ORCID Profile
0000-0002-2131-2068
Current Organisation
James Cook University
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Publisher: Portland Press Ltd.
Date: 06-2017
DOI: 10.1042/CS20160970
Abstract: Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1 gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman’s rho −0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40 95% confidence interval (CI): 0.19–0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1−/−ApoE−/−, n=20) and control mice (ApoE−/−, n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1−/− ApoE−/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1−/−ApoE−/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1−/−ApoE−/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1−/−ApoE−/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.
Publisher: Wiley
Date: 29-09-2021
DOI: 10.1111/JPC.15765
Abstract: To summarise existing evidence about barriers and enablers to breastfeeding babies with Down syndrome (DS) in peer‐reviewed literature. Ovid Medline, CINAHL, Scopus and Ovid Emcare were searched. Inclusion and exclusion criteria were used to screen yielded articles and those meeting the criteria were included for data extraction. Two authors extracted data including outcomes, design, definition of DS, barriers and enablers to breastfeeding babies with DS. Sixteen studies met the inclusion and exclusion criteria. Barriers and enablers were categorised into maternal, child and health professional factors. This review identified a significant literature gap related to breastfeeding babies with DS and more definitive research under current standards is needed. Mothers reported the need for high‐quality health professional breastfeeding support and evidence‐based effective breastfeeding techniques. A collaborated and concerted approach from both mothers and health professionals is important to optimise breastfeeding for babies with DS.
Publisher: Oxford University Press (OUP)
Date: 2021
Abstract: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. A sustained reduction in relative limb blood supply (P & 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.ATHEROSCLEROSIS.2013.04.030
Abstract: Current guidelines contain no advice on how to manage obesity and underweight in patients with peripheral vascular disease (PVD). The aim of this study was to assess the association of underweight, overweight and obesity with mortality in patients with PVD. We recruited 1472 patients with a broad range of presentations of PVD. Underweight, overweight and obesity were defined by body mass index (BMI) and associated with mortality using Kaplan Meier and Cox proportional hazard analyses. Survival at 3 years was 37.5, 78.1, 86.8 and 87.0% for patients that were underweight, normal weight, overweight and obese at recruitment, respectively, p<0.001. Patients that were underweight had approximately twice the risk of dying (RR 2.15, 95% CI 1.31-3.55, p=0.003), while patients that were overweight (RR 0.67, 95% CI 0.49-0.91, p=0.011) or obese (RR 0.59, 95% CI 0.41-0.85, p=0.005) had approximately half the risk of dying, after adjustment for other risk factors and using normal weight subjects as the reference group. 823 patients had waist circumference measured at recruitment. Patients with waist circumference in the top quartile had half the risk of dying (RR 0.50, 95% CI 0.26-0.98, p=0.045). In 267 patients we assessed the relationship between BMI and abdominal fat volumes using computed tomography. BMI was highly correlated with both intra-abdominal and subcutaneous fat volumes. Obesity whether assessed by BMI or central fat deposition is associated with reduced risk of dying in patients with established PVD. Underweight is highly predictive of early mortality in patients with PVD.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.ATHEROSCLEROSIS.2014.04.033
Abstract: To assess relevant features of abdominal aortic aneurysms (AAA) induced by calcium phosphate within a mouse model. Specifically we investigated: (1) whether apolipoprotein E deficiency and older age promoted AAA formation, and (2) whether the local application of calcium phosphate affected the size of distant aortic segments. AAA was induced by application of calcium phosphate to the infra-renal aortas of 3 and 7 month old male mice. AAA induction was assessed by calculating expansion of the infra-renal aortic diameter over 1-4 weeks. Aortic s les were assessed to quantify calcification, macrophages infiltration, elastic lamellar degradation and apoptosis. Blood pressure was measured by the tail cuff method, and plasma concentrations of total cholesterol, low density lipoprotein and very low density lipoprotein cholesterol, and pro-inflammatory cytokines were measured using commercially available kits. The maximum diameters of the aortic arch, thoracic and supra-renal aorta at sacrifice were measured by morphometry and the mean maximal diameter of these three aortic segments was calculated. The median expansion of the infra-renal aorta 2 weeks after AAA induction was significantly greater in apolipoprotein E deficient (ApoE(-/-)) mice than in age- and gender-matched wild type controls [275.8% (IQR 193.8%-348.5%) versus 94.7% (IQR 47.8%-163.4%), P = 0.02]. The greater aortic expansion in ApoE(-/-) mice was associated with aortic calcification, macrophage infiltration, elastic lamellar degradation and apoptosis of cells in the media and adventitia. The plasma low density lipoprotein/very low density lipoprotein cholesterol concentrations 2 weeks after AAA induction were positively correlated with the expansion of the infra-renal aorta induced by calcium phosphate. The median expansion of the infra-renal aorta 2 weeks after AAA induction was similar in 3 and 7 month old wild type mice. The local administration of calcium phosphate was associated with an increase in the mean maximal diameter of distant aortic segments, but not associated with changes in the concentrations of pro-inflammatory markers in either the plasma or the spleen. This study suggests that apolipoprotein E deficiency, but not age, predisposes to AAA induced within the calcium phosphate model. Increased AAA expansion in ApoE(-/-) mice was associated with calcification, macrophage infiltration, elastic lamellar degradation, and cell apoptosis. Local application of calcium phosphate also promoted dilation of distant aortic segments.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.EJVS.2015.06.023
Abstract: Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 μg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 μg/mL [IQR 3.44-5.84], respectively p = .48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32] p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively p < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.
Publisher: Springer Science and Business Media LLC
Date: 27-12-2021
DOI: 10.1186/S13063-021-05915-0
Abstract: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.EJVS.2021.12.038
Abstract: The role of atherosclerosis in abdominal aortic aneurysm (AAA) pathogenesis is controversial. The aim of this study was to compare AAA growth in patients who did and did not have concurrent athero-occlusive disease (AOD). Patients with an AAA measuring 35 - 49 mm in maximum diameter were recruited as part of the TElmisartan in the management of abdominal aortic aneurysm (TEDY) trial. TEDY participants who had infrarenal aortic volume and orthogonal diameter assessed by computed tomography at entry and at least one other time point during the trial (12 and/or 24 months) were included. AOD was defined by prior diagnoses of coronary heart disease, stroke, or peripheral arterial disease or an ankle brachial pressure index < 0.90. The increase in AAA volume and diameter from entry for participants who did and did not have AOD was assessed using linear mixed effects models 131 of the 210 participants recruited to TEDY were included. In an unadjusted analysis, the mean (95% confidence interval) annual increases in AAA volume and diameter for participants with AOD were 3.26 (0.82 - 5.70) cm In an exploratory analysis of a selective cohort from the TEDY trial, AOD was associated with slower AAA growth. Validation of these findings in other cohorts is needed.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2017
Publisher: Springer Science and Business Media LLC
Date: 04-11-2022
DOI: 10.1186/S12872-022-02918-W
Abstract: A previous study found that circulating angiopoietin-1 (angpt-1) concentrations were significantly lower in patients who had a recent ischaemic stroke compared to healthy controls. The primary aim of this study was to assess whether serum angpt-1 could be used as a diagnostic test of ischemic stroke in patients presenting to hospital as an emergency. Exploratory analyses investigated the association of proteins functionally related to angpt-1 (angpt-2, Tie-2, matrix metalloproteinase-9 and vascular endothelial growth factors A, C and D) with ischaemic stroke diagnosis. Patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were consecutively recruited and provided a blood s le. After assessment by a consultant neurologist, patients were grouped into those who did, or did not have ischaemic stroke. The potential for serum angpt-1 to diagnose ischaemic stroke was assessed using receiver operator characteristic (ROC) curves. Cross-sectional analyses appraised inter-group differences in the serum concentration of other proteins. One-hundred and twenty-six patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were recruited (median time from symptom onset to hospital presentation: 2.6 (inter-quartile range: 1.2–4.6) hours). Serum angpt-1 had poor ability to diagnose ischaemic stroke in analyses using the whole cohort, or in sensitivity analyses (area under the ROC curve 0.51 (95% CI: 0.41–0.62) and 0.52 (95% CI: 0.39–0.64), respectively). No associations of serum angpt-1 concentration with ischaemic stroke severity, symptom duration or aetiology were observed. Serum concentrations of the other assessed proteins did not differ between patient groups. Serum angpt-1 concentration is unlikely to be useful for emergency diagnosis of ischaemic stroke.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
DOI: 10.1038/S41598-021-91855-3
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Springer Science and Business Media LLC
Date: 16-05-2018
Publisher: Springer Science and Business Media LLC
Date: 03-09-2020
DOI: 10.1038/S41598-020-71454-4
Abstract: The aims of this study were, firstly, to assess the effect of concurrent peripheral artery disease (PAD) on the health-related quality of life (QOL) of people diagnosed with a small abdominal aortic aneurysm (AAA) and secondly, to test whether the peroxisome proliferator-activated receptor α agonist fenofibrate improved QOL of people diagnosed with a small AAA, including those diagnosed with concurrent PAD. The study included both a cross-sectional observational study and a randomized placebo-controlled clinical trial. 140 people diagnosed with a 35–49 mm diameter AAA, 56 (40%) of whom had concurrent PAD, and 25 healthy controls were prospectively recruited. QOL was assessed with the short form (SF) 36. Findings in participants that were diagnosed with both AAA and PAD were compared separately with those of participants that had a diagnosis of AAA alone or who had neither AAA nor PAD diagnosed (healthy controls). All participants diagnosed with an AAA were then randomly allocated to 145 mg of fenofibrate per day or identical placebo. Outcomes were assessed by changes in the domains of the SF-36 and ankle brachial pressure Index (ABPI) from randomization to 24 weeks. Data were analyzed using Mann–Whitney U tests. Participants diagnosed with both AAA and PAD had significantly worse QOL than participants diagnosed with AAA alone or healthy controls. Fenofibrate did not significantly alter SF-36 scores or ABPI over 24 weeks. Fenofibrate does not improve QOL of people diagnosed with small AAA, irrespective of whether they have concurrent PAD. Trial registration : ACTN12613001039774 Australian New Zealand Clinical Trials Registry.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.ATHEROSCLEROSIS.2015.10.011
Abstract: The association of vitamin D deficiency with cardiovascular disease is controversial. The present meta-analysis was performed to examine if circulating levels of 25-hydroxyvitamin D [25(OH)D] were lower in patients with peripheral artery disease (PAD) when compared to non-PAD controls. A comprehensive database search was conducted in Web of science, Scopus, PubMed, EMBASE and The Cochrane Library to identify observational studies reporting 25(OH)D concentrations in PAD patients and non-PAD participants. Data extraction and study quality assessments were conducted independently. A random-effects model was used to meta-analyse extracted data and generate standardized mean differences (SMDs) in circulating 25(OH)D levels between PAD patients and non-PAD controls. Subgroup analyses were conducted focussing on patients presenting with intermittent claudication (IC) and critical limb ischaemia (CLI). Six case-control studies assessing 6418 in iduals fulfilled the inclusion criteria. Two studies were considered to be of moderate methodological quality and four were considered to be of high quality. A meta-analysis of data from 1217 PAD patients and 5201 non-PAD participants showed that circulating 25(OH)D concentrations were lower in PAD patients compared with non-PAD participants (SMD = -0.32, 95% CI: -0.58, -0.05 P = 0.02). Subgroup analyses showed that 25(OH)D levels were significantly lower among PAD patients with CLI, but not IC, when compared to non-PAD controls (SMD = -1.29, 95% CI: -1.66, -0.91 P < 0.001 and SMD = -0.01, 95% CI: -0.15, 0.13 P=0.88, respectively). This meta-analysis suggests that low levels of circulating 25(OH)D are associated with PAD presence, particularly in patients presenting with CLI. These data suggest the possibility that vitamin D insufficiency may contribute to the development of more advanced PAD although this remains to be confirmed.
Publisher: Public Library of Science (PLoS)
Date: 25-05-2012
Publisher: Springer Science and Business Media LLC
Date: 25-02-2015
DOI: 10.1007/S12603-015-0483-2
Abstract: The effect of dietary salt intake on important population outcomes such as mortality is controversial. The aim of this study was to examine the association between the dietary habit of adding salt to food and mortality in older men. Design, participants, setting and measurements: A risk factor questionnaire which contained a question about the dietary habit of adding salt to food was completed by 11742 community recruited older men between 1996 and 1999. The men were followed by means of the Western Australia Data Linkage System until November 30th 2010. Deaths due to cardiovascular diseases and cancers were identified using ICD-10 codes in the ranges I00-I99 and C00-D48, respectively. The association between the frequencies of adding salt to food and mortality was assessed using Kaplan Meier estimates and Cox proportional hazard analysis. Median follow-up for survivors was 12.5 years (inter-quartile range 8.3-13.2 years). A total of 5399 deaths occurred of which the primary cause registered was cancer and cardiovascular disease in 1962 (36.3%) and 1835 (34.0%) men, respectively. The reported frequency of adding salt to food was strongly positively associated with all-cause (p<0.001), cancer-related (p<0.001) but not cardiovascular-related (p=0.649) mortality. Men reporting adding salt to their food always had a 1.12-fold (95% CI 1.05-1.20, p<0.001) and a 1.20-fold (95% CI 1.07-1.34, p=0.001) increased risk of all-cause and cancer-related mortality, respectively, after adjusting for other risk factors. Men reporting adding salt to their food sometimes had a 1.16-fold (95% CI 1.04-1.29, p=0.007) increased risk of cancer-related mortality after adjusting for other risk factors. A history of adding salt to food is associated with increased cancer-related mortality in older men.
Publisher: Oxford University Press (OUP)
Date: 31-01-2017
DOI: 10.1002/BJS.10460
Abstract: Angiography is used routinely in the assessment of lower-limb arteries, but there are few well validated angiographic scoring systems. The aim of this study was to develop and validate a novel angiographic scoring system for peripheral artery disease. An angiographic scoring system (the ANGIO score) was developed and applied to a s le of patients from a single vascular surgical department who underwent CT angiography of the lower limbs. The reproducibility of the ANGIO score was compared with those of the Bollinger and Trans-Atlantic inter-Society Consensus (TASC) IIb systems in a series of randomly selected patients. Associations between the ANGIO score and lower-limb ischaemia, as measured by the ankle : brachial pressure index (ABPI), and outcome events (major lower-limb utations and cardiovascular events – myocardial infarction, stroke and cardiovascular death) were assessed. Some 256 patients undergoing CT angiography were included. The interobserver reproducibility of the ANGIO score was better than that of the other scoring systems examined (κ = 0·90, P = 0·002). There was a negative correlation between the ANGIO score and ABPI (ρ = −0·33, P = 0·008). A higher ANGIO score was associated with an increased risk of major lower-limb utation (hazard ratio (HR) for highest versus lowest tertile 9·30, 95 per cent c.i. 1·95 to 44·38 P = 0·005) and cardiovascular events (HR 2·73, 1·31 to 5·70 P = 0·007) following adjustment for established risk factors. The ANGIO score provided a reproducible and valid assessment of the severity of lower-limb ischaemia and risk of major utation and cardiovascular events in these patients with peripheral artery disease.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JVS.2019.03.057
Abstract: Intraluminal thrombus (ILT) is present in most abdominal aortic aneurysms (AAAs), although its role in AAA progression is controversial. A literature search was performed to identify studies that investigated the association between ILT volume and AAA rupture. A study assessment tool was developed to assess the methodologic quality of included studies. A meta-analysis was conducted using an inverse variance-weighted random-effects model to compare the ILT volume in ruptured and asymptomatic intact AAAs. Leave-one-out sensitivity analyses were conducted to assess the robustness of the findings. A subanalysis was performed including studies in which patients with asymptomatic intact and ruptured AAAs were matched for aortic diameter. Interstudy heterogeneity was assessed using the I Eight studies involving 672 patients were included in this systematic review. Meta-analysis of all studies found a greater ILT volume in patients with ruptured AAAs than in patients with asymptomatic intact AAAs (standardized mean difference, 0.56 95% confidence interval, 0.17-0.96 P = .005 I This meta-analysis suggests that ILT volume is greater in patients with ruptured AAAs than in patients with asymptomatic intact AAAs, although this is most likely due to the larger diameter of ruptured AAAs.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2009
Abstract: An animal model commonly used to investigate pathways and potential therapeutic interventions relevant to abdominal aortic aneurysm (AAA) involves subcutaneous infusion of angiotensin II within the apolipoprotein E deficient mouse. The aim of this study was to investigate genes differentially expressed in aneurysms forming within this mouse model in order to assess the relevance of this model to human AAA. Using microarrays we identified genes relevant to aneurysm formation within apolipoprotein E deficient mice. Firstly we investigated genes differentially expressed in the aneurysm prone segment of the suprarenal aorta in these mice. Secondly we investigated genes that were differentially expressed in the aortas of mice developing aneurysms relative to those that did not develop aneurysms in response to angiotensin II infusion. Our findings suggest that a host of inflammation and extracellular matrix remodelling pathways are upregulated within the aorta in mice developing aneurysms. Kyoto Encyclopedia of Genes and Genome categories enriched in the aortas of mice with aneurysms included cytokine-cytokine receptor interaction, leukocyte transendothelial migration, natural killer cell mediated cytotoxicity and hematopoietic cell lineage. Genes associated with extracellular matrix remodelling, such as a range of matrix metalloproteinases were also differentially expressed in relation to aneurysm formation. This study is the first report describing whole genome expression arrays in the apolipoprotein E deficient mice in relation to aneurysm formation. The findings suggest that the pathways believed to be critical in human AAA are also relevant to aneurysm formation in this mouse model. The findings therefore support the value of this model to investigate interventions and mechanisms of human AAA.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-04-2021
Abstract: 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. 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. 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.
Publisher: Elsevier BV
Date: 03-2019
Publisher: MDPI AG
Date: 06-04-2022
Abstract: The coronavirus (COVID-19) disease pandemic has been associated with adverse psychological outcomes. This cross-cultural study (N = 1326, 71% female) aimed to investigate Canadian and Australian adolescents’ subjective experiences of COVID-19, gender differences, and psychological implications. Mixed-methods analyses were used to examine differences in COVID-19 experiences and mental health outcomes between country and gender in a Canadian (N = 913, 78% female) and an Australian s le (N = 413, 57% female) of adolescents. Canadian adolescents reported increased COVID-19 discussions and more concerns related to their COVID-19 experiences compared to Australian adolescents. Girls consistently reported more concerns related to COVID-19 and poorer psychological outcomes compared to boys. School lockdown for the Canadian s le may have played a role in these country differences. Further, girls might be at significantly more risk for mental health concerns during COVID-19, which should be considered in adolescent mental health initiatives during the pandemic. Although school disruption and separation of peers due to the pandemic likely have a role in adolescent perceived stressors and mental health, the differences between Canadian and Australian adolescents were less clear and future investigations comparing more objective pre-COVID-19 data to current data are needed.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2021
DOI: 10.1186/S13089-021-00211-Z
Abstract: Accurate repeat assessment of the diameter of an abdominal aortic aneurysm (AAA) is important. This study investigated the reproducibility of different methods of measuring AAA diameter from ultrasound images. Fifty AAA patients were assessed by ultrasound. Maximum AAA diameter was measured independently by three trained observers on two separate occasions using a standardised protocol. Five diameters were measured from each scan, three in the anterior–posterior (AP) and two in the transverse (TV) plane, including inner-to-inner (ITI), outer-to-outer (OTO) and leading edge-to-leading edge (LETLE). Intra- and inter-observer reproducibility were reported as reproducibility coefficients. Statistical comparison of methods was performed using linear mixed effects models. Intra-observer reproducibility coefficients (AP LETLE 2.2 mm AP ITI 2.4 mm AP OTO 2.6 mm) were smaller than inter-observer reproducibility coefficients (AP LETLE 4.6 mm: AP ITI 4.5 and AP OTO 4.8 mm). There was no statistically significant difference in intra-observer reproducibility of three types of measurements performed in the AP plane. Measurements obtained in the TV plane had statistically significant worse intra-observer reproducibility than those performed in the AP plane. This study suggests that the comparison of maximum AAA diameter between repeat images is most reproducibly performed by a single trained observer measuring diameters in the AP plane.
Publisher: Portland Press Ltd.
Date: 26-01-2016
DOI: 10.1042/CS20150547
Abstract: Abdominal aortic aneurysm (AAA) is a significant cause of mortality in older adults. A key mechanism implicated in AAA pathogenesis is inflammation and the associated production of reactive oxygen species (ROS) and oxidative stress. These have been suggested to promote degradation of the extracellular matrix (ECM) and vascular smooth muscle apoptosis. Experimental and human association studies suggest that ROS can be favourably modified to limit AAA formation and progression. In the present review, we discuss mechanisms potentially linking ROS to AAA pathogenesis and highlight potential treatment strategies targeting ROS. Currently, none of these strategies has been shown to be effective in clinical practice.
