Browsing by Author "Zygun, David"

Now showing 1 - 4 of 4
  • Thumbnail Image
    ItemOpen Access
    The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units
    (BioMed Central, 2008-12-18) Stelfox, Henry Thomas; Ahmed, Sofia B; Khandwala, Farah; Zygun, David; Shahpori, Reza; Laupland, Kevin B.
  • Thumbnail Image
    ItemOpen Access
    Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis
    (2024-11-19) Sligl, Wendy I.; Yan, Charles; Round, Jeff; Wang, Xiaoming; Chen, Justin Z.; Boehm, Cheyanne; Fong, Karen; Crick, Katelynn; Clua, Míriam G.; Codan, Cassidy; Dingle, Tanis C.; Prosser, Connie; Chen, Guanmin; Tse-Chang, Alena; Garros, Daniel; Zygun, David; Opgenorth, Dawn; Conly, John M.; Doig, Christopher J.; Lau, Vincent I.; Bagshaw, Sean M.
    Abstract Objective We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis. Methods We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer’s perspective. Two intensive care units in Alberta with 727 adult critically ill patients were included. Our bundled intervention was compared with pre-implementation standard care. We collected healthcare resource use and estimated unit costs in 2022 Canadian dollars (CAD) over a time horizon from study entry to hospital discharge or death. We calculated the incremental net monetary benefit (iNMB) of the intervention group compared with the pre-intervention group. The primary outcome was cost per sepsis case. Secondary outcomes included readmission rates, Clostridioides difficile infections, mortality, and lengths of stay. Uncertainty was investigated using cost-effectiveness acceptability curves, cost-effectiveness plane scatterplots, and sensitivity analyses. Results Mean (standard deviation [SD]) cost per index hospital admission was CAD $83,251 ($107,926) for patients in the intervention group and CAD $87,044 ($104,406) for the pre-intervention group, though the difference ($3,793 [$7,897]) was not statistically significant. Costs were higher in the pre-intervention group for antibiotics, readmissions, and C. difficile infections. The intervention group had a lower mean expected cost; $110,580 ($108,917) compared with pre-intervention ($125,745 [$113,210]), with a difference of $15,165 ($8278). There were no statistically significant differences in quality adjusted life years (QALYs) between groups. The iNMB of the intervention group compared with pre-intervention was greater than $15,000 for willingness-to-pay (WTP) per QALY values of between $0 and $100,000. In our sensitivity analysis, the intervention was most likely to be cost-effective in roughly 56% of simulations at all WTP thresholds. Conclusions Our bundled intervention of ASP, PCT, and BCID among adult critically ill patients with sepsis was potentially cost-effective, but with substantial decision uncertainty.
  • Thumbnail Image
    ItemOpen Access
    Identification and Evaluation of the Indications for Use of Damage Control Surgery and Damage Control Interventions in Civilian Trauma Patients
    (2015-04-30) Roberts, Derek; Zygun, David; Stelfox, Henry
    Although damage control (DC) surgery may improve survival in select, severely injured patients, the procedure is associated with significant morbidity, and therefore should only be used when appropriately indicated. The objective of this thesis was to identify and evaluate candidate indications for use of DC surgery and DC interventions in civilian trauma patients. We conducted a scoping review to identify candidate indications. Among 27,732 citations identified by the search, we included 270 articles that reported 1,107 indications for DC surgery and 424 indications for 16 DC interventions. We conducted a content analysis to synthesize these indications into 123 named, content-characteristic codes representing unique indications for DC surgery and 101 codes representing unique indications for DC interventions. An international panel of trauma surgery experts (n=9) subsequently assessed 101 (82.1%) of the coded indications for DC surgery and 78 (77.2%) of the coded indications for DC interventions to be appropriate. We conducted a systematic review to identify studies reporting data on the reliability or validity of indications or that assessed outcomes associated with utilization of an indication or indications or the conduct of DC versus definitive surgery for one or more indications. Among 31,014 citations identified, we included 36 studies that evaluated 79 unique indications. Of these, 19 had evidence of face validity or predictive criterion validity, six had evidence supporting that they were associated with improved survival when utilized or when DC was conducted instead of definitive surgery, and three had evidence suggesting that they were associated with reduced survival which may be improved with DC surgery. Finally, we conducted a cross-sectional survey of trauma centers and surgeons located in the United States, Canada, and Australasia. In total, 232 (64.8%) trauma centers responded. These centers nominated 366 surgeons to survey about indications for DC surgery, of whom 201 (56.0%) responded. Respondents assessed 15 (78.9%) preoperative and 23 (95.8%) intraoperative indications to be appropriate. The list of candidate indications for use of DC surgery and DC interventions identified in this thesis may provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient outcomes.
  • Thumbnail Image
    ItemOpen Access
    The Interrogation of Traumatic Brain Injury with MR Spectroscopy and Molecular Imaging
    (2016) Lama, Sanju; Sutherland, Garnette; Tomanek, Boguslaw; Colicos, Michael; Zygun, David; Gallagher, Clare
    Metabolic perturbations in early acute severe traumatic brain injury (TBI) using magnetic resonance (MR) spectroscopy, and the prospects of molecular imaging of repetitive mild TBI, form the driving principles of this thesis work. Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling, whereby glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. Using a weight drop model of severe TBI and MR spectroscopy with infusion of 13C labeled glucose, lactate and acetate, this portion of the thesis investigated the hypothesis that neuronal-glial metabolism is uncoupled following severe TBI. High resolution MR spectroscopy revealed significant labeling of lactate irrespective of the infused substrate and decreased labelling of other metabolites. Histopathology, while showing features of severe brain injury, also stained positive for tau. A microtubule associated protein, tau has been shown to accumulate in brains following TBI, particularly those related to sports and combat. It was further hypothesized that tau could be visualized through the administration of a unique anti-tau single domain antibody (sdAb)-nanoparticle complex. Through llama immunization, tau specific sdAbs were isolated, panned and characterized for bioconjugation to MR sensitive NaDyF4-NaGdF4 nanoparticles, towards non-invasive imaging of tau in vivo. At a ratio of ~4 sdAbs per nanoparticle, the complex was able to cross the neuronal membrane and bind to intracellular tau in live hippocampal neuronal cultures. Preliminary in vivo studies, establishing the model for repetitive mild TBI showed considerable tau staining within the entorhinal cortex, dentate gyrus and hippocampal CA3 sector sparing CA1. While there were some T1 changes in MR imaging, clinical translation will require further tests for sdAb – nanoparticle affinity to both tau and hyperphosphorylated tau, optimal dosage and safety, toxicology and clearance profile. It may be concluded that the early increase in brain lactate or lactate storm marks severe TBI; and tau abnormality and associated disrupted axonal transport, may be the hallmark of repetitive mild TBI, making it a potential MR visible biomarker for TBI. These concepts may guide future diagnostic and therapeutic directions.