Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR data set

OBJECTIVE: To determine the mortality rate following total ankle replacement (TAR) and incidence of 90 day pulmonary embolism (PE) along with the associated risk factors.  DESIGN: Data-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. Linkage was performed in a deterministic fashion. HES episodes 90 days after the index procedure were analysed for PE. Mortality data were obtained pertaining to all the index procedures from the NJR for analysis.  PARTICIPANTS: All primary and revision ankle replacement patients captured on the NJR between February 2008 and February 2013.  RESULTS: The 90-day mortality following TAR was 0.13% (95% CI 0.03 to 0.52) and 1-year mortality was 0.72% (95% CI 0.40 to 1.30); no deaths were as a result of PE. The incidence of PE within 90 days following primary TAR was 0.51% (95% CI 0.23 to 1.13). There was only one PE following revision surgery. Patients with an Royal College of Surgeons Charlson score greater than zero were at 13 times greater risk of PE (p=0.003).  CONCLUSIONS: There is low incidence of PE following TAR, but multiple comorbidities are a leading risk factor for its occurrence

How do patients with end-stage ankle arthritis decide between two surgical treatments?:A qualitative study

To examine how patients decide between ankle fusion and ankle replacement in end-stage ankle arthritis

Higher dietary flavonoid intakes are associated with lower objectively measured body composition in women: evidence from discordant monozygotic twins

Background: Although dietary flavonoid intake has been associated with less weight gain there are limited data on its impact on fat mass and the contribution of genetic factors to this relationship has not previously been assessed. Objective: To examine associations between flavonoid intakes and fat mass. Design: In a study of 2734 healthy female twins aged 18-83 years from the TwinsUK registry intakes oftotalflavonoids and seven subclasses(flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers and proanthocyanidins) were calculated from food frequency questionnaires. Measures of DXA-derived fat mass included limb-to-trunk fat ratio (FMR), fat mass index and central fat mass index. Results: In cross-sectional multivariable analyses, higher intake of anthocyanins, flavonols and proanthocyanidins were associated with lower FMR, with differences between extreme quintiles of -0.03 (SE 0.02 P-trend = 0.02), -0.03 (SE 0.02 P-trend = 0.03) and -0.05 (SE 0.02 P-trend <0.01), respectively. These associationsremained significant even after further adjustment for fibre and total fruit and vegetable intakes. In monozygotic intake-discordant twin-pairs, those with higher intakes of flavan-3-ols (n= 154, P = 0.03), flavonols (n= 173, P = 0.03) and proanthocyanidins (n= 172, P < 0.01)had significantly lower FMR than their cotwins with within-pair differences of 3-4%. Furthermore, in confirmatory food-based analyses, twins with higher intake of flavonol- (onion, tea and pears, P = 0.01) and proanthocyanidin- (apples and cocoa drinks, P = 0.04) and, in younger participants (< 50 y) only, anthocyanin-rich foods (berries, pears, grapes and wine, P = 0.01) had 3-9% lower FMR than their co-twins. Conclusions: These data suggest that higher habitual intake of a number of flavonoids, including anthocyanins,flavan-3-ols,flavonols and proanthocyanidins, are associated with lower fat massindependent ofshared genetic and common environmental factors. Intervention trials are now needed to further examine the effect of flavonoid-rich foods on body composition

Data quality predicts care quality: findings from a national clinical audit

Background: Missing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance. Methods: The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment. Results: Six thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p < 0.0001). Conclusions: We have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator

Patterns of risk of cancer in patients with metal-on-metal hip replacements versus other bearing surface types: a record linkage study between a prospective joint registry and general practice electronic health records in England.

BACKGROUND: There are concerns that metal-on-metal hip implants may cause cancer. The objective of this study was to evaluate patterns and timing of risk of cancer in patients with metal-on-metal total hip replacements (THR). METHODS: In a linkage study between the English National Joint Registry (NJR) and the Clinical Practice Research Datalink (CPRD), we selected all THR surgeries (NJR) between 2003 and 2010 (n = 11,540). THR patients were stratified by type of bearing surface. Patients were followed up for cancer and Poisson regression was used to derive adjusted relative rates (RR). RESULTS: The risk of cancer was similar in patients with hip resurfacing (RR 0.69; 95% Confidence Interval [CI] 0.39–1.22) or other types of bearing surfaces (RR 0.96; 95% CI 0.64–1.43) compared to individuals with stemmed metal-on-metal THR. The pattern of cancer risk over time did not support a detrimental effect of metal hip implants. There was substantial confounding: patients with metal-on-metal THRs used fewer drugs and had less comorbidity. CONCLUSIONS: Metal-on-metal THRs were not associated with an increased risk of cancer. There were substantial baseline differences between the different hip implants, indicating possibility of confounding in the comparisons between different types of THR implants

The role of flightless protein in hypertrophic scarring and its potential as a target for a novel therapy

