Imperial College London

ProfessorJanetPowell

Faculty of MedicineDepartment of Surgery & Cancer

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 8846 7312j.powell

 
 
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Location

 

4N17Charing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
to

432 results found

Parker LP, Powell JT, Kelsey LJ, Lim B, Ashleigh R, Venermo M, Koncar I, Norman PE, Doyle BJet 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.

Journal article

Bicknell C, Powell JT, 2019, Intramural haematoma remains an enigma, European Heart Journal, ISSN: 1522-9645

Journal article

Ulug P, Powell J, Warschkow R, Von Allmen RSet al., Sex-specific differences in the management of descending thoracic aortic aneurysms: systematic review with meta-analysis, European Journal of Vascular and Endovascular Surgery, 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.

Journal article

Paige E, Clement M, Lareyre F, Sweeting M, Raffort J, Grenier C, Finigan A, Harrison J, Peters JE, Sun BB, Butterworth AS, Harrison SC, Bown MJ, Lindholt JS, Badger SA, Kullo IJ, Powell J, Norman PE, Scott DJA, Bailey MA, Rose-John S, Danesh J, Freitag DF, Paul DS, Mallat Zet 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.

Journal article

Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, Dick F, van Herwaarden J, Karkos C, Koelemay M, Kölbel T, Loftus I, Mani K, Melissano G, Powell J, Szeberin Z, Esvs Guidelines Committee, de Borst GJ, Chakfe N, Debus S, Hinchliffe R, Kakkos S, Koncar I, Kolh P, Lindholdt J, de Vega M, Vermassen F, Document Reviewers, Björck M, Cheng S, Dalman R, Davidovic L, Donas K, Earnshaw J, Eckstein H-H, Golledge J, Haulon S, Mastracci T, Naylor R, Ricco J-B, Verhagen Het 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

Journal article

Powell J, Ambler GK, Svensjo S, Wanhainen A, Brown MJet 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

Journal article

Sakalihasan N, Michel J-B, Katsargyris A, Kuivaniemi H, Defraigne J, Nchimi A, Powell J, Hultgren Ret al., 2018, Abdominal aortic aneurysms, Nature Reviews Disease Primers, Vol: 4, ISSN: 2056-676X

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.

Journal article

Sweeting MJ, Masconi KL, Jones E, Ulug P, Glover MJ, Michaels JA, Bown MJ, Powell JT, Thompson SGet 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

Journal article

Thompson SG, Bown MJ, Glover MJ, Jones E, Masconi KL, Michaels JA, Powell JT, Ulug P, Sweeting MJet 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.

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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

Journal article

Sweeting MJ, Ulug P, Hultgren R, Indrakusuma R, Balm R, Thompson MM, Hinchliffe RJ, Thompson SG, Powell JT, the Ruptured Aneurysm Collaborators, including IMPROVE, AJAX, ECAR and STAR collaboratorset 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.

Journal article

Sweeting M, Masconi KL, Jones E, Ulug P, Glover MJ, Michaels JA, Bown MJ, Powell JT, Thompson SGet 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.

Journal article

Powell JT, Sweeting MJ, Ulug P, Thompson MM, Hinchliffe RJ, IMPROVE Trial Investigatorset 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

Journal article

Ulug P, Hinchliffe RJ, Sweeting MJ, Gomes M, Thompson MT, Thompson SG, Grieve RJ, Ashleigh R, Greenhalgh RM, Powell JTet 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

Journal article

Glover MJ, Jones E, Masconi KL, Sweeting MJ, Thompson SG, Powell JT, Ulug P, Bown MJet 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.

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Patel R, Powell JT, Sweeting MJ, Epstein DM, Barrett JK, Greenhalgh RMet 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

Journal article

Harrison SC, Holmes MV, Burgess S, Asselbergs FW, Jones GT, Baas AF, van 't Hof FN, de Bakker PIW, Blankensteijn JD, Powell JT, Saratzis A, de Borst GJ, Swerdlow DI, van der Graaf Y, van Rij AM, Carey DJ, Elmore JR, Tromp G, Kuivaniemi H, Sayers RD, Samani NJ, Bown MJ, Humphries SEet 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

Journal article

Powell JT, IMPROVE Trail Investigators, 2017, Comparative clinical effectiveness and cost-effectiveness of an endovascular strategy versus open repair for ruptured abdomina aortic aneurysm: 3-year results of the IMPROVE randomised trial, British Medical Journal, Vol: 359, ISSN: 0959-8138

Objective To assess the three year clinical outcomes and cost effectiveness of a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair for patients with suspected ruptured abdominal aortic aneurysm.Design Randomised controlled trial.Setting 30 vascular centres (29 in UK, one in Canada), 2009-16.Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm, of whom 502 underwent emergency repair for rupture.Interventions 316 patients were randomised to an endovascular strategy (275 with confirmed rupture) and 297 to open repair (261 with confirmed rupture).Main outcome measures Mortality, with reinterventions after aneurysm repair, quality of life, and hospital costs to three years as secondary measures.Results The maximum follow-up for mortality was 7.1 years, with two patients in each group lost to follow-up by three years. After similar mortality by 90 days, in the mid-term (three months to three years) there were fewer deaths in the endovascular than the open repair group (hazard ratio 0.57, 95% confidence interval 0.36 to 0.90), leading to lower mortality at three years (48% v 56%), but by seven years mortality was about 60% in each group (hazard ratio 0.92, 0.75 to 1.13). Results for the 502 patients with repaired ruptures were more pronounced: three year mortality was lower in the endovascular strategy group (42% v 54%; odds ratio 0.62, 0.43 to 0.88), but after seven years there was no clear difference between the groups (hazard ratio 0.86, 0.68 to 1.08). Reintervention rates up to three years were not significantly different between the randomised groups (hazard ratio 1.02, 0.79 to 1.32); the initial rapid rate of reinterventions was followed by a much slower mid-term reintervention rate in both groups. The early higher average quality of life in the endovascular strategy versus open repair group, coupled with the lower mortality at three years, led to a gain in average quality

Journal article

Sweeting MJ, Patel R, Powell JT, Greenhalgh RM, EVAR Trial Investigatorset al., 2017, Endovascular repair of abdominal aortic aneurysm in patients physically ineligible for open repair: very long-term follow-up in the EVAR-2 randomized controlled trial, Annals of Surgery, Vol: 266, Pages: 713-719, ISSN: 0003-4932

OBJECTIVE: The aim of the study was to compare long-term total and aneurysm-related mortality in physically frail patients with abdominal aortic aneurysm (AAA) randomized to either early endovascular aneurysm repair (EVAR) or no-intervention. SUMMARY BACKGROUND DATA: EVAR-2 remains the sole randomized trial to identify whether EVAR reduces mortality in patients physically ineligible for open repair. METHODS: Between September 1999 and August 2004, 404 patients from 33 centers in the United Kingdom aged ≥60 years with AAA >5.5 cm in diameter were randomized 1:1 using computer-generated sequences of randomly permuted blocks stratified by center to receive either EVAR (197) or no-intervention (207). The primary analysis compared total and aneurysm-related deaths in groups until June 30, 2015 (mean, 12.0 yrs; maximum 14.1 yrs). RESULTS: Mean follow-up until death or censoring was 4.2 years. There were 187 deaths (22.6 per 100 person-yrs) in the EVAR group and 194 (22.1 per 100 person-yrs) in the no-intervention group. By 12 years of follow-up the estimated survival was 5.3% [95% confidence interval (CI), 2.6-9.2] in the EVAR group and 8.5% (95% CI, 5.2-12.9) in the no-intervention group; there was no significant difference in life expectancy between the groups (both 4.2 yrs; P = 0.97). However, overall aneurysm-related mortality was significantly lower in the EVAR group [3.3 deaths per 100 person-yrs compared with 6.5 deaths per 100 person-yrs in the no-intervention group, adjusted hazard ratio 0.55 (95% CI, 0.34-0.91; P = 0.019)]. Patients surviving beyond 8 years were younger, with higher body mass index, estimated glomerular filtration rate, and forced expiratory volume in 1 second. CONCLUSIONS: EVAR does not increase overall life expectancy in patients ineligible for open repair, but can reduce aneurysm-related mortality.

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Powell JT, Ulug P, Sweeting MJ, von Allmen RS, Thompson SGet al., 2017, Abdominal aortic aneurysms in women Reply, Lancet, Vol: 390, Pages: 1643-1644, ISSN: 0140-6736

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Powell JT, Ulug P, Response to Kosmas Paraskevas, Lancet, ISSN: 0140-6736

Journal article

Mason AJ, Gomes M, Grieve R, Ulug P, Powell JT, Carpenter Jet al., 2017, Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial, Clinical Trials, Vol: 14, Pages: 357-367, ISSN: 1740-7745

Background/aims: The analyses of randomised controlled trials with missing data typically assume that, after conditioningon the observed data, the probability of missing data does not depend on the patient’s outcome, and so the data are ‘missingat random’ . This assumption is usually implausible, for example, because patients in relatively poor health may be more likelyto drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicitedexpert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrierto implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop anew practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data.Methods: We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategyversus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation,21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L).We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinionabout quality of life differences between patients with missing versus complete data. We show how this expert opinioncan define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing datato depend upon unobserved patient characteristics.Results: A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of lifescores were lower on average for the patients with missing versus complete data, but there was considerable uncertaintyin these

Journal article

Drewe CJ, Parker LP, Kelsey LJ, Norman PE, Powell JT, Doyle BJet al., 2017, Haemodynamics and stresses in abdominal aortic aneurysms: A fluid-structure interaction study into the effect of proximal neck and iliac bifurcation angle, Journal of Biomechanics, Vol: 60, Pages: 150-156, ISSN: 0021-9290

Our knowledge of how geometry influences abdominal aortic aneurysm (AAA) biomechanics is still developing. Both iliac bifurcation angle and proximal neck angle could impact the haemodynamics and stresses within AAA. Recent comparisons of the morphology of ruptured and intact AAA show that cases with large iliac bifurcation angles are less likely to rupture than those with smaller angles. We aimed to perform fluid-structure interaction (FSI) simulations on a range of idealised AAA geometries to conclusively determine the influence of proximal neck and iliac bifurcation angle on AAA wall stress and haemodynamics.Peak wall shear stress (WSS) and time-averaged WSS (TAWSS) in the AAA sac region only increased when the proximal neck angle exceeded 30°. Both peak WSS (p < 0.0001) and peak von Mises wall stress (p = 0.027) increased with iliac bifurcation angle, whereas endothelial cell activation potential (ECAP) decreased with iliac bifurcation angle (p < 0.001) and increased with increasing neck angle.These observations may be important as AAAs have been shown to expand, develop thrombus and rupture in areas of low WSS. Here we show that AAAs with larger iliac bifurcation angles have higher WSS, potentially reducing the likelihood of rupture. Furthermore, ECAP was lower in AAA geometries with larger iliac bifurcation angles, implying less likelihood of thrombus development and wall degeneration. Therefore our findings could help explain the clinical observation of lower rupture rates associated with AAAs with large iliac bifurcation angles.

Journal article

Sidloff DA, Saratzis A, Sweeting MJ, Michaels J, Powell JT, Thompson SG, Bown MJet al., 2017, Sex differences in mortality after abdominal aortic aneurysm repair in the UK., British Journal of Surgery, Vol: 104, Pages: 1656-1664, ISSN: 1365-2168

BACKGROUND: The UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK. METHODS: Anonymized data from the UK National Vascular Registry (NVR) for patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co-variables were extracted for analysis by sex. The primary outcome measure was in-hospital mortality. Secondary outcome measures included mortality by 5-year age groups and duration of hospital stay. Logistic regression was performed to adjust for age, calendar time, AAA diameter and smoking status. NVR-based outcomes were checked against Hospital Episode Statistics (HES) data. RESULTS: A total of 23 245 patients were included (13·0 per cent women). Proportionally, more women than men underwent open repair. For elective open AAA repair, the in-hospital mortality rate was 6·9 per cent in women and 4·0 per cent in men (odds ratio (OR) 1·48, 95 per cent c.i. 1·08 to 2·02; P = 0·014), whereas for elective endovascular AAA repair it was 1·8 per cent in women and 0·7 per cent in men (OR 2·86, 1·72 to 4·74; P < 0·001); the results in HES were similar. For ruptured AAA, there was no sex difference in mortality within the NVR; however, in HES, for ruptured open AAA repair, the in-hospital mortality rate was higher in women (33·6 versus 27·1 per cent; OR 1·36, 1·16 to 1·59; P < 0·001). CONCLUSION: Women have a higher in-hospital mortality rate than men after elective AAA repair even after adjustment. This higher mortality may have an impact on the benefit offered by any screening programme offered

Journal article

Powell JT, 2017, Mapping the workload associated with intact abdominal aortic aneurysm, European Journal of Vascular and Endovascular Surgery, Vol: 53, Pages: 765-765, ISSN: 1078-5884

Journal article

Ulug P, Sweeting MJ, von Allmen RS, Thompson SG, Powell JTet al., 2017, Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis, Lancet, Vol: 389, Pages: 2482-2491, ISSN: 0140-6736

Background: Prognosis for women with abdominal aortic aneurysm might be worse than the prognosis for men. We aimed to systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm using data from study periods after the year 2000.Methods: In these systematic reviews and meta-analysis, we identified studies (randomised, cohort, or cross-sectional) by searching MEDLINE, Embase, CENTRAL, and grey literature published between Jan 1, 2005, and Sept 2, 2016, for two systematic reviews and Jan 1, 2009, and Sept 2, 2016, for one systematic review. Studies were included if they were of both men and women, with data presented for each sex separately, with abdominal aortic aneurysms being assessed for aneurysm repair by either endovascular repair (EVAR) or open repair. We conducted three reviews based on whether studies reported the proportion morphologically suitable (within manufacturers' instructions for use) for EVAR (EVAR suitability review), non-intervention rates (non-intervention review), and 30-day mortality (operative mortality review) after intact aneurysm repair. Studies had to include at least 20 women (for the EVAR suitability review), 20 women (for the non-intervention review), and 50 women (for the operative mortality review). Studies were excluded if they were review articles, editorials, letters, or case reports. For the operative review, studies were also excluded if they only provided hazard ratios or only reported in-hospital mortality. We assessed the quality of the studies using the Newcastle–Ottawa scoring system, and contacted authors for the provision of additional data if needed. We combined results across studies by random-effects meta-analysis. This study is registered with PROSPERO, number CRD42016043227.Findings: Five studies assessed the morphological eligibility for EVAR (1507 men, 400 women). The overall pooled proportion of women eligible (34%) for EVAR was lower

Journal article

Powell JT, 2017, Abdominal Aortic Aneurysm Repair in England and the United States, New England Journal of Medicine, Vol: 376, Pages: 998-998, ISSN: 0028-4793

Journal article

Ulug P, Sweeting MJ, von Allmen RS, Thompson SG, Powell JTet al., Women assessed for intact abdominal aortic aneurysm repair fare worse than men: systematic reviews of morphological suitability for endovascular repair, non-intervention rates and operative mortality, Lancet, ISSN: 1474-547X

Objective: To systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm (AAA) in contemporary data (2000 or later). Methods: Three systematic reviews were undertaken, according to PRISMA guidelines of studies reporting separately for men and women the proportion morphologically suitable (within Manufacturers’ Instructions for Use) for endovascular repair (EVAR), non-intervention rates, and 30-day mortality after intact aneurysm repair. The minimum numbers for studies in each review were based on inclusion of 20, 20 and 50 women, respectively. Studies (randomised, cohort or cross-sectional) were identified by searching MEDLINE, Embase, CENTRAL and other sources until 2nd September 2016 and quality assessed using the Newcastle–Ottawa scoring system. Results were combined across studies by random-effects meta-analysis. The reviews are registered in PROSPERO: CRD42016043227. Results: Five studies evaluated the morphological eligibility for EVAR (1507 men, 400 women). The overall proportion of women eligible for EVAR was much lower than in men, 34% versus 54%, odds ratio 0.44 [95%CI 0.32,0.62]. Four single centre studies reported non-intervention rates (1365 men, 247 women). The overall non-intervention rates were higher in women than men, 34% versus 19%, odds ratio 2.27 [95%CI 1.21,4.23]. The review of 30-day mortality included nine studies (52018 men, 10076 women). The overall estimate for EVAR was higher in women than men: 2.3% versus 1.4%, odds ratio 1.67 [95%CI 1.38,2.04]. The overall estimate for open repair also was higher in women: 5.4% versus 2.8% in men, odds ratio 1.76 [95%CI 1.35,2.30]. Interpretation: A smaller proportion of women are eligible for EVAR, a higher proportion of women are not offered intervention, and operative mortality was much higher in women for both EVAR and open repair. The management of AAA in women needs improvement.

Journal article

Powell JT, Sweeting MJ, Ulug P, Blankensteijn JD, Lederle FA, Becquemin JP, Greenhalgh RMet al., 2017, Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years, British Journal of Surgery, Vol: 104, Pages: 166-178, ISSN: 1365-2168

BackgroundThe erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.MethodsAn individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.ResultsThe analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0–6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.ConclusionThe early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1

Journal article

von Allmen RS, Gahl B, Powell JT, 2016, Editor's choice - Incidence of stroke following thoracic endovascular aortic repair for descending aortic aneurysm: a systematic review of the literature with meta-analysis., European Journal of Vascular and Endovascular Surgery, Vol: 53, Pages: 176-184, ISSN: 1532-2165

OBJECTIVE: Stroke is an increasingly recognised complication following thoracic endovascular aortic repair (TEVAR). The aim of this study was to systematically synthesise the published data on perioperative stroke incidence during TEVAR for patients with descending thoracic aneurysmal disease and to assess the impact of left subclavian artery (LSA) coverage on stroke incidence. METHODS: A systematic review of English and German articles on perioperative (in-hospital or 30 day) stroke incidence following TEVAR for descending aortic aneurysm was performed, including studies with ≥50 cases, using MEDLINE and EMBASE (2005-2015). The pooled prevalence of perioperative stroke with 95% CI was estimated using random effect analysis. Heterogeneity was examined using I(2) statistic. RESULTS: Of 215 studies identified, 10 were considered suitable for inclusion. The included studies enrolled a total of 2594 persons (61% male) between 1997 and 2014 with a mean weighted age of 71.8 (95% CI 71.1-73.6) years. The pooled prevalence for stroke was 4.1% (95% CI 2.9-5.5) with moderate heterogeneity between studies (I(2) = 49.8%, p = .04). Five studies reported stroke incidences stratified by the management of the LSA, that is uncovered versus covered and revascularised versus covered and not-revascularised. In cases where the LSA remained uncovered, the pooled stroke incidence was 3.2% (95% CI 1.0-6.5). There was, however, an indication that stroke incidence increased following LSA coverage, to 5.3% (95% CI 2.6-8.6) in those with a revascularisation and 8.0% (95% CI 4.1-12.9) in those without revascularisation. CONCLUSION: Stroke incidence is an important morbidity after TEVAR, and probably increases if the LSA is covered during the procedure, particularly in those without revascularisation.

Journal article

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