Systematic review and meta-analysis of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms

BACKGROUND: Prior studies have suggested aortic peak wall stress (PWS) and peak wall rupture index (PWRI) can estimate the rupture risk of an abdominal aortic aneurysm (AAA), but whether these measurements have independent predictive ability over assessing AAA diameter alone is unclear. The aim of this systematic review was to compare PWS and PWRI in participants with ruptured and asymptomatic intact AAAs of similar diameter. METHODS AND RESULTS: Web of Science, Scopus, Medline, and The Cochrane Library were systematically searched to identify studies assessing PWS and PWRI in ruptured and asymptomatic intact AAAs of similar diameter. Random-effects meta-analyses were performed using inverse variance-weighted methods. Leave-one-out sensitivity analyses were conducted to assess the robustness of findings. Risk of bias was assessed using a modification of the Newcastle-Ottawa scale and standard quality assessment criteria for evaluating primary research papers. Seven case-control studies involving 309 participants were included. Meta-analyses suggested that PWRI (standardized mean difference, 0.42; 95% CI, 0.14–0.70; P=0.004) but not PWS (standardized mean difference, 0.13; 95% CI, −0.18 to 0.44; P=0.418) was greater in ruptured than intact AAAs. Sensitivity analyses suggested that the findings were not dependent on the inclusion of any single study. The included studies were assessed to have a medium to high risk of bias. CONCLUSIONS: Based on limited evidence, this study suggested that PWRI, but not PWS, is greater in ruptured than asymptomatic intact AAAs of similar maximum aortic diameter

Systematic review and meta-analysis of Mendelian randomisation analyses of abdominal aortic aneurysms

Introduction: Mendelian randomisation (MR) has been suggested to be able to overcome biases of observational studies, but no meta-analysis is available on MR studies on abdominal aortic aneurysm (AAA). This systematic review and Meta-analysis examined the evidence of causal risk factors for AAA identified in MR studies. Methods: Publicly available databases were systematically searched for MR studies that reported any causal risk factors for AAA diagnosis. Meta-analyses were performed using random effect models and reported as odds ratio (OR) and 95% confidence intervals (CI). Study quality was assessed using a modified version of Strengthening the Reporting of Mendelian Randomisation Studies (STROBE-MR) guidelines. Results: Sixteen MR studies involving 34,050 patients with AAA and 2,205,894 controls were included. Meta-analyses suggested that one standard deviation increase in high density lipoprotein (HDL) significantly reduced (OR: 0.66, 95% CI: 0.61, 0.72) and one standard deviation increase in low density lipoprotein (LDL) significantly increased the risk (OR: 1.68, 95%, CI: 1.55, 1.82) of AAA. One standard deviation increase in triglycerides did not significantly increase the risk of AAA (OR: 1.21, 95% CI: 0.86, 1.71). Quality assessment suggested that ten and five studies were of low and moderate risk of bias respectively, with one study considered as high risk of bias. Conclusion: This meta-analysis suggests LDL and HDL are positive and negative casual risk factors for AAA

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. © 2017 The Author(s)

Association of Oral Anticoagulation Prescription with Clinical Events in Patients with an Asymptomatic Unrepaired Abdominal Aortic Aneurysm

Background: Most abdominal aortic aneurysms (AAA) have large volumes of intraluminal thrombus which has been implicated in promoting the risk of major adverse events. The aim of this study was to examine the association of therapeutic anticoagulation with AAA-related events and major adverse cardiovascular events (MACE) in patients with an unrepaired AAA. Methods: Patients with an asymptomatic unrepaired AAA were recruited from four sites in Australia. The primary outcome was the combined incidence of AAA repair or AAA rupture-related mortality (AAA-related events). The main secondary outcome was MACE (the combined incidence of myocardial infarction, stroke, or cardiovascular death). The associations of anticoagulation with these outcomes were assessed using Cox proportional hazard analyses (reporting hazard ratio, HR, and 95% confidence intervals, CI) to adjust for other risk factors. Results: A total of 1161 patients were followed for a mean (standard deviation) of 4.9 (4.0) years. Of them, 536 (46.2%) patients had a least one AAA-related event and 319 (27.5%) at least one MACE. In the sample, 98 (8.4%) patients were receiving long-term therapeutic anticoagulation using warfarin (84), apixaban (7), rivaroxaban (6), or dabigatran (1). Prescription of an anticoagulant was associated with a reduced risk of an AAA-related event (adjusted HR 0.61; 95% CI 0.42, 0.90, p = 0.013), but not MACE (HR 1.16; 95% CI 0.78, 1.72, p = 0.476). Conclusions: These findings suggest that AAA-related events but not MACE may be reduced in patients prescribed an anticoagulant medication. Due to the inherent biases of observational studies, a randomized controlled trial is needed to assess whether anticoagulation reduces the risk of AAA-related events

Opinions of vascular surgeons and podiatrists in Australia and New Zealand on the use of hyperbaric oxygen therapy for lower limb ulcers

Introduction: Hyperbaric oxygen therapy (HBOT) has been suggested to improve healing of lower limb ulcers, though the quality of available evidence is weak to moderate. This study assessed the opinions and use of HBOT by specialists treating lower limb ulcers. Research design and methods: Accredited vascular surgeons and podiatrists in Australia and New Zealand were sent an online survey via their professional organizations. The survey asked about their use and opinions of HBOT in treating lower limb ischemic, neuropathic and venous ulcers. Data were summarized with descriptive statistics. Non-parametric tests were used to compare survey results obtained from vascular surgeons and podiatrists. Results: 61 vascular surgeons and 40 podiatrists completed the survey. Thirty-seven specialists used HBOT for treating lower limb ulcers, with the remainder indicating they did not feel there was a role for HBOT (n=25) or did not have access to HBOT (n=39). Less than 8% of specialists indicated that HBOT frequently or always had a role in treating ischemic, neuropathic or venous ulcers. Compared with podiatrists, vascular surgeons were significantly less likely to indicate HBOT had a treatment role for any ulcer type (p<0.001, p=0.004, and p<0.001, respectively), though significantly more likely to indicate they currently used HBOT for treating lower limb ulcers (p<0.001). Most specialists (n=76) believed that a large clinical trial is needed to determine the efficacy of HBOT in treating lower limb ulcers. Conclusions: Vascular surgeons and podiatrists do not feel HBOT has a frequent role in treating lower limb ulcers, but do feel there needs to be a large clinical trial to test its value