Publisher: MDPI AG
Date: 18-05-2015
Publisher: Oxford University Press (OUP)
Date: 26-06-2021
DOI: 10.1002/BJS.10587
Abstract: It has been suggested that diabetes medications, such as metformin, may have effects that inhibit abdominal aortic aneurysm (AAA) growth. The aim of this study was to examine the association of diabetes treatments with AAA growth in three patient cohorts. AAA growth was studied using ultrasound surveillance in cohort 1, repeated CT in cohort 2 and more detailed repeat CT in cohort 3. Growth was estimated by the mean annual increase in maximum AAA diameter. A total of 1697 patients with an AAA were studied, of whom 118, 39 and 16 patients were prescribed metformin for the treatment of diabetes in cohorts 1, 2 and 3 respectively. Prescription of metformin was associated with a reduced likelihood of median or greater AAA growth in all three cohorts (cohort 1: adjusted odds ratio (OR) 0·59, 95 per cent c.i. 0·39 to 0·87, P = 0·008 cohort 2: adjusted OR 0·38, 0·18 to 0·80, P = 0·011 cohort 3: adjusted OR 0·13, 0·03 to 0·61, P = 0·010). No other diabetes treatment was significantly associated with AAA growth in any cohort. These findings suggest a potential role for metformin in limiting AAA growth.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-10-2018
Abstract: 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. 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 utation 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. 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.
Publisher: Wiley
Date: 02-2010
DOI: 10.1111/J.1365-3024.2009.01171.X
Abstract: Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. Unlike the well characterized schistosomes, only the adult and juvenile stages of F. hepatica are implicated in disease, whereas the freely voided egg is not thought to contribute to host-parasite interactions. We investigated specific immune responses to soluble F. hepatica egg proteins (SFHEP), during a 14-week experimental infection, demonstrating significant increases in anti-SFHEP IgG1 (P = 0.001), transforming growth factor beta-1 (P = 0.008) and IL-10 (P < 0.001) titres at the onset of egg production. Western blot analysis of soluble SFHEP demonstrates that protein bands migrating at 61.6, 54.8 and 44 kDa become sero-reactive before the appearance of eggs within host faeces. Therefore, expression of some egg-associated proteins indicates progression to chronic disease. Antigenic bands were investigated through mass spectrometry, identifying a protein disulphide isomerase (PDI) (61.6 kDa), an enolase and ferritin-related proteins (54.8 kDa), and a cocktail of dehydrogenases (44 kDa). Biochemical analysis of egg secretions reveals proteolytic activity, which increases over time, indicating that proteases may be continually secreted during the course of egg maturation. The implications of egg-specific immune responses and proteolytic secretions are further discussed.
Publisher: Elsevier BV
Date: 10-2010
Publisher: Public Library of Science (PLoS)
Date: 26-07-2016
Publisher: Public Library of Science (PLoS)
Date: 13-11-0028
DOI: 10.1371/JOURNAL.PONE.0241802
Abstract: To assess whether survival and clinical events following elective abdominal aortic aneurysm (AAA) repair were associated with remoteness of residence in North Queensland, Australia. This retrospective cohort study included participants undergoing elective AAA repair between February 2002 and April 2020 at two hospitals in Townsville, North Queensland, Australia. Outcomes were all-cause survival and AAA-related events, defined as requirement for repeat AAA repair or AAA-related mortality. Remoteness of participant’s place of residence was assessed by the Modified Monash Model classifications and estimated distance from the participants’ home to the tertiary vascular centre. Cox proportional hazard analysis examined the association of remoteness with outcome. The study included 526 participants undergoing elective repair by open (n = 204) or endovascular (n = 322) surgery. Fifty-four (10.2%) participants had a place of residence at a remote or very remote location. Participants' were followed for a median of 5.2 (inter-quartile range 2.5–8.3) years, during which time there were 252 (47.9%) deaths. Survival was not associated with either measure of remoteness. Fifty (9.5%) participants had at least one AAA-related event, including 30 (5.7%) that underwent at least one repeat AAA surgery and 23 (4.4%) that had AAA-related mortality. AAA-related events were more common in participants resident in the most remote areas (adjusted hazard ratio 2.83, 95% confidence intervals 1.40, 5.70) but not associated with distance from the participants’ residence to the tertiary vascular centre The current study found that participants living in more remote locations were more likely to have AAA-related events but had no increased mortality following AAA surgery. The findings emphasize the need for careful follow-up after AAA surgery. Further studies are needed to examine the generalisability of the findings.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.AJPATH.2012.04.015
Abstract: There are currently no acceptable treatments to limit progression of abdominal aortic aneurysm (AAA). Increased serum concentrations of high-density lipoprotein (HDL) are associated with reduced risk of developing an AAA. The present study aimed to assess the effects of fenofibrate on aortic dilatation in a mouse model of AAA. Male low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice were maintained on a high-fat diet for 3 weeks followed by 6 weeks of oral administration of vehicle or fenofibrate. From 14 to 18 weeks of age, all mice were infused with angiotensin II (AngII). At 18 weeks of age, blood and aortas were collected for assessment of serum lipoproteins, aortic pathology, aortic Akt1 and endothelial nitric oxide synthase (eNOS) activities, immune cell infiltration, eNOS and inducible NOS (iNOS) expression, sphingosine 1 phosphate (S1P) receptor status, and apoptosis. Mice receiving fenofibrate had reduced suprarenal aortic diameter, reduced aortic arch Sudan IV staining, higher serum HDL levels, increased serum S1P concentrations, and increased aortic Akt1 and eNOS activities compared with control mice. Macrophages, T lymphocytes, and apoptotic cells were less evident and eNOS, iNOS, and S1P receptors 1 and 3 were up-regulated in aortas from mice receiving fenofibrate. The present findings suggest that fenofibrate antagonizes AngII-induced AAA and atherosclerosis by up-regulating serum HDL and S1P levels, with associated activation of NO-producing enzymes and reduction of aortic inflammation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2013
DOI: 10.1161/ATVBAHA.112.301006
Abstract: We aimed to determine the effect of mechanistic target of rapamycin inhibitor everolimus on abdominal aortic aneurysm within the angiotensin II (A2)-infused apolipoprotein E–deficient mouse model. Abdominal aortic aneurysm was induced via subcutaneous infusion of A2. Flow cytometry demonstrated increased circulating and aortic C-C chemokine receptor 2 (CCR2) monocytes during A2 infusion. The number of CCR2 monocytes present within the aorta was positively correlated with suprarenal aortic diameter. Simultaneous infusion of everolimus via a second subcutaneous osmotic micropump inhibited A2-induced aortic dilatation. Using flow cytometry and Western blot analysis, decreased aortic dilatation was associated with reduced development of CCR2 bone marrow monocytes, fewer numbers of circulating CCR2 monocytes, and lower aortic CCR2 concentration. In vitro, everolimus inhibited A2-stimulated production of interferon (IFN)-γ and IFNγ-induced CCR2 expression in apolipoprotein E–deficient mouse bone marrow monocytes. Further, everolimus diminished IFNγ/lipopolysaccharide-stimulated M1 polarization in apolipoprotein E–deficient mouse bone marrow monocyte–differentiated macrophages. Systemic administration of everolimus limits aortic aneurysm in the A2-infused apolipoprotein E–deficient mouse model via suppressed development of bone marrow CCR2 monocytes and reduced egress of these cells into the circulation.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.ATHEROSCLEROSIS.2011.07.105
Abstract: The role of transforming growth factor (TGF)-beta in abdominal aortic aneurysm (AAA) is controversial. The aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) within TGFBR1 and TGFBR2 with AAA and infrarenal aortic diameter by combining data from previously published studies. We performed a meta-analysis using in idual subject data from three independent case-control groups from Western Australia (n=1675), New Zealand (n=1209), and the Netherlands (n=1636) with 610, 601, and 693 cases of AAA (maximum infrarenal aortic diameter ≥30 mm), respectively. Data were available for two TGFBR1 (rs10819634, rs1571590) and six TGFBR2 (rs304839, rs1346907, rs1036095, rs9831477, rs9843143, rs764522) SNPs. There was marked heterogeneity between studies. The G alleles of the TGFBR2 rs764522 and rs1036095 SNPs were associated with AAA under a recessive model (OR=1.69, 95% CI 1.28-2.25, P<0.001 and OR=1.59, 95% CI 1.23-2.07, P<0.001) when a fixed effects model was used. Both associations remained significant after adjustment for multiple testing. This study suggests that two common genetic polymorphisms in TGFBR2 are associated with the risk of developing AAA although this association was mainly driven by findings in the Netherlands group and marked between study heterogeneity was detected.
Publisher: Public Library of Science (PLoS)
Date: 29-05-2012
Publisher: SAGE Publications
Date: 04-10-2019
Abstract: Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood–brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: –3.02 95% confidence intervals: –4.41, –1.63 p 0.001 n = 171 animals) and improved blood–brain barrier integrity (standardized mean difference: –2.02 95% confidence intervals: –3.27, –0.77 p = 0.002 n = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood–brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.VETPAR.2009.12.031
Abstract: Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. We report the first post-genomic investigation of cellular proteins expressed by embryonic F. hepatica via two-dimensional electrophoresis, image analysis and tandem mass spectrometry. Antioxidant proteins and protein chaperones are prominently expressed by embryonic F. hepatica. Molecular differences between the egg and other characterized F. hepatica lifecycle stages were noted. Furthermore, proteins expressed within liver fluke eggs differ to those isolated from the well-characterized eggs of the human blood flatworm Schistosoma mansoni were revealed. Plasticity in expression of major proteins, particularly a prominently expressed 65kDa protein cluster was seen between natural populations of embryonating F. hepatica eggs suggesting that liver fluke embryogenisis is a plastic process. Immunoblotting revealed that the abundant 65kDa protein cluster is recognised by infection sera from three F. hepatica challenged host species. Mass spectrometry and BLAST analyses demonstrated that the 65kDa antigen shows homology to egg antigens of other flatworm parasites, and is represented in a F. hepatica EST database constructed from adult fluke transcripts. EST clones encoding the egg antigen were re-sequenced, predicting two forms of the protein. Four clones predict a 312 aa polypeptide, three clones encode a putative 110 amino acid extension at the N-terminus which may be involved in protein secretion, although this extension was not expressed by natively extracted proteins. Consistent expression of alpha crystallin domains confirmed the protein to be a member of the alpha crystallin containing small heat shock protein (AC/sHSP) superfamily. AC/sHSPs are ubiquitous in nature, however, this is the first time a member of this protein superfamily has been described from F. hepatica. The antigenic AC/sHSP was named Fh-HSP35alpha based on predictions of molecular weight. Production of recombinant Fh-HSP35alpha reveals considerable mass discrepancy between native and recombinant proteins, although descriptions of other characterized flatworm AC/sHSPs, suggest that the native form is a dimer. Immunoblot analyses confirm that the recombinant protein is recognised by F. hepatica challenged hosts, but does not react with sera from non-infected animals. We discuss the potential of recombinant Fh-HSP35alpha as an egg-based diagnostic marker for liver fluke infection.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Springer Science and Business Media LLC
Date: 16-11-2017
Publisher: Springer Science and Business Media LLC
Date: 10-03-2023
DOI: 10.1007/S00330-023-09488-1
Abstract: 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. 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. 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 0.001) were associated with significantly higher risks of AAA events. In the CART analysis, PWRI was identified as the best single predictor of AAA events at a cut-off value of 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. • 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.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-05-2021
Abstract: No network meta‐analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short‐ ( year), moderate‐ (1 to years), and long‐term (≥2 years) follow‐up in people with intermittent claudication. A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health‐related quality of life. Network meta‐analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty‐six trials involving 4256 patients were included. At short‐term follow‐up, home exercise therapy (mean difference [MD], 89.4 m 95% credible interval [CrI], 20.9–157.7), SET (MD, 186.8 m 95% CrI, 136.4–237.6), and ER+SET (MD, 326.3 m 95% CrI, 222.6–430.6), but not ER (MD, 82.5 m 95% CrI, −2.4 to 168.2) and cilostazol (MD, 71.1 m 95% CrI, −24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate‐term follow‐up, SET (MD, 201.1 95% CrI, 89.8–318.3) and ER+SET (MD, 368.5 95% CrI, 195.3–546.9), but not home exercise therapy (MD, 99.4 95% CrI, −174.0 to 374.9) or ER (MD, 84.2 95% CrI, −35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long‐term follow‐up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta‐analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively. This network meta‐analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term ( year) but not beyond this. Durable treatments for intermittent claudication are needed.
