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Li L.,Vaxine Pty Ltd | Honda-Okubo Y.,Vaxine Pty Ltd | Li C.,Vaxine Pty Ltd | Sajkov D.,Australian Respiratory and Sleep Medicine Institute | And 2 more authors.
PLoS ONE | Year: 2015

There is a major need for new adjuvants to improve the efficacy of seasonal and pandemic influenza vaccines. Advax is a novel polysaccharide adjuvant based on delta inulin that has been shown to enhance the immunogenicity of influenza vaccine in animal models and human clinical trials. To better understand the mechanism for this enhancement, we sought to assess its effect on the plasmablast response in human subjects. This pilot study utilised cryopreserved 7 day post-vaccination (7dpv) peripheral blood mononuclear cell samples obtained from a subset of 25 adult subjects from the FLU006-12 trial who had been immunized intramuscularly with a standard dose of 2012 trivalent inactivated influenza vaccine (TIV) alone (n=9 subjects) or combined with 5mg (n=8) or 10mg (n=8) of Advax adjuvant. Subjects receiving Advax adjuvant had increased 7dpv plasmablasts, which in turn exhibited a 2-3 fold higher rate of non-silent mutations in the B-cell receptor CDR3 region associated with higher expression of activation-induced cytidine deaminase (AID), the major enzyme controlling BCR affinity maturation. Together, these data suggest that Advax adjuvant enhances influenza immunity in immunized subjects via multiple mechanisms including increased plasmablast generation, AID expression and CDR3 mutagenesis resulting in enhanced BCR affinity maturation and increased production of high avidity antibody. How Advax adjuvant achieves these beneficial effects on plasmablasts remains the subject of ongoing investigation. © 2015 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Lee S.-D.,University of Ulsan | Huang M.-S.,Kaohsiung Medical University | Kang J.,Liaoning Medical University | Lin C.-H.,Changhua Christian Hospital | And 5 more authors.
Respiratory Medicine | Year: 2014

We evaluated the predictive value of the COPD assessment test (CAT™) for exacerbation in the following six months or time to first exacerbation among COPD patients with previous exacerbations. COPD outpatients with a history of exacerbation from 19 hospitals completed the CAT questionnaire and spirometry over six months. Exacerbation events were prospectively collected using a structured questionnaire. The baseline CAT score categorised into four groups (0-9, 10-19, 20-29, and 30-40) showed strong prediction for time to first exacerbation and modest prediction for any exacerbation or moderate-severe exacerbation (AUC 0.83, 0.64, and 0.63 respectively). In multivariate analyses, the categorised CAT score independently predicted all three outcomes (p = 0.001 or p < 0.001). Compared with the lowest CAT score category, the higher categories were associated with significantly shorter time to first exacerbation and higher exacerbation risks. The corresponding adjusted median time was >24, 14, 9, and 5 weeks and the adjusted RR was 1.00, 1.30, 1.37, and 1.50 in the category of 0-9, 10-19, 20-29, and 30-40 respectively. Exacerbation history (≥2 vs. 1 event in the past year) was related to time to first exacerbation (adjusted HR 1.35; p = 0.023) and any exacerbation during the study period (adjusted RR 1.15; p = 0.016). The results of this study support the use of the CAT as a simple tool to assist in the identification of patients at increased risk of exacerbations. This could facilitate timely and cost-effective implementation of preventive interventions, and improve health resource allocation. Trial registration Clinicaltrials.gov: NCT01254032. © 2014 Elsevier Ltd. All rights reserved.

Zangiabadi A.,Australian Respiratory and Sleep Medicine Institute | De Pasquale C.G.,Flinders Medical Center | Sajkov D.,Australian Respiratory and Sleep Medicine Institute
BioMed Research International | Year: 2014

Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH. Copyright © 2014 Amirmasoud Zangiabadi et al.

Sajkov D.,Australian Respiratory and Sleep Medicine Institute | Gallus A.,Australian Respiratory and Sleep Medicine Institute | Gallus A.,Flinders Medical Center
Clinical Medicine Insights: Case Reports | Year: 2015

Rivaroxaban is an orally active direct factor Xa inhibitor used to treat venous thromboembolism with approved starting dose of 15 mg twice-daily. We present a case of an accidental overdose in a patient with pulmonary thromboembolism, when the patient received two 150 mg doses of rivaroxaban, instead of 15 mg as prescribed, given 12 hours apart. This error was recognised ten minutes after the second dose, when 50 gm oral activated charcoal was given. Rivaroxaban was stopped and rivaroxaban concentrations, INR, and APTT were monitored. The overdose was uncomplicated and 15 mg twice-daily rivaroxaban was restarted on day two. Apparently unlikely and potentially hazardous dispensing errors do happen. Each oral anticoagu-lant has a different dosing schedule. In our patient, the prescription for 15 mg twice-daily rivaroxaban was misread as 150 mg twice-daily (a correct dose for dabigatran in atrial fibrillation). Such errors are preventable. Prompt administration of activated charcoal under monitoring of a specific rivaroxaban assay can greatly help management of unusual situations like this one. © the authors, publisher and licensee Libertas Academica Limited.

Petrovsky N.,Vaxine Pty Ltd | Petrovsky N.,Flinders University | Petrovsky N.,Australian Respiratory and Sleep Medicine Institute | Honda-Okubo Y.,Vaxine Pty Ltd | And 3 more authors.
Trials in Vaccinology | Year: 2013

The Stratis® disposable syringe jet injection (DSJI) system (PharmaJet Inc., Denver, USA) delivers vaccine utilizing a spring powered energy source to create a fine high-velocity jet of liquid that directly penetrates the skin without using a needle. We performed a study to collect data on the effect of the Stratis DSJI device on influenza immunization in 46 predominantly elderly subjects (28M, 18F; mean age 61 years) who were randomized 1:1 to receive Fluvax 2012 trivalent inactivated influenza vaccine via prefilled N-S or Stratis DSJI. H1N1 seroprotection was not significantly different for vaccine delivered by DSJI (86.4%, 95% CI 72.1-100) or N-S (79.2%, 95% CI 63.0-95.4), and likewise for H3N2 and B strains. The DSJI had a ∼2-fold higher mean injection pain score (DSJI: 3.0 versus N-S 1.58, p = 0.045) plus increased rates of swelling and tenderness but this was offset by a lower rate of elicited systemic reactions, particularly the frequency of post-immunization headaches (DSJI: 9% vs N-S: 33.3%). This study suggests that subject to confirmation of non-inferiority in an appropriately powered study, the Stratis DSJI is a viable alternative strategy for the administration of seasonal influenza vaccines with particular appeal for individuals with needle phobia. Australia New Zealand Clinical Trials Register: ACTRN12612000709842. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

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