Review of harm-benefit analysis in the use of animals in research

This is the final version of the report. Available from the Home Office via the link in this recordReport of our review of the processes of harm-benefit analysis (HBA) carried out under the UK Animals (Scientific Procedures) Act 1986 (A(SP)A).Report of the Animals in Science Committee Harm-Benefit Analysis Sub-Group chaired by Professor Gail Davies. The Animals in Science Committee Harm-Benefit Analysis subgroup, chaired by Professor Gail Davies, has produced a review of the harm-benefit analysis (HBA). This review is an analysis of the underpinnings and implementation of the HBA which remains a crucial step in the justification of the use of animals in science. It is published in response to a ministerial commission.Animals in Science Committe

Deglacial grounding-line retreat in the Ross Embayment, Antarctica, controlled by ocean and atmosphere forcing

Modern observations appear to link warming oceanic conditions with Antarctic ice sheet grounding-line retreat. Yet, interpretations of past ice sheet retreat over the last deglaciation in the Ross Embayment, Antarctica’s largest catchment, differ considerably and imply either extremely high or very low sensitivity to environmental forcing. To investigate this, we perform regional ice sheet simulations using a wide range of atmosphere and ocean forcings. Constrained by marine and terrestrial geological data, these models predict earliest retreat in the central embayment and rapid terrestrial ice sheet thinning during the Early Holocene. We find that atmospheric conditions early in the deglacial period can enhance or diminish ice sheet sensitivity to rising ocean temperatures, thereby controlling the initial timing and spatial pattern of grounding-line retreat. Through the Holocene, however, grounding-line position is much more sensitive to subshelf melt rates, implicating ocean thermal forcing as the key driver of past ice sheet retreat

Association of computed tomographic leg muscle characteristics with lower limb and cardiovascular events in patients with peripheral artery disease

Background Poor lower extremity physical performance is an independent predictor of unfavorable outcome in patients with peripheral artery disease (PAD); however, few studies have assessed muscle characteristics on imaging directly. Method and Results A novel 3‐dimensional semi‐automated protocol was developed to estimate leg muscle volume and density (mean attenuation) from computed tomography images. Patients with PAD who underwent a lower extremity computed tomography scan at a tertiary vascular surgery center were included, and were followed up using hospital records and linked data as part of a retrospective cohort study. The primary outcomes were lower limb events (major amputation or peripheral revascularization) and cardiovascular events (myocardial infarction, stroke, or cardiovascular death). Two hundred and twenty‐three patients with PAD were included (median age 69.0 years; 73% men) and followed for a median of 4.9 [2.6–7.0] years. During this time there were 99 index lower limb events and 97 cardiovascular events. Low leg muscle density was associated with increased risk of lower limb (rate ratio 1.41 [1.11–1.80] per SD reduction) and cardiovascular events (rate ratio 1.60 [1.29–1.99] per SD reduction). Low muscle density remained an independent predictor of cardiovascular (but not lower limb) events, after adjusting for age, sex, traditional cardiovascular risk factors, and angiographic PAD severity (rate ratio 1.39 [1.09–1.77] per lower SD). In contrast, leg muscle volume was not associated with outcomes after adjusting for risk factors and PAD severity. Conclusions Low leg muscle density, but not volume, is a strong, independent predictor of major cardiovascular events among people with PAD. Further research is needed to understand the mechanisms underlying these associations

Affective disorders, psychosis and dementia in a community sample of older men with and without Parkinson's disease

Background: Dementia and affective and psychotic symptoms are commonly associated with Parkinson's disease, but information about their prevalence and incidence in community representative samples remains sparse. Methods: We recruited a community-representative sample 38173 older men aged 65-85 years in 1996 and used data linkage to ascertain the presence of PD, affective disorders, psychotic disorders and dementia. Diagnoses followed the International Classification of Disease coding system. Age was recorded in years. Follow up data were available until December 2011. Results: The mean age of participants was 72.5 years and 333 men (0.9%) had PD at study entry. Affective and psychotic disorders and dementia were more frequent in men with than without PD (respective odds ratios: 6.3 [95%CI = 4.7, 8.4]; 14.2 [95%CI = 8.4, 24.0] and 18.2 [95%CI = 13.4, 24.6]). Incidence rate ratios of affective and psychotic disorders were higher among men with than without PD, although ratios decreased with increasing age. The ageadjusted hazard ratio (HR) of an affective episode associated with PD was 5.0 (95%CI = 4.2, 5.9). PD was associated with an age-adjusted HR of 8.6 (95%CI = 6.1, 12.0) for psychotic disorders and 6.1 (95%CI = 5.5, 6.8) for dementia. PD and dementia increased the HR of depressive and psychotic disorders. Conclusions: PD increases the risk of affective and psychotic disorders, as well as dementia, among community dwelling older men. The risk of a recorded diagnosis of affective and psychotic disorders decreases with increasing age

Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm–related events

Objective: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. Methods: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. Results: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. Conclusion: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. Key Points: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone