Development of a Mobile Laboratory for Sudden Onset Disasters.

Objectives: Clinical diagnostics in sudden onset disasters have historically been limited. We set out to design, implement, and evaluate a mobile diagnostic laboratory accompanying a type 2 emergency medical team (EMT) field hospital.

Methods: Available diagnostic platforms were reviewed and selected against in field need.

Melioidosis Causing Critical Illness: A Review of 24 Years of Experience From the Royal Darwin Hospital ICU.

Objectives: Melioidosis is increasing in incidence with newly recognized foci of melioidosis in the Americas, Africa, and elsewhere. This review describes the demographics, management, and outcomes of a large cohort of critically ill patients with melioidosis.

Design: Data were extracted from two prospective databases-the Menzies School of Health Research Melioidosis Database (1989-2013) and the Royal Darwin Hospital ICU Melioidosis Database (2001-2013).

An observational cohort study of the kynurenine to tryptophan ratio in sepsis: association with impaired immune and microvascular function.

Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology.

Sepsis in the tropical Top End of Australia's Northern Territory: disease burden and impact on Indigenous Australians.

Objective: To describe the clinical and epidemiological features of sepsis and severe sepsis in the population of the tropical Top End of the Northern Territory of Australia and compare these with published estimates for temperate Australia, the United States and Europe.

Design, Setting And Participants: Prospective cohort study in the major hospital for tropical NT, a region where 27% of the population are Indigenous. We screened all adult (≥ 15 years) acute hospital admissions over a 12-month period (6 May 2007-5 May 2008) for sepsis by standard criteria, and collected standardised clinical data.

Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis.

Background: Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelial dysfunction, but the role of ADMA in acute inflammatory states is less well defined.

Methods And Results: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digital microvascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2-4 days later. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography.

Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity.

Introduction: Angiopoietin-2 (ang-2), an angiogenic peptide released by endothelial cell Weibel-Palade bodies (WPBs), increases endothelial activation and vascular permeability. Ang-2 is raised in severe sepsis but the mechanisms underlying this are not known. Nitric oxide (NO) inhibits WPB exocytosis, and bioavailability of endothelial NO is decreased in sepsis.

Particulate face masks for protection against airborne pathogens - one size does not fit all: an observational study.

Objective: To determine the proportion of hospital staff who pass fit tests with each of three commonly used particulate face masks, and factors influencing preference and fit test results.

Design: Observational study.

Setting And Participants: 50 healthy hospital staff volunteers in an 18-bed general intensive care unit in an Australian teaching hospital.

Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry: an observational study.

Introduction: Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations.

Septic shock: the changing Zeitgeist of management.

Most interventions in critically unwell patients with septic shock are poorly supported by evidence, in part reflecting the difficulty of conducting trials in this heterogeneous group. Four important clinical trials in 2001-2 appeared to demonstrate mortality benefits associated with early goal-directed resuscitation, intensive glycaemic control, physiological-dose steroid replacement and activated protein C. However, recent evidence has not confirmed the beneficial effect of these interventions.

Infective endocarditis with Abiotrophia defectiva: the first Australian experience.

A 40-year old Indigenous woman with a history of mitral valve replacement was admitted to the Royal Darwin Hospital, Northern Territory, for an elective cone biopsy of the cervix. During the admission, she had recurrent fever and joint pain of the left knee. Blood was cultured, and she was treated with broad-spectrum antibiotics.

Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock.

Objective: To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis.

Design: A randomized, placebo-controlled, double-blinded clinical trial.

Setting And Patients: Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit.

A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand.

Background: Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis.

Methods: In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 mu g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand.

A clinical audit of the efficacy of tegaserod as a prokinetic agent in the intensive care unit.

Objective: To formally document the effectiveness of tegaserod as a prokinetic agent in intensive care patients.

Methods: The audit was designed in consultation with the Northern Territory Drug and Therapeutics Committee. Tegaserod was added to the feeding protocol and prokinetic algorithm in the ICU, and a prospective audit was performed of patients receiving the medication between May and September 2006.

Murray Valley encephalitis in an adult traveller complicated by long-term flaccid paralysis: case report and review of the literature.

Murray Valley encephalitis (MVE) virus, a mosquito-borne flavivirus, is the most common cause of viral encephalitis in the tropical 'Top End' of northern Australia. Clinical encephalitis due to MVE virus has a mortality rate of approximately 30%, with a similar proportion of patients being left with significant neurological deficits. We report the case of a 25-year-old man from the UK who acquired MVE while travelling through northern Australia.

Leptospirosis: an unusual presentation.

Leptospirosis is a common zoonosis that is endemic in the tropical Top End of the Northern Territory. Disease ranges from mild to very severe. We report a patient with anicteric leptospirosis who became critically ill, challenging the view that anicteric leptospirosis is less severe than the icteric form.

Outcomes of patients with melioidosis treated with meropenem.

Melioidosis, an infection due to Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We reviewed our experience with meropenem in the treatment of severe melioidosis in 63 patients over a 6-year period. Outcomes were similar to those of ceftazidime-treated patients (n = 153) despite a deliberate selection bias to more-unwell patients receiving meropenem.

Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis.

Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is endemic in northern Australia and Southeast Asia. Risk factors for this infection have also been associated with functional neutrophil defects. Because of this, granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients with septic shock due to melioidosis in December 1998.

Ethical problems of evaluating a new treatment for melioidosis.

When mortality from melioidosis fell sharply after multiple changes in management at an Australian hospital, doctors wanted to identify whether a new drug was responsible. But designing a trial that was ethically acceptable proved impossible