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1. Atomic Modeling of Photoionization Fronts in Nitrogen Gas

Author

Gray, William J., Keiter, P. A., Lefevre, H., Patterson, C. R., Davis, J. S., Powell, K. G., Kuranz, C. C., and Drake, R. P.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies, Physics - Plasma Physics
Abstract

Photoionization fronts play a dominant role in many astrophysical environments, but remain difficult to achieve in a laboratory experiment. Recent papers have suggested that experiments using a nitrogen medium held at ten atmospheres of pressure that is irradiated by a source with a radiation temperature of T$_{\rm R}\sim$ 100 eV can produce viable photoionization fronts. We present a suite of one-dimensional numerical simulations using the \helios\ multi-material radiation hydrodynamics code that models these conditions and the formation of a photoionization front. We study the effects of varying the atomic kinetics and radiative transfer model on the hydrodynamics and ionization state of the nitrogen gas, finding that more sophisticated physics, in particular a multi-angle long characteristic radiative transfer model and a collisional-radiative atomics model, dramatically changes the atomic kinetic evolution of the gas. A photoionization front is identified by computing the ratios between the photoionization rate, the electron impact ionization rate, and the total recombination rate. We find that due to the increased electron temperatures found using more advanced physics that photoionization fronts are likely to form in our nominal model. We report results of several parameter studies. In one of these, the nitrogen pressure is fixed at ten atmospheres and varies the source radiation temperature while another fixes the temperature at 100 eV and varied the nitrogen pressure. Lower nitrogen pressures increase the likelihood of generating a photoionization front while varying the peak source temperature has little effect., Comment: 17 pages, 10 figures, accepted to physics of plasmas

Published
2019
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2. Laboratory Photoionization Fronts in Nitrogen Gas: A Numerical Feasibility and Parameter Study

Author

Gray, William J, Keiter, P. A., Lefevre, H., Patterson, C. R., Davis, J. S., van Der Holst, B., Powell, K. G., and Drake, R. P.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Solar and Stellar Astrophysics
Abstract

Photoionization fronts play a dominant role in many astrophysical situations, but remain difficult to achieve in a laboratory experiment. We present the results from a computational parameter study evaluating the feasibility of the photoionization experiment presented in the design paper by Drake, R. P., Hazak, G., Keiter, P. A., Davis, J. S., Patterson, C. R., Frank, A., Blackman, E. G., & Busquet, M. 2016, ApJ, 833, 249 in which a photoionization front is generated in a nitrogen medium . The nitrogen gas density and the Planckian radiation temperature of the x-ray source define each simulation. Simulations modeled experiments in which the x-ray flux is generated by a laser-heated gold foil, suitable for experiments using many kJ of laser energy, and experiments in which the flux is generated by a "z-pinch" device, which implodes a cylindrical shell of conducting wires. The models are run using CRASH, our block-adaptive-mesh code for multi-material radiation hydrodynamics. The radiative transfer model uses multi-group, flux-limited diffusion with thirty radiation groups. In addition, electron heat conduction is modeled using a single-group, flux-limited diffusion. In the theory, a photoionization front can exist only when the ratios of the electron recombination rate to the photoionization rate and the electron impact ionization rate to the recombination rate lie in certain ranges. These ratios are computed for several ionization states of nitrogen. Photoionization fronts are found to exist for laser driven models with moderate nitrogen densities ($\sim$10$^{21}$ cm$^{-3}$) and radiation temperatures above 90 eV. For "z-pinch" driven models, lower nitrogen densities are preferred ($<$10$^{21}$ cm$^{-3}$). We conclude that the proposed experiments are likely to generate photoionization fronts., Comment: 22 pages, 14 figures, comments welcome

Published
2018
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3. Experimental characterization of railgun-driven supersonic plasma jets motivated by high energy density physics applications

Author

Hsu, S. C., Merritt, E. C., Moser, A. L., Awe, T. J., Brockington, S. J. E., Davis, J. S., Adams, C. S., Case, A., Cassibry, J. T., Dunn, J. P., Gilmore, M. A., Lynn, A. G., Messer, S. J., and Witherspoon, F. D.

