Imperial College London

DrPinarUlug

Faculty of MedicineDepartment of Surgery & Cancer

Trial Manager
 
 
 
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Contact

 

+44 (0)20 3311 7307p.ulug Website

 
 
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Location

 

North Wing - 4N12Charing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
to

36 results found

Machin M, Ulug P, Pandirajan K, Bown MJ, Powell JTet al., 2021, Towards a Core Outcome Set for Abdominal Aortic Aneurysm: Systematic Review of Outcomes Reported Following Intact and Ruptured Abdominal Aortic Aneurysm Repair, Journal of Vascular Surgery, Vol: 74, Pages: 338-339, ISSN: 0741-5214

Journal article

Machin M, Ulug P, Pandirajan K, Bown M, Powell Jet al., 2021, Towards a core outcome set for abdominal aortic aneurysm: systematic review of outcomes reported following intact and ruptured abdominal aortic aneurysm repair, European Journal of Vascular and Endovascular Surgery, Vol: 61, Pages: 909-918, ISSN: 1078-5884

Objective:To encompass the needs of all stakeholders and allow effective data synthesis from trials, registries, and other studies; a core outcome set for infrarenal abdominal aortic aneurysm (AAA) repair is needed. In this first stage, the aim was to report the range, frequency, and time of pre-specified outcomes reported following AAA repair.Data Sources:Medline, Embase, and CENTRAL databases 2010 – 2019 were searched using ProQuest Dialog™.Review Methods:The systematic review was reported to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), PROSPERO registration CRD42019130119. Outcomes were coded using Core Outcome Measures in Effectiveness Trials (COMET) taxonomy and presented separately for intact and rupture repairs, endovascular aneurysm repair (EVAR) and open repair, and time from repair (acute < 90 days vs. ≥ 1 year) (COMET Initiative 1582).Results:For intact AAA and rupture repair, a total of 231 and 70 reports with 589 255 and 177 465 patients respectively were included: only 98 and 19 respectively provided ≥ 1 year outcomes. Most studies were retrospective, with 13 randomised trials of intact AAA repair and five randomised trials of ruptured AAA repair. For intact AAA, the most common pre-specified COMET taxonomy outcomes were mortality (181), vascular complications (137), and re-intervention (52). EVAR studies dominated the vascular outcomes in acute and later time periods: excluding 47 reports from device registries, reduced vascular outcomes to 83. For ruptured AAA, the three most common outcomes were mortality (64), vascular (11), and hospital stay (10). The range of outcomes reported was wide with functioning outcomes reported from most randomised trials but few retrospective studies.Conclusion:This review identifies the paucity of long term data and the disproportionate attention paid to vascular complications vs. patient functioning outcomes, this skew being accentuated by reporting from

Journal article

Ulug P, Powell JT, 2020, Clinical trial reporting, LANCET, Vol: 396, Pages: 1489-1489, ISSN: 0140-6736

Journal article

Ulug P, Powell JT, Martinez MA-M, Ballard DJ, Filardo Get 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

Journal article

Ulug P, Powell J, Warschkow R, Von Allmen RSet 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.

Journal article

Grootes I, Barrett JK, Ulug P, Rohlffs FEV, Laukontaus SJ, Tulamo R, Venermo M, Greenhalgh RM, Sweeting MJet al., 2018, Predicting risk of rupture and rupture-preventing re-interventions utilising repeated measures on aneurysm sac diameter following endovascular abdominal aortic aneurysm repair, British Journal of Surgery, Vol: 105, Pages: 1294-1304, ISSN: 1365-2168

