Search

Background: A number of published economic evaluations of elective endovascular aneurysm repair (EVAR) versus open repair for abdominal aortic aneurysm (AAA) have come to differing conclusions about whether EVAR is cost-effective. This paper reviews the current evidence base and presents up-to-date cost-effectiveness analyses in the light of results of four randomized clinical trials: EVAR-1, DREAM, OVER and ACE., Methods: Markov models were used to estimate lifetime costs from a UK perspective and quality-adjusted life-years (QALYs) based on the results of each of the four trials. The outcomes included in the model were: procedure costs, surveillance costs, reintervention costs, health-related quality of life, aneurysm-related mortality and other-cause mortality. Alternative scenarios about complications, reinterventions and deaths beyond the trial were explored., Results: Models based on the results of the EVAR-1, DREAM or ACE trials did not find EVAR to be cost-effective at thresholds used in the UK (up to £30,000 per QALY). EVAR seemed cost-effective according to models based on the OVER trial. These results seemed robust to alternative model scenarios about events beyond the trial intervals., Conclusion: These analyses did not find that EVAR is cost-effective compared with open repair in the long term in trials conducted in European centres. EVAR did appear to be cost-effective based on the OVER trial, conducted in the USA. Caution must be exercised when transferring the results of economic evaluations from one country to another., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Background: Surveillance is a common management strategy for small abdominal aortic aneurysm (AAA) (3.0-5.4 cm in diameter). Individual characteristics, other than diameter, may influence aneurysm growth or rupture rates., Methods: Individual data were collated from 15 475 people under follow-up for a small aneurysm in 18 studies. The influence of co-variables (including demographics, medical and drug history) on aneurysm growth and rupture rates (analysed using longitudinal random-effects modelling and survival analysis with adjustment for aneurysm diameter) were summarized in an individual patient meta-analysis., Results: The mean aneurysm growth rate of 2.21 mm/year was independent of age and sex. Growth rate was increased in smokers (by 0.35 mm/year) and decreased in patients with diabetes (by 0.51 mm/year). Mean arterial pressure had no effect and antihypertensive or other cardioprotective medications had only small, non-significant effects on aneurysm growth, consistent with the observation that calendar year of enrollment was not associated with growth rate. Rupture rates were almost fourfold higher in women than men (P < 0.001), were double in current smokers (P = 0.001) and increased with higher blood pressure (P = 0.001)., Conclusion: Follow-up schedules for individuals with a small AAA may need to consider diabetes and smoking, in addition to aneurysm diameter. The differing risk factors for growth and rupture suggest that a lower threshold for surgical intervention in women may be justified. No single drug used for cardiovascular risk reduction had a major effect on the growth or rupture of small aneurysms., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: The aim was to compare rates of myocardial infarction, stroke and cardiovascular death in patients with a large abdominal aortic aneurysm who had endovascular (EVAR) or open repair to determine whether cardiovascular mortality explains the convergence in survival curves after these procedures., Methods: Between 1999 and 2004, 1252 patients were randomized to EVAR or open repair in the UK EVAR trial 1. All patients were followed for death, myocardial infarction or stroke until September 2009. Cox regression was used to compare cardiovascular events and deaths between the randomized groups during different time intervals., Results: Over 5 years of follow-up, a total of 187 first non-fatal or fatal cardiovascular events (98 myocardial infarctions and 89 strokes) and 256 cardiovascular deaths occurred. Although the endovascular group had a lower cardiovascular event rate than the open repair group (2·6 versus 3·2 per 100 person-years respectively) this was not statistically significant (adjusted hazard ratio (HR) 0·83, 95 per cent confidence interval 0·62 to 1·10; P = 0·199). Overall, there was little difference in cardiovascular mortality between the randomized groups (adjusted HR 1·06, 0·83 to 1·36; P = 0·638), but a non-significant excess of cardiovascular deaths was apparent in the endovascular group during the 6-24-month interval (adjusted HR 1·44, 0·79 to 2·62; P = 0·237)., Conclusion: Patients who had EVAR appeared to have a lower subsequent cardiovascular event rate during all time intervals. Cardiovascular mortality was similar between the two groups overall, but more cardiovascular deaths in the EVAR group appeared to contribute to the convergence in all-cause mortality during the