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A Pragmatic Bayesian Adaptive Trial Design Based on the Value of Information: The Value-Driven Adaptive Design

Clinical trial designs are typically narrowly focused on error control in hypothesis testing, but this approach is inadequate in many contexts, particularly when a decision maker intends to, or must, consider multiple relevant clinical and health economic outcomes under uncertainty. Value-of-information (VoI) metrics can be used to estimate the monetary value of data collection to the decision maker. 

Higher Promoter Methylation of the Ubiquitin-Associated and SH3 Domain Containing A (UBASH3A) Gene Is Associated With T-Lymphocyte Ontogeny and Reduced Susceptibility to Early-Onset Sepsis

We investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes, and immune cell counts from the EPIC-HIPC newborn cohort, we report that promoter methylation was negatively correlated with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. 

Safety, tolerability, and pharmacokinetics of a 2 g subcutaneous dose of ceftriaxone as an alternative to intravenous delivery

Subcutaneous delivery of antibiotics is a practical alternative to intravenous administration. Ceftriaxone is commonly used for a variety of infections with limited data on the safety and pharmacokinetics of a 2 g subcutaneous dose. This was a prospective, self-controlled cross-over study in 20 stable inpatients receiving ceftriaxone for their infection. Following an intravenous dose, participants received a single dose of 2 g subcutaneous ceftriaxone, in 50 mL normal saline via gravity feed.

Modelling Micro-Elimination: Third-Trimester Tenofovir Prophylaxis for Perinatal Transmission of Hepatitis B in the Remote Dolpa District of Nepal

Hepatitis B (HBV) prevalence is very high in pregnant women in the Dolpa district of Nepal, a region characterised by a remote geographic landscape and low vaccination coverage. Using mathematical modelling, we evaluated the impact of third-trimester tenofovir disoproxil fumarate (TDF) prophylaxis on HBV burden and estimated the time required to achieve HBV elimination in Dolpa. 

Fatigue Is a Key Contributor to Quality of Life in Heart Valve Disease and After Valve Replacement/Repair: A Qualitative Study

Heart valve disease (HVD) can cause morbidity and impairment of quality of life (QOL) both before and after intervention. However, descriptions of the QOL of people with HVD across the disease course are limited. We aimed to collect the experience of people living with HVD through qualitative interviews, focusing on how HVD impacts their self-perceived QOL.

Australian Group on Antimicrobial Resistance surveillance outcome programs - bloodstream infections and antimicrobial resistance patterns in Australian children and adolescents 2022 - 2023

Between January 2022 and December 2023, there were 1,827 bloodstream infection (BSI) isolates in 1,745 children and adolescents reported to the Australian Group on Antimicrobial Resistance (AGAR) surveillance outcome programs, with 40% of episodes in children aged < 12 months. 

Automated reporting of primaquine dose efficacy, tolerability and safety for Plasmodium vivax malaria using a systematic review and individual patient data meta-analysis

The antirelapse efficacy of primaquine is related to the total dose administered, whereas the risks of haemolysis and gastrointestinal intolerance are associated with the daily dose administered. National Malaria Control Programmes require local information on efficacy, tolerability and safety to optimize antimalarial treatment policies for Plasmodium vivax malaria control and elimination efforts.

Drug-resistant gram-negative bacterial infections in children in the Oceania region: review of the epidemiology, antimicrobial availability, treatment, clinical trial and pharmacokinetic

Gram-negative bacterial infections remain a major cause of morbidity and mortality in children and neonates globally, compounded by the rise of antimicrobial resistance. Barriers to paediatric antibiotic licencing lead to reduced availability of potentially effective agents for treatment. For children and neonates in the Oceania region, specific challenges remain including a paucity of surveillance data on local rates of antimicrobial resistance, and lack of availability of newer, more costly agents.

Understanding parental decisions to decline or delay infant RSV immunisation, nirsevimab, in Western Australia in 2024

In 2024, the government of Western Australia introduced 'nirsevimab', a monoclonal antibody offering protection from respiratory syncytial virus (RSV), for eligible infants. This study explores why parents of infants who were eligible to receive nirsevimab opted to decline or delay the immunisation.

BEAT-BK: An Adaptive, Randomized Controlled Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Kidney-pancreas Transplantation Recipients (BEAT-BK) Study Protocol

BK polyomavirus (BKPyV) is a common opportunistic infection in kidney transplant recipients, typically reactivating in the context of immunosuppression. Although asymptomatic in immunocompetent individuals, reactivation in transplant recipients can cause BKPyV-associated nephropathy (BKPyVAN), a leading cause of graft dysfunction and loss. BKPyV viremia affects approximately 10%-15% of transplant recipients, and once BKPyVAN is established, the risk of graft failure can exceed 50%.