BackgroundClinical and imaging surveillance practices following endovascular aneurysm repair (EVAR) for intact abdominal aortic aneurysm (AAA) vary considerably and compliance with recommended lifelong surveillance is poor. The aim of this study was to develop a dynamic prognostic model to enable stratification of patients at risk of future secondary aortic rupture or the need for intervention to prevent rupture (rupture‐preventing reintervention) to enable the development of personalized surveillance intervals.MethodsBaseline data and repeat measurements of postoperative aneurysm sac diameter from the EVAR‐1 and EVAR‐2 trials were used to develop the model, with external validation in a cohort from a single‐centre vascular database. Longitudinal mixed‐effects models were fitted to trajectories of sac diameter, and model‐predicted sac diameter and rate of growth were used in prognostic Cox proportional hazards models.ResultsSome 785 patients from the EVAR trials were included, of whom 155 (19·7 per cent) experienced at least one rupture or required a rupture‐preventing reintervention during follow‐up. An increased risk was associated with preoperative AAA size, rate of sac growth and the number of previously detected complications. A prognostic model using predicted sac growth alone had good discrimination at 2 years (C‐index 0·68), 3 years (C‐index 0·72) and 5 years (C‐index 0·75) after operation and had excellent external validation (C‐index 0·76–0·79). More than 5 years after operation, growth rates above 1 mm/year had a sensitivity of over 80 per cent and specificity over 50 per cent in identifying events occurring within 2 years.ConclusionSecondary sac growth is an important predictor of rupture or rupture‐preventing reintervention to enable the development of personalized surveillance intervals. A dynamic prognostic model has the potential to tailor surveillance by identi

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

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.

Journal article

Sweeting MJ, Ulug P, Roy J, Hultgren R, Indrakusuma R, Balm R, Thompson MM, Hinchliffe RJ, Thompson SG, Powell JTet al., 2018, Value of risk scores in the decision to palliate patients with ruptured abdominal aortic aneurysm, BRITISH JOURNAL OF SURGERY, Vol: 105, Pages: 1135-1144, ISSN: 0007-1323

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.

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

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

Journal article

Powell JT, Ulug P, 2017, 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

Wang J, Dumartin L, Mafficini A, Ulug P, Sangaralingam A, Alamiry NA, Radon TP, Salvia R, Lawlor RT, Lemoine NR, Scarpa A, Chelala C, Crnogorac-Jurcevic Tet al., 2017, Splice variants as novel targets in pancreatic ductal adenocarcinoma, Scientific Reports, Vol: 7, ISSN: 2045-2322

Despite a wealth of genomic information, a comprehensive alternative splicing (AS) analysis of pancreatic ductal adenocarcinoma (PDAC) has not been performed yet. In the present study, we assessed whole exome-based transcriptome and AS profiles of 43 pancreas tissues using Affymetrix exon array. The AS analysis of PDAC indicated on average two AS probe-sets (ranging from 1–28) in 1,354 significantly identified protein-coding genes, with skipped exon and alternative first exon being the most frequently utilised. In addition to overrepresented extracellular matrix (ECM)-receptor interaction and focal adhesion that were also seen in transcriptome differential expression (DE) analysis, Fc gamma receptor-mediated phagocytosis and axon guidance AS genes were also highly represented. Of note, the highest numbers of AS probe-sets were found in collagen genes, which encode the characteristically abundant stroma seen in PDAC. We also describe a set of 37 ‘hypersensitive’ genes which were frequently targeted by somatic mutations, copy number alterations, DE and AS, indicating their propensity for multidimensional regulation. We provide the most comprehensive overview of the AS landscape in PDAC with underlying changes in the spliceosomal machinery. We also collate a set of AS and DE genes encoding cell surface proteins, which present promising diagnostic and therapeutic targets in PDAC.

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, 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

Ulug P, Powell J, Sweeting MJ, Bown MJ, Thompson SGet al., 2016, Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women, British Journal of Surgery, Vol: 103, Pages: 1097-1104, ISSN: 1365-2168

BackgroundAlthough women represent an increasing proportion of those presenting with abdominal aortic aneurysm (AAA) rupture, the current prevalence of AAA in women is unknown. The contemporary population prevalence of screen-detected AAA in women was investigated by both age and smoking status.MethodsA systematic review was undertaken of studies screening for AAA, including over 1000 women, aged at least 60 years, done since the year 2000. Studies were identified by searching MEDLINE, Embase and CENTRAL databases until 13 January 2016. Study quality was assessed using the Newcastle–Ottawa scoring system.ResultsEight studies were identified, including only three based on population registers. The largest studies were based on self-purchase of screening. Altogether 1 537 633 women were screened. Overall AAA prevalence rates were very heterogeneous, ranging from 0·37 to 1·53 per cent: pooled prevalence 0·74 (95 per cent c.i. 0·53 to 1·03) per cent. The pooled prevalence increased with both age (more than 1 per cent for women aged over 70 years) and smoking (more than 1 per cent for ever smokers and over 2 per cent in current smokers).ConclusionThe current population prevalence of screen-detected AAA in older women is subject to wide demographic variation. However, in ever smokers and those over 70 years of age, the prevalence is over 1 per cent.