first 2 years., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Small abdominal aortic aneurysms are usually asymptomatic and managed safely in ultrasound surveillance programmes until they grow to a diameter threshold where intervention is considered. The aim of this study was to synthesize systematically the published data on growth rates for small aneurysms to investigate the evidence basis for surveillance intervals., Methods: This was a systematic review of the literature published before January 2010, which identified 61 potentially eligible reports. Detailed review yielded 15 studies providing growth rates for aneurysms 3·0-5·5 cm in diameter (14 in millimetres per year, 1 as percentage change per year). These studies included 7630 people (predominantly men) enrolled during 1976-2005., Results: The pooled mean growth rate was 2·32 (95 per cent confidence interval 1·95 to 2·70) mm/year but there was very high heterogeneity between studies; the growth rate ranged from - 0·33 to + 3·95 mm/year. Six studies reported growth rates by 5-mm diameter bands, which showed the trend for growth rate to increase with aneurysm diameter. Simple methods to determine growth rate were associated with higher estimates. Meta-regression analysis showed that a 10-mm increase in aneurysm diameter was associated with a mean(s.e.m.) 1·62(0·20) mm/year increase in growth rate. Neither mean age nor percentage of women in each study had a significant effect. On average, a 3·5-cm aneurysm would take 6·2 years to reach 5·5 cm, whereas a 4·5-cm aneurysm would take only 2·3 years., Conclusion: There was considerable variation in the reported growth rates of small aneurysms beyond that explained by aneurysm diameter. Fuller evidence on which to base surveillance intervals for patients in screening programmes requires a meta-analysis based on individual patient data., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: It is uncertain which baseline factors are associated with graft-related complications and reinterventions after endovascular aneurysm repair (EVAR) in patients with a large abdominal aortic aneurysm., Methods: Patients randomized to elective EVAR in EVAR Trial 1 or 2 were followed for serious graft-related complications (type 2 endoleaks excluded) and reinterventions. Cox regression analysis was used to investigate whether any prespecified baseline factors were associated with time to first serious complication or reintervention., Results: A total of 756 patients who had elective EVAR were followed for a mean of 3.7 years, by which time there were 179 serious graft complications (rate 6.5 per 100 person years) and 114 reinterventions (rate 3.8 per 100 person years). The highest rate was during the first 6 months, with an apparent increase again after 2 years. Multivariable analysis indicated that graft-related complications increased significantly with larger initial aneurysm diameter (P < 0.001) and older age (P = 0.040). There was also evidence that patients with larger common iliac diameters experienced higher complication rates (P = 0.011)., Conclusion: Graft-related complication and reintervention rates were common after EVAR in patients with a large aneurysm. Younger patients and those with aneurysms closer to the 5.5-cm threshold for intervention experienced lower rates., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) are both associated with excellent technical, clinical and patient-reported outcomes for the treatment of varicose veins. The aim of this study was to compare the techniques in a randomized clinical trial., Methods: Consecutive patients with primary great saphenous vein reflux were randomized to EVLA (980 nm) or RFA (VNUS ClosureFAST) at a single centre. The primary outcome measure was postprocedural pain after 3 days. Secondary outcome measures were quality of life at 6 weeks, determined by the Aberdeen Varicose Vein Questionnaire (AVVQ) and Short Form 12 (SF-12), and clinical improvement assessed by the Venous Clinical Severity Score (VCSS). Analyses were performed on the basis of intention to treat using multivariable linear regression., Results: Some 131 patients were randomized to EVLA (64 patients) or RFA (67). Mean(s.d.) pain scores over 3 days were 26.4(22.1) mm for RFA and 36.8(22.5) mm for EVLA (P = 0.010). Over 10 days, mean(s.d.) pain scores were 22.0(19.8) mm versus 34.3(21.1) mm for RFA and EVLA respectively (P = 0.001). The mean(s.d.) number of analgesic tablets used was lower for RFA than for EVLA over 3 days (8.8(9.5) versus 14.2(10.7); P = 0.003) and 10 days (20.4(22.6) versus 35.9(29.4) respectively; P = 0.001). Changes in AVVQ, SF-12 and VCSS scores at 6 weeks were similar in the two groups: AVVQ (P = 0.887), VCSS (P = 0.993), SF-12 physical component score (P = 0.276) and mental component score (P = 0.449)., Conclusion: RFA using VNUS ClosureFAST was associated with less postprocedural pain than EVLA. However, clinical and quality-of-life improvements were similar after 6 weeks for the two treatments.