Subjects
Physics - Plasma Physics
Abstract

We report experimental results on the parameters, structure, and evolution of high-Mach-number (M) argon plasma jets formed and launched by a pulsed-power-driven railgun. The nominal initial average jet parameters in the data set analyzed are density \approx 2 x 10^(16) cm^(-3), electron temperature \approx 1.4 eV, velocity \approx 30 km/s, M \approx 14, ionization fraction \approx 0.96, diameter \approx 5 cm, and length \approx 20 cm. These values approach the range needed by the Plasma Liner Experiment (PLX), which is designed to use merging plasma jets to form imploding spherical plasma liners that can reach peak pressures of 0.1-1 Mbar at stagnation. As these jets propagate a distance of approximately 40 cm, the average density drops by one order of magnitude, which is at the very low end of the 8-160 times drop predicted by ideal hydrodynamic theory of a constant-M jet., Comment: 35 pages, 2 tables, 14 figures, accepted for publication in Physics of Plasmas (12/11/2012)

Published
2012
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4. One-dimensional radiation-hydrodynamic simulations of imploding spherical plasma liners with detailed equation-of-state modeling

Author

Davis, J. S., Hsu, S. C., Golovkin, I. E., MacFarlane, J. J., and Cassibry, J. T.

Subjects
Physics - Plasma Physics
Abstract

This work extends the one-dimensional radiation-hydrodynamic imploding spherical argon plasma liner simulations of T. J. Awe et al. [Phys. Plasmas 18, 072705 (2011)] by using a detailed tabular equation-of-state (EOS) model, whereas Awe et al. used a polytropic EOS model. Results using the tabular EOS model give lower stagnation pressures by a factor of 3.9-8.6 and lower peak ion temperatures compared to the polytropic EOS results. Both local thermodynamic equilibrium (LTE) and non-LTE EOS models were used in this work, giving similar results on stagnation pressure. The lower stagnation pressures using a tabular EOS model are attributed to a reduction in the liner's ability to compress arising from the energy sink introduced by ionization and electron excitation, which are not accounted for in a polytropic EOS model. Variation of the plasma liner species for the same initial liner geometry, mass density, and velocity was also explored using the LTE tabular EOS model, showing that the highest stagnation pressure is achieved with the highest atomic mass species for the constraints imposed., Comment: 21 pages, 3 tables, 7 figures, accepted for publication by Phys. Plasmas (9/24/2012)

Published
2012
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5. One-dimensional radiation-hydrodynamic scaling studies of imploding spherical plasma liners

Author

Awe, T. J., Adams, C. S., Davis, J. S., Hanna, D. S., Hsu, S. C., and Cassibry, J. T.

Subjects
Physics - Plasma Physics
Abstract

One-dimensional radiation-hydrodynamic simulations are performed to develop insight into the scaling of stagnation pressure with initial conditions of an imploding spherical plasma shell or "liner." Simulations reveal the evolution of high-Mach-number (M), annular, spherical plasma flows during convergence, stagnation, shock formation, and disassembly, and indicate that cm- and {\mu}s-scale plasmas with peak pressures near 1 Mbar can be generated by liners with initial kinetic energy of several hundred kilo-joules. It is shown that radiation transport and thermal conduction must be included to avoid non-physical plasma temperatures at the origin which artificially limit liner convergence and thus the peak stagnation pressure. Scalings of the stagnated plasma lifetime ({\tau}stag) and average stagnation pressure (Pstag, the pressure at the origin, averaged over {\tau}stag) are determined by evaluating a wide range of liner initial conditions. For high-M flows, {\tau}stag L0/v0, where L0 and v0 are the initial liner thickness and velocity, respectively. Furthermore, for argon liners, Pstag scales approximately as v0^(15/4) over a wide range of initial densities (n0), and as n0^(1/2) over a wide range of v0. The approximate scaling Pstag ~ M 3/2 is also found for a wide range of liner-plasma initial conditions., Comment: 28 pages, 12 figures, accepted by Physics of Plasmas (June 23, 2011)

Published
2011
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12. Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)—an open-labelled pilot randomized controlled trial

Author

Campbell, A. J., primary, Dotel, R., additional, Braddick, M., additional, Britton, P. N., additional, Eisen, D. P., additional, Francis, J. R., additional, Lynar, S., additional, McMullan, B., additional, Meagher, N., additional, Nelson, J., additional, O’Sullivan, M. V. N., additional, Price, D. J., additional, Robinson, J. O., additional, Whelan, A., additional, Tong, S. Y. C., additional, Bowen, A. C., additional, and Davis, J. S., additional

Published
2022
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19. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Author

