Efficacy and cost-effectiveness of a community-based model of care for older patients with complex needs: A study protocol for a multicentre randomised controlled trial using a stepped wedge cluster design

© 2018 The Author(s). Background: Community-dwelling older persons with complex care needs may deteriorate rapidly and require hospitalisation if they receive inadequate support for their conditions in the community. Intervention: A comprehensive, multidimensional geriatric assessment with care coordination was performed in a community setting - Older Persons ENablement And Rehabilitation for Complex Health conditions (OPEN ARCH). Objectives: This study will assess the acceptability and determine the impact of the OPEN ARCH intervention on the health and quality of life outcomes, health and social services utilisation of older people with multiple chronic conditions and emerging complex care needs. An economic evaluation will determine whether OPEN ARCH is cost-effective when compared to the standard care. Methods/design: This multicentre randomised controlled trial uses a stepped wedge cluster design with repeated cross-sectional samples. General practitioners (GPs; n ≥ 10) will be randomised as 'clusters' at baseline using simple randomisation. Each GP cluster will recruit 10-12 participants. Data will be collected on each participant at 3-month intervals (- 3, 0, 3, 6 and 9 months). The primary outcome is health and social service utilisation as measured by Emergency Department presentations, hospital admissions, in-patient bed days, allied health and community support services. Secondary outcomes include functional status, quality of life and participants' satisfaction. Cost-effectiveness of the intervention will be assessed as the change to cost outcomes, including the cost of implementing the intervention and subsequent use of services, and the change to health benefits represented by quality adjusted life years. Discussion: The results will have direct implications for the design and wider implementation of this new model of care for community-dwelling older persons with complex care needs. Additionally, it will contribute to the evidence base on acceptability, efficacy and cost-effectiveness of the intervention for this high-risk group of older people. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12617000198325p. Registered on 6 February 2017

MUGEN mouse database; Animal models of human immunological diseases

The MUGEN mouse database (MMdb) (www.mugen-noe.org/database/) is a database of murine models of immune processes and immunological diseases. Its aim is to share and publicize information on mouse strain characteristics and availability from participating institutions. MMdb's basic classification of models is based on three major research application categories: Models of Human Disease, Models of Immune Processes and Transgenic Tools. Data on mutant strains includes detailed information on affected gene(s), mutant allele(s) and genetic background (DNA origin, gene targeted, host and backcross strain background). Each gene/transgene index also includes IDs and direct links to Ensembl, ArrayExpress, EURExpress and NCBI's Entrez Gene database. Phenotypic description is standardized and hierarchically structured, based on MGI's mammalian phenotypic ontology terms. Availability (e.g. live mice, cryopreserved embryos, sperm and ES cells) is clearly indicated, along with handling and genotyping details (in the form of documents or hyperlinks) and all relevant contact information (including EMMA and Jax/IMSR hyperlinks where available). MMdb's design offers a user-friendly query interface and provides instant access to the list of mutant strains and genes. Database access is free of charge and there are no registration requirements for data querying

The Mouse Genome Database: enhancements and updates

The Mouse Genome Database (MGD) is a major component of the Mouse Genome Informatics (MGI, http://www.informatics.jax.org/) database resource and serves as the primary community model organism database for the laboratory mouse. MGD is the authoritative source for mouse gene, allele and strain nomenclature and for phenotype and functional annotations of mouse genes. MGD contains comprehensive data and information related to mouse genes and their functions, standardized descriptions of mouse phenotypes, extensive integration of DNA and protein sequence data, normalized representation of genome and genome variant information including comparative data on mammalian genes. Data for MGD are obtained from diverse sources including manual curation of the biomedical literature and direct contributions from individual investigator’s laboratories and major informatics resource centers, such as Ensembl, UniProt and NCBI. MGD collaborates with the bioinformatics community on the development and use of biomedical ontologies such as the Gene Ontology and the Mammalian Phenotype Ontology. Recent improvements in MGD described here includes integration of mouse gene trap allele and sequence data, integration of gene targeting information from the International Knockout Mouse Consortium, deployment of an MGI Biomart, and enhancements to our batch query capability for customized data access and retrieval

Let's CHAT (community health approaches to) dementia in Aboriginal and Torres Strait Islander communities: protocol for a stepped wedge cluster randomised controlled trial

