A Randomised Controlled Trial Assessing the Effects of Peri-operative Fenofibrate Administration on Abdominal Aortic Aneurysm Pathology: Outcomes From the FAME Trial.

OBJECTIVE: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. METHODS: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. RESULTS: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. CONCLUSION: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs.

Relationship Between Disease Specific Quality of Life Measures, Physical Performance, and Activity in People with Intermittent Claudication Caused by Peripheral Artery Disease.

OBJECTIVE: The aims of this study were firstly to assess the correlation between disease specific measures of quality of life (QOL) and physical performance and activity, and secondly to identify demographic, clinical, functional, and physical activity measures independently associated with QOL in people with intermittent claudication. METHODS: This was a cross sectional observational study of 198 people with intermittent claudication caused by peripheral artery disease who were recruited prospectively. QOL was assessed with the intermittent claudication questionnaire (ICQ) and the eight-theme peripheral artery disease quality of life questionnaire. Physical performance was assessed with the six minute walk test (6MWT) and short physical performance battery (SPPB), and an accelerometer was used to measure seven day step count. The associations between QOL scores and 6MWT distance, SPPB scores and seven day step count were examined using Spearman Rho's (ρ) correlation and multivariable linear regression. RESULTS: ICQ scores were significantly correlated with 6MWT distance (ρ = 0.472, p < .001), all four SPPB scores (balance ρ = 0.207, p = .003; gait speed ρ = 0.303, p < .001; chair stand ρ = 0.167, p = .018; total ρ = 0.265, p < .001), and seven day step count (ρ = 0.254, p < .001). PADQOL social relationships and interactions (ρ = 0.343, p < .001) and symptoms and limitations in physical functioning (ρ = 0.355, p < .001) themes were correlated with 6MWT distance. The 6MWT distance was independently positively associated with ICQ and both PADQOL theme scores (ICQ: B 0.069, p < .001; PADQOL social relationships and interactions: B 0.077, p < .001; PADQOL symptoms and limitations in physical functioning: B 0.069, p < .001). CONCLUSION: Longer 6MWT distance independently predicted better physical and social aspects of QOL in people with intermittent claudication supporting its value as an outcome measure.

Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): study protocol for a randomised controlled trial.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall. METHODS/DESIGN: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers. DISCUSSION: At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612001226897 . Registered on 20 November 2012.

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial.

BACKGROUND: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. METHODS: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation. Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. DISCUSSION: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. TRIAL REGISTRATION: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014.

Important observations made managing carotid body tumors during a 25-year experience.

OBJECTIVES: Our objective was to assess the short- and long-term outcome for patients after carotid body tumor (CBT) resection and discuss the potential pitfalls of the treatment. METHODS: An analysis was undertaken of all patients who underwent CBT resection at Royal Brisbane and Women's Hospital and Greenslopes Private Hospital between 1982 and 2007. Primary tumor characteristics, surgical technique, and outcomes were recorded and analyzed. RESULTS: A total of 49 consecutive CBT resections (2 recurrent tumors) were carried out in 39 patients (26 women [56%]) who were a mean age of 49 years (range, 17-75 years). A nontender neck mass was the presenting complaint in 85%, followed by screening in familial or contralateral tumors in 26%. Familial cases occurred in 11 patients (28%). There were no operative deaths. Complications occurred in 13 of the 49 operations (27%), predominantly temporary nerve palsies and were more likely to occur in tumors of large volume or in cases of removal of coexisting vagal tumors. Malignant disease was present in seven cases (15%). All patients have been followed-up postoperatively for a mean of 11 years (range, 2-26 years). Metachronous paragangliomas have been discovered in six patients, all with familial disease. CONCLUSIONS: Early resection of carotid body tumors should be undertaken while still small to minimize the risk of neural injury, which increases with tumor size. In cases of bilateral CBT, we recommend that the smaller tumor be resected first, before the staged resection of the larger contralateral tumor. In familial or bilateral tumor cases, other synchronous and metachronous paragangliomas should be excluded. Mandatory lifelong follow-up is essential.

Open surgery for atherosclerotic chronic mesenteric ischemia.

BACKGROUND: This study was undertaken to document the results of our current practice of open mesenteric revascularization to enable comparison with the recent trend of percutaneous endovascular therapy for the treatment of chronic mesenteric ischemia. METHODS: Patients were identified via operation code data as well ongoing audit data from 1992 until 2006. Only patients with a history of chronic mesenteric ischemia secondary to atherosclerosis for 3 months or longer were included in the study. Follow-up data have been collected prospectively and include clinical examination and history, as well as graft surveillance consisting of mesenteric duplex ultrasonography, computed tomography, and/or angiography every 6 months for 3 years and then yearly thereafter. RESULTS: Thirty-nine consecutive patients underwent 41 open revascularization procedures for chronic mesenteric ischemia, comprising 67 bypass grafts. The mean patient age was 65 years (range, 45-85 years), and 44% (n = 17) were male. Symptoms were present on average for 11 months (range, 4-48 months) before treatment. The average weight loss was 11.4 kg, and three patients (7.6%) also had evidence of ischemic enteritis. There was one perioperative death, thus giving a perioperative mortality rate of 2.5%. Perioperative morbidity occurred in five patients (12.2%). Primary graft patency was 92% at 5 years. Seven patients died during follow-up, which ranged from 4 to 161 months (mean, 39 months)-one (2.5%) from mesenteric ischemia. Two (5%) other patients have had recurrent mesenteric ischemic symptoms. CONCLUSIONS: Open surgical mesenteric revascularization by bypass grafting for atherosclerotic-induced chronic mesenteric ischemia can be performed with low mortality and morbidity and provides excellent long-term primary patency rates and symptom-free outcomes. Pending more data on the acute and long-term results of endovascular techniques, open mesenteric revascularization remains the gold standard for most patients with chronic mesenteric ischemia.