447 results found
Powell JT, 2020, Lost in Translation From Mice to Men: Grief and Pain and FAME, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 60, Pages: 461-461, ISSN: 1078-5884
Doyle BJ, Bappoo N, Syed MBJ, et al., 2020, Biomechanical assessment predicts aneurysm related events in patients with abdominal aortic aneurysm, European Journal of Vascular and Endovascular Surgery, Vol: 60, Pages: 365-373, ISSN: 1078-5884
ObjectiveTo test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events.MethodsIn a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair.ResultsThe majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09–1.83 [p = .010]).ConclusionIt has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.
Powell JT, Wanhainen A, 2020, Analysis of the differences between the European Society for Vascular Surgery 2019 and National Institute for Health and Care Excellence 2020 guidelines for abdominal aortic aneurysm, European Journal of Vascular and Endovascular Surgery, Vol: 60, Pages: 7-15, ISSN: 1078-5884
ObjectiveThe aim was to understand why two recently published guidelines for the diagnosis and management of patients with abdominal aortic aneurysm, the National Institute for Health and Care Excellence (NICE) 2020 guidelines and the European Society for Vascular Surgery (ESVS) 2019 guidelines, have discordant recommendations in several important areas.MethodsA review of the approach, methodology, and evidence used by the two guideline committees was carried out to understand potential reasons for their differing recommendations in their two final published guidelines.ResultsNICE guidelines use a multidisciplinary committee to address a limited number of prospectively identified questions, using rigorous methods heavily reliant on evidence from randomised controlled trials (RCTs) supported by in house economic modelling, with the purpose of providing the best, cost-effective health care in the UK in 46 main recommendations. The ESVS guidelines use an expert committee to encourage clinical effectiveness across a range of European health economies. ESVS guideline topics, but not questions, are prospectively identified, assessment of evidence was less rigorous, and 125 recommendations were made. More up to date evidence searches by the ESVS committee partially underscore the differences in recommendations for screening women. The NICE committee did not consider sex specific analysis or evidence for thresholds for intervention but relied on sex specific modelling to support their advice to use endovascular repair (EVAR) for ruptures in women. Their recommendation to use open repair for ruptured abdominal aortic aneurysms (AAAs) in men aged < 71 years was based on in house economic modelling. NICE recommends an open first strategy for non-ruptured AAA mainly based on earlier RCTs and UK specific economic modelling, while the ESVS guidelines recommend an EVAR first strategy after consideration of modern, but lower quality, evidence from observational studies. Similar
Ulug P, Powell JT, Martinez MA-M, et al., 2020, Surgery for small asymptomatic abdominal aortic aneurysms., Cochrane Database of Systematic Reviews, Vol: 7, Pages: CD001835-CD001835, ISSN: 1469-493X
BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors, but the size of the aneurysm is important, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (greater than 5.5 cm in diameter) are usually repaired surgically; very small AAAs (less than 4.0 cm diameter) are monitored with ultrasonography. Debate continues over the roles of early repair versus surveillance with repair on subsequent enlargement in people with asymptomatic AAAs of 4.0 cm to 5.5 cm diameter. This is the fourth update of the review first published in 1999. OBJECTIVES: To compare mortality and costs, as well as quality of life and aneurysm rupture as secondary outcomes, following early surgical repair versus routine ultrasound surveillance in people with asymptomatic AAAs between 4.0 cm and 5.5 cm in diameter. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, two other databases, and two trials registers to 10 July 2019. We handsearched conference proceedings and checked reference lists of relevant studies. SELECTION CRITERIA: We included randomised controlled trials where people with asymptomatic AAAs of 4.0 cm to 5.5 cm were randomly allocated to early repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, which were cross-checked by other team members. Outcomes were mortality, costs, quality of life, and aneurysm rupture. For mortality, we estimated risk ratios (RR) (endovascular aneurysm repair only), hazard ratios (HR) (open repair only), and 95% confidence intervals (CI) based on Mantel-Haenszel Chi2 statistics at one and six years (open repair only) following randomisation
