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1. Designing a Direct Feedback Loop between Humans and Convolutional Neural Networks through Local Explanations

Author

Sun, Tong Steven, Gao, Yuyang, Khaladkar, Shubham, Liu, Sijia, Zhao, Liang, Kim, Young-Ho, and Hong, Sungsoo Ray

Subjects
Computer Science - Human-Computer Interaction, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

The local explanation provides heatmaps on images to explain how Convolutional Neural Networks (CNNs) derive their output. Due to its visual straightforwardness, the method has been one of the most popular explainable AI (XAI) methods for diagnosing CNNs. Through our formative study (S1), however, we captured ML engineers' ambivalent perspective about the local explanation as a valuable and indispensable envision in building CNNs versus the process that exhausts them due to the heuristic nature of detecting vulnerability. Moreover, steering the CNNs based on the vulnerability learned from the diagnosis seemed highly challenging. To mitigate the gap, we designed DeepFuse, the first interactive design that realizes the direct feedback loop between a user and CNNs in diagnosing and revising CNN's vulnerability using local explanations. DeepFuse helps CNN engineers to systemically search "unreasonable" local explanations and annotate the new boundaries for those identified as unreasonable in a labor-efficient manner. Next, it steers the model based on the given annotation such that the model doesn't introduce similar mistakes. We conducted a two-day study (S2) with 12 experienced CNN engineers. Using DeepFuse, participants made a more accurate and "reasonable" model than the current state-of-the-art. Also, participants found the way DeepFuse guides case-based reasoning can practically improve their current practice. We provide implications for design that explain how future HCI-driven design can move our practice forward to make XAI-driven insights more actionable., Comment: 32 pages, 6 figures, 5 tables. Accepted for publication in the Proceedings of the ACM on Human-Computer Interaction (PACM HCI), CSCW 2023

Published
2023

2. A blueprint for a multi-disease, multi-domain Bayesian adaptive platform trial incorporating adult and paediatric subgroups: the Staphylococcus aureus Network Adaptive Platform trial.

Author

Mahar, Robert, McGlothlin, Anna, Dymock, Michael, Lee, Todd, Lewis, Roger, Lumley, Thomas, Mora, Jocelyn, Price, David, Saville, Benjamin, Snelling, Tom, Turner, Rebecca, Webb, Steven, Davis, Joshua, Tong, Steven, and Marsh, Julie

Subjects
Adaptive, Bayesian, Platform, Randomised, Staphylococcus aureus, Trial, Adult, Child, Humans, Bayes Theorem, Sepsis, Staphylococcal Infections, Staphylococcus aureus
Abstract

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registration NCT05137119 . Registered on 30 November 2021.

Published
2023

4. Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Author

Xie, Ouli, Morris, Jacqueline M., Hayes, Andrew J., Towers, Rebecca J., Jespersen, Magnus G., Lees, John A., Ben Zakour, Nouri L., Berking, Olga, Baines, Sarah L., Carter, Glen P., Tonkin-Hill, Gerry, Schrieber, Layla, McIntyre, Liam, Lacey, Jake A., James, Taylah B., Sriprakash, Kadaba S., Beatson, Scott A., Hasegawa, Tadao, Giffard, Phil, Steer, Andrew C., Batzloff, Michael R., Beall, Bernard W., Pinho, Marcos D., Ramirez, Mario, Bessen, Debra E., Dougan, Gordon, Bentley, Stephen D., Walker, Mark J., Currie, Bart J., Tong, Steven Y. C., McMillan, David J., and Davies, Mark R.

Published
2024
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6. RES: A Robust Framework for Guiding Visual Explanation

Author

Gao, Yuyang, Sun, Tong Steven, Bai, Guangji, Gu, Siyi, Hong, Sungsoo Ray, and Zhao, Liang

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Despite the fast progress of explanation techniques in modern Deep Neural Networks (DNNs) where the main focus is handling "how to generate the explanations", advanced research questions that examine the quality of the explanation itself (e.g., "whether the explanations are accurate") and improve the explanation quality (e.g., "how to adjust the model to generate more accurate explanations when explanations are inaccurate") are still relatively under-explored. To guide the model toward better explanations, techniques in explanation supervision - which add supervision signals on the model explanation - have started to show promising effects on improving both the generalizability as and intrinsic interpretability of Deep Neural Networks. However, the research on supervising explanations, especially in vision-based applications represented through saliency maps, is in its early stage due to several inherent challenges: 1) inaccuracy of the human explanation annotation boundary, 2) incompleteness of the human explanation annotation region, and 3) inconsistency of the data distribution between human annotation and model explanation maps. To address the challenges, we propose a generic RES framework for guiding visual explanation by developing a novel objective that handles inaccurate boundary, incomplete region, and inconsistent distribution of human annotations, with a theoretical justification on model generalizability. Extensive experiments on two real-world image datasets demonstrate the effectiveness of the proposed framework on enhancing both the reasonability of the explanation and the performance of the backbone DNNs model., Comment: Published in KDD 2022

Published
2022
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7. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe.

Author

Tong, Steven, Mora, Jocelyn, Bowen, Asha, Cheng, Matthew, Daneman, Nick, Goodman, Anna, Heriot, George, Lee, Todd, Lewis, Roger, Lye, David, Mahar, Robert, Marsh, Julie, McGlothlin, Anna, McQuilten, Zoe, Morpeth, Susan, Paterson, David, Price, David, Roberts, Jason, Robinson, J, van Hal, Sebastiaan, Walls, Genevieve, Webb, Steve, Whiteway, Lyn, Yahav, Dafna, and Davis, Joshua

Subjects
Staphylococcus aureus, adaptive platform, bacteremia, bloodstream infection, randomized controlled trial, Humans, Anti-Bacterial Agents, Bacteremia, Staphylococcal Infections, Staphylococcus aureus
Abstract

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this,

Published
2022

8. The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) – Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions

Author

James, Fiona, Goh, Michelle S., Vogrin, Sara, Ng, Irvin, Douglas, Abby P., Holmes, Natasha E., Chua, Kyra YL., De Luca, Joseph, Sharma, Pooja, Zubrinich, Celia, Aung, Ar K., Gin, Douglas, Lambros, Belinda, Baker, Chris, Foley, Peter, Chong, Alvin H., Thien, Francis, Fok, Jie S., Su, John, Scardamaglia, Laura, Awad, Andrew, Tong, Steven, Johnson, Douglas, Godsell, Jack, Arasu, Alexis, Barnes, Sara, Ojaimi, Samar, Mar, Adrian, Yun, James, Ange, Nikhita, Tong, Winnie W.Y., Carr, Andrew, Loprete, Jacqueline, Katelaris, Constance H., Slape, Dana, Keat, Karuna, West, Timothy A., Lee, Monique, Smith, William, Hissaria, Pravin, Sidhu, Shireen, Janson, Sonja, Venkatesan, Sudharsan, Davies, Jane, Lane, Michael J., Redmond, Andrew M., Robertson, Ivan, Legg, Amy, Fernando, Suran, Boyle, Therese, Li, Jamma, Phillips, Elizabeth J., Cleland, Heather, Kern, Johannes S., and Trubiano, Jason A.

Published
2024
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9. Evaluating a novel model of hepatitis B care, Hep B PAST, in the Northern Territory of Australia: results from a prospective, population-based study

Author

Hosking, Kelly, Binks, Paula, De Santis, Teresa, Wilson, Phillip Merrdi, Gurruwiwi, George Garambaka, Bukulatjpi, Sarah Mariyalawuy, Vintour-Cesar, Emily, McKinnon, Melita, Nihill, Peter, Fernandes, Tammy-Allyn, Greenwood-Smith, Belinda, Batey, Robert, Ross, Cheryl, Tong, Steven Y.C., Stewart, Geoffrey, Marshall, Catherine, Gargan, Catherine, Manchikanti, Prashanti, Fuller, Karen, Tate-Baker, Jaclyn, Stewart, Sami, Cowie, Benjamin, Allard, Nicole, MacLachlan, Jennifer H., Qama, Ashleigh, Boettiger, David, Davis, Joshua S., Connors, Christine, and Davies, Jane

Published
2024
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12. Global and local epidemiology of Group A Streptococcus indicates that naturally-acquired immunity is enduring and strain-specific

Author

Chisholm, Rebecca H., Lacey, Jake A., Kokko, Jan, Campbell, Patricia T., McDonald, Malcolm I., Corander, Jukka, Davies, Mark R., Tong, Steven Y. C., McVernon, Jodie, and Geard, Nicholas

Subjects
Quantitative Biology - Populations and Evolution
Abstract

The bacterium Group A Streptococcus (Streptococcus pyogenes, GAS) is a human-specific pathogen and a major cause of global morbidity and mortality. Despite decades of research our knowledge of GAS infection and immunity is incomplete, hampering vaccine design and other efforts to reduce disease prevalence. Epidemiological studies indicate positive associations between the prevalence of GAS-related disease, the diversity of circulating strains and the degree of poverty in host populations. However, the infection and immune mechanisms underlying these associations are not clear. In this work, we use an agent-based model to demonstrate that observed diversity and prevalence are best accounted for by the hypothesis that GAS infection confers enduring strain-specific immunity, with reduced or absent cross-protection against infection by other strains. Our results suggest that the success of GAS vaccines will depend on their ability to elicit long-lasting cross-protective immunity over multiple strain types.

