., Lawler, P.R., Linstrum, K., Litton, E., Lorenzi, E., MacLennan, S., Marshall, J., McAuley, D.F., McDyer, J.F., McGlothlin, A., McGuinness, S., Miflin, G., Montgomery, S., Mouncey, P.R., Murthy, S., Nichol, A., Parke, R., Parker, J.C., Priddee, N., Purcell, D.F.J., Reyes, L.F., Richardson, P., Robitaille, N., Rowan, K.M., Rynne, J., Saito, H., Santos, M., Saunders, C.T., Neto, A. Serpa, Seymour, C.W., Silversides, J.A., Tinmouth, A.A., Triulzi, D.J., Turner, A.M., Veerdonk, F.L. van de, Walsh, T.S., Wood, E.M., Berry, S., Lewis, R.J., Menon, D.K., McArthur, C., Zarychanski, R., Angus, D.C., Webb, S.A., Roberts, D.J., Shankar-Hari, M., Estcourt, L.J., Turgeon, A.F., McQuilten, Z.K., McVerry, B.J., Al-Beidh, F., Annane, D., Arabi, Y.M., Arnold, D.M., Beane, A., Bégin, P., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Birchall, J.E., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Callum, J.L., Chassé, M., Cheng, A.C., Cove, M.E., Daly, J., Derde, L., Detry, M.A., Jong, Menno de, Evans, A., Fergusson, D.A., Fish, M., Fitzgerald, M., Foley, C., Goossens, H., Gordon, A.C., Gosbell, I.B., Green, C., Haniffa, R., Harvala, H., Higgins, A.M., Hills, T.E., Hoad, V.C., Horvat, C., Huang, D.T., Hudson, C.L., Ichihara, N., Laing, E., Lamikanra, A.A., Lamontagne, F., Lawler, P.R., Linstrum, K., Litton, E., Lorenzi, E., MacLennan, S., Marshall, J., McAuley, D.F., McDyer, J.F., McGlothlin, A., McGuinness, S., Miflin, G., Montgomery, S., Mouncey, P.R., Murthy, S., Nichol, A., Parke, R., Parker, J.C., Priddee, N., Purcell, D.F.J., Reyes, L.F., Richardson, P., Robitaille, N., Rowan, K.M., Rynne, J., Saito, H., Santos, M., Saunders, C.T., Neto, A. Serpa, Seymour, C.W., Silversides, J.A., Tinmouth, A.A., Triulzi, D.J., Turner, A.M., Veerdonk, F.L. van de, Walsh, T.S., Wood, E.M., Berry, S., Lewis, R.J., Menon, D.K., McArthur, C., Zarychanski, R., Angus, D.C., Webb, S.A., Roberts, D.J., and Shankar-Hari, M.
- Abstract
Item does not contain fulltext, IMPORTANCE: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. OBJECTIVE: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONS: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURES: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromb
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- 2021
45. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
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Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., Zarychanski, R., Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Zarychanski, R.
- Abstract
Item does not contain fulltext, BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati
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- 2021
46. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19
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Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., Zarychanski, R., Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., and Zarychanski, R.
- Abstract
Item does not contain fulltext, BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul
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- 2021
47. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
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Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., Webb, S.A., Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., and Webb, S.A.
- Abstract
Item does not contain fulltext, PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
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- 2021
48. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients with COVID-19: A Randomized Clinical Trial.
- Author
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Estcourt L.J., Turgeon A.F., McQuilten Z.K., McVerry B.J., Al-Beidh F., Annane D., Arabi Y.M., Arnold D.M., Beane A., Begin P., Van Bentum-Puijk W., Berry L.R., Bhimani Z., Birchall J.E., Bonten M.J.M., Bradbury C.A., Brunkhorst F.M., Buxton M., Callum J.L., Chasse M., Cheng A.C., Cove M.E., Daly J., Derde L., Detry M.A., De Jong M., Evans A., Fergusson D.A., Fish M., Fitzgerald M., Foley C., Goossens H., Gordon A.C., Gosbell I.B., Green C., Haniffa R., Harvala H., Higgins A.M., Hills T.E., Hoad V.C., Horvat C., Huang D.T., Hudson C.L., Ichihara N., Laing E., Lamikanra A.A., Lamontagne F., Lawler P.R., Linstrum K., Litton E., Lorenzi E., Maclennan S., Marshall J., McAuley D.F., McDyer J.F., McGlothlin A., McGuinness S., Miflin G., Montgomery S., Mouncey P.R., Murthy S., Nichol A., Parke R., Parker J.C., Priddee N., Purcell D.F.J., Reyes L.F., Richardson P., Robitaille N., Rowan K.M., Rynne J., Saito H., Santos M., Saunders C.T., Serpa Neto A., Seymour C.W., Silversides J.A., Tinmouth A.A., Triulzi D.J., Turner A.M., Van De Veerdonk F., Walsh T.S., Wood E.M., Berry S., Lewis R.J., Menon D.K., McArthur C., Zarychanski R., Angus D.C., Webb S.A., Roberts D.J., Shankar-Hari