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Aim: To describe the hospital costs, hospital types and differences across states and territories for children with medical complexity cared for in Australian public hospitals.Methods: Retrospective national administrative database study of 212 Australian public hospitals from six states (excluding Queensland) and two territories that submitted cost data to the National Hospital Costing Data Collection for 2010-2011. Participants included all hospitalised patients with comparisons between adults and children (17 years of age and younger), and adults with chronic diseases and children with medical complexity. Total hospital costs were the main outcome measure.Results: The National Hospital Costing Data Collection contained data from 212 public hospitals; total admissions (adults and children) were 3 519 140 at a total hospital cost of $16 187 400 000. Children accounted for 350 499 (9.9%) of the admissions at a total hospital cost of $1 931 585 123 (11.9%). Of all children, those with medical complexity accounted for 48 758 (13.9%), and their total hospital costs were $620 948 769 (32.1%). Six children's hospitals had 145 213 (41%) of the total children admissions at a total hospital cost of $936 041 843 (48%). Across the states and territories, the number of childhood admissions ranged from 9164 to 146 618 with 4.7-14.8% for children with medical complexity. Total hospital costs ranged from $44 to $592 million with 15.4-39.4% for children with medical complexity.Conclusions: The national burden of hospitalised children is substantial. Children with medical complexity only account for a small percentage of hospitalisations but almost one third of total hospital costs for children, with children's hospitals bearing the major costs. [ABSTRACT FROM AUTHOR]

Background: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab.Methods: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, had adequate organ function, had resolution of toxic effects of the most recent previous chemotherapy to grade 1 or less, had no active autoimmune disease requiring systemic steroids or immunosuppressive agents, had no active non-infectious pneumonitis, had no uncontrolled thyroid dysfunction or diabetes, had no active brain metastases, and had not received previous immune checkpoint inhibitor therapy. Patients received intravenous pembrolizumab 2 mg/kg plus intravenous ipilimumab 1 mg/kg every 3 weeks for four doses, followed by intravenous pembrolizumab 2 mg/kg every 3 weeks for up to 2 years or disease progression, intolerable toxicity, withdrawal of consent, or investigator decision. The primary endpoint was safety and tolerability. The proportion of patients achieving an objective response assessed per RECIST version 1.1 by independent central review and overall survival were secondary endpoints. We also assessed progression-free survival. The primary endpoint was assessed in all patients who received at least one dose of combination therapy. Activity was assessed in all enrolled patients. This trial is registered with ClinicalTrials.gov, number NCT02089685. Enrolment into this cohort is closed, but patients are still being monitored for safety and anti-tumour activity.Findings: Between Jan 13, 2015, and Sept 17, 2015, we enrolled and treated 153 patients. As of the Oct 17, 2016, cutoff date, median follow-up was 17·0 months (IQR 14·8-18·8). 110 (72%) of 153 patients received all four pembrolizumab plus ipilimumab doses; 64 (42%) remained on pembrolizumab monotherapy. 110 grade 3-4 treatment-related adverse events occurred in 69 (45%) patients. No treatment-related deaths occurred. Treatment-related adverse events led to discontinuation of pembrolizumab and ipilimumab in 22 (14%) patients, including 17 (11%) who discontinued both treatments for the same event and five (3%) who discontinued ipilimumab for one event and later discontinued pembrolizumab for another. 12 (8%) patients discontinued ipilimumab only and 14 (9%) discontinued pembrolizumab only because of treatment-related adverse events. 158 immune-mediated adverse events of any grade occurred in 92 (60%) patients, and 50 immune-mediated adverse events of grade 3-4 occurred in 42 (27%) patients; the most common immune-mediated adverse events were hypothyroidism (25 [16%]) and hyperthyroidism (17 [11%]). 93 (61% [95% CI 53-69]) patients achieved an objective response. Estimated 1 year progression-free survival was 69% (95% CI 60-75), and estimated 1 year overall survival was 89% (95% CI 83-93).Interpretation: Standard-dose pembrolizumab given in combination with four doses of reduced-dose ipilimumab followed by standard-dose pembrolizumab has a manageable toxicity profile and provides robust anti-tumour activity in patients with advanced melanoma. These data suggest that standard-dose pembrolizumab plus reduced-dose ipilimumab might be a tolerable, efficacious treatment option for patients with advanced melanoma. A randomised phase 2 trial of alternative dosing strategies of this combination is underway.Funding: Merck & Co, Inc. [ABSTRACT FROM AUTHOR]