Published
2021

14. Universal Risk Factors for Mortality in Bloodstream Infections (UNIFORM): a systematic review and Delphi survey

Author

Bonten, Marc, Carmeli, Yehuda, Carrara, Elena, Chambers, Henry F., Davis, Joshua S., Daikos, George L., de Kraker, Marlieke, Durante-Mangoni, Emanuele, Huttner, Angela, Kalil, Andre C., Kaye, Keith, Lee, Todd C., Leibovici, Leonard, Palacios-Baena, Zaira R., Paterson, David, Paul, Mical, Gentil, Pilar Retamar, Baño, Jesus Rodríiguez, Scudeller, Luigia, Tacconelli, Evelina, Thwaites, Guy, Tong, Steven, Varon, Ben, Yahav, Dafna, de Kraker, Marlieke E.A., and Rodríguez-Baño, Jesús

Published
2024
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15. Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

Author

Davies, Mark R., Keller, Nadia, Brouwer, Stephan, Jespersen, Magnus G., Cork, Amanda J., Hayes, Andrew J., Pitt, Miranda E., De Oliveira, David M. P., Harbison-Price, Nichaela, Bertolla, Olivia M., Mediati, Daniel G., Curren, Bodie F., Taiaroa, George, Lacey, Jake A., Smith, Helen V., Fang, Ning-Xia, Coin, Lachlan J. M., Stevens, Kerrie, Tong, Steven Y. C., Sanderson-Smith, Martina, Tree, Jai J., Irwin, Adam D., Grimwood, Keith, Howden, Benjamin P., Jennison, Amy V., and Walker, Mark J.

Published
2023
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19. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Author

Arabi, Yaseen M, Gordon, Anthony C, Derde, Lennie PG, Nichol, Alistair D, Murthy, Srinivas, Beidh, Farah Al, Annane, Djillali, Swaidan, Lolowa Al, Beane, Abi, Beasley, Richard, Berry, Lindsay R, Bhimani, Zahra, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, De Jong, Menno, Detry, Michelle A, Duffy, Eamon J, Estcourt, Lise J, Fitzgerald, Mark, Fowler, Rob, Girard, Timothy D, Goligher, Ewan C, Goossens, Herman, Haniffa, Rashan, Higgins, Alisa M, Hills, Thomas E, Horvat, Christopher M, Huang, David T, King, Andrew J, Lamontagne, Francois, Lawler, Patrick R, Lewis, Roger, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Malakouti, Salim, McAuley, Daniel F, McGlothlin, Anna, Mcguinness, Shay, McVerry, Bryan J, Montgomery, Stephanie K, Morpeth, Susan C, Mouncey, Paul R, Orr, Katrina, Parke, Rachael, Parker, Jane C, Patanwala, Asad E, Rowan, Kathryn M, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Tong, Steven YC, Turgeon, Alexis F, Turner, Anne M, Van de Veerdonk, Frank Leo, Zarychanski, Ryan, Green, Cameron, Berry, Scott, Marshall, John C, McArthur, Colin, Angus, Derek C, and Webb, Steven A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Comparative Effectiveness Research, Clinical Research, Clinical Trials and Supportive Activities, Good Health and Well Being, Adult, Antiviral Agents, Bayes Theorem, Critical Illness, Drug Combinations, Humans, Hydroxychloroquine, Lopinavir, Ritonavir, SARS-CoV-2, COVID-19 Drug Treatment, Adaptive platform trial, Intensive care, Pneumonia, Pandemic, COVID-19, Lopinavir-ritonavir, REMAP-CAP Investigators, Public Health and Health Services, Emergency & Critical Care Medicine, Clinical sciences
Abstract

PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsCritically 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.ResultsWe 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).ConclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Published
2021

27. Evaluating the role of asymptomatic throat carriage of Streptococcus pyogenes in impetigo transmission in remote Aboriginal communities in Northern Territory, Australia: a retrospective genomic analysis

Author

Lacey, Jake A, Marcato, Adrian J, Chisholm, Rebecca H, Campbell, Patricia T, Zachreson, Cameron, Price, David J, James, Taylah B, Morris, Jacqueline M, Gorrie, Claire L, McDonald, Malcolm I, Bowen, Asha C, Giffard, Philip M, Holt, Deborah C, Currie, Bart J, Carapetis, Jonathan R, Andrews, Ross M, Davies, Mark R, Geard, Nicholas, McVernon, Jodie, and Tong, Steven Y C

Published
2023
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29. Case Commentary: Daptomycin Resistance in Staphylococcus argenteus-from Northern Australia to San Francisco.

