https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Generalist solutions to complex problems: generating practice-based evidence - the example of managing multi-morbidity https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14772 2 diseases) is a product of the design of health care systems which define health care need on the basis of disease status. So does the solution lie in an alternative model of healthcare? Discussion: Strengthening generalist practice has been proposed as part of the solution to tackling multi-morbidity. Generalism is a professional philosophy of practice, deeply known to many practitioners, and described as expertise in whole person medicine. But generalism lacks the evidence base needed by policy makers and planners to support service redesign. The challenge is to fill this practice-research gap in order to critically explore if and when generalist care offers a robust alternative to management of this complex problem. We need practice-based evidence to fill this gap. By recognising generalist practice as a ‘complex intervention’ (intervening in a complex system), we outline an approach to evaluate impact using action-research principles. We highlight the implications for those who both commission and undertake research in order to tackle this problem. Summary: Answers to the complex problem of multi-morbidity won’t come from doing more of the same. We need to change systems of care, and so the systems for generating evidence to support that care. This paper contributes to that work through outlining a process for generating practice-based evidence of generalist solutions to the complex problem of person-centred care for people with multi-morbidity.]]> Wed 11 Apr 2018 13:41:48 AEST ]]> Reevaluation of the BRCA<sub>2</sub> truncating allele c.9976A > T (p.Lys3326Ter) in a familial breast cancer context https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22707 BRCA2, has a large number of genetic variants of unknown effect. The variant rs11571833, an A > T transversion in the final exon of the gene that leads to the creation of a stop codon 93 amino acids early (K3326*), is reported as a neutral polymorphism but there is some evidence to suggest an association with an increased risk of breast cancer. We assessed whether this variant was enriched in a cohort of breast cancer cases ascertained through familial cancer clinics compared to population-based non-cancer controls using a targeted sequencing approach. We identified the variant in 66/2634 (2.5%) cases and 33/1996 (1.65%) controls, indicating an enrichment in the breast cancer cases (p = 0.047, OR 1.53, 95% CI 1.00–2.34). This data is consistent with recent iCOGs data suggesting that this variant is not neutral with respect to breast cancer risk. rs11571833 may need to be included in SNP panels for evaluating breast cancer risk.]]> Wed 11 Apr 2018 09:55:17 AEST ]]> Panel testing for familial breast cancer: calibrating the tension between research and clinical care https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24890 Sat 24 Mar 2018 07:14:53 AEDT ]]> Reevaluation of RINT1 as a breast cancer predisposition gene https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23843 0.999) or in the number of variants predicted to be pathogenic by various in silico tools (Condel, Polyphen2, SIFT, and CADD) in the cases compared to the controls. In addition, there was no difference in the incidence of classic Lynch syndrome cancers in RINT1 rare variant-carrying families compared to RINT1 wild-type families. This study had 90 % power to detect an odds ratio of at least 2.06, and the results do not provide any support for RINT1 being a moderate-penetrance breast cancer susceptibility gene, although larger studies will be required to exclude more modest effects. This study emphasizes the need for caution before designating a cancer predisposition role for any gene based on very rare truncating variants and in silico-predicted missense variants.]]> Sat 24 Mar 2018 07:12:12 AEDT ]]>