Background: Documented rates of dementia and cognitive impairment not dementia (CIND) in older Aboriginal and Torres Strait Islander Peoples is 3–5 times higher than the rest of the population, and current evidence suggests this condition is under-diagnosed and under-managed in a clinical primary care setting. This study aims to implement and evaluate a culturally responsive best practice model of care to optimise the detection and management of people with cognitive impairment and/or dementia, and to improve the quality of life of carers and older Aboriginal and Torres Islander Peoples with cognitive impairment. Methods/design: The prospective study will use a stepped-wedge cluster randomised controlled trial design working with 12 Aboriginal Community Controlled Health Services (ACCHSs) across four states of Australia. Utilising a co-design approach, health system adaptations will be implemented including (i) development of a best practice guide for cognitive impairment and dementia in Aboriginal and Torres Strait Islander communities (ii) education programs for health professionals supported by local champions and (iii) development of decision support systems for local medical software. In addition, the study will utilise a knowledge translation framework, the Integrated Promoting Action on Research Implementation in Health Services (iPARIHS) Framework, to promote long-term sustainable practice change. Process evaluation will also be undertaken to measure the quality, fidelity and contextual influences on the outcomes of the implementation. The primary outcome measures will be rates of documentation of dementia and CIND, and evidence of improved management of dementia and CIND among older Indigenous peoples attending Aboriginal and Torres Strait Islander primary care services through health system changes. The secondary outcomes will be improvements to the quality of life of older Indigenous peoples with dementia and CIND, as well as that of their carers and families. Discussion: The Let’s CHAT Dementia project will co-design, implement and evaluate a culturally responsive best practice model of care embedded within current Indigenous primary health care. The best practice model of care has the potential to optimise the timely detection (especially in the early stages) and improve the ongoing management of people with dementia or cognitive impairmentKate Bradley, Robyn Smith, Jo-anne Hughson, David Atkinson, Dawn Bessarab, Leon Flicker ... et al

LSD1 inhibition attenuates androgen receptor V7 splice variant activation in castration resistant prostate cancer models

Background: Castrate resistant prostate cancer (CRPC) is often driven by constitutively active forms of the androgen receptor such as the V7 splice variant (AR-V7) and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. The lysine demethylase LSD1 is a co-activator of the wild type androgen receptor and a potential therapeutic target in hormone sensitive prostate cancer. We evaluated whether LSD1 could also be therapeutically targeted in CRPC models driven by AR-V7. Methods: We utilised cell line models of castrate resistant prostate cancer through over expression of AR-V7 to test the impact of chemical LSD1 inhibition on AR activation. We validated findings through depletion of LSD1 expression and in prostate cancer cell lines that express AR-V7. Results: Chemical inhibition of LSD1 resulted in reduced activation of the androgen receptor through both the wild type and its AR-V7 splice variant forms. This was confirmed and validated in luciferase reporter assays, in LNCaP and 22Rv1 prostate cancer cell lines and in LSD1 depletion experiments. Conclusion: LSD1 contributes to activation of both the wild type and V7 splice variant forms of the androgen receptor and can be therapeutically targeted in models of CRPC. Further development of this approach is warranted

Addressing the increased prevalence of dementia in Australian Torres Strait Islander comunities

Indigenous Australians have higher rates of chronic disease and poorer health outcomes than the general population. Recently, a fivefold risk of dementia, one of the highest rates worldwide, has been identified in Aboriginal Australians aged 45 years and over (12.4% compared to 2.4%). It is not known if Torres Strait Islanders, who comprise 10% of all Indigenous Australians, share this increased risk of dementia, although high rates of vascular disease, which may increase this risk, are found in these communities. The aim of this study was to assess the prevalence of dementia in the Torres Strait. A total of 111 Torres Strait residents (34 male) aged 41 to 91 years (M=64.1, SD11.4) underwent a diagnostic assessment by a Geriatrician. The prevalence of dementia was 11.7%, which was significantly higher than in the general population. All but one were diagnosed with Alzheimer’s disease (AD), vascular dementia (VaD) or mixed AD/VaD. Cognitive impairment was present in 31% of the sample and 91% of those with cognitive impairment and 76% of those with normal cognition had at least one vascular risk factor. Results highlight the need for screening for cognitive impairment and dementia in Australian Indigenous communities aged 45 and over to ensure early diagnosis and intervention for those affected by dementia. The need for a culturally appropriate model of care is also crucial to effectively address this problem and there is a role for all health professionals to actively promote healthy lifestyles across the lifespan to reduce dementia risk