Lyons O, Powell JT, 2020, The world is not enough: how can "big data" inform guidelines for elective AAA repair?, European Journal of Vascular and Endovascular Surgery, Vol: 59, Pages: 898-898, ISSN: 1078-5884
Powell JT, Hegele RA, 2020, From laundry list to rating scheme selection of the best scientific method, Arteriosclerosis, Thrombosis and Vascular Biology, Vol: 40, Pages: 1018-1019, ISSN: 1079-5642
Parker L, Powell J, Kelsey L, et al., 2020, Morphology and computational fluid dynamics support a novel classification of common iliac aneurysms, European Journal of Vascular and Endovascular Surgery, Vol: 59, Pages: 786-793, ISSN: 1078-5884
Objectives: Isolated common iliac artery aneurysms (CIAAs) are uncommon and evidence concerning their development, progression and management is weak. Our objective was to describe the morphology and haemodynamics of isolated CIAAs in a retrospective study.Methods: Initially a series of 25 isolated CIAAs (15 intact, 10 ruptured) in 23 patients were gathered from multiple centres, reconstructed from computed tomography (CT), then morphologically classified and analysed with computational fluid dynamics. The morphological classification was applied in a separate, consecutive cohort of 162 patients assessed for elective aorto-iliac intervention, in which 45 patients had intact CIAAs.Results: In the isolated CIAA cohort, three distinct morphologies were identified: complex, fusiform and kinked (distal to a sharp bend in the CIA), with mean diameters 90.3, 48.3 and 31.7 mm, and mean time-averaged wall shear stress of 0.16, 0.31 and 0.71 Pa, respectively (both ANOVA p<.001). Kinked cases, compared to fusiform cases, had less thrombus and favourable haemodynamics similar to the non-aneurysmal contralateral CIA. Ruptured isolated CIAA were large (mean diameter 87.5mm, range 55.5-138.0mm) and predominantly complex. Mean CIA length for aneurysmal arteries was greatest in kinked cases followed by complex and fusiform (100.8mm, 91.1mm and 80.6mm respectively). The morphological classification was readily applicable to a separate elective patient cohort.Conclusions: A new morphological categorization of CIAAs is proposed. This is potentially associated with both haemodynamics and clinical course. Further research is required to determine whether the kinked CIAA is haemodynamically protected from aneurysm progression and establish the wider applicability of the categorization presented.
Mitchell GF, Powell J, 2020, Arteriosclerosis: a primer for “In Focus” reviews on arterial stiffness, Arteriosclerosis, Thrombosis and Vascular Biology, Vol: 40, Pages: 1025-1027, ISSN: 1079-5642
Wanhainen A, Verzini F, Van Herzeele I, et al., 2020, Corrigendum to 'European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms' [European Journal of Vascular & Endovascular Surgery 57/1 (2019) 8-93]., Eur J Vasc Endovasc Surg, Vol: 59
Soares Ferreira R, Powell JT, 2020, Elective repair of abdominal aortic aneurysm: the evidence is in but the jury may still be out, European Journal of Vascular and Endovascular Surgery, Vol: 59, Pages: 398-398, ISSN: 1078-5884
Kontopodis N, Galanakis N, Antoniou SA, et al., 2020, Meta-analysis and meta-regression analysis of outcomes of endovascular and open repair for ruptured abdominal aortic aneurysm, European Journal of Vascular and Endovascular Surgery, Vol: 59, Pages: 399-410, ISSN: 1078-5884
ObjectivesThe aim was to assess peri-operative mortality of endovascular aneurysm repair (EVAR) vs. open repair for ruptured abdominal aortic aneurysm (AAA) and to investigate whether outcomes have improved over the years and whether there is an association between institutional caseload and peri-operative mortality.MethodsElectronic information sources (MEDLINE, EMBASE, CINAHL and CENTRAL) were searched up to August 2019. A systematic review was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using a registered protocol (CRD42018106084). Studies were selected that reported peri-operative mortality of EVAR for ruptured AAA. A proportion meta-analysis was conducted, and summary estimates of odds ratios (ORs) and 95% confidence intervals (CIs) for EVAR vs. open surgical repair were obtained using random effects models. Mixed effects regression models were developed to investigate outcome changes over time and with institutional caseload.ResultsOne hundred and thirty-six studies were included in quantitative synthesis reporting a total of 267 259 patients (EVAR 58 273; open surgery 208 986). The pooled peri-operative mortality of EVAR and open surgical repair was 0.245 (95% CI 0.234–0.257) and 0.378 (95% CI 0.364–0.392), respectively. EVAR was associated with reduced peri-operative mortality (OR 0.54, 95% CI 0.51–0.57, p < .001). Meta-regression analysis found decreasing peri-operative mortality over the years following EVAR (p < .001) and open repair (p < .001), and a decreasing OR of peri-operative mortality in favour of EVAR (p = .053). Meta-regression found a significant positive association between peri-operative mortality and institutional case load for open repair (p = .004).ConclusionsIf EVAR can be done, it is a better treatment for ruptured AAA in view of the reduced peri-operative mortality compared with open surgery. The outcomes of both EVAR and open surgical repair