M., Estcourt L.J., Turgeon A.F., McQuilten Z.K., McVerry B.J., Al-Beidh F., Annane D., Arabi Y.M., Arnold D.M., Beane A., Begin P., Van Bentum-Puijk W., Berry L.R., Bhimani Z., Birchall J.E., Bonten M.J.M., Bradbury C.A., Brunkhorst F.M., Buxton M., Callum J.L., Chasse M., Cheng A.C., Cove M.E., Daly J., Derde L., Detry M.A., De Jong M., Evans A., Fergusson D.A., Fish M., Fitzgerald M., Foley C., Goossens H., Gordon A.C., Gosbell I.B., Green C., Haniffa R., Harvala H., Higgins A.M., Hills T.E., Hoad V.C., Horvat C., Huang D.T., Hudson C.L., Ichihara N., Laing E., Lamikanra A.A., Lamontagne F., Lawler P.R., Linstrum K., Litton E., Lorenzi E., Maclennan S., Marshall J., McAuley D.F., McDyer J.F., McGlothlin A., McGuinness S., Miflin G., Montgomery S., Mouncey P.R., Murthy S., Nichol A., Parke R., Parker J.C., Priddee N., Purcell D.F.J., Reyes L.F., Richardson P., Robitaille N., Rowan K.M., Rynne J., Saito H., Santos M., Saunders C.T., Serpa Neto A., Seymour C.W., Silversides J.A., Tinmouth A.A., Triulzi D.J., Turner A.M., Van De Veerdonk F., Walsh T.S., Wood E.M., Berry S., Lewis R.J., Menon D.K., McArthur C., Zarychanski R., Angus D.C., Webb S.A., Roberts D.J., and Shankar-Hari M.
- Abstract
Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective(s): To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Intervention(s): The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL +/- 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; veno
- Published
- 2021
49. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
- Author
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Arabi, YM, Gordon, AC, Derde, LPG, Nichol, AD, Murthy, S, Beidh, FA, Annane, D, Swaidan, LA, Beane, A, Beasley, R, Berry, LR, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buxton, M, Buzgau, A, Cheng, A, De Jong, M, Detry, MA, Duffy, EJ, Estcourt, LJ, Fitzgerald, M, Fowler, R, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Higgins, AM, Hills, TE, Horvat, CM, Huang, DT, King, AJ, Lamontagne, F, Lawler, PR, Lewis, R, Linstrum, K, Litton, E, Lorenzi, E, Malakouti, S, McAuley, DF, McGlothlin, A, Mcguinness, S, McVerry, BJ, Montgomery, SK, Morpeth, SC, Mouncey, PR, Orr, K, Parke, R, Parker, JC, Patanwala, AE, Rowan, KM, Santos, MS, Saunders, CT, Seymour, CW, Shankar-Hari, M, Tong, SYC, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Berry, S, Marshall, JC, McArthur, C, Angus, DC, Webb, SA, Orford, Neil, Arabi, YM, Gordon, AC, Derde, LPG, Nichol, AD, Murthy, S, Beidh, FA, Annane, D, Swaidan, LA, Beane, A, Beasley, R, Berry, LR, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buxton, M, Buzgau, A, Cheng, A, De Jong, M, Detry, MA, Duffy, EJ, Estcourt, LJ, Fitzgerald, M, Fowler, R, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Higgins, AM, Hills, TE, Horvat, CM, Huang, DT, King, AJ, Lamontagne, F, Lawler, PR, Lewis, R, Linstrum, K, Litton, E, Lorenzi, E, Malakouti, S, McAuley, DF, McGlothlin, A, Mcguinness, S, McVerry, BJ, Montgomery, SK, Morpeth, SC, Mouncey, PR, Orr, K, Parke, R, Parker, JC, Patanwala, AE, Rowan, KM, Santos, MS, Saunders, CT, Seymour, CW, Shankar-Hari, M, Tong, SYC, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Berry, S, Marshall, JC, McArthur, C, Angus, DC, Webb, SA, and Orford, Neil
- Published
- 2021
50. Allocating Public Spending Efficiently: Is There a Need for a Better Mechanism to Inform Decisions in the UK and Elsewhere?
- Author
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Cubi-Molla, P, Buxton, M, Devlin, N, Cubi-Molla, P, Buxton, M, and Devlin, N
- Abstract
In the UK few if any regular processes explicitly address comparisons of value for money between spending in different government departments, despite the existence of mechanisms that could in principle achieve that. This leaves a very important gap in evidence and means that decisions about public spending allocations are likely to miss opportunities to improve social welfare from existing budgets. Greater attention to the development of methods and evidence to better inform the allocation of public sector spending between departments is therefore urgently needed. We identify a number of possible approaches to this-some of which are being used in different countries-and highlight their strengths and weaknesses. We propose a new, pragmatic approach that incorporates a generic descriptive system to measure the disparate outcomes produced by public sector activities in a commensurate manner. Discrete-choice experiments could be used to generate evidence of the relative importance placed on different aspects of public sector outcomes by members of the general public. The proposed approach would produce evidence on value for money across departments, and the generation of evidence on public preferences to support that.
- Published
- 2021
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