13 results found
Wong JLC, Romano M, Kerry LE, et al., 2019, OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723
Wong JLC, Mason A, Gordon A, et al., 2018, Are large randomized controlled trials in severe sepsis and septic shock statistically disadvantaged by repeated inadvertent underestimates of required sample size, BMJ Open, Vol: 8, ISSN: 2044-6055
Objectives: We sought to understand why randomized controlled trials in septic shock have failed to demonstrate effectiveness in the face of improving overall outcomes for patients and seemingly promising results of early phase trials of interventions. Design: We performed a retrospective analysis of large critical care trials of severe sepsis and septic shock. Data were collected from the primary trial manuscripts, pre-published statistical plans or by direct communication with corresponding authors. Setting: Critical care randomized control trials in severe sepsis and septic shock. Participants: 14619 patients randomized in 13 trials published between 2005 to 2015, enrolling greater than 500 patients and powered to a primary outcome of mortality. Intervention: Multiple interventions including the evaluation of treatment strategies and novel therapeutics. Primary and secondary outcome measures: Our primary outcome measure was the difference between the anticipated and actual control arm mortality. Secondary analysis examined the actual effect size and the anticipated effect size employed in sample size calculation. Results: In this post-hoc analysis of 13 trials with 14 619 patients randomised, we highlight a global tendency to overestimate control arm mortality in estimating sample size (absolute difference 9.8%, 95% confidence interval, -14.7% to -5%, p<0.001). When we compared anticipated and actual effect size of a treatment there was also a substantial overestimation in proposed values (absolute difference 7.4%, 95% confidence interval -9.0% to -5.8%, p<0.0001). Conclusions: An interpretation of our results is that trials are consistently underpowered in the planning phase by employing erroneous variables to calculate a satisfactory sample size. Our analysis cannot establish if, given a larger sample size, a trial would have had a positive result. It is disappointing so many promising phase II res
Mullineaux-Sanders C, Colins JW, Ruano-Gallego D, et al., 2017, Citrobacter rodentium relies on commensals for colonization of the colonic mucosa, Cell Reports, Vol: 21, Pages: 3381-3389, ISSN: 2211-1247
We investigated the role of commensals at the peak of infection with the colonic mouse pathogen Citrobacter rodentium. Bioluminescent and kanamycin (Kan)-resistant C. rodentium persisted avirulently in the cecal lumen of mice continuously treated with Kan. A single Kan treatment was sufficient to displace C. rodentium from the colonic mucosa, a phenomenon not observed following treatment with vancomycin (Van) or metronidazole (Met). Kan, Van, and Met induce distinct dysbiosis, suggesting C. rodentium relies on specific commensals for colonic colonization. Expression of the master virulence regulator ler is induced in germ-free mice, yet C. rodentium is only seen in the cecal lumen. Moreover, in conventional mice, a single Kan treatment was sufficient to displace C. rodentium constitutively expressing Ler from the colonic mucosa. These results show that expression of virulence genes is not sufficient for colonization of the colonic mucosa and that commensals are essential for a physiological infection course.
Singleton J, Grailey KE, Simon JB, et al., 2015, Variability in aminoglycoside dosing in Intensive Care Units across London – should our methods be standardized?
Grailey KE, Singleton JM, Simon JB, et al., 2015, Peaks and Troughs: Variations in the Availability of Therapeutic Drug Monitoring in Critical Care Units across London
Cunningham ME, Javaid A, Waters J, et al., 2015, Development and validation of a “capture-fusion” model to study drug sensitivity of patient-derived hepatitis C, Hepatology, Vol: 61, Pages: 1192-1204, ISSN: 0270-9139
Wong JLC, Harb HF, Bamford KB, et al., 2014, Time post out-of-hospital cardiac arrest determines the prevalence of different pathogenic organisms from respiratory secretions., ESCIM LIVES 2014
Wong JLC, Bamford KB, Harb HF, et al., 2014, Gram-negative resistance is highly prevalent in initial out-of-hospital cardiac arrest respiratory isolates., ESICM LIVES 2014
Wong JLC, Harb HF, Bamford KB, et al., 2014, A retrospective analysis of respiratory isolates post out-of-hospital cardiac arrest (OOHCA) to establish choices in empirical antibiotic cover., ISICEM 2014
Lahiri R, Wong JLC, Bhattacharya S, et al., 2013, Enhanced monocyte function and surface TLR expression predict post-operative systemic inflammatory response syndrome in patients immediately following major hepatic and pancreatic resection., British Society for Gastroenterology
Lahiri R, Wong JLC, Waters J, et al., 2013, Increased expression of TLR4 and TLR5 following complex hepato-pancreatico-biliary (HPB) surgery predicts development of post-operative systemic inflammatory response syndrome (SIRS)., Society of Academic and Research Surgery (SARS) January Conference
Wong JLC, Brett SJ, 2013, The assessment and risk stratification of psychological morbidity in critical care survivors, CRITICAL CARE, Vol: 17, ISSN: 1466-609X
Mckie AB, Vaughan S, Zanini E, et al., 2012, The OPCML Tumor Suppressor Functions as a Cell Surface Repressor–Adaptor, Negatively Regulating Receptor Tyrosine Kinases in Epithelial Ovarian Cancer, Cancer Discovery
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