Powell JT, 2020, The Missing Biomarker or Biomarker Panel in the Recovery of Muscle Mitochondrial Function, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 59, Pages: 116-116, ISSN: 1078-5884
Parker L, Doyle B, Powell J, et al., 2019, Morphology and computational flow dynamics support a novel classification of isolated common Iliac aneurysms, with impact on aneurysm progno, European Journal of Vascular and Endovascular Surgery, Vol: 58, Pages: e215-e215, ISSN: 1078-5884
Introduction - Isolated common iliac artery aneurysms (CIAA) are rare and quantifying the risk of CIAA progression and rupture is difficult, typically based on diameter. We hypothesised that morphology and hemodynamics will better correlate with outcome, and also provide new insights into aortoiliac remodeling.Methods - A series of 25 isolated CIAAs (n = 15 intact, n = 10 ruptured) in 23 patients were reconstructed from computed tomography angiography (CTA) and analysed with computational fluid dynamics. The relationship between hemodynamics and morphology was assessed. Based on the patient-specific dimensions, a series of 24 aortoiliac geometries with varying iliac bifurcation angle and abdominal aorta deflection were simulated. A further 162 consecutive patients assessed with CTA prior to aortoiliac endovascular intervention were used for morphological studies only.Results - There were three distinct isolated CIAA morphologies; saccular, fusiform and kinked CIAA. Kinked cases (in tortuous left CIA) had similar diameter to fusiform cases but less calcification and thrombus, a narrower aortic bifurcation and more favourable hemodynamics than fusiform cases. Saccular CIAAs were largest and usually ruptured (at sites of low and oscillatory shear). CIAA and associated hemodynamic disturbances were associated with lateral shifting of the infrarenal aorta towards the CIAA side.Conclusion - A new morphological categorisation, predictive of the clinical course, of isolated CIAAs is suggested, with CIAAs in tortuous vessels being relatively benign. Patient and hemodynamic modelling data support the hypothesis that flow disturbances in the common iliac artery are causative for aortic remodelling.
Ulug P, Powell J, Warschkow R, et al., 2019, Editor's Choice – Sex Specific Differences in the Management of Descending Thoracic Aortic Aneurysms: Systematic Review with Meta-Analysis, European Journal of Vascular and Endovascular Surgery, Vol: 58, Pages: 503-511, ISSN: 1078-5884
Objectives: To assess sex-specific differences in 30-day mortality, length of hospital stay and adverse neurological events following repair of intact degenerative descending thoracic aortic aneurysms, by either endovascular (TEVAR) or open repair.Data Sources: Medline, Embase and CENTRAL databases searched from 2005-2019 using ProQuest Dialog™.Review methods: The reviews were registered in PROSPERO (CRD42017020026) and performed according to PRISMA guidelines. The primary outcome was 30-day mortality with secondary outcomes of length of hospital stay and adverse neurological events. Forest plots with random effects meta-analysis to provide odds ratios (OR) were used for primary assessment.Results: For TEVAR, a total of seven studies were identified including 2758 women and 4674 men; of these six were eligible for the primary outcome of 30-day mortality including 1756 women and 2619 men. There were 94/1756 deaths in women and 82/2619 deaths in men, yielding a pooled 30-day mortality of 5% (95% c.i. 3 to 7) in women and 3% (95% c.i. 2 to 4) in men (OR 1.75 [95%CI 1.29; 2.38]). Length of hospital stay was longer in women, with standardised mean difference 0.3 days [95%CI 0.14; 0.47] (6 studies): meta-regression analysis did not identify the slightly older age of women as significant factor in these differences. Stroke rate was not different between the sexes. For open repair only a single study, with national coverage, was identified that reported 30-day mortality, which was similar in men and women. Conclusion: In the management of intact degenerative descending thoracic aortic aneurysms, 30-day mortality following TEVAR appears to be much higher in women than men with no reasons for this difference identified. For open repair however, there is a lack of contemporary evidence due to insufficient recent data.