Author

Bayer, Arnold and Tong, Steven

Subjects
Staphylococcus argenteus, daptomycin resistance, Anti-Bacterial Agents, Australia, Daptomycin, Humans, Microbial Sensitivity Tests, San Francisco, Staphylococcal Infections, Staphylococcus
Abstract

Staphylococcus argenteus infection was initially described in Aboriginal patients in the Northern Territories of Australia as a predominant cause of skin infections and is rare outside Southeast Asia. A first well-characterized case of S. argenteus infection has now been described in the United States, involving a recurrent hemodialysis catheter infection, in which unstable daptomycin resistance evolved during daptomycin therapy. The unique colonial pigmentation of S. argenteus isolates in strains otherwise identified as Staphylococcus aureus is noteworthy.

Published
2020

30. Epidemiological trends in notified influenza cases in Australias Northern Territory, 2007-2016.

Author

Weinman, Aaron, Sullivan, Sheena, Vijaykrishna, Dhanasekaran, Markey, Peter, Levy, Avram, Miller, Adrian, and Tong, Steven

Subjects
Northern Territory, epidemics, epidemiology, influenza, Adolescent, Adult, Child, Child, Preschool, Disease Outbreaks, Healthcare Disparities, Hospitalization, Humans, Immunization Programs, Incidence, Indigenous Peoples, Infant, Infant, Newborn, Influenza, Human, Middle Aged, Northern Territory, Vaccination, Young Adult
Abstract

BACKGROUND: The Northern Territory (NT) of Australia has a mix of climates, sparsely distributed population and a large proportion of the populace are Indigenous Australians, and influenza is known to have a disproportionate impact upon this group. Understanding the epidemiology of influenza in this region would inform public health strategies. OBJECTIVES: To assess if there are consistent patterns in characteristics of influenza outbreaks in the NT. METHODS: Laboratory confirmed influenza cases in the NT are notified to the NT Centre for Disease Control. We conducted analyses on notified cases from 2007-2016 to determine incidence rates (by age group, Indigenous status and area), seasonality of cases and spatial distribution of influenza types. Notified cases were linked to laboratory datasets to update information on influenza type or subtype RESULTS: The disparity in Indigenous and non-Indigenous notification rates varied by age group, with rate ratios for Indigenous versus non-Indigenous ranging from 1.58 (95% CI:1.39, 1.80) for ages 15-24 to 5.56 (95% CI: 4.71, 6.57) for ages 55-64. The disparity between Indigenous and non-Indigenous notification rates appeared higher in the Central Australia region. Indigenous versus non-Indigenous hospitalisation and mortality rate ratios were 6.51 (95% CI: 5.91, 7.18) and 5.46 (95% CI: 2.40, 12.71) respectively. Inter-seasonal peaks during February and March occurred in 2011, 2013 and 2014, and were due to influenza activity in the tropical north of the NT. CONCLUSIONS: Our results highlight the importance of influenza vaccination across all age groups for Indigenous Australians. An early vaccination campaign targeted against outbreaks in February-March would be best focused on the tropical north.