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Society for Clinical Investigation
Date: 02-05-2016
DOI: 10.1172/JCI87977
Publisher: Springer Science and Business Media LLC
Date: 11-2014
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.YJMCC.2011.06.002
Abstract: Acquired cardiovascular diseases such as coronary heart disease, peripheral artery disease and related vascular problems contribute to more than one-third of worldwide morbidity and mortality. In many instances, particularly in the under developed world, cardiovascular diseases are diagnosed at a late stage limiting the scope for improving outcomes. A range of therapies already exist for established cardiovascular disease, although there is significant interest in further understanding disease pathogenesis in order to improve diagnosis and achieve primary and secondary therapeutic goals. The urocortins are a group of recently defined peptide members of the corticotrophin-releasing factor family. Previous pre-clinical work and human association studies suggest that urocortins have potential to exert some beneficial and other detrimental effects on the heart and major blood vessels. More current evidence however favours beneficial effects of urocortins, for ex le these peptides have been shown to inhibit production of reactive oxygen species and vascular cell apoptosis, and thus may have potential to antagonise the progression of cardiovascular disease. This review summarises published data on the potential role of urocortins in cardiovascular disease.
Publisher: American Medical Association (AMA)
Date: 12-2020
Publisher: Portland Press Ltd.
Date: 02-01-2018
DOI: 10.1042/CS20171522
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.ATHEROSCLEROSIS.2016.05.022
Abstract: Experimental studies using a rodent model have suggested that iron overload may contribute to abdominal aortic aneurysm (AAA) pathogenesis. We assessed the association of total body iron, as measured by plasma ferritin, with AAA diagnosis, size and growth in 4024 community-dwelling older men screened for AAA, using logistic regression and linear mixed effects models. Plasma ferritin concentrations were similar in men who did (n = 293) and did not (n = 3731) have an AAA (median [inter-quartile range] concentrations 115.4 [63.0-203.1] and 128.5 [66.1-229.1] ng/mL respectively, p = 0.124). There was no association between plasma ferritin concentration and AAA diagnosis in unadjusted logistic regression (odds ratio (OR) for a 1 standard deviation increase: 0.880 [95%CI: 0.764-1.015] p = 0.078), or when adjusting for AAA risk factors and factors known to influence circulating ferritin (OR for a 1 standard deviation increase: 0.898 [95% CI: 0.778-1.035] p = 0.138). Iron overload prevalence (plasma ferritin concentrations >200 ng/mL) was lower in men with an AAA (25.3%) than those without (30.8% p = 0.048), but was not associated with AAA diagnosis after adjusting as above (OR: 0.781 [95% CI:0.589-1.035] p = 0.086). The association of iron overload with AAA growth was investigated in 265 men with small AAAs who received at least 1 repeat ultrasound scan in the 3 years following screening. We saw no difference in AAA growth between men who did and did not have iron overload (n = 65 and 185 respectively, p = 0.164). Our data suggest that iron overload is unlikely to be important in AAA pathogenesis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2014
DOI: 10.1161/CIRCGENETICS.113.000343
Abstract: Currently, the relationship between circulating lipids and abdominal aortic aneurysm (AAA) is unclear. We conducted a lipidomic analysis to identify serum lipids associated with AAA presence. Secondary analyses assessed the ability of models incorporating lipidomic features to improve stratification of patient groups with and without AAA beyond traditional risk factors. Serum lipids were profiled via liquid chromatography tandem mass spectrometry analysis of serum from 161 patients with AAA and 168 controls with peripheral artery disease. Binary logistic regression was used to identify AAA-associated lipids. Classification models were created based on a combination of (1) traditional risk factors only or (2) lipidomic features and traditional risk factors. Model performance was assessed using receiver operator characteristic curves. Three diacylglycerols and 7 triacylglycerols were associated with AAA. Combining lipidomic features with traditional risk factors significantly improved stratification of AAA and peripheral artery disease groups when compared with traditional risk factors alone (mean area under the receiver operator characteristic curve [95% confidence interval], 0.760 [0.756–0.763] and 0.719 [0.716–0.723], respectively P .05). A group of linoleic acid containing triacylglycerols and diacylglycerols were significantly associated with AAA presence. Inclusion of lipidomic features in multivariate analyses significantly improved prediction of AAA presence when compared with traditional risk factors alone.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.ATHEROSCLEROSIS.2018.08.004
Abstract: Diets enriched with tree nuts have been demonstrated to reduce the risk of atherosclerosis-related cardiovascular events. Abdominal aortic aneurysm (AAA) shares common risk factors with atherosclerosis and AAA patients commonly have atherosclerosis related cardiovascular events. AAA has some distinct pathological and clinical characteristics to those of atherosclerosis. No previous study has examined the effect of a diet enriched with tree nuts on experimental or clinical AAA. This study investigated the effect of a diet enriched with tree nuts on the development and severity of AAA within an experimental rodent model. Male apolipoprotein E deficient mice were allocated to a diet enriched with tree nuts or control diet for 56 days (n = 17 per group). After 28 days, all mice were infused with angiotensin II whilst being maintained on their respective diets. The primary outcome was AAA severity assessed by the supra-renal aortic diameter, measured by ultrasound and ex vivo morphometric analysis. The severity of atherosclerosis was assessed by computer-aided analysis of Sudan IV stained aortic arches and sections of brachiocephalic arteries prepared with Van Gieson's stain. The diet enriched with tree nuts did not influence aortic diameter or aortic rupture incidence. Mice receiving the diet enriched with tree nuts had significantly less atherosclerosis within the brachiocephalic artery (p = 0.033) but not in the aortic arch. This experimental study suggests that a diet enriched with tree nuts does not reduce the severity of AAA, but does reduce the severity of atherosclerosis within the brachiocephalic artery. The study was not powered to identify a moderate effect of the diet on the primary outcome and therefore this cannot be excluded.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2018
DOI: 10.1161/STROKEAHA.118.022922
Abstract: Current guidelines recommend prescription of a number of medications to prevent cardiovascular events in patients with peripheral artery disease (PAD). The impact that these medications have on the incidence of stroke in PAD patients has not been thoroughly investigated. This study aimed to investigate the association of prescription of antihypertensive drugs, antiplatelet medications, and statins, as well as cardiovascular disease risk factors, with stroke incidence in patients with symptoms of PAD. A database search was completed to identify studies reporting the incidence of stroke and prescription of antihypertensive drugs, antiplatelet medications, and statins in patients with PAD symptoms. A random-effects model was used to meta-analyze the incidence of stroke in patients with symptoms of PAD and in subgroups with intermittent claudication and critical limb ischemia. Metaregression was performed to explore the association between the incidence of stroke and the prescription of medications and the presence of cardiovascular disease risk factors. Twelve studies including 67 915 patients with symptoms of PAD were included. A meta-analysis of data from 7 studies demonstrated an incidence of stroke of 1.31 per 100 patient-years. Patients with critical limb ischemia experienced stroke 2.3× more frequently than those with intermittent claudication (95% CI, 1.58–3.36 P .01). The reported prescription of antihypertensive agents varied between 10% and 71%, antiplatelet drugs between 49% and 90%, and statins between 11% and 79% in different studies. Metaregression suggested an association between a lower incidence of stroke and the prescription of antiplatelet drugs ( R 2 =0.81, P .01), and statins ( R 2 =0.85, P .01), but not antihypertensives medications. A prior history of cerebrovascular events was associated with a higher incidence of stroke ( R 2 =0.58, P .05). This review supports previous research which suggests the need for more effective means of ensuring more widespread prescription of preventative medications in patients with PAD.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2023
DOI: 10.1186/S12872-023-03225-8
Abstract: Cerebrovascular disorders pose a global health concern. Advances in basic and clinical research, including induced pluripotent stem cell models and multi-omic approaches, have improved our understanding and management of these disorders. However, gaps in our knowledge remain. BMC Cardiovascular Disorders invites authors to submit articles investigating what drives and affects Cerebrovascular disorders to improve patient care.
Publisher: Elsevier BV
Date: 09-2020
Publisher: MDPI AG
Date: 18-05-2015
Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.ATHEROSCLEROSIS.2017.06.925
Abstract: Despite current best care, patients with peripheral artery disease (PAD) remain at high risk of myocardial infarction, and biomarkers to more accurately assess cardiovascular risk are needed. This study assessed the relationship between the serum lipidome and incident myocardial infarction in a cohort of PAD patients. 265 PAD patients were followed up for a median of 23 months, during which 18 people suffered a myocardial infarction. Fasting serum concentrations of 332 lipid species were measured via mass spectrometry and their association with incident myocardial infarction was assessed via Cox regression. Secondary analyses investigated prognostic potential of specific lipid species. Total serum concentrations of alkyl-phosphatidylcholine and alkenylphospatidylcholine (plasmalogen) lipids were inversely associated with incident myocardial infarction after adjusting for multiple testing (hazards ratio (95% confidence intervals): 0.43 (0.24-0.74) p = 0.032 and 0.28 (0.14-0.56), p = 0.010, respectively). Specifically, 10 alkenylphosphatidylcholine species and 6 alkyl-phosphatidylcholine species were negatively associated with incident myocardial infarction after adjusting for traditional risk factors and correcting for multiple testing (hazards ratios ranging from 0.07 to 0.51, p < 0.05). Incorporation of serum phosphatidylcholine plasmalogen species PC(P-40:6) concentration within analyses designed to determine subsequent myocardial infarction incidence led to an improvement in predictive accuracy compared to traditional risk factors alone. Serum concentrations of phosphatidylcholine plasmalogens and alkyl-phosphatidylcholines were negatively associated with incident myocardial infarction and have potential to act as novel prognostic markers in at-risk populations.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.EJVS.2022.07.042
Abstract: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among in iduals with small AAAs. Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p < .100) or systolic blood pressure (SBP) at one year. Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19 95% CI -8.24, -0.14 kPa/year p = .043) and PWRI (-0.014 95% CI -0.026, -0.001 p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.
Publisher: Oxford University Press (OUP)
Date: 17-10-2017
DOI: 10.1002/BJS.10675
Abstract: The role of atherosclerosis in the pathogenesis of abdominal aortic aneurysm (AAA) is controversial. Atherosclerosis-associated peripheral artery disease (PAD) has been reported to be a risk factor for AAA in population screening studies its relationship with AAA growth is controversial. A systematic search of MEDLINE, Scopus, CINAHL and the Cochrane Central Register of Controlled Trials was conducted in April 2016 and repeated in January 2017. Databases were screened for studies reporting AAA growth rates in patients with, and without PAD. The included studies underwent quality assessment and, where possible, were included in the meta-analysis. A subgroup analysis was performed, including only studies that adjusted for confounding factors. Seventeen studies, including a total of 4873 patients, met the review entry criteria. Data from 15 studies were included in the meta-analysis. There was marked heterogeneity in study design, methodology and statistical analyses used. In the main analysis, PAD was associated with reduced AAA growth (mean difference – 0·13, 95 per cent c.i. –0·27 to –0·00 P = 0·04). However, statistical significance was not maintained in sensitivity analysis. In a subanalysis that included only data adjusted for other risk factors, no significant association between PAD and AAA growth was found (mean difference –0·11, –0·23 to 0·00 P = 0·05). This systematic review suggests that currently reported studies demonstrate no robust and consistent association between PAD and reduced AAA growth.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-03-2019
Abstract: Hypertension is an important risk factor for cardiovascular events in patients with peripheral artery disease however, optimal blood pressure targets for these patients are poorly defined. This study investigated the association between systolic blood pressure ( SBP ) and cardiovascular events in a prospectively recruited patient cohort with peripheral artery disease. A total of 2773 patients were included and were grouped according to SBP at recruitment (≤120 mm Hg, n=604 121–140 mm Hg, n=1065 and mm Hg, n=1104). Adjusted Cox proportional hazards analyses suggested that patients with SBP ≤120 mm Hg were at greater risk of having a major cardiovascular event (myocardial infarction, stroke, or cardiovascular death) than patients with SBP of 121–140 mm Hg (adjusted hazard ratio, 1.36 95% CI, 1.08–1.72 P =0.009). Patients with SBP mm Hg had an adjusted hazard ratio of 1.23 (95% CI, 1.00–1.51 P =0.051) of major cardiovascular events compared with patients with SBP of 121–140 mm Hg. These findings were similar in sensitivity analyses only including patients receiving antihypertensive medications or focused on patients with a minimum of 3 months of follow‐up. This cohort study suggests that patients with peripheral artery disease and SBP ≤120 mm Hg are at increased risk of major cardiovascular events. The findings suggest caution in intensive SBP lowering in this patient group.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.CARPATH.2010.01.001
Abstract: Abdominal aortic aneurysm is a common degenerative disorder associated with sudden death due to aortic rupture. Current therapy is limited to open surgical repair of the aorta or endovascular placement of covered stents to exclude the abdominal aortic aneurysm from the circulation. A number of different animal models have been developed in order to study abdominal aortic aneurysm in an effort to advance current management deficiencies. Large animal models have been mostly used to assist in developing novel methods to surgically treat abdominal aortic aneurysms. Small animal models, particularly those developed in rodents, have been employed to further the understanding of the mechanisms involved in abdominal aortic aneurysm in order to identify potential new medical treatments. It is expected that findings from these animal models will contribute importantly to new treatments for human abdominal aortic aneurysm. This review explores the animal models which are used in abdominal aortic aneurysm research and highlights their advantages and disadvantages.
Publisher: Frontiers Media SA
Date: 03-05-2022
Abstract: The benefit of controlling cardiovascular risk factors in slowing the progression of small abdominal aortic aneurysm (AAA) is controversial. This study investigated the association of optimal blood pressure control at entry with the growth of small AAA. A total of 1,293 patients with initial AAA diameter & mm were followed by a median 5 (inter-quartile range, IQR, 3–7) ultrasound scans for a median of 3.6 years (IQR 1.8, 5.3). Optimal blood pressure control was defined as blood pressure ≤140/90 mmHg at recruitment. The association of optimal blood pressure control at entry with AAA growth was assessed using linear mixed effects models adjusted for established risk factors of AAA growth and factors which were unequally distributed among the blood pressure groups. Optimal blood pressure control at entry was not significantly associated with AAA growth. In the risk factor adjusted model the mean difference in AAA growth between blood pressure groups was 0.04 mm/year (95% CI −0.20, 0.13 p = 0.65). The results were similar in sensitivity analyses excluding outliers or focused on systolic or diastolic blood pressure alone. This observational study suggests that optimal blood pressure control at entry is not associated with slower AAA growth.
Publisher: Elsevier BV
Date: 11-2021
Publisher: AVES Publishing Co.
Date: 2012
DOI: 10.5152/AKD.2012.037
Publisher: Oxford University Press (OUP)
Date: 11-08-2014
DOI: 10.1002/BJS.9578
Abstract: Abdominal aortic aneurysm (AAA) is an important cause of sudden death however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. The MEDLINE database was searched on 25 May 2013. Case–control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. Nine studies assessing 348 in iduals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18 P & 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96 P & 0·001). Minimal heterogeneity between studies was noted (I2 = 0 per cent). This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA.
Publisher: Public Library of Science (PLoS)
Date: 12-11-2020
DOI: 10.1371/JOURNAL.PONE.0242228
Abstract: Ankle-brachial pressure index (ABPI) is commonly measured in people referred to vascular specialists. This study aimed to assess the association of high ABPI (≥ 1.4) with cardiovascular events in people with peripheral artery disease (PAD). 1533 participants with PAD diagnosed by a vascular specialist were prospectively recruited from four out-patient clinics in Australia. ABPI was measured at recruitment and the occurrence of myocardial infarction (MI), stroke or cardiovascular death (major cardiovascular events MACE) and any utation were recorded over a median (inter-quartile range) follow-up of 3.3 (1.0–7.1) years. The association of high, compared to normal, low (0.5–0.9) or very low ( .5), ABPI with clinical events was estimated using Cox proportional hazard analyses, adjusting for traditional risk factors and reported as hazard ratio with 95% confidence intervals. 596 (38.9%), 676 (44.1%), 157 (10.2%) and 104 (6.8%) participants had normal, low, very low and high ABPI, respectively. Participants with high ABPI had increased risk of MACE, MI and death by comparison to those with either normal ABPI [1.69 (1.07, 2.65), 1.93 (1.07, 3.46) and 1.67 (1.09, 2.56)] or either low or very low ABPI [1.51 (1.02, 2.23), 1.92 (1.16, 3.19) and 1.47 (1.02, 2.14)] after adjusting for other risk factors. Findings were similar in a sensitivity analysis excluding people with ABPI only measured in one leg (n = 120). Participants with high ABPI also had an increased risk of MACE and MI compared to those with very low ABPI alone. High ABPI is a strong indicator of excess risk of cardiovascular events amongst people with PAD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2017
DOI: 10.1161/ATVBAHA.117.310129
Abstract: Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. Ace2 deletion in apolipoprotein-deficient mice ( ApoE −/− Ace2 −/y ) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated with AAA diagnosis. ACE2 expression was lower in infrarenal biopsies of patients with AAA than organ donors. AAA was more severe in ApoE −/− Ace2 −/y mice compared with controls in 2 experimental models. Resveratrol (0.05/100-g chow) inhibited growth of pre-established AAAs in ApoE −/− mice fed high-fat chow and infused with angiotensin II continuously for 56 days. Reduced suprarenal aorta dilatation in mice receiving resveratrol was associated with elevated serum ACE2 and increased suprarenal aorta tissue levels of ACE2 and sirtuin 1 activity. In addition, the relative phosphorylation of Akt and ERK (extracellular signal-regulated kinase) 1/2 within suprarenal aorta tissue and gene expression for nuclear factor of kappa light polypeptide gene enhancer in B cells 1, angiotensin type-1 receptor, and metallopeptidase 2 and 9 were significantly reduced. Upregulation of ACE2 in human aortic smooth muscle cells by resveratrol in vitro was sirtuin 1-dependent. This study provides experimental evidence of an important role for ACE2 in limiting AAA development and growth. Resveratrol upregulated ACE2 and inhibited AAA growth in a mouse model.
Publisher: Hindawi Limited
Date: 30-09-2022
DOI: 10.1155/2022/5299370
Abstract: Background and Aims. The nacht domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is upregulated in human abdominal aortic aneurysm (AAA), but its pathogenic role is unclear. The aims of this study were firstly to examine whether the inflammasome was upregulated in a mouse model of AAA and secondly to test whether the inflammasome inhibitor colchicine limited AAA growth. Methods. AAA was induced in eight-week-old male C57BL6/J mice with topical application of elastase to the infrarenal aorta and oral 3-aminopropionitrile (E-BAPN). For aim one, inflammasome activation, abdominal aortic diameter, and rupture were compared between mice with AAA and sham controls. For aim two, 3 weeks after AAA induction, mice were randomly allocated to receive colchicine ( n = 28 , 0.2 mg/kg/d) or vehicle control ( n = 29 ). The primary outcome was the rate of maximum aortic diameter increase measured by ultrasound over 13 weeks. Results. There was upregulation of NLRP3 markers interleukin- (IL-) 1β (median, IQR 15.67, 7.11-22.60 pg/mg protein versus 6.87, 4.54-11.60 pg/mg protein, p = .048 ) and caspase-1 (109, 83-155 relative luminosity units (RLU) versus 45, 38-65 RLU, p .001 ) in AAA s les compared to controls. Aortic diameter increase over 80 days (mean difference, MD, 4.3 mm, 95% CI 3.3, 5.3, p .001 ) was significantly greater in mice in which aneurysms were induced compared to sham controls. Colchicine did not significantly limit aortic diameter increase over 80 days (MD -0.1 mm, 95% CI -1.1, 0.86, p = .922 ). Conclusions. The inflammasome was activated in this mouse model of AAA however, daily oral administration of colchicine did not limit AAA growth.
Publisher: Wiley
Date: 29-07-2019
DOI: 10.1111/JOIM.12958
Abstract: Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo-controlled drug trials in patients with small AAAs. Eleven previously published randomized-controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta-analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure-lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small s le sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.
Publisher: Wiley
Date: 10-2014
Abstract: Abdominal aortic aneurysm (AAA) is an important cause of mortality in the elderly. Mouse models are widely used to investigate AAA pathogenesis but their suitability for biomarker discovery is unexplored. We conducted a three-phase study. Phase 1: Aortas from angiotensin-II-infused apolipoprotein E deficient (ApoE(-/-) ) mice with and without AAA were assessed via iTRAQ and analyzed in silico to identify potential circulating markers. Microarray data from ApoE(-/-) mice and human patients were analyzed in parallel. Phase 2: Putative markers were compared between datasets to shortlist common candidates. Phase 3: The relationship of two shortlisted markers and AAA presence was assessed. iTRAQ identified eight proteins with biomarker potential. Microarray data identified 72 and 96 potential biomarkers from ApoE(-/-) mice and human patients, respectively. All three datasets suggested apolipoprotein C1 (ApoC1) as a marker for AAA microarray data identified matrix metalloproteinase 9 (MMP9) as a second potential marker. Plasma ApoC1 and MMP9 concentrations positively correlated with AAA diameter in ApoE(-/-) mice. ApoC1 may be a novel biomarker for AAA.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.ATHEROSCLEROSIS.2011.08.013
Abstract: Abdominal aortic aneurysm (AAA) is usually accompanied by the formation of a large volume of intra-luminal thrombus (ILT). ILT-derived proteins have been suggested as circulating markers for AAA. We conducted a proteomic study screening whole and hexapeptide ligand library (HLL) treated ILT explant secretions to identify potential ILT-derived markers for AAA. Unfractionated and HLL-treated ILT secretions from 3 AAA patients were analysed in parallel using liquid chromatography tandem mass spectrometry (LC-MS/MS). In silico analyses were employed to identify proteins with biomarker potential. Proteomic findings were validated by measuring serum concentrations of 2 representative ILT proteins in 313 AAA patients and 690 controls. A total of 150 proteins were identified from thrombus conditioned media HLL treatment enabled the detection of 53 previously unseen polypeptides. Gene ontology analysis revealed high representation of platelet-secreted proteins. Thrombospondin-1 (TSP-1) and clusterin were selected for further assessment. Serum TSP-1 and clusterin were negatively associated with AAA after adjusting for other risk factors. Odds ratio and 95% confidence intervals were 0.62, 0.41-0.94, and 0.50, 0.33-0.75, for men with serum TSP-1 and clusterin in the fourth compared to first quartiles, respectively. This proteomic analysis has identified a group of proteins concentrated in AAA ILT. Assessment of circulating concentrations of two representative polypeptides suggests for the first time that the ILT selectively sequesters proteins rather than actively releasing them. Further work is required to assess the mechanisms underpinning this observation and the associated clinical implications.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2021
DOI: 10.1186/S12902-021-00764-Z
Abstract: This study estimated the incidence of major utation for people in North Queensland, Australia, examined changes in utation rates over time and investigated survival after major utation. This was a retrospective study of patients who underwent a major utation above the ankle between 2000 and 2015. Major utation rates and incidence rate ratios (IRR) were calculated using census data to define the at-risk population. Associations between risk factors and calendar year with major utation were assessed using quasipoisson regression. Kaplan-Meier survival and Cox-proportional hazard analyses estimated the incidence of and risk factors for all-cause mortality. The annual incidence of major utation was estimated to be greater in Aboriginal and Torres Strait Islanders than non-Indigenous people (IRR 2.75, 95 % CI 1.92 to 3.84). After adjusting for population growth, the annual incidence of major utations did not change significantly over time for either groups. Aboriginal and Torres Strait Islander people were at greater risk of all-cause mortality after major utation compared to non-Indigenous people, although this association was not significant after adjusting for other risk factors (hazard ratio 1.24, 95 % CI 0.82 to 1.90). The incidence of major utation in North Queensland has not reduced over time, indicating the need for better preventative treatments, particularly in Aboriginal and Torres Strait Islander people.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.EJVS.2018.05.026
Abstract: An exercise programme is part of the initial management of peripheral artery disease (PAD). Nordic walking uses poles and a core-focused walking technique to reduce the load on the legs, which may have advantages as an exercise programme for PAD. This systematic review examined the benefit of a Nordic walking programme for treating PAD compared with other programmes. A systematic approach was used to identify clinical trials comparing Nordic walking and control programmes in PAD patients. For inclusion, studies had to report maximum walking distance (MWD) measured with a treadmill test or corridor walking test both at entry and follow up. Study quality was appraised using the Cochrane collaboration tool for assessing risk of bias. An inverse variance weighted meta-analysis was performed to compare improvements in MWD. Five independent trials involving 294 patients were identified. In three trials, supervised Nordic walking programmes were compared with supervised standard walking. One trial compared a home based Nordic walking programme with a similar standard walking programme. One trial compared a partly supervised Nordic walking programme with best medical management. Meta-analysis of all data suggested that MWD improvements were similar for patients treated by Nordic and standard walking programmes (standardised mean difference, SMD = 1.31, 95% CI -1.28 to 3.91 p = .322). Findings for completely supervised programmes were similar to the primary analysis (SMD = -0.79, 95% CI -2.81 to 1.24 p = .446) while those from partially supervised or home based programmes favoured Nordic walking (SMD = 4.46, 95% CI 3.39, 5.53 p < .001), mainly due to results from one home based trial. This systematic review suggests no benefit of Nordic over standard walking as supervised exercise for PAD. Favourable results were reported for one home based Nordic walking programme. A larger trial is needed to assess whether this finding can be replicated or not.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.EJVS.2017.05.009
Abstract: Patients with peripheral artery disease (PAD) are at substantial risk of cardiovascular events. There is interest in using blood markers, such as C-reactive protein (CRP), to monitor prognosis and treatment efficacy in PAD patients. The aim of this meta-analysis was to assess the association between CRP and major cardiovascular events in PAD patients. Studies evaluating the association between CRP and major cardiovascular events (myocardial infarction, stroke, cardiac revascularisation and mortality) were identified using MEDLINE and the Cochrane library. Studies that did not include participants with PAD, measure CRP, or follow-up patients for cardiovascular events were excluded. Meta-analyses of published adjusted hazard ratios (HR) were conducted using an inverse variance-weighted random effects model, and heterogeneity was assessed with the I A total of 16 studies involving 5041 participants met the inclusion criteria for the systematic review. Eight studies were included in the meta-analyses. Summary effect estimates were reported as HR comparing higher and lower quantiles, and HR per unit increase in log The present findings suggest that high circulating CRP is predictive of major cardiovascular events in PAD patients.
Publisher: BMJ
Date: 16-11-2015
DOI: 10.1136/HEARTJNL-2015-308322
Abstract: Stem cell (SC) administration is a potential therapeutic strategy to improve blood supply in patients with peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to investigate the efficacy of extraembryonic tissue-derived SC (ETSC) in improving blood flow within animal models of hindlimb ischaemia (HLI). PubMed, ScienceDirect and Web of Science were searched to identify studies which investigated ETSCs within animal HLI models. A meta-analysis was performed focusing on the effect of ETSCs on limb blood flow assessed by laser Doppler imaging using a random effects model. Methodological quality was assessed using a newly devised quality assessment tool. Five studies investigating umbilical cord-derived SCs (three studies), placental SCs (one study), amnion and chorionic SCs (one study) were included. A meta-analysis suggested that administration of ETSCs improved the restoration of blood flow within the HLI models used. The methodological quality of the included studies was assessed as poor. Problems identified included lack of randomised design and blinding of outcome assessors that the animal models did not incorporate recognised risk factors for human PAD or atherosclerosis the models used did not have established chronic ischaemia as is the cases in most patients presenting with PAD and the studies lacked a clear rationale for the dosage and frequency of SCs administered. The identified studies suggest that ETSCs improve recovery of limb blood supply within current animal HLI models. Improved study quality is, however, needed to provide support for the likelihood of translating these findings to patients with PAD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-05-2015
Publisher: American Medical Association (AMA)
Date: 04-2023
DOI: 10.1001/JAMACARDIO.2022.5437
Abstract: It is unclear how to effectively promote walking in people with peripheral artery disease (PAD). To test whether brief counseling delivered by allied health professionals increases step count in participants with PAD. In this randomized clinical trial, participants with symptomatic PAD were recruited from sites in Australia and randomly allocated 1:1 to the counseling intervention or an attention control. Data were collected from January 2015 to July 2021, and data were analyzed from March to November 2022. Two 1-hour face-to-face and two 15-minute telephone counseling sessions designed to increase walking. The primary outcome was the between-group difference in change in daily step count estimated by accelerometer recordings over 7 days at baseline and 4 months, using imputation for missing values. Other outcomes at 4, 12, and 24 months included step count, 6-minute walk distance, and disease-specific and generic measures of health-related quality of life. Risk of major adverse limb events was assessed over 24 months. Of 200 included participants, 144 (72.0%) were male, and the mean (SD) age was 69.2 (9.3) years. The planned s le of 200 participants was allocated to the counseling intervention group (n = 102) or attention control group (n = 98). Overall, 198 (99.0%), 175 (87.5%), 160 (80.0%) and 143 (71.5%) had step count assessed at entry and 4, 12, and 24 months, respectively. There was no significant between-group difference in the primary outcome of change in daily step count over 4 months (mean steps, 415 95% CI, −62 to 893 P = .07). Participants in the counseling group had significantly greater improvement in the secondary outcome of disease-specific Intermittent Claudication Questionnaire score at 4 months (3.2 points 95% CI, 0.1-6.4 P = .04) and 12 months (4.3 points 95% CI, 0.5-8.1 P = .03) but not at 24 months (1.2 points 95% CI, −3.1 to 5.6 P = .57). Findings were similar for mean PAD Quality of Life Questionnaire component assessing symptoms and limitations in physical functioning (4 months: 1.5 points 95% CI, 0.3-2.8 P = .02 12 months: 1.8 points 95% CI, 0.3-3.3 P = .02 24 months: 1.3 points 95% CI. −0.5 to 3.1 P = .16). There was no significant effect of the intervention on change in mean 6-minute walking distance (4 months: 9.3 m 95% CI, −3.7 to 22.3 P = .16 12 months: 13.8 m 95% CI, −4.2 to 31.7 P = .13 24 months: 1.2 m 95% CI, −20.0 to 22.5 P = .91). The counseling intervention did not affect the rate of major adverse limb events over 24 months (12 [6.0%] in the intervention group vs 11 [5.5%] in the control group P & .99). This randomized clinical trial found no significant effect of brief counseling on step count in people with PAD. Alternate interventions are needed to enable walking. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614000592640