Bicknell C, Powell JT, 2019, Intramural haematoma remains an enigma, European Heart Journal, Vol: 40, Pages: 2737-2739, ISSN: 1522-9645
Parker LP, Powell JT, Kelsey LJ, et al., 2019, Morphology and hemodynamics in isolated common iliac artery aneurysms impacts proximal aortic remodeling, Arteriosclerosis, Thrombosis, and Vascular Biology, Vol: 39, Pages: 1125-1136, ISSN: 1079-5642
Objective- Isolated common iliac artery aneurysms (CIAA) are rare. Their prognosis and influence on aortoiliac blood flow and remodeling are unclear. We evaluated the hypotheses that morphology at and distal to the aortic bifurcation, together with the associated hemodynamic changes, influence both the natural history of CIAA and proximal aortic remodeling. Approach and Results- Twenty-five isolated CIAAs (15 intact, 10 ruptured), in 23 patients were reconstructed and analyzed with computational fluid dynamics: all showed abnormal flow. Then we studied a series of 24 hypothetical aortoiliac geometries in silico with varying abdominal aortic deflection and aortic bifurcation angles: key findings were assessed in an independent validation cohort of 162 patients. Wall shear stress in isolated unilateral CIAAs was lower than the contralateral common iliac artery, 0.38±0.33 Pa versus 0.61±0.24 Pa, inversely associated with CIAA diameter ( P<0.001) and morphology (high shear stress in variants distal to a sharp kink). Rupture usually occurred in regions of elevated low and oscillatory shear with a wide aortic bifurcation angle. Abdominal aortas deflected towards the CIAA for most unilateral isolated CIAAs (14/21). In silico, wider bifurcation angles created high focal regions of low and oscillatory shear in the common iliac artery. The associations of unilateral CIAA with aortic deflection and common iliac artery diameter with bifurcation angle were confirmed in the validation cohort. Conclusions- Decreasing wall shear stress is strongly associated with CIAA progression (larger aneurysms and rupture), whereas abnormal blood flow in the CIAA seems to promote proximal aortic remodeling, with adaptive lateral deflection of the abdominal aorta towards the aneurysmal side.
Paige E, Clement M, Lareyre F, et al., 2019, Interleukin-6 receptor signalling and abdominal aortic aneurysm growth rates, Circulation: Genomic and Precision Medicine, Vol: 12, ISSN: 2574-8300
Background:The Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor (IL6R) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R-Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection.Methods:Using data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R-Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death.Results:After adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13–0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was −0.06 mm per year (−0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival (P<0.05).Conclusions:Our proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.
Wanhainen A, Verzini F, Van Herzeele I, et al., 2019, European Society for Vascular Surgery Guidelines on the management of Aort0-iliac Abdominal Aortic Aneurysms, European Journal of Vascular and Endovascular Surgery, Vol: 57, Pages: 8-93, ISSN: 1078-5884
Powell J, Ambler GK, Svensjo S, et al., 2019, Beyond the AAA guidelines: core outcome sets to make life better for patients, European Journal of Vascular and Endovascular Surgery, Vol: 57, Pages: 6-7, ISSN: 1078-5884
An abdominal aortic aneurysm (AAA) is a localized dilatation of the infrarenal aorta. AAA is a multifactorial disease, and genetic and environmental factors play a part; smoking, male sex and a positive family history are the most important risk factors, and AAA is most common in men >65 years of age. AAA results from changes in the aortic wall structure, including thinning of the media and adventitia due to the loss of vascular smooth muscle cells and degradation of the extracellular matrix. If the mechanical stress of the blood pressure acting on the wall exceeds the wall strength, the AAA ruptures, causing life-threatening intra-abdominal haemorrhage — the mortality for patients with ruptured AAA is 65–85%. Although AAAs of any size can rupture, the risk of rupture increases with diameter. Intact AAAs are typically asymptomatic, and in settings where screening programmes with ultrasonography are not implemented, most cases are diagnosed incidentally. Modern functional imaging techniques (PET, CT and MRI) may help to assess rupture risk. Elective repair of AAA with open surgery or endovascular aortic repair (EVAR) should be considered to prevent AAA rupture, although the morbidity and mortality associated with both techniques remain non-negligible.
Sweeting MJ, Masconi KL, Jones E, et al., 2018, Analysis of clinical benefit, harms, and cost-effectiveness of screening women for abdominal aortic aneurysm, Lancet, Vol: 392, Pages: 487-495, ISSN: 0140-6736
BACKGROUND: A third of deaths in the UK from ruptured abdominal aortic aneurysm (AAA) are in women. In men, national screening programmes reduce deaths from AAA and are cost-effective. The benefits, harms, and cost-effectiveness in offering a similar programme to women have not been formally assessed, and this was the aim of this study. METHODS: We developed a decision model to assess predefined outcomes of death caused by AAA, life years, quality-adjusted life years, costs, and the incremental cost-effectiveness ratio for a population of women invited to AAA screening versus a population who were not invited to screening. A discrete event simulation model was set up for AAA screening, surveillance, and intervention. Relevant women-specific parameters were obtained from sources including systematic literature reviews, national registry or administrative databases, major AAA surgery trials, and UK National Health Service reference costs. FINDINGS: AAA screening for women, as currently offered to UK men (at age 65 years, with an AAA diagnosis at an aortic diameter of ≥3·0 cm, and elective repair considered at ≥5·5cm) gave, over 30 years, an estimated incremental cost-effectiveness ratio of £30 000 (95% CI 12 000-87 000) per quality-adjusted life year gained, with 3900 invitations to screening required to prevent one AAA-related death and an overdiagnosis rate of 33%. A modified option for women (screening at age 70 years, diagnosis at 2·5 cm and repair at 5·0 cm) was estimated to have an incremental cost-effectiveness ratio of £23 000 (9500-71 000) per quality-adjusted life year and 1800 invitations to screening required to prevent one AAA-death, but an overdiagnosis rate of 55%. There was considerable uncertainty in the cost-effectiveness ratio, largely driven by uncertainty about AAA prevalence, the distribution of aortic sizes for women at different ages, and the effect of screening on quality of life. INTERPRETATION: B
Thompson SG, Bown MJ, Glover MJ, et al., 2018, Screening women aged 65 years or over for abdominal aortic aneurysm: a modelling study and health economic evaluation, HEALTH TECHNOLOGY ASSESSMENT, Vol: 22, Pages: 1-+, ISSN: 1366-5278
BackgroundAbdominal aortic aneurysm (AAA) screening programmes have been established for men in the UK to reduce deaths from AAA rupture. Whether or not screening should be extended to women is uncertain.ObjectiveTo evaluate the cost-effectiveness of population screening for AAAs in women and compare a range of screening options.DesignA discrete event simulation (DES) model was developed to provide a clinically realistic model of screening, surveillance, and elective and emergency AAA repair operations. Input parameters specifically for women were employed. The model was run for 10 million women, with parameter uncertainty addressed by probabilistic and deterministic sensitivity analyses.SettingPopulation screening in the UK.ParticipantsWomen aged ≥ 65 years, followed up to the age of 95 years.InterventionsInvitation to ultrasound screening, followed by surveillance for small AAAs and elective surgical repair for large AAAs.Main outcome measuresNumber of operations undertaken, AAA-related mortality, quality-adjusted life-years (QALYs), NHS costs and cost-effectiveness with annual discounting.Data sourcesAAA surveillance data, National Vascular Registry, Hospital Episode Statistics, trials of elective and emergency AAA surgery, and the NHS Abdominal Aortic Aneurysm Screening Programme (NAAASP).Review methodsSystematic reviews of AAA prevalence and, for elective operations, suitability for endovascular aneurysm repair, non-intervention rates, operative mortality and literature reviews for other parameters.ResultsThe prevalence of AAAs (aortic diameter of ≥ 3.0 cm) was estimated as 0.43% in women aged 65 years and 1.15% at age 75 years. The corresponding attendance rates following invitation to screening were estimated as 73% and 62%, respectively. The base-case model adopted the same age at screening (65 years), definition of an AAA (diameter of ≥ 3.0 cm), surveillance intervals (1 year for AAAs with diameter of 3.0–4.
Powell JT, 2018, The first living legend: International Lifetime Achievement Award from the Society of Vascular Surgery, European Journal of Vascular and Endovascular Surgery, Vol: 56, Pages: 5-6, ISSN: 1078-5884
Sweeting MJ, Ulug P, Hultgren R, et al., 2018, Value of risk scores in the decision to palliate patients withruptured abdominal aortic aneurysm, British Journal of Surgery, Vol: 105, Pages: 1135-1144, ISSN: 1365-2168
Background:The aim of this study was to develop a 48‐h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care.Methods:Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C‐statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified.Results:Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48‐h mortality in the IMPROVE data was reasonable (C‐statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C‐statistic was estimated compared with using age alone.Conclusion:The assessed risk scores did not have sufficient accuracy to enable potentially life‐saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non‐intervention rates, while respecting the wishes of the patient and family.
Sweeting M, Masconi KL, Jones E, et al., Should we screen women for abdominal aortic aneurysm? Analysis of clinical benefit, harms and cost-effectivenes, Lancet, ISSN: 0140-6736
Backgroud:One-third of UK deaths from ruptured abdominal aortic aneurysm (AAA) are in women. In men, national screening programmes reduce deaths from AAA and are cost-effective. The benefits, harms and cost-effectiveness in offering a similar programme to women have not been formally assessed.Methods:A discrete event simulation model was set up for AAA screening, surveillance and intervention. Relevant women-specific parameters were obtained from sources including systematic literature reviews, national registry/administrative databases, major AAA surgery trials, and UK National Health Service reference costs.Findings:AAA screening for women, as currently offered to UK men (at age 65, AAA diagnosis at an aortic diameter of ≥3.0cm and elective repair considered at ≥5.5cm) gave, over a 30-yeartime horizon, an estimated incremental cost effectiveness ratio (ICER) of £30,000 (95% CI 12,000 to 87,000) per quality adjusted life-year (QALY) gained, with 3,900 invitations to screening required to prevent one AAA-death and an over-diagnosis rate of 33%. A modified option for women (screening at age 70, diagnosis at 2.5cm and repair at 5.0cm) was estimated to be more cost-effective, with an ICER of £23,000 (9,500 to 71,000) per QALY and 1,800 invitations to screening required to prevent one AAA-death, but an over-diagnosis rate of 55%. There was considerable uncertainty in the ICER, largely driven by uncertainty about AAA prevalence,the distribution of aortic sizes for women at different ages and the impact of screening on quality-of-life.Interpretation:By UK standards an AAA screening programme for women, mimicking that in men, is unlikely to be cost-effective. Further research on the aortic diameter distribution in women and potential quality of life decrements associated with screening are needed to assess the full benefits and harms of modified options.
Powell JT, Sweeting MJ, Ulug P, et al., 2018, Re-interventions after repair of ruptured abdominal aortic aneurysm: a report from the IMPROVE randomised trial, European Journal of Vascular and Endovascular Surgery, Vol: 55, Pages: 625-632, ISSN: 1078-5884
OBJECTIVE/BACKGROUND: The aim was to describe the re-interventions after endovascular and open repair of rupture, and investigate whether these were associated with aortic morphology. METHODS: In total, 502 patients from the IMPROVE randomised trial (ISRCTN48334791) with repair of rupture were followed-up for re-interventions for at least 3 years. Pre-operative aortic morphology was assessed in a core laboratory. Re-interventions were described by time (0-90 days, 3 months-3 years) as arterial or laparotomy related, respectively, and ranked for severity by surgeons and patients separately. Rare re-interventions to 1 year, were summarised across three ruptured abdominal aortic aneurysm trials (IMPROVE, AJAX, and ECAR) and odds ratios (OR) describing differences were pooled via meta-analysis. RESULTS: Re-interventions were most common in the first 90 days. Overall rates were 186 and 226 per 100 person years for the endovascular strategy and open repair groups, respectively (p = .20) but between 3 months and 3 years (mid-term) the rates had slowed to 9.5 and 6.0 re-interventions per 100 person years, respectively (p = .090) and about one third of these were for a life threatening condition. In this latter, mid-term period, 42 of 313 remaining patients (13%) required at least one re-intervention, most commonly for endoleak or other endograft complication after treatment by endovascular aneurysm repair (EVAR) (21 of 38 re-interventions), whereas distal aneurysms were the commonest reason (four of 23) for re-interventions after treatment by open repair. Arterial re-interventions within 3 years were associated with increasing common iliac artery diameter (OR 1.48, 95% confidence interval [CI] 0.13-0.93; p = .004). Amputation, rare but ranked as the worst re-intervention by patients, was less common in the first year after treatment with EVAR (OR 0.2, 95% CI 0.05-0.88) from meta-analysis of three trials. CONCLUSION: The rate of mid-term re-inte
Ulug P, Hinchliffe RJ, Sweeting MJ, et al., 2018, Strategy of endovascular versus open repair for patients with clinical diagnosis of ruptured abdominal aortic aneurysm: the IMPROVE RCT, Health Technology Assessment, Vol: 22, ISSN: 1366-5278
BackgroundRuptured abdominal aortic aneurysm (AAA) is a common vascular emergency. The mortality from emergency endovascular repair may be much lower than the 40–50% reported for open surgery.ObjectiveTo assess whether or not a strategy of endovascular repair compared with open repair reduces 30-day and mid-term mortality (including costs and cost-effectiveness) among patients with a suspected ruptured AAA.DesignRandomised controlled trial, with computer-generated telephone randomisation of participants in a 1 : 1 ratio, using variable block size, stratified by centre and without blinding.SettingVascular centres in the UK (n = 29) and Canada (n = 1) between 2009 and 2013.ParticipantsA total of 613 eligible participants (480 men) with a ruptured aneurysm, clinically diagnosed at the trial centre.InterventionsA total of 316 participants were randomised to the endovascular strategy group (immediate computerised tomography followed by endovascular repair if anatomically suitable or, if not suitable, open repair) and 297 were randomised to the open repair group (computerised tomography optional).Main outcome measuresThe primary outcome measure was 30-day mortality, with 30-day reinterventions, costs and disposal as early secondary outcome measures. Later outcome measures included 1- and 3-year mortality, reinterventions, quality of life (QoL) and cost-effectiveness.ResultsThe 30-day mortality was 35.4% in the endovascular strategy group and 37.4% in the open repair group [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.66 to 1.28; p = 0.62, and, after adjustment for age, sex and Hardman index, OR 0.94, 95% CI 0.67 to 1.33]. The endovascular strategy appeared to be more effective in women than in men (interaction test p = 0.02). More discharges in the endovascular strategy group (94%) than in the open repair group (77%) were directly to home (p < 0.001). Average 30-day costs
Glover MJ, Jones E, Masconi KL, et al., 2018, Discrete Event Simulation for Decision Modeling in Health Care: Lessons from Abdominal Aortic Aneurysm Screening, Medical Decision Making, Vol: 38, Pages: 439-451, ISSN: 0272-989X
Markov models are often used to evaluate the cost-effectiveness of new healthcare interventions but they are sometimes not flexible enough to allow accurate modeling or investigation of alternative scenarios and policies. A Markov model previously demonstrated that a one-off invitation to screening for abdominal aortic aneurysm (AAA) for men aged 65 y in the UK and subsequent follow-up of identified AAAs was likely to be highly cost-effective at thresholds commonly adopted in the UK (£20,000 to £30,000 per quality adjusted life-year). However, new evidence has emerged and the decision problem has evolved to include exploration of the circumstances under which AAA screening may be cost-effective, which the Markov model is not easily able to address. A new model to handle this more complex decision problem was needed, and the case of AAA screening thus provides an illustration of the relative merits of Markov models and discrete event simulation (DES) models. An individual-level DES model was built using the R programming language to reflect possible events and pathways of individuals invited to screening v. those not invited. The model was validated against key events and cost-effectiveness, as observed in a large, randomized trial. Different screening protocol scenarios were investigated to demonstrate the flexibility of the DES. The case of AAA screening highlights the benefits of DES, particularly in the context of screening studies.