Axfors, C., Janiaud, P., Schmitt, A. M., van't Hooft, J., Smith, E. R., Haber, N. A., Abayomi, A., Abduljalil, M., Abdulrahman, A., Acosta-Ampudia, Y., Aguilar-Guisado, M., Al-Beidh, F., Alejandria, M. M., Alfonso, R. N., Ali, M., Alqahtani, M., Alzamrooni, A., Anaya, J. -M., Ang, M. A. C., Aomar, I. F., Argumanis, L. E., Averyanov, A., Baklaushev, V. P., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L. B., Bowen, A. C., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D. H., Cardesa, A., Carnate, J. M., Castillo, G. J. J., Cavallo, R., Chowdhury, F. R., Chowdhury, F. U. H., Ciccone, G., Cingolani, Antonella, Climacosa, F. M. M., Compernolle, V., Cortez, C. F. N., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J. S., De Rosa, F. G., Denholm, J. T., Denkinger, C. M., Desmecht, D., Diaz-Coronado, J. C., Diaz Ponce-Medrano, J. A., Donneau, A. -F., Dumagay, T. E., Dunachie, S., Dungog, C. C., Erinoso, O., Escasa, I. M. S., Estcourt, L. J., Evans, A., Evasan, A. L. M., Fareli, C. J., Fernandez-Sanchez, V., Galassi, C., Gallo, J. E., Garcia, P. J., Garcia, P. L., Garcia, J. A., Garigliany, M., Garza-Gonzalez, E., Gauiran, D. T. V., Gaviria Garcia, P. A., Giron-Gonzalez, J. -A., Gomez-Almaguer, D., Gordon, A. C., Gothot, A., Grass Guaqueta, J. S., Green, C., Grimaldi, D., Hammond, N. E., Harvala, H., Heralde, F. M., Herrick, J., Higgins, A. M., Hills, T. E., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J. M., Ivanov, A. V., Janssen, M., Jennings, J. H., Jha, V., King, R. A. N., Kjeldsen-Kragh, J., Klenerman, P., Kotecha, A., Krapp, F., Labanca, L., Laing, E., Landin-Olsson, M., Laterre, P. -F., Lim, L. -L., Lim, J., Ljungquist, O., Llaca-Diaz, J. M., Lopez-Robles, C., Lopez-Cardenas, S., Lopez-Plaza, I., Lucero, J. A. C., Lundgren, M., Macias, J., Maganito, S. C., Malundo, A. F. G., Manrique, R. D., Manzini, P. M., Marcos, M., Marquez, I., Martinez-Marcos, F. J., Mata, A. M., Mcarthur, C. J., Mcquilten, Z. K., Mcverry, B. J., Menon, D. K., Meyfroidt, G., Mirasol, M. A. L., Misset, B., Molton, J. S., Mondragon, A. V., Monsalve, D. M., Moradi Choghakabodi, P., Morpeth, S. C., Mouncey, P. R., Moutschen, M., Muller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A. D., Nielsen, H., Novak, R. M., O'Sullivan, M. V. N., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J. M., Patel, M. C., Paterson, D. L., Pena-Perez, C. A., Perez-Calatayud, A. A., Perez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D. J., Quero, A. K. H., Rahman, M. M., Rahman, M. S., Ramesh, M., Ramirez-Santana, C., Rasmussen, M., Rees, M. A., Rego, E., Roberts, J. A., Roberts, D. J., Rodriguez, Y., Rodriguez-Bano, J., Rogers, B. A., Rojas, M., Romero, A., Rowan, K. M., Saccona, F., Safdarian, M., Santos, M. C. M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P. Y., Tang, A., Tatem, G., Teofili, Luciana, Tong, S. Y. C., Turgeon, A. F., Veloso, J. D., Venkatesh, B., Ventura-Enriquez, Y., Webb, S. A., Wiese, L., Wiken, C., Wood, E. M., Yusubalieva, G. M., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S. N., Ioannidis, J. P. A., Hemkens, L. G., Cingolani A. (ORCID:0000-0002-3793-2755), Teofili L. (ORCID:0000-0002-7214-1561), Axfors, C., Janiaud, P., Schmitt, A. M., van't