Journal article

Powell JT, Ulug P, 2015, PATIENTS AND TRIAL ENROLMENT DECISIONS Flexibility in trial enrolment decisions, BMJ, Vol: 351, ISSN: 1756-1833

Journal article

Sweeting MJ, Balm R, Desgranges P, Ulug P, Powell JT, Ruptured Aneurysm Trialistset al., 2015, Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm, British Journal of Surgery, Vol: 102, Pages: 1229-1239, ISSN: 1365-2168

BACKGROUND: The benefits of endovascular repair of ruptured abdominal aortic aneurysm remain controversial, without any strong evidence about advantages in specific subgroups. METHODS: An individual-patient data meta-analysis of three recent randomized trials of endovascular versus open repair of abdominal aortic aneurysm was conducted according to a prespecified analysis plan, reporting on results to 90 days after the index event. RESULTS: The trials included a total of 836 patients. The mortality rate across the three trials was 31·3 per cent for patients randomized to endovascular repair/strategy and 34·0 per cent for those randomized to open repair at 30 days (pooled odds ratio 0·88, 95 per cent c.i. 0·66 to 1·18), and 34·3 and 38·0 per cent respectively at 90 days (pooled odds ratio 0·85, 0·64 to 1·13). There was no evidence of significant heterogeneity in the odds ratios between trials. Mean(s.d.) aneurysm diameter was 8·2(1·9) cm and the overall in-hospital mortality rate was 34·8 per cent. There was no significant effect modification with age or Hardman index, but there was indication of an early benefit from an endovascular strategy for women. Discharge from the primary hospital was faster after endovascular repair (hazard ratio 1·24, 95 per cent c.i. 1·04 to 1·47). For open repair, 30-day mortality diminished with increasing aneurysm neck length (adjusted odds ratio 0·69 (95 per cent c.i. 0·53 to 0·89) per 15 mm), but aortic diameter was not associated with mortality for either type of repair. CONCLUSION: Survival to 90 days following an endovascular or open repair strategy is similar for all patients and for the restricted population anatomically suitable for endovascular repair. Women may benefit more from an endovascular strategy than men and patients are, on average, discharged sooner after endovascular repair.

Journal article

Sweeting MJ, Ulug P, Powell JT, Desgranges P, Balm R, Ruptured Aneurysm Trialistset al., 2015, Ruptured aneurysm trials: The importance of longer-term outcomes and meta-analysis for 1-year mortality., European Journal of Vascular and Endovascular Surgery, Vol: 50, Pages: 297-302, ISSN: 1532-2165

OBJECTIVE: To assess current knowledge for the management of ruptured abdominal aortic aneurysm (AAA), based on the 1-year outcomes of 3 recent randomised trials. METHODS: An individual patient data meta-analysis of three recent randomised trials of endovascular versus open repair, including 817 patients, was conducted according to a pre-specified analysis plan, report all-cause mortality and re-interventions at 1 year after the index event. RESULTS: Mortality across the 3 trials at 1-year was 38.6% for the EVAR or endovascular strategy patient groups and 42.8% for the open repair groups, pooled odds ratio 0.84 (95% CI 0.63-1.11), p = .209. There was no evidence of heterogeneity in the odds ratios between trials. When the patients in the endovascular strategy group of the IMPROVE trial were restricted to those with proven rupture who were anatomically suitable for endovascular repair, the pooled odds ratio reduced slightly to 0.80 (95% CI 0.56-1.16), p = .240. CONCLUSIONS: After 1 year there is a consistent but non-significant trend for lower mortality for EVAR or an endovascular strategy. Taken together with the recent gains in health economic outcomes demonstrated at 1 year in the IMPROVE trial, the evidence suggests that endovascular repair should be used more widely for ruptured aneurysms.

Journal article

Grieve R, Gomes M, Sweeting MJ, Ulug P, Hinchliffe RJ, Thompson MM, Thompson SG, Ashleigh R, Greenhalgh RM, Powell JT, IMPROVE trial investigatorset al., 2015, Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial., European Heart Journal, Vol: 36, Pages: 2061-2069, ISSN: 1522-9645

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791.