Patel R, Powell JT, Sweeting MJ, et al., 2018, The UK EndoVascular Aneurysm Repair (EVAR) randomised controlled trials: long-term follow-up and cost-effectiveness analysis, HEALTH TECHNOLOGY ASSESSMENT, Vol: 22, Pages: 1-+, ISSN: 1366-5278
BackgroundShort-term survival benefits of endovascular aneurysm repair (EVAR) compared with open repair (OR) of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is soon lost. Survival benefit of EVAR was unclear at follow-up to 10 years.ObjectiveTo assess the long-term efficacy of EVAR against OR in patients deemed fit and suitable for both procedures (EVAR trial 1; EVAR-1); and against no intervention in patients unfit for OR (EVAR trial 2; EVAR-2). To appraise the long-term significance of type II endoleak and define criteria for intervention.DesignTwo national, multicentre randomised controlled trials: EVAR-1 and EVAR-2.SettingPatients were recruited from 37 hospitals in the UK between 1 September 1999 and 31 August 2004.ParticipantsMen and women aged ≥ 60 years with an aneurysm of ≥ 5.5 cm (as identified by computed tomography scanning), anatomically suitable and fit for OR were randomly assigned 1 : 1 to either EVAR (n = 626) or OR (n = 626) in EVAR-1 using computer-generated sequences at the trial hub. Patients considered unfit were randomly assigned to EVAR (n = 197) or no intervention (n = 207) in EVAR-2. There was no blinding.InterventionsEVAR, OR or no intervention.Main outcome measuresThe primary end points were total and aneurysm-related mortality until mid-2015 for both trials. Secondary outcomes for EVAR-1 were reinterventions, costs and cost-effectiveness.ResultsIn EVAR-1, over a mean of 12.7 years (standard deviation 1.5 years; maximum 15.8 years), we recorded 9.3 deaths per 100 person-years in the EVAR group and 8.9 deaths per 100 person-years in the OR group [adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.97 to 1.27; p = 0.14]. At 0–6 months after randomisation, patients in the EVAR group had a lower mortality (adjusted HR 0.61, 95% CI 0.37 to 1.02 for total mort
Harrison SC, Holmes MV, Burgess S, et al., 2017, Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm: A Meta-analysis., JAMA Cardiology, Vol: 3, Pages: 26-33, ISSN: 2380-6583
Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective: To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants: Genetic risk scores, composed of lipid trait-associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR, and multivariable MR method was used to test the independent association of lipids with AAA risk. The association between AAA and SNPs in loci that can act as proxies for drug targets was also assessed. Data collection took place between January 9, 2015, and January 4, 2016. Data analysis was conducted between January 4, 2015, and December 31, 2016. Exposures: Genetic elevation of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Main Outcomes and Measures: The association between genetic risk scores of lipid-associated SNPs and AAA risk, as well as the association between SNPs in lipid drug targets (HMGCR, CETP, and PCSK9) and AAA risk. Results: Up to 4914 cases and 48 002 controls were included in our analysis. A 1-SD genetic elevation of LDL-C was associated with increased AAA risk (odds ratio [OR], 1.66; 95% CI, 1.41-1.96; P = 1.1 × 10-9). For HDL-C, a 1-SD increase was associated with reduced AAA risk (OR, 0.67; 95% CI, 0.55-0.82; P = 8.3 × 10-5), whereas a 1-SD increase in triglycerides was associated with increased AAA risk (OR, 1.69; 95% CI, 1.38-2.07; P = 5.2 × 10-7). In multivariable MR analysis an
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