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This paper reviews our current state of knowledge of the roles the small leucine-rich proteoglycans (SLRPs) play in the formation of connective tissue and mineralised tissue matrices. Both, the SLRPs biglycan and decorin are highly expressed in extracellular bone matrix and there is now substantial evidence to support an increasing role for biglycan and decorin in influencing bone cell differentiation and proliferative activity. In addition decorin and biglycan have been implicated in regulating mineral deposition and crystal morphology, whilst decorin has also roles in organic matrix assembly. In order to further assess the role of these SLRPs during bone formation we have initiated studies investigating primary bone cell culture models from rats (bone marrow stromal cells, and bone cells from alveolar bone explants), and identified periods relating to cell proliferation, organic matrix deposition, remodeling of the osteoid, and mineral deposition. Analysis of mRNA levels and the nature of the proteoglycan demonstrated that dermatan sulphate substituted biglycan was expressed during phases relating to cell proliferation, ceased at early matrix deposition, and then biglycan was re-expressed at the onset of mineralisation, but was conjugated to chondroitin sulphate. Decorin was expressed later than biglycan, was associated with early matrix deposition, but then continued to the mineralisation stages. Again, dermatan sulphate-decorin prevailed earlier within osteoid matrix, whilst chondroitin sulphate-decorin predominated later within the mineralizing matrix. The nature of the GAG chain conjugated to SLRP and the timing of its expression would seem to dictate the functions biglycan and decorin play in bone formation.

Background: PDSAFE is an individually-tailored, physiotherapist-delivered, balance, strength and strategy training programme aimed at preventing falls among people with Parkinson's. We evaluated the cost-effectiveness of PDSAFE compared with usual care for people with Parkinson's at higher risk of falling, from a UK National Health Service and Personal Social Service perspective.Methods: Resource use and quality of life data (EQ-5D-3L) were collected from 238 participants randomised to the PDSAFE intervention and 236 participants randomised to control, at baseline, 3 months, 6 months (primary outcome), and 12 months. Adjusted cost and quality-adjusted life-years (QALYs) were estimated using generalised linear models and uncertainty estimated using a non-parametric bootstrap.Results: Over 6 months, the PDSAFE intervention was associated with an incremental cost of £925 (95% CI £428 to £1422) and a very small and statistically insignificant QALY gain of 0.008 (95% CI - 0.006 to 0.021). The resulting incremental cost-effectiveness ratio (ICER) was £120,659 per QALY and the probability of the intervention being cost-effective at a UK threshold of £30,000/QALY was less than 1%. The ICER varied substantially across subgroups although no subgroup had an ICER lower than the £30,000 threshold. The result was sensitive to the time horizon with the ICER reducing to £55,176 per QALY when adopting a 12-month time horizon and assuming a sustained treatment effect on QoL, nevertheless, the intervention was still not cost-effective according to the current UK threshold.Conclusions: Evidence from this trial suggests that the PDSAFE intervention is unlikely to be cost-effective at 6 months. The 12-month analysis suggested that the intervention became closer to being cost-effective if quality of life effects were sustained beyond the intervention period, however this would require confirmation. Further research, including qualitative studies, should be conducted to better understand the treatment effect of physiotherapy and its impact on quality of life in people with Parkinson's given existing mixed evidence on this topic.Trial Registration: ISRCTN48152791. Registered 17 April 2014. http://www.isrctn.com/ISRCTN48152791. [ABSTRACT FROM AUTHOR]

Introduction multiple conditions in later life (multi-morbidity) is a major challenge for health and care systems worldwide, is of particular relevance for older people, but has not (until recently) received high priority as a topic for research. We have identified the top 10 research priorities from the perspective of older people, their carers, and health and social care professionals using the methods of a James Lind Alliance Priority Setting Partnership. Methods in total, 354 participants (162 older people and carers, 192 health professionals) completed a survey and 15 older people and carers were interviewed to produce 96 'unanswered questions'. These were further refined by survey and interviews to a shortlist of 21 topics, and a mix of people aged 80+ living with three or more conditions, carers and health and social care providers to prioritised the top 10. Results the key priorities were about the prevention of social isolation, the promotion of independence and physical and emotional well-being. In addition to these broad topics, the process also identified detailed priorities including the role of exercise therapy, the importance of falls (particularly fear of falling), the recognition and management of frailty and Comprehensive Geriatric Assessment. Conclusion these topics provide a unique perspective on research priorities on multiple conditions in later life and complement existing UK and International recommendations about the optimisation of health and social care systems to deliver essential holistic models of care and the prevention and treatment of multiple co-existing conditions. [ABSTRACT FROM AUTHOR]