'Fighting every day': exploring caregiver quality of life and perspectives on healthcare services for children with dementia - a cross-sectional, mixed-methods study.

Objective: To explore quality of life outcomes for caregivers of children with childhood dementia including the positive and negative impact of caregiving. The secondary aim was to explore caregivers' perspectives on healthcare services for children with dementia.

Design: Cross-sectional, mixed-methods study with analyses of quantitative and qualitative data collected via online survey.

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Leukemia escapes immunity by imposing a Type-1 regulatory program on neoantigen-specific CD4+ T cells.

The significance of endogenous immune surveillance in acute lymphoblastic leukemia (ALL) remains controversial. Using clinical B-ALL samples and a novel mouse model, we show that neoantigen-specific CD4+ T cells are induced to adopt type-1 regulatory (Tr1) function in the leukemia microenvironment. Tr1s then inhibit cytotoxic CD8+ T cells, preventing effective leukemia clearance.

A contemporary analysis of the Australian clinical and genetic landscape of spinal muscular atrophy: a registry based study.

Background: New paradigms of diagnosis and treatment have changed the neurodegenerative trajectory for individuals with spinal muscular atrophy (SMA). Registries are a critical tool to provide real-world data on treatment patterns, their effects and health care provision within this evolving paradigm of care. This study aimed to evaluate the phenotypic and genotypic landscape, treatment patterns and health impact of SMA in Australia through the national registry.

Codesign and evaluation of advanced therapeutic information resources for and with families of children with neurological conditions: a mixed methods cross-sectional study.

Objective: Parents and caregivers of children with neurological conditions express interest in new and developing treatments and trials; however, they have limited knowledge of, and access to, reliable information. This study aims to empower and equip decision-making and support communication in the application of advanced neurotherapeutics and personalised medicine, covering gene therapy, stem cell therapy, neurostimulation and neuroimmunotherapies.

Design: A suite of online psychoeducational resources has been created and evaluated to establish implementation success.

Clinician Understanding, Acceptance and utilization of Ketogenic diet therapy for epilepsy in Australia and New Zealand: An online survey.

Ketogenic diet therapy (KDT) is an established treatment for people with epilepsy. As increasing evidence demonstrates effectiveness and safety of KDT on seizure reduction, cognition and behaviour, it is essential to evaluate factors hindering and supporting neurologists in prescribing KDT to strengthen quality, evidence-based, appropriate and equitable care. A study of Australian and New Zealand (ANZ) neurologists was undertaken via an online survey.

A feasibility study of controlled human infection with intradermal Bacillus Calmette-Guérin (BCG) injection: Pilot BCG controlled human infection model.

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden.

Patient Preferences for First-Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma: An Application of Multidimensional Thresholding.

Objectives: Patient preferences have the potential to influence the development of new treatments for locally advanced/metastatic urothelial carcinoma (la/mUC), and therefore we explored how patients with la/mUC value different attributes of first-line treatments.

Methods: An online preference survey and multidimensional thresholding (MDT) exercise were developed following a targeted literature review and qualitative interviews with physicians, patients with la/mUC, and their caregivers. Treatment attributes included two benefits (overall response rate [ORR], pain related to bladder cancer [scored 0-100; 100 being the worst pain possible]) and four treatment-related risks (peripheral neuropathy, severe side effects, mild to moderate nausea, mild to moderate skin reactions).

RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding.

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus.

Clinician Perceptions of Family-Centered Care in Pediatric and Congenital Heart Settings.

Importance: Family-centered care recognizes families as central to child health and well-being and prioritizes clinician collaboration with families to ensure optimal pediatric care and outcomes. Clinician interpersonal sensitivity and communication skills are key to this approach.

Objective: To examine perceptions of and factors associated with family-centered care among clinicians working in pediatric and congenital heart care.

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

Introduction: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs.

Newborn screening for Duchenne muscular dystrophy: the perspectives of stakeholders.

Background: The rapidly evolving clinical landscape of Duchenne muscular dystrophy (DMD) is driving innovative approaches for early diagnosis through genomic newborn bloodspot screening (NBS). However, the potential impact of these programs on families and healthcare systems remains unexplored. This study assessed the perceived benefits, harms, barriers, and enablers for DMD NBS amongst primary caregivers of children with DMD and healthcare professionals (HCPs).

'Integrating Ethics and Equity with Economics and Effectiveness for newborn screening in the genomic age: A qualitative study protocol of stakeholder perspectives.

Background: Newborn bloodspot screening is a well-established population health initiative that detects serious, childhood-onset, treatable conditions to improve health outcomes. With genomic technologies advancing rapidly, many countries are actively discussing the introduction of genomic assays into newborn screening programs. While adding genomic testing to Australia's newborn screening program could improve outcomes for infants and families, it must be considered against potential harms, ethical, legal, equity and social implications, and economic and health system impacts.

Radiological outcomes following surgical fixation with wires versus moulded cast for patients with a dorsally displaced fracture of the distal radius: a radiographic analysis from the DRAFFT2 trial.

Aims: The primary aim of this study was to report the radiological outcomes of patients with a dorsally displaced distal radius fracture who were randomized to a moulded cast or surgical fixation with wires following manipulation and closed reduction of their fracture. The secondary aim was to correlate radiological outcomes with patient-reported outcome measures (PROMs) in the year following injury.

Methods: Participants were recruited as part of DRAFFT2, a UK multicentre clinical trial.

Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3).

Introduction: Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed.

Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

Background: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD).

Objective: We sought to understand the mechanisms of eczema in DOCK8 deficiency.

Methods: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression.