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ObjectivesTo adapt and apply a model for evaluating the functional benefits and cost efficiency of specialist inpatient rehabilitation to the Australian context, comparing functional outcomes and savings in the cost of ongoing care after acquired brain injury.DesignAn observational cohort analysis of prospectively collected clinical data from admission to discharge, with follow-up to 3 years.SettingA newly established state-wide inpatient postacute rehabilitation unit in Victoria, Australia for patients with moderate to severe acquired brain injury.ParticipantsThis study included consecutive patients admitted to the programme during its first 2 years’ operation (January 2016 to December 2017). Inclusion criteria consisted of complete outcome measures recorded on admission and discharge, total n=196, mean age 44.6 years (range 17–78), males:females 72:28%, aetiology:trauma n=124 (63%), stroke n=42 (21%), diffuse n=18 (9%) and other-mixed n=12 (7%).InterventionsSpecialist inpatient multidisciplinary rehabilitation.Outcome measuresDependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPCNA); Functional independence: UK Functional Assessment Measure. Cost efficiency: (a) Time is taken to offset rehabilitation costs by savings in NPCNA-estimated costs of ongoing care and (b) net projected lifetime savings.ResultsMedian length of stay 75 (IQR: 33.5–169.5) days, mean episode costs were $A147 044 (95% CI $A126 436, $A167 652). There was a significant reduction in dependency between admission and discharge on all measures (Holm-Bonferroni corrected p<0.001) which was sustained at follow-up in those traced at 1–3 years. Savings were greatest in the highest-dependency group. Estimated mean overall reduction in ‘weekly care costs’ was $A7206, offsetting the cost of rehabilitation within 5.53 months (95% CI 2.27, 8.78). Mean projected net lifetime savings were $A13.4 million (95% CI $A11.4, $A15.4) per patient.ConclusionsThis study provides proof of principle for use of the NPCNA cost-efficiency model outside the UK and yields further evidence that rehabilitation for patients with complex disabilities represents value for money. For every dollar spent on inpatient rehabilitation in this cohort, an estimated $A91 was saved in ongoing care costs.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10 −8 , at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD , SP11 and EIF1 , genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.