Journal article

Powell JT, Sweeting MJ, Thompson MM, Hinchliffe RJ, Ashleigh R, Bell R, Greenhalgh RM, Thompson SG, Ulug Pet al., 2015, The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm, European Heart Journal, Vol: 36, Pages: 1328-U137, ISSN: 1522-9645

The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality,proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigatedin rAAA patients randomized before morphological assessment in the Immediate Management of the Patient withRupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwentrepair and had their admission computerized tomography scan submitted to the core laboratory, were included.Among 458 patients (364 men, mean age 76 years), who had either EVAR (n ¼ 177) or open repair (n ¼ 281) started,there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specifiedplan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphologicalvariables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length(mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameterswith reinterventions.

Journal article

Powell JT, Hinchliffe RJ, Thompson MM, Sweeting MJ, Ashleigh R, Bell R, Gomes M, Greenhalgh RM, Grieve RJ, Heatley F, Thompson SG, Ulug Pet al., 2014, An Endovascular Strategy for Suspected Ruptured Abdominal Aortic Aneurysm Brings Earlier Home Discharge but Not Early Survival or Cost Benefits, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 47, Pages: 333-334, ISSN: 1078-5884

Journal article

Powell JT, Hinchliffe RJ, Thompson MM, Sweeting MJ, Ashleigh R, Bell R, Gomes M, Greenhalgh RM, Grieve RJ, Heatley F, Thompson SG, Ulug Pet al., 2014, Observations from the IMPROVE trial concerning the clinical care of patients with ruptured abdominal aortic aneurysm, British Journal of Surgery, Vol: 101, Pages: 216-224, ISSN: 1365-2168

Background: Single-centre series of the management of patients with ruptured abdominal aorticaneurysm (AAA) are usually too small to identify clinical factors that could improve patient outcomes.Methods: IMPROVE is a pragmatic, multicentre randomized clinical trial in which eligible patients witha clinical diagnosis of ruptured aneurysm were allocated to a strategy of endovascular aneurysm repair(EVAR) or to open repair. The influences of time and manner of hospital presentation, fluid volumestatus, type of anaesthesia, type of endovascular repair and time to aneurysm repair on 30-day mortalitywere investigated according to a prespecified plan, for the subgroup of patients with a proven diagnosisof ruptured or symptomatic AAA. Adjustment was made for potential confounding factors.Results: Some 558 of 613 randomized patients had a symptomatic or ruptured aneurysm: diagnosticaccuracy was 91·0 per cent. Patients randomized outside routine working hours had higher operativemortality (adjusted odds ratio (OR) 1·47, 95 per cent confidence interval 1·00 to 2·17). Mortality ratesafter primary and secondary presentation were similar. Lowest systolic blood pressure was stronglyand independently associated with 30-day mortality (51 per cent among those with pressure below 70mmHg). Patients who received EVAR under local anaesthesia alone had greatly reduced 30-day mortalitycompared with those who had general anaesthesia (adjusted OR 0·27, 0·10 to 0·70).Conclusion: These findings suggest that the outcome of ruptured AAA might be improved by wider useof local anaesthesia for EVAR and that a minimum blood pressure of 70 mmHg is too low a thresholdfor permissive hypotension.

Journal article

Powell JT, Sweeting MJ, Thompson MM, Ashleigh R, Bell R, Gomes M, Greenhalgh RM, Grieve R, Heatley F, Hinchliffe RJ, Thompson SG, Ulug Pet al., 2014, Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial, British Medical Journal, Vol: 348, Pages: 1-12, ISSN: 1468-5833

Objective To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm.Design Randomised controlled trial.Setting 30 vascular centres (29 UK, 1 Canadian), 2009-13.Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm.Interventions 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures).Main outcome measures 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes.Results 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval −£625 to £2997).Conclusions A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women.

Journal article

Hinchliffe RJ, Ribbons T, Ulug P, Powell JTet al., 2013, Transfer of patients with ruptured abdominal aortic aneurysm from general hospitals to specialist vascular centres: results of a Delphi consensus study, EMERGENCY MEDICINE JOURNAL, Vol: 30, Pages: 483-486, ISSN: 1472-0205

Journal article

Ulug P, McCaslin JE, Stansby G, Powell JTet al., 2012, Endovascular versus conventional medical treatment for uncomplicated chronic type B aortic dissection, COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSN: 1469-493X

Journal article

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