Aspirin and fracture risk: a systematic review and exploratory meta-analysis of observational studies.

OBJECTIVES: This review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin. METHODS: We conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018. Studies were included if: participants were men or women aged ≥18 years; the exposure of interest was aspirin; and relative risks, ORs and 95% CIs for the risk of fracture or difference (percentage or absolute) in BMD (measured by dual energy X-ray absorptiometry) between aspirin users and non-users were presented. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists for observational studies. Pooled ORs for any fracture and standardised mean differences (SMDs) for BMD outcomes were calculated using random-effects models. RESULTS: Twelve studies met the inclusion criteria and were included in the meta-analysis. Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99; I2=71%; six studies; n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI -0.02 to 0.07; I2=0%; three studies; n=9686) and men (SMD 0.06, 95% CI -0.02 to 0.13, I2=0%; two studies; n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI -0.03 to 0.09; I2=34%; four studies; n=11 330) and men (SMD 0.08; 95% CI -0.01 to 0.18; one study; n=432). CONCLUSIONS: While the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for individuals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people.

RESPOND: a programme to prevent secondary falls in older people presenting to the emergency department with a fall: protocol for an economic evaluation.

BACKGROUND: Falls remain common for community-dwelling older people and impose a substantial economic burden to the healthcare system. RESPOND is a novel falls prevention programme that aims to reduce secondary falls and fall injuries among older people who present to a hospital emergency department (ED) with a fall. The present protocol describes a prospective economic evaluation examining the incremental cost-effectiveness of the RESPOND programme, compared with usual care practice, from the Australian health system perspective. METHODS AND DESIGN: This economic evaluation will recruit 528 participants from two major tertiary hospital EDs in Australia and will be undertaken alongside a multisite randomised controlled trial. Outcome and costing data will be collected for all participants over the 12-month trial. It will compare the RESPOND falls prevention programme with usual care practice (current community-based falls prevention practices) to determine its incremental cost-effectiveness according to three intermediate clinical outcomes: (1) falls prevented, (2) fall injuries prevented and (3) injurious falls prevented. In addition, utilities will be derived from a generic quality-of-life measure (EQ-5D-5L) and used to calculate the 'incremental cost per quality-adjusted life years gained'. DISCUSSION: The results of this study will provide healthcare decision makers with evidence to assist with setting spending thresholds for preventive health programmes and inform selection of emergency and community service models of care. TRIAL REGISTRATION NUMBER: The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684); Pre-results.

RESPOND: a patient-centred programme to prevent secondary falls in older people presenting to the emergency department with a fall-protocol for a mixed methods programme evaluation.

BACKGROUND: Programme evaluations conducted alongside randomised controlled trials (RCTs) have potential to enhance understanding of trial outcomes. This paper describes a multi-level programme evaluation to be conducted alongside an RCT of a falls prevention programme (RESPOND). OBJECTIVES: (1) To conduct a process evaluation in order to identify the degree of implementation fidelity and associated barriers and facilitators. (2) To evaluate the primary intended impact of the programme: participation in fall prevention strategies and the factors influencing participation. (3) To identify the factors influencing RESPOND RCT outcomes: falls, fall injuries and emergency department (ED) re-presentations. METHODS/DESIGN: 528 community-dwelling adults aged 60-90 years presenting to two EDs with a fall will be recruited and randomly assigned to the intervention or standard care group. All RESPOND participants and RESPOND clinicians will be included in the evaluation. A mixed methods design will be used and a programme logic model will frame the evaluation. Data will be sourced from interviews, focus groups, questionnaires, clinician case notes, recruitment records, participant-completed calendars, hospital administrative datasets and audio-recordings of intervention contacts. Quantitative data will be analysed via descriptive and inferential statistics and qualitative data will be interpreted using thematic analysis. DISCUSSION: The RESPOND programme evaluation will provide information about contextual and influencing factors related to the RESPOND RCT outcomes. The results will assist researchers, clinicians and policy makers regarding decisions about future falls prevention interventions. Insights gained may be applicable to a range of chronic conditions where similar preventive intervention approaches are indicated. TRIAL REGISTRATION NUMBER: This programme evaluation is linked to the RESPOND RCT which is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).

RESPOND--A patient-centred programme to prevent secondary falls in older people presenting to the emergency department with a fall: protocol for a multicentre randomised controlled trial.

INTRODUCTION: Participation in falls prevention activities by older people following presentation to the emergency department (ED) with a fall is suboptimal. This randomised controlled trial (RCT) will test the RESPOND programme, an intervention designed to improve older persons' participation in falls prevention activities through delivery of patient-centred education and behaviour change strategies. DESIGN AND SETTING: A RCT at two tertiary referral EDs in Melbourne and Perth, Australia. PARTICIPANTS: 528 community-dwelling people aged 60-90 years presenting to the ED with a fall and discharged home will be recruited. People who require an interpreter or hands-on assistance to walk; live in residential aged care or >50 km from the trial hospital; have terminal illness, cognitive impairment, documented aggressive behaviour or a history of psychosis; are receiving palliative care or are unable to use a telephone will be excluded. METHODS: Participants will be randomly allocated to the RESPOND intervention or standard care control group. RESPOND incorporates (1) a home-based risk factor assessment; (2) education, coaching, goal setting and follow-up telephone support for management of one or more of four risk factors with evidence of effective interventions and (3) healthcare provider communication and community linkage delivered over 6 months. Primary outcomes are falls and fall injuries per person-year. DISCUSSION: RESPOND builds on prior falls prevention learnings and aims to help individuals make guided decisions about how they will manage their falls risk. Patient-centred models have been successfully trialled in chronic and cardiovascular disease; however, evidence to support this approach in falls prevention is limited. TRIAL REGISTRATION NUMBER: The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).

Scanning electrochemical microscopy as a local probe of oxygen permeability in cartilage.

The use of scanning electrochemical microscopy, a high-resolution chemical imaging technique, to probe the distribution and mobility of solutes in articular cartilage is described. In this application, a mobile ultramicroelectrode is positioned close ( approximately 1 microm) to the cartilage sample surface, which has been equilibrated in a bathing solution containing the solute of interest. The solute is electrolyzed at a diffusion-limited rate, and the current response measured as the ultramicroelectrode is scanned across the sample surface. The topography of the samples was determined using Ru(CN)(6)(4-), a solute to which the cartilage matrix was impermeable. This revealed a number of pit-like depressions corresponding to the distribution of chondrocytes, which were also observed by atomic force and light microscopy. Subsequent imaging of the same area of the cartilage sample for the diffusion-limited reduction of oxygen indicated enhanced, but heterogeneous, permeability of oxygen across the cartilage surface. In particular, areas of high permeability were observed in the cellular and pericellular regions. This is the first time that inhomogeneities in the permeability of cartilage toward simple solutes, such as oxygen, have been observed on a micrometer scale.