Hooft, J., Smith, E. R., Haber, N. A., Abayomi, A., Abduljalil, M., Abdulrahman, A., Acosta-Ampudia, Y., Aguilar-Guisado, M., Al-Beidh, F., Alejandria, M. M., Alfonso, R. N., Ali, M., Alqahtani, M., Alzamrooni, A., Anaya, J. -M., Ang, M. A. C., Aomar, I. F., Argumanis, L. E., Averyanov, A., Baklaushev, V. P., Balionis, O., Benfield, T., Berry, S., Birocco, N., Bonifacio, L. B., Bowen, A. C., Bown, A., Cabello-Gutierrez, C., Camacho, B., Camacho-Ortiz, A., Campbell-Lee, S., Cao, D. H., Cardesa, A., Carnate, J. M., Castillo, G. J. J., Cavallo, R., Chowdhury, F. R., Chowdhury, F. U. H., Ciccone, G., Cingolani, Antonella, Climacosa, F. M. M., Compernolle, V., Cortez, C. F. N., Costa Neto, A., D'Antico, S., Daly, J., Danielle, F., Davis, J. S., De Rosa, F. G., Denholm, J. T., Denkinger, C. M., Desmecht, D., Diaz-Coronado, J. C., Diaz Ponce-Medrano, J. A., Donneau, A. -F., Dumagay, T. E., Dunachie, S., Dungog, C. C., Erinoso, O., Escasa, I. M. S., Estcourt, L. J., Evans, A., Evasan, A. L. M., Fareli, C. J., Fernandez-Sanchez, V., Galassi, C., Gallo, J. E., Garcia, P. J., Garcia, P. L., Garcia, J. A., Garigliany, M., Garza-Gonzalez, E., Gauiran, D. T. V., Gaviria Garcia, P. A., Giron-Gonzalez, J. -A., Gomez-Almaguer, D., Gordon, A. C., Gothot, A., Grass Guaqueta, J. S., Green, C., Grimaldi, D., Hammond, N. E., Harvala, H., Heralde, F. M., Herrick, J., Higgins, A. M., Hills, T. E., Hines, J., Holm, K., Hoque, A., Hoste, E., Ignacio, J. M., Ivanov, A. V., Janssen, M., Jennings, J. H., Jha, V., King, R. A. N., Kjeldsen-Kragh, J., Klenerman, P., Kotecha, A., Krapp, F., Labanca, L., Laing, E., Landin-Olsson, M., Laterre, P. -F., Lim, L. -L., Lim, J., Ljungquist, O., Llaca-Diaz, J. M., Lopez-Robles, C., Lopez-Cardenas, S., Lopez-Plaza, I., Lucero, J. A. C., Lundgren, M., Macias, J., Maganito, S. C., Malundo, A. F. G., Manrique, R. D., Manzini, P. M., Marcos, M., Marquez, I., Martinez-Marcos, F. J., Mata, A. M., Mcarthur, C. J., Mcquilten, Z. K., Mcverry, B. J., Menon, D. K., Meyfroidt, G., Mirasol, M. A. L., Misset, B., Molton, J. S., Mondragon, A. V., Monsalve, D. M., Moradi Choghakabodi, P., Morpeth, S. C., Mouncey, P. R., Moutschen, M., Muller-Tidow, C., Murphy, E., Najdovski, T., Nichol, A. D., Nielsen, H., Novak, R. M., O'Sullivan, M. V. N., Olalla, J., Osibogun, A., Osikomaiya, B., Oyonarte, S., Pardo-Oviedo, J. M., Patel, M. C., Paterson, D. L., Pena-Perez, C. A., Perez-Calatayud, A. A., Perez-Alba, E., Perkina, A., Perry, N., Pouladzadeh, M., Poyato, I., Price, D. J., Quero, A. K. H., Rahman, M. M., Rahman, M. S., Ramesh, M., Ramirez-Santana, C., Rasmussen, M., Rees, M. A., Rego, E., Roberts, J. A., Roberts, D. J., Rodriguez, Y., Rodriguez-Bano, J., Rogers, B. A., Rojas, M., Romero, A., Rowan, K. M., Saccona, F., Safdarian, M., Santos, M. C. M., Sasadeusz, J., Scozzari, G., Shankar-Hari, M., Sharma, G., Snelling, T., Soto, A., Tagayuna, P. Y., Tang, A., Tatem, G., Teofili, Luciana, Tong, S. Y. C., Turgeon, A. F., Veloso, J. D., Venkatesh, B., Ventura-Enriquez, Y., Webb, S. A., Wiese, L., Wiken, C., Wood, E. M., Yusubalieva, G. M., Zacharowski, K., Zarychanski, R., Khanna, N., Moher, D., Goodman, S. N., Ioannidis, J. P. A., Hemkens, L. G., Cingolani A. (ORCID:0000-0002-3793-2755), and Teofili L. (ORCID:0000-0002-7214-1561)