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JSTROKECEREBROVASDIS.2017.09.058
Abstract: Acute ischemic stroke is a leading cause of death and disability worldwide. Unlike myocardial infarction, there is no current blood test to diagnose acute ischemic stroke. MicroRNAs (miRNAs) are very stable in the blood and have been suggested as potential diagnostic markers. This review aimed to systematically assess case-control studies investigating the association of circulating miRNAs with acute ischemic stroke. Medline, CINAHL, Cochrane Library, Web of Science, Scopus, and PubMed were searched for studies that examined the association of circulating miRNAs in patients with acute ischemic stroke. Studies meeting specific inclusion and exclusion criteria (such as blood s les obtained within 24 hours of an acute ischemic stroke) were selected for data extraction. Two authors extracted data from the included studies relevant to the study design, the patient characteristics, and the relative miRNA expression. Eight studies were included involving 572 cases and 431 healthy controls. Twenty-two miRNAs (12 upregulated and 10 downregulated) were reported as differentially expressed. Only 1 miRNA, miR-106b, was reported as differentially expressed in at least 2 studies. Significant heterogeneity in the design and methods of the included studies was noted. Differential expression of a large number of miRNAs has been reported early following acute ischemic stroke. More research is required in larger patient populations to further evaluate the diagnostic potential of the reported miRNAs.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-10-2018
Abstract: There is no drug therapy for abdominal aortic aneurysm ( AAA ). FAME‐2 (Fenofibrate in the Management of Abdominal Aortic Aneurysm 2) was a placebo‐controlled randomized trial designed to assess whether administration of 145 mg of fenofibrate/d for 24 weeks favorably modified circulating markers of AAA. Patients with AAA s measuring 35 to 49 mm and no contraindication were randomized to fenofibrate or identical placebo. The primary outcome measures were the differences in serum osteopontin and kallistatin concentrations between groups. Secondary analyses compared changes in the circulating concentration of AAA ‐associated proteins, and AAA growth, between groups using multivariable linear mixed‐effects modeling. A total of 140 patients were randomized to receive fenofibrate (n=70) or placebo (n=70). By the end of the study 3 (2.1%) patients were lost to follow‐up and 18 (12.9%) patients had ceased trial medication. A total of 85% of randomized patients took ≥80% of allocated tablets and were deemed to have complied with the medication regimen. Patients’ allocated fenofibrate had expected reductions in serum triglycerides and estimated glomerular filtration rate, and increases in serum homocysteine. No differences in serum osteopontin, kallistatin, or AAA growth were observed between groups. Administering 145 mg/d of fenofibrate for 24 weeks did not significantly reduce serum concentrations of osteopontin and kallistatin concentrations, or rates of AAA growth in this trial. The findings do not support the likely benefit of fenofibrate as a treatment for patients with small AAA s. URL : www.anzctr.org.au . Unique identifier: ACTRN 12613001039774.
Publisher: Wiley
Date: 08-2021
DOI: 10.1111/AJR.12776
Abstract: To assess whether outcomes of peripheral artery disease (PAD) were related to remoteness from the treating tertiary vascular centre. Participants with a variety of types of occlusive and aneurysmal diseases were recruited from a tertiary hospital in North Queensland, Australia. Remoteness was assessed by residence outside Townsville and estimated distance to the vascular centre. Cox proportional hazard analyses were used to examine the association of remoteness with outcome. Cohort study. The primary outcome was requirement for surgery to treat PAD. Secondary outcomes were major adverse cardiovascular events (MACE) and all‐cause mortality. Of 2487 patients recruited, 1274 (51.2%) had at least one PAD surgery, 720 (29.0%) at least one MACE, and 909 (36.6%) died during a median of 4.2 (inter‐quartile range 1.3‐7.7) years. Compared to Townsville residents (n = 1287), those resident outside Townsville (n = 1200) had higher rates of PAD surgery (hazard ratio, HR 1.55, 95% confidence intervals, CI, 1.39, 1.73) but no increased risk of MACE (HR 1.00, 95% CI 0.86, 1.16) or death (HR 1.03, 95% CI 0.90, 1.17). This association was attenuated when adjusting for distance from the vascular centre (HR 1.31, 95% CI 1.14, 1.51). Patients in the highest quartile of distance presented with lower ankle‐brachial pressure index, more severe carotid artery disease and larger aortic diameter. People with PAD in North Queensland residing furthest from the tertiary hospital presented with more severe artery disease and had greater rates of PAD surgery.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JVS.2019.01.079
Abstract: Readmission to the hospital after revascularization for peripheral artery disease (PAD) is frequently reported. No consensus exists as to the exact frequency and risk factors for readmission. This review aimed to determine the incidence of and risk factors for 30-day readmission after revascularization for PAD. PubMed/Medline (Ovid), Scopus, Web of Science, the Cochrane Library, and CINAHL were searched systematically from inception until May 20, 2018. Studies were eligible for inclusion if they included patients with diagnosed PAD undergoing revascularization and reported the readmission rate and a statistical evaluation of the association of at least one risk factor with readmission. Studies were excluded if data for other procedures could not be distinguished from revascularization. Two authors undertook study selection independently with the final inclusion decision resolved through consensus. The PRISMA and Meta-analyses of Observational Studies in Epidemiology guidelines were followed regarding data extraction and quality assessment, which was performed by two authors independently. Data were pooled using a random effects model. The primary outcome was readmission within 30 days of revascularization. Fourteen publications reporting the outcomes of 526,008 patients were included. Reported readmission rates ranged from 10.9% to 30.0% with a mean of 16.4% (95% confidence interval [CI], 15.1%-17.9%). Meta-analyses suggested the following risk factors had a significant association with readmission: female sex (odds ratio [OR], 1.13 95% CI, 1.05-1.21), black race (OR, 1.36 95% CI, 1.28-1.46), dependent functional status (OR, 1.72 95% CI, 1.43-2.06), critical limb ischemia (OR, 2.12 95% CI, 1.72-2.62), emergency admission (OR, 1.75 95% CI, 1.43-2.15), hypertension (OR, 1.39 95% CI, 1.26-1.54), heart failure (OR, 1.82 95% CI, 1.50-2.20), chronic pulmonary disease (OR, 1.19 95% CI, 1.08-1.32), diabetes (OR, 1.47 95% CI, 1.32-1.63), chronic kidney disease (OR, 1.93 95% CI, 1.62-2.31), dialysis dependence (OR, 2.08 95% CI, 1.75-2.48), smoking (OR, 0.83 95% CI, 0.78-0.89), postoperative bleeding (OR, 1.70 95% CI, 1.23-2.35), and postoperative sepsis (OR, 4.13 95% CI, 2.02-8.47). Approximately one in six patients undergoing revascularization for PAD are readmitted within 30 days of their procedure. This review identified multiple risk factors predisposing to readmission, which could potentially serve as a way to target interventions to reduce readmissions.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Portland Press Ltd.
Date: 11-12-2014
DOI: 10.1042/CS20130425
Abstract: AAA (abdominal aortic aneurysm) is an important cause of sudden death in older adults, but there is no current effective drug therapy for this disease. The UCNs (urocortins1–3) and their receptors: CRFR (corticotrophin-releasing factor receptor)-1 and -2 have been implicated in various CVDs (cardiovascular diseases). We assessed the relative expression of UCN1–3 in AAA by qRT-PCR (quantitative reverse transcription–PCR) and ELISA, and examined in vitro how UCN2 affects human aortic VSMC (vascular smooth muscle cell) Akt phosphorylation, pro-inflammatory cytokine IL (interleukin)-6 secretion, proliferation, cell cycle and apoptosis. UCN2 and CRFR2 expression were significantly up-regulated in biopsies from the AAA body. AAA body biopsies released high amounts of UCN2 in vitro. Median plasma UCN2 concentrations were 2.20 ng/ml (interquartile range 1.14–4.55 ng/ml, n=67) in AAA patients and 1.11 ng/ml (interquartile range 0.76–2.55 ng/ml, n=67) in patients with non-aneurysmal PAD (peripheral artery disease) (P=0.001). Patients with UCN2 in the highest quartile had a 4.12-fold (95% confidence interval, 1.37–12.40) greater prevalence of AAA independent of other risk factors, P=0.012. In vitro, UCN2 significantly inhibited VSMC Akt phosphorylation and proliferation in a dose-dependent manner. UCN2 induced VSMC G1 cell-cycle arrest and increased IL-6 secretion over 24 h. The CRFR2 antagonist astressin-2B significantly abrogated the effects of UCN2 on VSMCs. In conclusion, UCN2 is significantly associated with AAA and inhibits VSMC proliferation by inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA pathogenesis.
Publisher: Wiley
Date: 12-2006
Abstract: The parasite Fasciola hepatica causes major global disease of livestock, with increasing reports of human infection. Vaccine candidates with varying protection rates have been identified by pre-genomic approaches. As many candidates are part of protein superfamilies, sub-proteomics offers new possibilities to systematically reveal the relative importance of in idual family proteins to vaccine formulations within populations. The superfamily glutathione transferase (GST) from liver fluke has phase II detoxification and housekeeping roles, and has been shown to contain protective vaccine candidates. GST were purified from cytosolic fractions of adult flukes using glutathione- and S-hexylglutathione-agarose, separated by 2-DE, and identified by MS/MS, with the support of a liver fluke EST database. All previously described F. hepatica GST isoforms were identified in 2-DE. Amongst the isoforms mapped by 2-DE, a new GST, closely related to the Sigma class enzymes is described for the first time in the liver fluke. We also describe cDNA encoding putative Omega class GST in F. hepatica.
