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Executive Summary: Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock 2021.

Laura Evans, Andrew Rhodes, Waleed Alhazzani, Massimo Antonelli, Craig M Coopersmith, Craig French, Flávia R Machado, Lauralyn Mcintyre, Marlies Ostermann, Hallie C Prescott, Christa Schorr, Steven Simpson, W Joost Wiersinga, Fayez Alshamsi, Derek C Angus, Yaseen Arabi, Luciano Azevedo, Richard Beale, Gregory Beilman, Emilie Belley-Cote, Lisa Burry, Maurizio Cecconi, John Centofanti, Angel Coz Yataco, Jan De Waele, R Phillip Dellinger, Kent Doi, Bin Du, Elisa Estenssoro, Ricard Ferrer, Charles Gomersall, Carol Hodgson, Morten Hylander Møller, Theodore Iwashyna, Shevin Jacob, Ruth Kleinpell, Michael Klompas, Younsuck Koh, Anand Kumar, Arthur Kwizera, Suzana Lobo, Henry Masur, Steven McGloughlin, Sangeeta Mehta, Yatin Mehta, Mervyn Mer, Mark Nunnally, Simon Oczkowski, Tiffany Osborn, Elizabeth Papathanassoglou, Anders Perner, Michael Puskarich, Jason Roberts, William Schweickert, Maureen Seckel, Jonathan Sevransky, Charles L Sprung, Tobias Welte, Janice Zimmerman, Mitchell Levy,

Crit Care Med (Critical care medicine)
[2021, 49(11):1974-1982]

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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.

Laura Evans, Andrew Rhodes, Waleed Alhazzani, Massimo Antonelli, Craig M Coopersmith, Craig French, Flávia R Machado, Lauralyn Mcintyre, Marlies Ostermann, Hallie C Prescott, Christa Schorr, Steven Simpson, W Joost Wiersinga, Fayez Alshamsi, Derek C Angus, Yaseen Arabi, Luciano Azevedo, Richard Beale, Gregory Beilman, Emilie Belley-Cote, Lisa Burry, Maurizio Cecconi, John Centofanti, Angel Coz Yataco, Jan De Waele, R Phillip Dellinger, Kent Doi, Bin Du, Elisa Estenssoro, Ricard Ferrer, Charles Gomersall, Carol Hodgson, Morten Hylander Møller, Theodore Iwashyna, Shevin Jacob, Ruth Kleinpell, Michael Klompas, Younsuck Koh, Anand Kumar, Arthur Kwizera, Suzana Lobo, Henry Masur, Steven McGloughlin, Sangeeta Mehta, Yatin Mehta, Mervyn Mer, Mark Nunnally, Simon Oczkowski, Tiffany Osborn, Elizabeth Papathanassoglou, Anders Perner, Michael Puskarich, Jason Roberts, William Schweickert, Maureen Seckel, Jonathan Sevransky, Charles L Sprung, Tobias Welte, Janice Zimmerman, Mitchell Levy,

Crit Care Med (Critical care medicine)
[2021, 49(11):e1063-e1143]

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Population pharmacokinetics of vancomycin in critically ill adult patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

Vesa Cheng, Mohd H Abdul-Aziz, Fay Burrows, Hergen Buscher, Young-Jae Cho, Amanda Corley, Arne Diehl, Eileen Gilder, Stephan M Jakob, Hyung-Sook Kim, Bianca J Levkovich, Sung Yoon Lim, Shay McGuinness, Rachael Parke, Vincent Pellegrino, Yok-Ai Que, Claire Reynolds, Sam Rudham, Steven C Wallis, Susan A Welch, David Zacharias, John F Fraser, Kiran Shekar, Jason A Roberts,

Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analysed using a ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2021, :AAC0137721]

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Advancing our commitment to our peer reviewers.

Rashmi B Halker Singh, Sarah M Bobker, Jason L Roberts, Larry Charleston, Matthew S Robbins, Amynah Pradhan, Till Sprenger, Patricia Pozo-Rosich, Serena L Orr, Scott W Powers, Timothy T Houle, Dana P Turner, Amy A Gelfand,

Headache (Headache)
[2021, :]

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Epigenetic Age and the Risk of Incident Atrial Fibrillation.

Jason D Roberts, Eric Vittinghoff, Ake T Lu, Alvaro Alonso, Biqi Wang, Colleen M Sitlani, Pedrum Mohammadi-Shemirani, Myriam Fornage, Jelena Kornej, Jennifer A Brody, Dan E Arking, Honghuang Lin, Susan R Heckbert, Ivana Prokic, Mohsen Ghanbari, Allan C Skanes, Traci M Bartz, Marco V Perez, Kent D Taylor, Steven A Lubitz, Patrick T Ellinor, Kathryn L Lunetta, James S Pankow, Guillaume Paré, Nona Sotoodehnia, Emelia J Benjamin, Steve Horvath, Gregory M Marcus,

<b>Background:</b> The most prominent risk factor for atrial fibrillation (AF) is chronological age, however underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge, a phenomenon termed epigenetic age acceleration (EAA), which may reflect accelerated biological aging. ... Read more >>

Circulation (Circulation)
[2021, :]

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Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.

Laura Evans, Andrew Rhodes, Waleed Alhazzani, Massimo Antonelli, Craig M Coopersmith, Craig French, Flávia R Machado, Lauralyn Mcintyre, Marlies Ostermann, Hallie C Prescott, Christa Schorr, Steven Simpson, W Joost Wiersinga, Fayez Alshamsi, Derek C Angus, Yaseen Arabi, Luciano Azevedo, Richard Beale, Gregory Beilman, Emilie Belley-Cote, Lisa Burry, Maurizio Cecconi, John Centofanti, Angel Coz Yataco, Jan De Waele, R Phillip Dellinger, Kent Doi, Bin Du, Elisa Estenssoro, Ricard Ferrer, Charles Gomersall, Carol Hodgson, Morten Hylander Møller, Theodore Iwashyna, Shevin Jacob, Ruth Kleinpell, Michael Klompas, Younsuck Koh, Anand Kumar, Arthur Kwizera, Suzana Lobo, Henry Masur, Steven McGloughlin, Sangeeta Mehta, Yatin Mehta, Mervyn Mer, Mark Nunnally, Simon Oczkowski, Tiffany Osborn, Elizabeth Papathanassoglou, Anders Perner, Michael Puskarich, Jason Roberts, William Schweickert, Maureen Seckel, Jonathan Sevransky, Charles L Sprung, Tobias Welte, Janice Zimmerman, Mitchell Levy,

Intensive Care Med (Intensive care medicine)
[2021, :]

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Pharmacokinetics of fluconazole and ganciclovir as combination antimicrobial chemotherapy on ECMO: a case report.

Jayesh A Dhanani, Jeffrey Lipman, Jason Pincus, Shane Townsend, Amelia Livermore, Steven C Wallis, Mohd H Abdul-Aziz, Jason A Roberts,

Extracorporeal membrane oxygenation (ECMO) can affect antimicrobial pharmacokinetics. This case report describes a 33-year-old male with newly diagnosed acquired immunodeficiency syndrome presenting in acute severe type 1 respiratory failure. On investigation, the patient had positive cultures for Candida albicans from respiratory specimens and high blood cytomegalovirus titres, and required venovenous ... Read more >>

Int J Antimicrob Agents (International journal of antimicrobial agents)
[2021, :106431]

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Dose optimisation of antibiotics used for meningitis.

Aaron J Heffernan, Jason A Roberts,

<h4>Purpose of review</h4>Central nervous system (CNS) infections such as ventriculitis and meningitis are associated with significant morbidity and mortality. In part, this may be due to increased difficulties in achieving a therapeutic antibiotic concentration at the site of infection due to both the pharmacokinetic (PK) changes observed during critical illness ... Read more >>

Curr Opin Infect Dis (Current opinion in infectious diseases)
[2021, :]

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Headache Assistant Editors 2021-2022.

Jason Roberts,

Headache (Headache)
[2021, 61(8):1156-1158]

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Human RyR2 (Ryanodine Receptor 2) Loss-of-Function Mutations: Clinical Phenotypes and In Vitro Characterization.

Yanhui Li, Jinhong Wei, Wenting Guo, Bo Sun, John Paul Estillore, Ruiwu Wang, Ayhan Yoruk, Thomas M Roston, Shubhayan Sanatani, Arthur A M Wilde, Michael H Gollob, Jason D Roberts, Zian H Tseng, Henrik K Jensen, S R Wayne Chen,

[Figure: see text]. ... Read more >>

Circ Arrhythm Electrophysiol (Circulation. Arrhythmia and electrophysiology)
[2021, 14(9):e010013]

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Population pharmacokinetics of piperacillin and tazobactam in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

Vesa Cheng, Mohd H Abdul-Aziz, Fay Burrows, Hergen Buscher, Young-Jae Cho, Amanda Corley, Arne Diehl, Eileen Gilder, Stephan M Jakob, Hyung-Sook Kim, Bianca J Levkovich, Sung Yoon Lim, Shay McGuinness, Rachael Parke, Vincent Pellegrino, Yok-Ai Que, Claire Reynolds, Sam Rudham, Steven C Wallis, Susan A Welch, David Zacharias, John F Fraser, Kiran Shekar, Jason A Roberts,

Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2021, :AAC0143821]

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Individualized precision dosing approaches to optimize antimicrobial therapy in pediatric populations.

Quyen Tu, Menino Cotta, Sainath Raman, Nicolette Graham, Luregn Schlapbach, Jason A Roberts,

<b>Introduction</b>:Severe infections continue to impose a major burden on critically ill children and mortality rates remain stagnant. Outcomes rely on accurate and timely delivery of antimicrobials achieving target concentrations in infected tissue. Yet, developmental aspects, disease-related variables, and host factors may severely alter antimicrobial pharmacokinetics in pediatrics. The emergence of ... Read more >>

Expert Rev Clin Pharmacol (Expert review of clinical pharmacology)
[2021, :1-17]

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Population Pharmacokinetics of Vancomycin and Meropenem in Pediatric Extracorporeal Membrane Oxygenation Support.

Brenda Zylbersztajn, Suzanne Parker, Daniel Navea, Giannina Izquierdo, Paula Ortiz, Juan Pablo Torres, Cristian Fajardo, Rodrigo Diaz, Cristian Valverde, Jason Roberts,

<b>Objective:</b> Describe primary pharmacokinetic/pharmacodynamic (PK/PD) parameters of vancomycin and meropenem in pediatric patients undergoing ECMO and analyze utilized dosing to reach PK/PD target. <b>Design:</b> Prospective, multicentric, population PK analysis. <b>Setting:</b> Two hospitals with pediatric intensive care unit. <b>Patients:</b> Pediatric patients (1 month - 15 years old) receiving vancomycin and meropenem for empiric ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2021, 12:709332]

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Emerging therapeutic drug monitoring of anti-infective agents in Australian hospitals: Availability, performance and barriers to implementation.

Indy Sandaradura, Jan-Willem Alffenaar, Menino O Cotta, Kathryn Daveson, Richard O Day, Sebastiaan Van Hal, Cindy Lau, Deborah J E Marriott, Jonathan Penm, Jason A Roberts, Alexis Tabah, Paul Williams, Sahand Imani,

<h4>Aims</h4>The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti-infective agents in Australian hospitals.<h4>Methods</h4>A nationwide cross-sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding ... Read more >>

Br J Clin Pharmacol (British journal of clinical pharmacology)
[2021, :]

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Management of Congenital Long-QT Syndrome: Commentary From the Experts.

Elizabeth S Kaufman, Lee L Eckhardt, Michael J Ackerman, Peter F Aziz, Elijah R Behr, Marina Cerrone, Mina K Chung, Michael J Cutler, Susan P Etheridge, Andrew D Krahn, Steven A Lubitz, Marco V Perez, Silvia G Priori, Jason D Roberts, Dan M Roden, Eric Schulze-Bahr, Peter J Schwartz, Wataru Shimizu, M Benjamin Shoemaker, Raymond W Sy, Jeffrey A Towbin, Sami Viskin, Arthur A M Wilde, Wojciech Zareba,

While published guidelines are useful in the care of patients with long-QT syndrome, it can be difficult to decide how to apply the guidelines to individual patients, particularly those with intermediate risk. We explored the diversity of opinion among 24 clinicians with expertise in long-QT syndrome. Experts from various regions ... Read more >>

Circ Arrhythm Electrophysiol (Circulation. Arrhythmia and electrophysiology)
[2021, 14(7):e009726]

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A meta-analysis of protein binding of flucloxacillin in healthy volunteers and hospitalized patients.

Eveline Wallenburg, Roger J M Brüggemann, Jason A Roberts, Nynke G L Jager, Marta Ulldemolins, Sarah Wilkes, Jeroen Schouten, Paul K L Chin, Rob Ter Heine,

<h4>Objectives</h4>The aim of this study was to develop a mechanistic protein-binding model to predict the unbound flucloxacillin concentrations in different patient populations.<h4>Methods</h4>A mechanistic protein-binding model was fitted to the data using non-linear mixed-effects modelling. Data were obtained from four datasets, containing 710 paired total and unbound flucloxacillin concentrations from healthy ... Read more >>

Clin Microbiol Infect (Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases)
[2021, :]

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Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT).

Adam D Irwin, Lachlan J M Coin, Patrick N A Harris, Menino Osbert Cotta, Michelle J Bauer, Cameron Buckley, Ross Balch, Peter Kruger, Jason Meyer, Kiran Shekar, Kara Brady, Cheryl Fourie, Natalie Sharp, Luminita Vlad, David Whiley, Scott A Beatson, Brian M Forde, David Paterson, Julia Clark, Krispin Hajkowicz, Sainath Raman, Seweryn Bialasiewicz, Jeffrey Lipman, Luregn J Schlapbach, Jason A Roberts,

<h4>Background</h4>Sepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days ... Read more >>

Front Cell Infect Microbiol (Frontiers in cellular and infection microbiology)
[2021, 11:667680]

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Short-coupled ventricular fibrillation represents a distinct phenotype among latent causes of unexplained cardiac arrest: a report from the CASPER registry.

Christian Steinberg, Brianna Davies, Greg Mellor, Rafik Tadros, Zachary W Laksman, Jason D Roberts, Martin Green, Wael Alqarawi, Paul Angaran, Jeffrey Healey, Shubhayan Sanatani, Richard Leather, Colette Seifer, Anne Fournier, Henry Duff, Martin Gardner, Ciorsti McIntyre, Robert Hamilton, Christopher S Simpson, Andrew D Krahn,

<h4>Aims</h4>The term idiopathic ventricular fibrillation (IVF) describes survivors of unexplained cardiac arrest (UCA) without a specific diagnosis after clinical and genetic testing. Previous reports have described a subset of IVF individuals with ventricular arrhythmia initiated by short-coupled trigger premature ventricular contractions (PVCs) for which the term short-coupled ventricular fibrillation (SCVF) ... Read more >>

Eur Heart J (European heart journal)
[2021, 42(29):2827-2838]

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Prospective Cohort Study of Micafungin Population Pharmacokinetic Analysis in Plasma and Peritoneal Fluid in Septic Patients with Intra-abdominal Infections.

