Sydney Children's Hospital, Randwick, is an Australian children's hospital located in the eastern suburbs of Sydney, New South Wales.On 1 July 2010 it became part of the newly formed Sydney Children's Hospitals Network (Randwick and Westmead) incorporating the Royal Alexandra Hospital for Children' and the children's hospice Bear Cottage.The Sydney Children's Hospital, Randwick, is located approximately 6 kilometres from the Sydney Central Business District in the suburb of Randwick. Sydney Children's Hospital, Randwick, is also a major teaching hospital and is a teaching facility for the University of New South Wales. The Sydney Children's Hospital shares the Randwick Hospitals' Campus site with the Prince of Wales Hospital and the Royal Hospital for Women, as well as the Prince of Wales Private Hospital.
Purpose This cross-sectional survey study explored health-related quality of life (HRQoL) across adult survivors of childhood- or adult-onset cancer in Australia, compared to controls with no history of cancer, and assessed factors associated with HRQoL among cancer survivors. Methods Participants completed a survey including clinical and demographic factors and HRQoL (assessed using EQ-5D-5L). Results Childhood cancer survivors (< 16 years at diagnosis, n = 403) and adult-onset cancer survivors (> 16 years at diagnosis, n = 656) participated, alongside 901 controls. Overall HRQoL was comparable between childhood cancer survivors and controls, whilst adult cancer survivors reported better HRQoL than controls. Over 50% of child and adult cancer survivors reported meaningful reductions in overall HRQoL compared to perfect health (i.e. EQ-5D-5L index < 0.92). Childhood survivors reported more mobility and activity limitations on the EQ-5D-5L domains compared to controls, whilst adult survivors reported fewer self-care issues. Childhood survivors' poorer HRQoL was significantly associated with cancer diagnosis and treatment, greater health issues, lower resilience, and smoking history. Adult survivors' poorer HRQoL was associated with older age, lower education, fewer health issues, lower resilience, and less physical activity. Conclusion This study provides a comprehensive examination of HRQoL among Australian cancer survivors, shedding light on age-specific differences and the multifaceted nature of associated factors. Implications for cancer survivors Factors associated with HRQoL highlight modifiable opportunities for targeted survivorship care interventions that may improve survivors' long-term coping and adaptation, as well as broader physical health after cancer.
Patients with loss-of-function DOCK8 or dominant-negative STAT3 variants have hyper-IgE syndrome, although only DOCK8 deficiency consistently presents with elevated food-specific IgE and symptomatic allergy. We previously found in mice that DOCK8 restricts the differentiation of IL-13+ T follicular helper (Tfh13) cells that drive anaphylactic IgE, although the mechanisms were unclear. Here, we show that DOCK8 promotes STAT3 activity, which inhibits GATA3 in T cells. However, only patients with DOCK8, but not STAT3, deficiency had elevated Tfh13 cells. Cell-specific deletion of either Dock8 (T-Dock8-/-) or Stat3 (T-Stat3-/-) augmented peanut-specific IgE and Tfh13s when oral sensitization was promoted by adjuvants. However, the phenotypes diverged during adjuvant-free oral peanut exposure: only T-Dock8-/- mice developed Tfh13 cells and peanut-specific IgE, accompanied by reduced Foxp3+ Tregs. Treg depletion in T-Stat3-/- mice unmasked Tfh13 induction to oral antigen alone. Thus, DOCK8 and STAT3 cooperate to restrain Tfh13 differentiation to food allergens, and additional Treg impairment in DOCK8 deficiency allows for Tfh13 cell induction and allergy.
IntroductionAsthma is the most common chronic respiratory condition among Australian children. However, adherence to clinical guidelines for paediatric asthma care in general practice (GP) settings requires attention—it is estimated to be below 60% in some contexts. The National Paediatric Applied Research Translation Initiative (N-PARTI) is a three-phased, co-designed research program aiming to optimise guideline-concordant paediatric care across three priority conditions, including asthma, Type 1 Diabetes (T1D), and antibiotic stewardship in Australian general practices. This protocol outlines Phase I of the N-PARTI asthma stream, focusing on developing an Implementation Bundle to support evidence-based asthma management in general practices.Methods and analysisUsing a mixed-method design, Phase I will employ a multi-method, co-design approach comprising three Aims: (i) to verify and refine a multicomponent asthma Implementation Bundle tailored for general practice through evidence synthesis, and co-design workshops, involving children with asthma and their parents and carers, alongside with key stakeholders; (ii) to map asthma-related clinical workflows across diverse general practice settings through interviews and observations, analysed using the Functional Resonance Analysis Method (FRAM) to capture variations in routine practice; and (iii) to explore contextual factors within Primary Health Networks (PHNs) through stakeholder interviews, informing the development of locally tailored implementation strategies. Qualitative data will be analysed using a reflexive thematic analysis approach informed by the Consolidated Framework for Implementation Research (CFIR). Outputs will include a refined, contextually adapted paediatric asthma Implementation Bundle and resources to support real-world simulation, testing and tailoring (Phase II), as well as the scale-up, embedding and evaluation of the implementation (Phase III).Ethics and disseminationThis research project has been approved by the Macquarie University Human Research Ethics Committee (Reference No. 520251855660911). Findings will be disseminated through peer-reviewed publications, conferences, stakeholder forums, and policy briefings. Co-designed outputs will also be shared with participating PHNs to inform wider implementation and scale-up efforts.
End-of-life conversations with adolescents and young adults (AYAs) with cancer rarely occur without the guidance of healthcare professionals. As a part of the 'Difficult Discussions' study, focused on palliative care and advance care planning discussions with AYAs with cancer, we investigated the factors that healthcare professionals identify as barriers and facilitators to end-of-life conversations. Twenty-eight multidisciplinary healthcare professionals participated in semi-structured interviews exploring conversations focused on end-of-life care (29% oncologists/haematologists, 39% nurses and 32% allied health professionals). Data were analysed through qualitative content analysis using an inductive approach. The conversations were shaped by factors at the healthcare professionals' personal, interpersonal, teams and hospital system levels, as well as being influenced by cultural and societal influences. Barriers at each level included patients' and caregivers' emotional needs; patients' maturity levels; lack of relational trust between patient, caregiver and healthcare professional; and the social taboo of speaking about death with young people. Conversely, good communication between members of the multidisciplinary team was identified as a facilitator, as working effectively in a team was found to mitigate some of the emotional burden and logistical constraints of conducting end-of-life conversations. The results of this study offer new insights into how the interplay of these factors acts as facilitators and barriers to communication. Further research could explore the communication processes that facilitate trust between the AYA and healthcare team, factors associated with AYAs' readiness and the optimal time to conduct end-of-life conversations.
BACKGROUND:Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS:In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS:Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS:Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).
