Additional file 2: of Use of the Theoretical Domains Framework to evaluate factors driving successful implementation of the Accelerated Chest pain Risk Evaluation (ACRE) project

Collated survey responses. (XLSX 22 kb

1955-1956

ACRE project implementation evaluation questionnaire. (DOC 105 kb

The spectrum, severity and outcomes of rheumatic mitral valve disease in pregnant women in Australia and New Zealand

Background: Rheumatic heart disease (RHD) poses significant perinatal risks. We aimed to describe the spectrum, severity and outcomes of rheumatic mitral valve disease in pregnancy in Australia and New Zealand. Methods: A prospective, population-based cohort study of pregnant women with RHD recruited 2013–14 through the hospital-based Australasian Maternity Outcomes Surveillance System. Outcome measures included maternal and perinatal morbidity and mortality. Univariable and multivariable logistic regression analyses were undertaken to test for predictors of adverse maternal and perinatal outcomes. Results: Of 274 pregnant women identified with RHD, 124 (45.3%) had mitral stenosis (MS) and 150 (54.7%) had isolated mitral regurgitation (MR). One woman with mild MS/moderate MR died. There were six (2.2%) stillbirths and two (0.7%) neonatal deaths. Babies born to women with MS were twice as likely to be small-for-gestational-age (22.7% vs 11.4%, p=0.013). In women with MS, use of cardiac medication (AOR 7.42) and having severe stenosis (AOR 16.35) were independently associated with adverse cardiac outcomes, while NYHA class >1 (AOR 3.94) was an independent predictor of adverse perinatal events. In women with isolated MR, use of cardiac medications (AOR 7.03) and use of anticoagulants (AOR 6.05) were independently associated with adverse cardiac outcomes. Conclusions: Careful monitoring and specialist care for women with RHD in pregnancy is required, particularly for women with severe MS, those on cardiac medication, and those on anticoagulation, as these are associated with increased risk of adverse maternal cardiac outcomes. In the context of pregnancy, contraception and preconception planning are important for young women diagnosed with RHD

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial

<div><p>Background</p><p>Group A streptococcus (GAS) is a serious human pathogen that affects people of different ages and socio-economic levels. Although vaccination is potentially one of the most effective methods to control GAS infection and its sequelae, few prototype vaccines have been investigated in humans. In this study, we report the safety and immunogenicity of a novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX (J8-DT), when delivered intramuscularly to healthy adults.</p><p>Methods</p><p>A randomized, double-blinded, controlled Phase I clinical trial was conducted in 10 healthy adult participants. Participants were randomized 4:1 to receive the vaccine candidate (N = 8) or placebo (N = 2). A single dose of the vaccine candidate (MJ8VAX), contained 50 μg of peptide conjugate (J8-DT) adsorbed onto aluminium hydroxide and re-suspended in PBS in a total volume of 0.5 mL. Safety of the vaccine candidate was assessed by monitoring local and systemic adverse reactions following intramuscular administration. The immunogenicity of the vaccine was assessed by measuring the levels of peptide (anti-J8) and toxoid carrier (anti-DT)—specific antibodies in serum samples.</p><p>Results</p><p>No serious adverse events were reported over 12 months of study. A total of 13 adverse events (AEs) were recorded, two of which were assessed to be associated with the vaccine. Both were mild in severity. No local reactogenicity was recorded in any of the participants. MJ8VAX was shown to be immunogenic, with increase in vaccine-specific antibodies in the participants who received the vaccine. The maximum level of vaccine-specific antibodies was detected at 28 days post immunization. The level of these antibodies decreased with time during follow-up. Participants who received the vaccine also had a corresponding increase in anti-DT serum antibodies.</p><p>Conclusions</p><p>Intramuscular administration of MJ8VAX was demonstrated to be safe and immunogenic. The presence of DT in the vaccine formulation resulted in a boost in the level of anti-DT antibodies.</p><p>Trial registration</p><p>ACTRN12613000030774</p></div

AEs recorded in the study.

<p>AEs recorded in the study.</p

J8-specific (Panel A) and DT-specific (Panel B) serum IgG concentrations for each participant at Days 0, 28, 180, 266 and 350.

<p>J8-specific (Panel A) and DT-specific (Panel B) serum IgG concentrations for each participant at Days 0, 28, 180, 266 and 350.</p

Demographic profile of enrolled participants.

<p>Demographic profile of enrolled participants.</p

Participation flow.

<p>Ten (10) out of 38 participants that were screened for this study, were randomized to receive either the vaccine candidate or placebo. None of the participants received a second vaccination. Five of participants that received a vaccine candidate withdrew from the study by Day 287. All efficacy and safety data recorded at different time points for the participants in this study were included in the analysis.</p