3D microelectrode arrays, pushing the bounds of sensitivity toward a generic platform for point-of-care diagnostics.

The increased sensitivity of microelectrode arrays (MEAs) over macroelectrodes for biosensing is well established, and results from reducing the diffusion gradient of the target species to and from the electrode surfaces. The current study describes the fabrication and characterisation of a polymer-based MEA, which exploits the advantages of three dimensionality (3D). Firstly, the unique 3D formfactor promotes release of the gold tips from an inert layer in a controlled fashion, to form a highly reproducible array of microelectrodes in a single step. The 3D topography of the fabricated MEAs significantly enhances the diffusion profile of the target species to the electrode which results in higher sensitivity. Furthermore, the "sharpness" of the 3D structure induces differential current distribution that is focused at the apices of the individual electrodes, reducing the active area, and thereby overcoming the requirement for the electrodes to be sub-micron in size before true MEA behaviour can be achieved. The electrochemical characteristics of the 3D MEAs shows ideal micro-electrode behaviour, with a level of sensitivity of three orders of magnitude greater than that of enzyme-linked immunosorbent assays (ELISA), as the optical based gold standard. The application of the 3D MEAs uses the combination of enzyme-label and substrate approach employed in ELISAs as a generic basis for biosensing and can hence be applied to the plethora of targets that utilise the ELISA approach. As an example, the 3D MEAs are applied to the detection of RNA and demonstrate a level of detection down to single digit picomolar concentrations.

Raising the D-dimer threshold for ruling out pulmonary embolism: A single-site, observational study with a historical comparison.

OBJECTIVE: The objective of this study was to assess the impact of introduction of a new pulmonary embolism (PE) diagnostic guideline with a raised D-dimer threshold. METHODS: This is a single-site, observational, cohort study with a historical comparison. The new guideline raised the D-dimer threshold to 1000 ng/mL for most patients with a Wells' score of 4 or less. Patients investigated for PE with a D-dimer level and/or definitive imaging in 6-month periods before and after the introduction of the guideline were eligible. Patients with D-dimers of 500-1000 ng/mL were prospectively followed up at 3 months for missed PE. RESULTS: During the pre-intervention period, 688 patients were investigated for PE, 366 (53.2%) received definitive imaging and 39 PE were diagnosed (5.7% overall, 10.7% of those imaged). For the 121 patients with D-dimers ≥500 and <1000 ng/mL, 87 (71.9%) were imaged with 7 (5.8%) having a PE diagnosed. Post intervention there were 930 patients, of which 426 (45.8%) received definitive chest imaging and there were 50 patients with PE diagnosed (5.4% overall, 11.7% of those imaged). For the 185 patients with D-dimers ≥500 and <1000 ng/mL, 60 (32.4%) were imaged with 5 (2.7%) having PE diagnosed. No cases of missed PE were identified at 3 months. CONCLUSION: The introduction of the new guideline was associated with a reduction in overall imaging rates without evidence of missed PE. Further evaluation in other settings is recommended.

The profile, clinical characteristics, and outcomes of alcohol- and non-alcohol-related patient presentations to Queensland emergency departments: a multi-site observational study.

Objective The harmful use of alcohol is a global issue. This study aimed to describe and compare the profiles, emergency department (ED) clinical characteristics, and outcomes of alcohol-related ED presentations (ARPs) and non-alcohol-related ED presentations (NARPs). Methods A multi-site observational study of all presentations to four EDs between 4 April 2016 and 31 August 2017, was conducted. Routinely collected ED clinical, administrative and costings data were used. Classification of ARPs were prospectively recorded by clinicians. Analysis was performed at the presentation, rather than person level. Univariate tests were undertaken to compare demographics, ED clinical characteristics and outcomes between ARPs and NARPs. Results A total of 418 051 ED presentations occurred within the 17-month study period; 5% (n = 19 875) were ARPs. Presentations made by people classified as ARPs were younger, more likely to be male, present on weekends or at night, and arrive by ambulance or police compared to NARPs. Compared with NARPs, ARPs had a longer median ED length of stay of over 20 min (95% CI 18-22, median 196 min vs 177 min, P < 0.001), a 5.5% (95% CI 4.9-5.3) lower admission rate (36% vs 42%, P < 0.001), and a AUD69 (95% CI 64-75) more expensive ED episode-of-care (AUD689 vs AUD622, P < 0.001). Conclusion Clinically meaningful differences were noted between alcohol-related and non-alcohol-related ED presentations. The higher cost of care for ARPs likely reflects their longer time in the ED. The healthcare and economic implications of incidents of alcohol-related harm extend beyond the ED, with ARPs having higher rates of ambulance and police use than NARPs.

Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study.

RATIONALE: Severe acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only. OBJECTIVES: To identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma. METHODS: Retrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS). MEASUREMENTS AND MAIN RESULTS: Of 14 029 children (median age 3 (IQR 1-3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3-63.2 hours) than children without escalation 6.7 hours, IQR 3.5-16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%). CONCLUSIONS: Overall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation.

Diagnosis and management of idiopathic pulmonary fibrosis: Thoracic Society of Australia and New Zealand and Lung Foundation Australia position statements summary.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with debilitating symptoms of dyspnoea and cough, resulting in respiratory failure, impaired quality of life and ultimately death. Diagnosing IPF can be challenging, as it often shares many features with other interstitial lung diseases. In this article, we summarise recent joint position statements on the diagnosis and management of IPF from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia, specifically tailored for physicians across Australia and New Zealand. Main suggestions: A comprehensive multidisciplinary team meeting is suggested to establish a prompt and precise IPF diagnosis. Antifibrotic therapies should be considered to slow disease progression. However, enthusiasm should be tempered by the lack of evidence in many IPF subgroups, particularly the broader disease severity spectrum. Non-pharmacological interventions including pulmonary rehabilitation, supplemental oxygen, appropriate treatment of comorbidities and disease-related symptoms remain crucial to optimal management. Despite recent advances, IPF remains a fatal disease and suitable patients should be referred for lung transplantation assessment.

Treatment of idiopathic pulmonary fibrosis in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand and the Lung Foundation Australia.

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease (ILD) of unknown aetiology with a median survival of only 2-5 years. It is characterized by progressive dyspnoea and worsening lung function, ultimately resulting in death. Until recently, there were no effective therapies for IPF; however, with the publication of two landmark clinical trials in 2014, the anti-fibrotic therapies, nintedanib and pirfenidone, have gained widespread approval. This position paper aims to highlight the current evidence for the treatment of IPF, with particular application to the Australian and New Zealand population. We also consider areas in which evidence is currently lacking, especially with regard to the broader IPF severity spectrum and treatment of co-morbid conditions. The utility of non-pharmacological therapies including pulmonary rehabilitation, oxygen as well as symptom management thought to be important in the holistic care of IPF patients are also discussed.

Self-assembly of cross-linked beta-cyclodextrin nanocapsules.

Stirring of perthiolated beta-cyclodextrin in water yields cross-linked hollow capsules ca. 50 nm in diameter, which can be used for encapsulation and controlled release of large molecules as shown using Reichardt's dye.

Inclusion complexes of cyclodextrins with nitroxide-based spin probes in aqueous solutions.

Formation of inclusion complexes between several cyclodextrin derivatives and TEMPO and DOXYL-based spin probes was studied by EPR spectroscopy. Competition between alkyl chains and nitroxide functionalities for cyclodextrin cavities leads to different types of complexation. Long alkyl chains in amphiphilic spin probes interact preferentially with cyclodextrins, and TEMPO units in such molecules are unaffected by complexation. DOXYL-type spin probes however form stronger complexes with cyclodextrins; this complexation changes hyperfine splitting and tumbling rate of the nitroxide group. Comparison of EPR spectra of free cyclodextrin and cyclodextrin-based polymeric nanocapsules made it possible to assess the tumbling of the spin probe inside the cyclodextrin units without the contribution of the tumbling of the whole complex.