Hypertrophic scarring is a poorly understood condition which affects the lives of millions of people around the world annually. Despite its common occurrence following burn injury, trauma or surgery the present treatments are of limited efficacy. Research over the past decade in the Cowin laboratory has identified Flightless (Flii), a highly conserved cytoskeletal protein, as a negative regulator of wound healing. Wounding leads to an increased expression of Flii, while Flii has been shown to inhibit cellular migration and proliferation. Reducing Flii in vivo leads to improved wound healing. The aim of this study was to investigate the role of Flii in the fibroproliferative process underlying hypertrophic scarring. Chapter three shows for the first time that Flii expression in increased in human burn and hypertrophic scar tissue. Chapter four details the development of a novel murine model of hypertrophic scarring. Previous animal models have focused on reproducing the clinical characteristics of the human hypertrophic scar, which often required significant derangement of the animal immune response. The novel model used bleomycin to stimulate the fibroproliferative process that underlies hypertrophic scarring. Results in this chapter use histology and immunohistochemistry to verify the bleomycin model as a valid model of hypertrophic scarring. Chapter five uses the bleomycin mode to demonstrate that Flii is a key determinant of the extent of fibroproliferation that underlies hypertrophic scarring. Increasing Flii genetically in this animal model leads to increased dermal thickening and increases in key determinants of hypertrophic scarring, such as myofibroblasts, transforming growth factorβ-1 (TGFβ-1) and scar collagen composition. Decreasing Flii genetically causes a reduction in hypertrophic scarring using the same measures. Decreasing Flii using a monoclonal antibody therapy in the bleomycin model also led to a reduction in hypertrophic scarring, confirming Flii as a potential target for a novel therapy for hypertrophic scarring. Chapter six investigates potential mechanisms for the findings observed in previous chapters by using in vivo techniques. Focusing on the fibroblast, the key cell type in fibroproliferation, immunocytochemistry and cell migration assays, were used to show that decreasing Flii genetically or using a monoclonal antibody, reverses the fibroblast-myofibroblast phenotypic change that characterizes fibroproliferartive pathology. Flii appears to be a key determinant of the fibroproliferative process underlying hypertrophic scarring. This study uses human tissue, a novel small animal model and in vivo techniques to demonstrate this and identify Flii as a potential target for a novel therapy to reduce or prevent hypertrophic scarring.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201

Trajectory of physical activity after hip fracture: An analysis of community-dwelling individuals from the English Longitudinal Study of Ageing

Introduction: To analyse physical activity participation in a community-dwelling people in England with hip fracture the interval prior to fracture, in the fracture recovery period, and a minimum of two years post-fracture. Materials and methods: 215 individuals were identified from the English Longitudinal Study of Ageing cohort (2002–2014) who sustained a hip fracture following a fall and for whom data were available on physical activity participation relating to the period pre-fracture, within-fracture recovery phase and post-fracture (minimum of two years). Physical activity was assessed using the validated ELSA physical activity questionnaire. Prevalence of ‘low’ physical activity participation was calculated and multi-level modelling analyses were performed to explore physical activity trajectories over the follow-up phase, and whether age, depression, gender and frailty were associated with physical activity participation. Results: Prevalence of low physical activity participation within two years prior to hip fracture was 16.7% (95% Confidence Intervals (CI): 11.6% to 21.8%). This increased at the final follow-up phase to 21.3% (95% CI: 15.1% to 27.6%). This was not a statistically significant change (P = 0.100). Age (P = 0.005) and frailty (P < 0.001) were statistically significant explanatory variables (P = 0.005) where older age and greater frailty equated to lower physical activity participation. Neither gender (P = 0.288) nor depression (P = 0.121) were significant explanatory variables. Conclusion: Physical activity levels do not significantly change between pre-fracture to a minimum of two years post-hip fracture for community-dwelling individuals. This contrasts with previous reports of reduced mobility post-hip fracture, suggesting that ‘physical activity’ and ‘mobility’ should be considered as separate outcomes in this population

‘It’s my own fault’: Accounts and consequences of falling when living with rheumatoid arthritis

Introduction: Rheumatoid Arthritis (RA) leads to biomechanical joint changes which increases risk of falling. The consequence of falling may be physical injury. However, as important can be the psychological consequences including fear of falling. Methods: Participants were recruited from a larger prospective study which explored the incidence of falls in people with RA. Purposive sampling considered age, sex, time since diagnosis and fall history. The recruitment site was a regional hospital. Data from semi-structured qualitative interviews and, after each fall, brief telephone interviews. Thematic analysis methods were used to investigate the psychological and social impact of falling in people with RA. Results: Twelve participants were interviewed (aged 64-85, mean 74 years: 6 had fallen between 1-23 times: 6 had no reported fall in last 12 months). Data was supplemented with telephone notes from 287 post-fall telephone calls. Three themes were developed: 1) The falls Imaginary illustrates that fear of falling is not dependent on experience; 2) Agentic risk management reports on the ways people self-manage and display resilience when at risk of falling; 3) The absence of the health professional explores the ways in which people reported being unsupported by health care services. Conclusion: Fear of falling when living with RA is tangible in those who have and have not fallen. This fear may limit opportunities for full participation in life. However some people display personal resourcefulness continuing to live purposeful lives. Understanding personal responses to falling will support the development of community interventions specific to this high risk group