Publisher: Wiley
Date: 10-05-2018
DOI: 10.1002/JCP.26610
Abstract: Atherosclerosis is a systemic disease characterized by the deposition of cholesterol and inflammatory cells within the arterial wall. Removal of cholesterol from the vessel wall may have an impact on the size and composition of atherosclerotic lesions. Anionic phospholipids or liposome vesicles composed of a lipid bilayer such as nanoliposomes have been suggested as treatments for dyslipidemia. In this study, we investigated the effect of anionic nanoliposomes on atherosclerosis in a mouse model. Low‐density lipoprotein receptor knockout mice ( Ldlr –/– ) were fed with an atherosclerosis promoting high fat and cholesterol (HFC) diet for 12 weeks. Anionic nanoliposomes including hydrogenated soy phosphatidylcholine (HSPC) and distearoyl phosphatidylglycerol (DSPG) (molar ratio: 1:3) were injected intravenously into HFC‐fed Ldlr −/− mice once a week for 4 weeks. Mice receiving nanoliposomes had significantly reduced atherosclerosis within the aortic arch as assessed by Sudan IV staining area ( p = 0.007 ), and reduced intima/media ratio ( p = 0.030 ) and greater collagen deposition within atherosclerosis plaques within the brachiocephalic artery ( p = 0.007 ), compared to control mice. Administration of nanoliposomes enhanced markers of reverse cholesterol transport (RCT) and increased markers of plaque stability in HFC‐fed Ldlr −/ − mice. Reduced cholesterol accumulation was observed in the liver along with the up‐regulation of the major genes involved in the efflux of cholesterol such as hepatic ATP‐binding cassette transporters (ABC) including Abc‐a1 , Abc‐g1 , Abc‐g5 , and Abc‐g8 , Scavenger receptor class B, member 1 ( Scarb1 ), and Liver X receptor alpha ( Lxr )‐ α . Lecithin Cholesterol Acyltransferase activity within the plasma was also increased in mice receiving nanoliposomes. Anionic nanoliposome administration reduced atherosclerosis in HFC‐fed Ldlr −/− mice by promoting RCT and upregulating the ABC‐A1/ABC‐G1 pathway.
Publisher: Oxford University Press (OUP)
Date: 21-02-2019
DOI: 10.1002/BJS.11101
Abstract: Supervised exercise is recommended for the management of peripheral artery disease (PAD) however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme. A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences. Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0·32, 95 per cent c.i. 0·15 to 0·50 P & 0·001), intermittent claudication onset distance (MD 0·45, 0·27 to 0·62 P & 0·001), walking distance in a 6-min walking test (MD 0·28, 0·09 to 0·47 P = 0·004) and physical activity (MD 0·27, 0·11 to 0·43 P = 0·001). This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-08-2014
Abstract: Peripheral artery disease ( PAD ) is associated with impaired mobility and a high rate of mortality. The aim of this systematic review was to investigate whether reduced lower extremity performance was associated with an increased incidence of cardiovascular and all‐cause mortality in people with PAD . A systematic search of the MEDLINE , EMBASE , SCOPUS , Web of Science, and Cochrane Library databases was conducted. Studies assessing the association between measures of lower extremity performance and cardiovascular or all‐cause mortality in PAD patients were included. A meta‐analysis was conducted combining data from commonly assessed performance tests. The 10 identified studies assessed lower extremity performance by strength tests, treadmill walking performance, 6‐minute walk, walking velocity, and walking impairment questionnaire ( WIQ ). A meta‐analysis revealed that shorter maximum walking distance was associated with increased 5‐year cardiovascular (unadjusted RR =2.54, 95% CI 1.86 to 3.47, P −5 , n=1577, fixed effects) and all‐cause mortality (unadjusted RR =2.23 95% CI 1.85 to 2.69, P −5 , n=1710, fixed effects). Slower 4‐metre walking velocity, a lower WIQ stair‐climbing score, and poor hip extension, knee flexion, and plantar flexion strength were also associated with increased mortality. No significant associations were found for hip flexion strength, WIQ distance score, or WIQ speed score with mortality. A number of lower extremity performance measures are prognostic markers for mortality in PAD and may be useful clinical tools for identifying patients at higher risk of death. Further studies are needed to determine whether interventions that improve measures of lower extremity performance reduce mortality.
Publisher: Wiley
Date: 08-06-2020
DOI: 10.1111/DME.14323
Publisher: Wiley
Date: 15-10-2019
DOI: 10.1111/JOIM.12978
Publisher: SAGE Publications
Date: 15-01-2021
Abstract: The inter and intra-observer reproducibility of measuring the Wound Ischemia foot Infection (WIfI) score is unknown. The aims of this study were to compare the reproducibility, completion times and ability to predict 30-day utation of the WIfI, University of Texas Wound Classification System (UTWCS), Site, Ischemia, Neuropathy, Bacterial Infection and Depth (SINBAD) and Wagner classifications systems using photographs of diabetes-related foot ulcers. Three trained observers independently scored the diabetes-related foot ulcers of 45 participants on two separate occasions using photographs. The inter- and intra-observer reproducibility were calculated using Krippendorff’s α. The completion times were compared with Kruskal-Wallis and Dunn’s post-hoc tests. The ability of the scores to predict 30-day utation rates were assessed using receiver operator characteristic curves and area under the curves. There was excellent intra-observer agreement (α .900) and substantial agreement between observers (α=0.788) in WIfI scoring. There was moderate, substantial, or excellent agreement within the three observers (α .599 in all instances except one) and fair or moderate agreement between observers (α of UTWCS=0.306, α of SINBAD=0.516, α of Wagner=0.374) for the other three classification systems. The WIfI score took significantly longer ( P .001) to complete compared to the other three scores (medians and inter quartile ranges of the WIfI, UTWCS, SINBAD, and Wagner being 1.00 [0.88-1.00], 0.75 [0.50-0.75], 0.50 [0.50-0.50], and 0.25 [0.25-0.50] minutes). None of the classifications were predictive of 30-day utation ( P .05 in all instances). The WIfI score can be completed with substantial agreement between trained observers but was not predictive of 30-day utation.
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB115
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.EJVS.2018.07.035
Abstract: Currently there is no drug therapy for abdominal aortic aneurysm (AAA) and most previous investigations have focused on imaging rather than clinical outcomes. The aim of this study was to assess whether AAA related clinical events were lower in patients prescribed metformin. This was a prospective cohort observational study performed in three cities in Australia, which was designed to study risk factors for clinical events not simply to focus on metformin. Patients with an asymptomatic unrepaired AAA of any diameter ≥30 mm were recruited from hospital outpatient clinics and surveillance programs run at four centres. The main outcome was the requirement for AAA repair or AAA related mortality (AAA events). The association between metformin prescription and AAA events was assessed using Kaplan-Meier analysis and Cox proportional hazard analysis. Patients (1,080) with a mean (SD) initial AAA diameter of 46.1 (11.3) mm were followed for a mean (SD) of 2.5 (3.1) years until an AAA event (n = 454), death (n = 176), loss to follow up (n = 128), or completion of current follow up (n = 322). Patients with diabetes who were prescribed metformin (adjusted HR 0.63, 95% CI 0.44-0.93), but not patients with diabetes who were not prescribed metformin (adjusted HR 1.15, 95% CI 0.83-1.59), had a lower incidence of AAA events compared with those without diabetes. Findings were similar in sensitivity analyses restricted to patients with an initial AAA diameter ≤50 mm and patients with a minimum follow up of six months before an AAA event. These findings suggest that clinically important AAA events may be reduced in patients with diabetes who are prescribed metformin, but not those with diabetes receiving other treatments. A randomised controlled trial is needed to definitively test whether metformin reduces AAA related clinical events in patients with small AAAs who do not have diabetes.
Publisher: Elsevier BV
Date: 09-2009
Publisher: Public Library of Science (PLoS)
Date: 02-06-2017
Publisher: Oxford University Press (OUP)
Date: 22-03-2018
DOI: 10.1002/BJS.10765
Abstract: Revascularization is being used increasingly for the treatment of intermittent claudication and yet few studies have reported the long-term outcomes of this strategy. The aim of this study was to compare the long-term outcome of patients with intermittent claudication who underwent revascularization compared with a group initially treated without revascularization. Patients with symptoms of intermittent claudication and a diagnosis of peripheral arterial disease were recruited from outpatient clinics at three hospitals in Queensland, Australia. Based on variation in the practices of different vascular specialists, patients were either treated by early revascularization or received initial conservative treatment. Patients were followed in outpatient clinics using linked hospital admission record data. The primary outcome was the requirement for major utation. Kaplan–Meier curves, Cox regression and competing risks analyses were used to compare major utation rates. Some 456 patients were recruited 178 (39·0 per cent) underwent early revascularization and 278 (61·0 per cent) had initial conservative treatment. Patients were followed for a mean(s.d.) of 5·00(3·37) years. The estimated 5-year major utation rate was 6·2 and 0·7 per cent in patients undergoing early revascularization and initial conservative treatment respectively (P = 0·003). Early revascularization was associated with an increased requirement for major utation in models adjusted for other risk factors (relative risk 5·40 to 4·22 in different models). Patients presenting with intermittent claudication who underwent early revascularization appeared to be at higher risk of utation than those who had initial conservative treatment.
Publisher: Elsevier BV
Date: 11-2017
Publisher: Public Library of Science (PLoS)
Date: 25-07-2017
Publisher: Springer Science and Business Media LLC
Date: 13-11-1971
DOI: 10.1038/S41598-021-86128-Y
Abstract: Disease modifying anti-rheumatic drugs (DMARDs) were developed to treat joint inflammation. There is growing evidence that anti-inflammatory drugs prevent major cardiovascular events (MACE). The aim of this systematic review and meta-analysis was to examine whether DMARDs reduce the risk of MACE. A systematic literature search was performed to identify randomized controlled trials (RCTs) testing the effect of DMARDs on cardiovascular events. The primary outcome was MACE defined as the first occurrence of non-fatal myocardial infarction (MI), non-fatal stroke or cardiovascular death. Secondary outcomes were myocardial infarction or stroke alone and all-cause mortality. Safety was assessed by fatal or life threatening infection. Meta-analyses were performed using random effect models and reported as risk ratios (RR) and 95% confidence intervals (CI). Study quality and publication bias were assessed using the Cochrane Collaboration’s tool for assessing risk of bias and funnel plots. Twelve RCTs involving 18,056 participants testing three different DMARDs subclasses (Tumor Necrosis Factor inhibitors—4 trials Janus Kinase inhibitors—5 trials Interleukin inhibitors—3 trials) were included. Meta-analysis suggested that none of the DMARD subclasses had any effect on MACE, MI alone, stroke alone, risk of fatal or life threatening infection or death. Risk of bias was high, low and unclear in five, six and one studies respectively. Funnel plots suggested a low possibility of publication bias. This meta-analysis suggests that DMARDs do not affect the incidence of MACE. More trials are needed for firm conclusions.
Start Date: 2019
End Date: End date not available
Funder: National Health and Medical Research Council
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