Nicolas Garbez, Litaty Mbatchi, Steven C Wallis, Laurent Muller, Jeffrey Lipman, Jason A Roberts, Jean-Yves Lefrant, Claire Roger,

The objective of this study was to describe the pharmacokinetics (PK) of micafungin in plasma and peritoneal fluid in septic patients with intra-abdominal infections. Twelve patients with secondary peritonitis in septic shock receiving 100 mg micafungin once daily were included. Total micafungin plasma and peritoneal fluid were subjected to a population ... Read more >>

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2021, 65(7):e0230720]

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Germination biology, distribution and control of the invasive species Eragrostis curvula [Schard. Nees] (African Lovegrass): A global synthesis of current and future management challenges

Jason Roberts, Singarayer Florentine, Eddie van Etten, Christopher Turville,

Eragrostis curvula (African Lovegrass) is an invasive C₄ perennial grass that is threatening natural ecosystems globally. Native to Africa, this species can tolerate a wide range of environmental conditions, from acidic soils to areas with low rainfall and regions with frequent fires, which assists in its widespread distribution. With its ... Read more >>

Weed Res (Weed research)
[2021, 61(3):154-163]

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Antibiotic pharmacokinetics/pharmacodynamics: where are we heading?

Jian Li, Jason Roberts, ,

Int J Antimicrob Agents (International journal of antimicrobial agents)
[2021, 58(2):106369]

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Personalized Piperacillin Dosing for the Critically Ill: A Retrospective Analysis of Clinical Experience with Dosing Software and Therapeutic Drug Monitoring to Optimize Antimicrobial Dosing.

Ute Chiriac, Daniel C Richter, Otto R Frey, Anka C Röhr, Sophia Helbig, Judit Preisenberger, Stefan Hagel, Jason A Roberts, Markus A Weigand, Alexander Brinkmann,

Optimization of antibiotic dosing is a treatment intervention that is likely to improve outcomes in severe infections. The aim of this retrospective study was to describe the therapeutic exposure of steady state piperacillin concentrations (c<sub>PIP</sub>) and clinical outcome in critically ill patients with sepsis or septic shock who received continuous ... Read more >>

Antibiotics (Basel) (Antibiotics (Basel, Switzerland))
[2021, 10(6):]

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Development and validation of a UHPLC-MS/MS method to measure cefotaxime and metabolite desacetylcefotaxime in blood plasma: a pilot study suitable for capillary microsampling in critically ill children.

Yarmarly C Guerra Valero, Tavey Dorofaeff, Jason A Roberts, Jeffrey Lipman, Mark G Coulthard, Louise Sparkes, Steven C Wallis, Suzanne L Parker,

Critical illness has been shown to affect the pharmacokinetics of antibiotics, which can lead to ineffective antibiotic exposure and the potential emergence of resistant bacteria. The lack of studies describing antibiotic pharmacokinetics in critically ill children has led to significant off-label dosing. This is, in part, due to the ethical ... Read more >>

Anal Bioanal Chem (Analytical and bioanalytical chemistry)
[2021, 413(17):4483-4491]

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Personalized ß-lactam dosing in patients with coronavirus disease 2019 (COVID-19) and pneumonia: A retrospective analysis on pharmacokinetics and pharmacokinetic target attainment.

Ute Chiriac, Otto R Frey, Anka C Roehr, Andreas Koeberer, Patrick Gronau, Thomas Fuchs, Jason A Roberts, Alexander Brinkmann,

<h4>Abstract</h4>Pathophysiological changes are important risk factors for critically ill patients with pneumonia manifesting sub-therapeutic antibiotic exposures during empirical treatment. The effect of coronavirus disease 2019 (COVID-19) on antibiotic dosing requirements is uncertain. We aimed to determine the effect of COVID-19 on ß-lactam pharmacokinetics (PK) and PK target attainment in critically ... Read more >>

Medicine (Baltimore) (Medicine)
[2021, 100(22):e26253]

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Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in 'lone' atrial fibrillation.

Julieta Lazarte, Zachary W Laksman, Jian Wang, John F Robinson, Jacqueline S Dron, Emma Leach, Janet Liew, Adam D McIntyre, Allan C Skanes, Lorne J Gula, Peter Leong-Sit, Henian Cao, Brett Trost, Stephen W Scherer, Robert A Hegele, Jason D Roberts,

<h4>Aims</h4>Atrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy ... Read more >>

Europace (Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology)
[2021, 23(6):844-850]

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