Published
2020

31. A minimal common outcome measure set for COVID-19 clinical research

Author

infection, WHO Working Group on the Clinical Characterisation and Management of COVID-19, Marshall, John C, Murthy, Srinivas, Diaz, Janet, Adhikari, NK, Angus, Derek C, Arabi, Yaseen M, Baillie, Kenneth, Bauer, Michael, Berry, Scott, Blackwood, Bronagh, Bonten, Marc, Bozza, Fernando, Brunkhorst, Frank, Cheng, Allen, Clarke, Mike, Dat, Vu Quoc, de Jong, Menno, Denholm, Justin, Derde, Lennie, Dunning, Jake, Feng, Xiaobin, Fletcher, Tom, Foster, Nadine, Fowler, Rob, Gobat, Nina, Gomersall, Charles, Gordon, Anthony, Glueck, Thomas, Harhay, Michael, Hodgson, Carol, Horby, Peter, Kim, YaeJean, Kojan, Richard, Kumar, Bharath, Laffey, John, Malvey, Denis, Martin-Loeches, Ignacio, McArthur, Colin, McAuley, Danny, McBride, Stephen, McGuinness, Shay, Merson, Laura, Morpeth, Susan, Needham, Dale, Netea, Mihai, Oh, Myoung-Don, Phyu, Sabai, Piva, Simone, Qiu, Ruijin, Salisu-Kabara, Halima, Shi, Lei, Shimizu, Naoki, Sinclair, Jorge, Tong, Steven, Turgeon, Alexis, Uyeki, Tim, van de Veerdonk, Frank, Webb, Steve, Williamson, Paula, Wolf, Timo, and Zhang, Junhua

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Infectious Diseases, Infection, Good Health and Well Being, Betacoronavirus, COVID-19, Clinical Trials as Topic, Coronavirus Infections, Humans, Outcome Assessment, Health Care, Pandemics, Patient Outcome Assessment, Pneumonia, Viral, SARS-CoV-2, Survival Analysis, Treatment Outcome, Viral Load, WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection, Medical Microbiology, Public Health and Health Services, Microbiology, Clinical sciences, Medical microbiology, Epidemiology
Abstract

Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.

Published
2020

33. Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians

Author

Hensen, Luca, Nguyen, Thi H. O., Rowntree, Louise C., Damelang, Timon, Koutsakos, Marios, Aban, Malet, Hurt, Aeron, Harland, Kim L., Auladell, Maria, van de Sandt, Carolien E., Everitt, Anngie, Blacker, Cath, Oyong, Damian A., Loughland, Jessica R., Webb, Jessica R., Wines, Bruce D., Hogarth, P. Mark, Flanagan, Katie L., Plebanski, Magdalena, Wheatley, Adam, Chung, Amy W., Kent, Stephen J., Miller, Adrian, Clemens, E. Bridie, Doherty, Peter C., Nelson, Jane, Davies, Jane, Tong, Steven Y. C., and Kedzierska, Katherine

Published
2021

37. Good Studies Evaluate the Disease While Great Studies Evaluate the Patient: Development and Application of a Desirability of Outcome Ranking Endpoint for Staphylococcus aureus Bloodstream Infection.

Author

Doernberg, Sarah B, Tran, Thuy Tien Tram, Tong, Steven YC, Paul, Mical, Yahav, Dafna, Davis, Joshua S, Leibovici, Leonard, Boucher, Helen W, Corey, G Ralph, Cosgrove, Sara E, Chambers, Henry F, Fowler, Vance G, Evans, Scott R, and Holland, Thomas L

Subjects
Clinical Trials and Supportive Activities, Emerging Infectious Diseases, Infectious Diseases, Clinical Research, Infection, Good Health and Well Being, Adult, Anti-Bacterial Agents, Bacteremia, Humans, Methicillin-Resistant Staphylococcus aureus, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Risk Factors, Staphylococcal Infections, Staphylococcus aureus, Surveys and Questionnaires, Survival Analysis, clinical trial, bloodstream infection, Antibacterial Resistance Leadership Group, Staphylococcus aureus, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

BackgroundDesirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data.MethodsWe administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks.ResultsForty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis.ConclusionsUsing S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.

Published
2019

39. Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter

Author

Rodrigo, M. Kalindu D., Saiganesh, Aarti, Hayes, Andrew J., Wilson, Alisha M., Anstey, Jack, Pickering, Janessa L., Iwasaki, Jua, Hillas, Jessica, Winslow, Scott, Woodman, Tabitha, Nitschke, Philipp, Lacey, Jake A., Breese, Karen J., van der Linden, Mark P. G., Giffard, Philip M., Tong, Steven Y. C., Gray, Nicola, Stubbs, Keith A., Carapetis, Jonathan R., Bowen, Asha C., Davies, Mark R., and Barnett, Timothy C.

Published
2022
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40. Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial

Author

Lee, I. Russel, Tong, Steven Y. C., Davis, Joshua S., Paterson, David L., Syed-Omar, Sharifah F., Peck, Kwong Ran, Chung, Doo Ryeon, Cooke, Graham S., Libau, Eshele Anak, Rahman, Siti-Nabilah B. A., Gandhi, Mihir P., Shi, Luming, Zheng, Shuwei, Chaung, Jenna, Tan, Seow Yen, Kalimuddin, Shirin, Archuleta, Sophia, and Lye, David C.

