Publications by authors named "Stephen P J Macdonald"

Background: Anaphylaxis is a severe, potentially life-threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department (ED).

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Objective: We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement.

Methods: This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway.

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Introduction: Accurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown.

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Objective And Design: Hypertonic saline administered during fluid resuscitation may mitigate endothelial glycocalyx (EG) shedding and inflammation. The objective of this pilot randomised controlled trial was to measure the effect of hypertonic saline, compared to isotonic saline, on biomarkers of EG shedding and inflammation in emergency department patients with suspected sepsis.

Methods: Patients received either 5 mL/kg of 3% saline (hypertonic group, n = 34) or 10 mL/kg of 0.

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Purpose: To determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis.

Methods: A prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6 h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100 mmHg, after minimum 1000 ml of IV fluid. Primary outcome was total fluid administered within 6 h post randomisation.

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Background: We have previously identified the upregulation of the innate immune response, neutrophil activation, and apoptosis during anaphylaxis using a microarray approach. This study aimed to validate the differential gene expression and investigate protein concentrations of "hub genes" and upstream regulators during anaphylaxis.

Methods: Samples were collected from patients with anaphylaxis on their arrival at the emergency department, and after 1 and 3 h.

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Purpose: Endocan, a component of the endothelial glycocalyx (EG), has been linked with respiratory failure in sepsis. This study explored the temporal patterns of three EG biomarkers, including endocan, and their relationships with inflammation and respiratory failure.

Materials And Methods: Plasma endocan, syndecan-1, and hyaluronan concentrations were measured in Emergency Department (ED) patients with sepsis due to pneumonia (n = 44) on ED arrival (T0), 1 h (T1), 3 h (T3) and 12-24 h (T24) later, with change over time tested using mixed regression models.

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Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion.

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Objectives: Sepsis is acute organ dysfunction in the setting of infection. An accurate diagnosis is important to guide treatment and disposition. Tissue oxygen saturation (StO2) can be estimated noninvasively by near-infrared spectroscopy (NIRS), and may be an indicator of microcirculatory dysfunction in early sepsis.

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Background: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis.

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Purpose: Endothelial glycocalyx (EG) shedding may promote organ failure in sepsis. This study describes temporal changes in EG biomarkers from Emergency Department (ED) arrival, and associations with clinical characteristics.

Materials And Methods: This prospective observational study included 23 patients with simple infection, 86 with sepsis and 29 healthy controls.

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Objective And Design: Resistin and neutrophil gelatinase-associated lipocalin (NGAL) are upregulated in circulating leucocytes in sepsis, but the significance of this is uncertain. We evaluated associations between Resistin and NGAL with endothelial cell activation and clinical outcomes in a prospective observational study in the Emergency Department (ED).

Methods: Serum levels of Resistin, NGAL, inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules (VCAM-1, ICAM-1) were measured at defined time points up to 24 h.

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Objectives: The Predisposition Insult Response and Organ failure (PIRO) scoring system has been developed for use in the emergency department (ED) to risk stratify sepsis cases, but has not been well studied among high-risk patients with severe sepsis and septic shock. The PIRO score was compared with the Sequential Organ Failure Assessment (SOFA) and Mortality in ED Sepsis (MEDS) scores to predict mortality in ED patients with features suggesting severe sepsis or septic shock in the ED.

Methods: This was an analysis of sepsis patients enrolled in a prospective observational ED study of patients presenting with evidence of shock, hypoxemia, or other organ failure.

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Article Synopsis
  • The study aimed to identify specific biomarkers that can differentiate severe sepsis/septic shock from uncomplicated sepsis in patients visiting the Emergency Department.
  • Researchers collected blood samples from patients at multiple time points and analyzed messenger RNA levels of 13 genes linked to immune response and organ dysfunction, alongside serum protein concentrations.
  • Results showed that certain genes and proteins, particularly IL-10, NGAL, and Resistin, were significantly elevated in severe sepsis cases and remained higher over the first 24 hours, suggesting their potential role in early identification and risk assessment for patient deterioration.
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Study Objective: Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia.

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Background And Aims: The conventional approach to sepsis resuscitation involves early interventions targeting global oxygenation and macro-haemodynamic variables such as central venous and systemic arterial pressures. There is increasing recognition of the importance of microcirculatory changes in shock states, including sepsis, and the relationship of these to outcome. Near-infrared spectroscopy (NIRS) is a recently developed non-invasive technology that measures tissue oxygen saturations (StO2), which may be an indirect measure of the adequacy of the microcirculation.

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Aim: The Thrombolysis in Myocardial Infarction (TIMI) risk score (range 0-7), used for emergency department (ED) risk stratification of patients with suspected acute coronary syndrome (ACS), underestimates risk associated with ECG changes or cardiac troponin elevation. A modified TIMI score (mTIMI, range 0-10), which gives increased weighting to these variables, has been proposed. We aimed to evaluate the performance of the mTIMI score in ED patients with suspected ACS.

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Objectives: To determine whether a booked appointment time improves early outpatient exercise stress testing (EST) guideline adherence in patients discharged from the ED following assessment for possible acute coronary syndrome (ACS).

Methods: In this pre and post study with a historical control group, patients classified as intermediate risk after negative ECG and serial troponin work-up for possible ACS were referred for EST. The intervention group were given an appointment time for EST at discharge, and the control group were given a referral but asked to book their own appointment.

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Objective: To evaluate the accuracy of a 2-h serial multiple biomarker (SMB) protocol for exclusion of myocardial infarction (MI) in the Emergency Department.

Methods: A prospective, multicentre, observational study enrolled patients undergoing evaluation for possible MI. Blood samples at presentation and 2 h later were analysed for myoglobin, creatinine kinase-MB, troponin-I and B-natriuretic peptide.

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Objective: To compare two methods of risk stratification for suspected acute coronary syndrome (ACS) in the ED.

Methods: A prospective observational multicentre study was undertaken of patients undergoing evaluation in the ED for possible ACS. We compared the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (NHF/CSANZ) guideline and the Thrombolysis in Myocardial Infarction (TIMI) risk score for differentiating high- and low-risk patients.

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