The Telethon Kids Institute is an Australian medical research institute focused on the prevention of paediatric disease and the development of improved treatments to improve the health and wellbeing of children. Telethon Kids has developed a particular focus on Aboriginal health and has more than 500 staff, post-graduate students and visiting scholars. Telethon Kids is located in the Perth suburb of Nedlands, in the Perth Children's Hospital building. Telethon Kids is an independent not-for-profit, non-government organisation with close affiliations with the University of Western Australia and the Perth Children's Hospital. It is named after the Channel Seven Perth Telethon.Established in 1990 by Professor Fiona Stanley AC, FAA, the Director of the Institute since July 2012 is Professor Jonathan Carapetis. Stanley presently holds the role of Patron.
Objective To estimate the global, regional and national burden of maternal haemorrhage (2000–2021) and its 2050 projections in 204 countries and territories.Design This study systematic analysis of the burden of maternal haemorrhage sourced data from the Global Burden of Disease (GBD) 2021 study. We estimated the incidence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs) and years of life lost (YLLs) due to maternal haemorrhage. Changes in the burden from 2000 to 2021 were computed using AAPC. To detect statistically notable changes in the trends of maternal haemorrhage metrics between 2000 and 2021, Joinpoint regression analysis using the Joinpoint Regression Programme was conducted. We also projected mortality rates, YLDs and YLLs through to 2050 using maps and trends generated by the GBD Foresight visualisation tool.Results Globally, the incidence of maternal haemorrhage among women aged 15–49 years declined from 881.98 per 100 000 reproductive aged women (95% uncertainty interval (UI) 687.01 to –1150.23) in 2000 to 714.00 (95% UI 556.97 o t908.54) in 2021, with an average annual percentage change (AAPC) of –0.91 (–1.37 to –0.49). Similar downward trends were observed for maternal deaths, DALYs, YLDs and YLLs attributable to maternal haemorrhage, with AAPCs of –3.78 (–4.39 to –3.18), –4.68 (–4.83 to –4.55), –1.21 (–1.54 to –0.89) and –4.80 (–5.10 to –4.52), respectively. Sub-Saharan Africa, particularly Western Sub-Saharan Africa, recorded the highest burden in 2021, which is almost 300 times higher than in Western Europe. Elevated rates of mortality, DALYs and YLDs were also evident in Sierra Leone, Chad, Niger, Mali, Nigeria, Burkina Faso, Central African Republic, Somalia and South Sudan in 2021 and projections for 2050. However, the high-income Asia Pacific region had the lowest incidence, DALYs and YLDs at 151.32 (109.63–203.68), 2.21 (1.72–2.86) and 0.87 (0.46–1.38) per 1 00 000 women, respectively. Australasia recorded the lowest maternal death count and YLLs attributed to maternal haemorrhage at 0.69 (0.50–0.90) and 0.56 (0.41–0.74) per 1 00 000 women, respectively.Conclusion While the global burden of maternal haemorrhage has declined over time, significant regional and national inequities persist. Even though the 2050 projections show improvement in the burden of maternal haemorrhage, there is also regional and national variation in the rate of decrease in maternal haemorrhage burden. Targeted, context-specific interventions are urgently needed to reduce maternal haemorrhage-related mortality and morbidity.
Hemagglutination inhibiting (HI) antibody responses against influenza A(H3N2) vaccine strains decline with increasing years of vaccination. It is hypothesized that memory B cell dominance may direct antibody responses towards epitopes conserved with previously-encountered vaccine strains, including non-HI epitopes. To investigate this, we compared healthcare workers with zero versus five consecutive years of vaccination prior to enrolment in 2020 or 2021. We evaluated HI antibody reactivity across 25 A(H3N2) viruses spanning 2007-2022 and antibody binding to recombinant hemagglutinins (HA). HI antibody responses were poor across strains for participants vaccinated five compared to zero of five prior years, independent of pre-vaccination titre. HA and HA-stem binding antibody titre-rises were likewise attenuated in the repeatedly vaccinated group. These results provide no evidence that repeated vaccination promotes antibodies targeting conserved epitopes, rather, repeated vaccination broadly attenuates antibody responses. Work is ongoing to investigate whether attenuation reflects deficient memory B cell differentiation into plasmablasts.
Neonatal sepsis-induced cardiovascular dysfunction includes impaired myocardial function (which may be systolic and/or diastolic) and vasoregulatory failure (which may lead to vasodilation or vasoconstriction). The haemodynamic response in neonatal sepsis may therefore be hyperdynamic or hypodynamic, and the underlying pathophysiological mechanisms are heterogenous. The assessment of the neonate with sepsis and cardiovascular dysfunction is critical for targeted pathophysiology-based management. However, this assessment is challenging; it may include clinical features, echocardiography, electrocardiography and heart rate variability monitoring, non-invasive cardiac output monitoring (NICOM), near-infrared spectroscopy (NIRS) and biomarkers. Neonatologist performed echocardiography (NPE), in particular, can aid in the evaluation of the pathophysiological mechanism of cardiovascular dysfunction specific to each patient and further guide individualised management. IMPACT: WHAT DOES THIS ARTICLE ADD TO THE EXISTING LITERATURE?: This review provides an integrative overview of current methods for assessing cardiovascular dysfunction in neonatal sepsis, combining clinical evaluation with echocardiographic, electrocardiographic, non-invasive hemodynamic (NICOM, NIRS), and biomarker-based approaches to support early recognition and management.
Chronic Pseudomonas aeruginosa lung infections are becoming harder to treat due to global escalation of antimicrobial resistance (AMR). Bacteriophage (phage) therapy has emerged as a promising adjunct to conventional antibiotics, especially in chronic lung infections such as those seen in cystic fibrosis (CF). However, phage monotherapy may be limited by the emergence of phage-resistant bacterial populations and there remains limited preclinical evidence evaluating both antimicrobial efficacy and host safety in physiologically relevant human airway models. Here, we evaluated the safety and antimicrobial activity of Kara-mokiny 3, a myovirus bacteriophage, alone and in combination with subinhibitory concentrations of tobramycin using fully differentiated paediatric primary airway epithelial cells (pAECs) cultured at the air-liquid interface (ALI). Kara-mokiny 3 rapidly reduced P. aeruginosa viability and exhibited synergistic activity with tobramycin, resulting in significantly greater bacterial killing than either treatment alone. Importantly, phage treatment replicated efficiently in the presence of its bacterial host while preserving epithelial morphology, mucin production and epithelial barrier architecture., without inducing cytotoxicity or excessive IL-6 and IL-8 inflammatory responses. These findings demonstrate that phage-antibiotic combination therapy can enhance antimicrobial activity while maintaining epithelial safety in a physiologically relevant human airway model. This study represents one of the first comprehensive evaluations of phage-antibiotic combination therapy in differentiated primary airway epithelial cultures, providing important preclinical evidence supporting the development of personalised phage-based therapies for the treatment of MDR pulmonary infections.