Published
2022
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43. ASCOT ADAPT study of COVID-19 therapeutics in hospitalised patients: an international multicentre adaptive platform trial

Author

Denholm, Justin T., Venkatesh, Balasubramanian, Davis, Joshua, Bowen, Asha C., Hammond, Naomi E., Jha, Vivekanand, McPhee, Grace, McQuilten, Zoe, O’Sullivan, Matthew V. N., Paterson, David, Price, David, Rees, Megan, Roberts, Jason, Jones, Mark, Totterdell, James, Snelling, Thomas, Trask, Nanette, Morpeth, Susan, and Tong, Steven YC

Published
2022
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46. Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study.

Author

Ong, Sean W X, Luo, Jin, Fridman, Daniel J, Lee, Samantha M, Johnstone, Jennie, Schwartz, Kevin L, Diong, Christina, Patel, Samir N, Macfadden, Derek R, Langford, Bradley J, Tong, Steven Y C, Brown, Kevin A, and Daneman, Nick

Subjects
SOFT tissue infections, BACTEREMIA, LOGISTIC regression analysis, DRUG resistance in microorganisms, GRAM-negative bacteria, NOSOCOMIAL infections
Abstract

Objectives The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. Methods We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2–5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. Results In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29–2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24–1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. Conclusions Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Multi-Methods Evaluation of the Stop (See, Treat, Prevent) Trial: A Cluster Randomised, Stepped Wedge Trial to Support Healthy Skin

Author

Thomas, Hannah, primary, Amgarth-Duff, Ingrid, additional, Carapetis, Jonathan, additional, Coffin, Juli, additional, Christophers, Raymond, additional, Enkel, Stephanie, additional, Famlonga, Rebecca, additional, Jacky, John, additional, Jones, Mark, additional, Marsh, Julie A., additional, McIntosh, Kelli, additional, McRae, Tracy, additional, Mullane, Marianne, additional, O’Donnell, Vicki, additional, Pan, Edward, additional, Pearson, Glenn, additional, Sibosado, Slade, additional, Smith, Bec, additional, Snelling, Thomas, additional, Steer, Andrew, additional, Tong, Steven Y.C., additional, Walker, Roz, additional, Whelan, Alexandra, additional, White, Kristen, additional, Wright, Edie, additional, Bowen, Asha, additional, and Trial, SToP (See, Treat, Prevent skin sores and scabies), additional

Published
2024
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49. Evaluating the impact of a SIMPlified LaYered consent process on recruitment of potential participants to theStaphylococcus aureusNetwork Adaptive Platform trial: study protocol for a multicentre pragmatic nested randomised clinical trial (SIMPLY-SNAP trial)

Author

Ong, Sean W X, primary, Lee, Todd C, additional, Fowler, Robert A, additional, Mahar, Robert, additional, Pinto, Ruxandra L, additional, Rishu, Asgar, additional, Petrella, Lina, additional, Whiteway, Lyn, additional, Cheng, Matthew, additional, McDonald, Emily, additional, Johnstone, Jennie, additional, Mertz, Dominik, additional, Kandel, Christopher, additional, Somayaji, Ranjani, additional, Davis, Joshua S, additional, Tong, Steven Y C, additional, and Daneman, Nick, additional

Published
2024
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50. Universal Risk Factors for Mortality in Bloodstream Infections (UNIFORM): a systematic review and Delphi survey

Author

Varon, Ben, primary, Palacios-Baena, Zaira R., additional, de Kraker, Marlieke E.A., additional, Rodríguez-Baño, Jesús, additional, Leibovici, Leonard, additional, Paul, Mical, additional, Bonten, Marc, additional, Carmeli, Yehuda, additional, Carrara, Elena, additional, Chambers, Henry F., additional, Davis, Joshua S., additional, Daikos, George L., additional, Kraker, Marlieke de, additional, Durante-Mangoni, Emanuele, additional, Huttner, Angela, additional, Kalil, Andre C., additional, Kaye, Keith, additional, Lee, Todd C., additional, Paterson, David, additional, Gentil, Pilar Retamar, additional, Baño, Jesus Rodríiguez, additional, Scudeller, Luigia, additional, Tacconelli, Evelina, additional, Thwaites, Guy, additional, Tong, Steven, additional, Varon, Ben, additional, and Yahav, Dafna, additional

Published
2024
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