Abstract

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of

Published
2021

42. Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition

Author

Harris, P. N. A., McNamara, J. F., Lye, D. C., Davis, J. S., Bernard, L., Cheng, A. C., Doi, Y., Fowler, V. G., Jr., Kaye, K. S., Leibovici, L., Lipman, J., Llewelyn, M. J., Munoz-Price, S., Paul, M., Peleg, A. Y., Rodriguez-Bano, J., Rogers, B. A., Seifert, H., Thamlikitkul, V., Thwaites, G., Tong, S. Y. C., Turnidge, J., Utili, R., Webb, S. A. R., Paterson, D. L., Harris, P. N. A., McNamara, J. F., Lye, D. C., Davis, J. S., Bernard, L., Cheng, A. C., Doi, Y., Fowler, V. G., Jr., Kaye, K. S., Leibovici, L., Lipman, J., Llewelyn, M. J., Munoz-Price, S., Paul, M., Peleg, A. Y., Rodriguez-Bano, J., Rogers, B. A., Seifert, H., Thamlikitkul, V., Thwaites, G., Tong, S. Y. C., Turnidge, J., Utili, R., Webb, S. A. R., and Paterson, D. L.

Abstract

Objectives: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). Methods: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. Results: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. Conclusions: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Published
2017

43. Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition

Author

University of Queensland, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), National Health and Medical Research Council (Australia), German Center for Infection Research, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, Innovative Medicines Initiative, Harris, P. N. A., McNamara, J. F., Lye, D. C., Davis, J. S., Bernard, Louis, Cheng, A. C., Doi, Y., Fowler, Vance G., Kaye, K. S., Leibovici, Leonard, Lipman, Jeffrey, Llewelyn, Martin J., Muñoz-Price, S., Paul, Mical, Peleg, A. Y., Rodríguez-Baño, Jesús, Rogers, B. A., Seifert, Harald, Thamlikitkul, V., Thwaites, Guy, Tong, S. Y. C., Turnidge, J., Utili, R., Webb, S. A. R., Paterson, David L., University of Queensland, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), National Health and Medical Research Council (Australia), German Center for Infection Research, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Red Española de Investigación en Patología Infecciosa, Innovative Medicines Initiative, Harris, P. N. A., McNamara, J. F., Lye, D. C., Davis, J. S., Bernard, Louis, Cheng, A. C., Doi, Y., Fowler, Vance G., Kaye, K. S., Leibovici, Leonard, Lipman, Jeffrey, Llewelyn, Martin J., Muñoz-Price, S., Paul, Mical, Peleg, A. Y., Rodríguez-Baño, Jesús, Rogers, B. A., Seifert, Harald, Thamlikitkul, V., Thwaites, Guy, Tong, S. Y. C., Turnidge, J., Utili, R., Webb, S. A. R., and Paterson, David L.

Abstract

[Objectives] To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI)., [Methods] Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process., [Results] Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed., [Conclusions] These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.

Published
2017

46. 109 Cows with follicular fluid androgen excess exhibit anovulation and have altered circulating sex hormone binding globulin, gonadotropin secretion, and plasma and follicular fluid composition

Author

Gomes, R. Spuri, primary, Tenley, S. C., additional, Romereim, S., additional, Abedal-Majed, M., additional, Summers, A. F., additional, Kurz, S. G., additional, Bergman, J., additional, McFee, R. M., additional, Neto, J. C. Gomes, additional, Cushman, R. A., additional, Davis, J. S., additional, Wood, J. R., additional, and Cupp, A. S., additional

Published
2017
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47. Adjunctive protein synthesis inhibitor antibiotics for toxin suppression in Staphylococcus aureus infections: a systematic appraisal.

Author

Campbell, A J, Dotel, R, Blyth, C C, Davis, J S, Tong, S Y C, and Bowen, A C

Subjects
PATHOGENIC microorganisms, PROTEIN synthesis, METHICILLIN-resistant staphylococcus aureus, ANTI-infective agents, LINEZOLID
Abstract

Protein synthesis inhibitor antibiotics inhibit synthesis of new proteins, including exotoxins and other important virulence determinants in Staphylococcus aureus. A summary of the literature regarding the use of adjunctive protein synthesis inhibitors for toxin suppression in the setting of S. aureus infections is presented. [ABSTRACT FROM AUTHOR]

Published
2019
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