Background: Recent randomized trials have shown that endovascular abdominal aortic aneurysm repair (EVAR) has a 3 per cent aneurysm-related survival benefit in patients fit for open surgery, but it also has uncertain long-term outcomes and higher costs. This study assessed the cost-effectiveness of EVAR., Methods: A decision model was constructed to estimate the lifetime costs and quality-adjusted life years (QALYs) with EVAR and open repair in men aged 74 years. The model includes the risks of death from aneurysm, other cardiovascular and non-cardiovascular causes, secondary reinterventions and non-fatal cardiovascular events. Data were taken largely from the EVAR trial 1 and supplemented from other sources., Results: Under the base-case (primary) assumptions, EVAR cost 3800 pounds sterling (95 per cent confidence interval (c.i.) 2400 pounds sterling to 5200 pounds sterling) more per patient than open repair but produced fewer lifetime QALYs (mean -0.020 (95 per cent c.i. -0.189 to 0.165)). These results were sensitive to alternative model assumptions., Conclusion: EVAR is unlikely to be cost-effective on the basis of existing devices, costs and evidence, but there remains considerable uncertainty., (2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: The aim was to use a validated fitness score to determine whether fitter patients with a large abdominal aortic aneurysm (AAA) benefited from having open rather than endovascular repair., Methods: The Customized Probability Index (CPI) was applied to patients in the Endovascular Aneurysm Repair (EVAR) I and II trials. Interaction tests between CPI and randomized group assessed the effect of fitness and type of AAA repair on elective 30-day mortality and 4-year survival., Results: The mean(s.d.) CPI scores were 3.6(9.3) for 1252 EVAR I patients and 10.0(11.3) for 404 EVAR II patients (range - 25 to + 43) (P < 0.001). The fitness of EVAR I patients was classified as good (579 patients, mean CPI - 4.2), moderate (331 patients, mean CPI 5.7) or poor (338 patients, mean CPI 15.1). Only in the good fitness group did 30-day mortality convincingly favour endovascular repair (odds ratio 0.24, P = 0.030), but overall the test of interaction was not significant (P = 0.363). For 4-year all-cause and aneurysm-related mortality, there was no benefit for either treatment across all fitness scores (P = 0.281 and P = 0.371 respectively)., Conclusion: The benefit of endovascular repair was most convincing in the fittest patients. There was no evidence that the fittest patients benefited more from open surgery., ((c) 2007 British Journal of Surgery Society Ltd.)

Background: The aim was to determine whether early open surgical repair would benefit patients with small abdominal aortic aneurysm compared with surveillance on long-term follow-up., Methods: The 1090 patients who were enrolled into the UK Small Aneurysm Trial between 1991 and 1995 were followed up for aneurysm repair and mortality until November 2005., Results: By November 2005, 714 patients (65.5 per cent) had died, 929 (85.2 per cent) had undergone aneurysm repair, 150 (13.8 per cent) had died without aneurysm repair and 11 (1.0 per cent) remained alive without aneurysm repair. After 12 years, mortality in the surgery and surveillance groups was 63.9 and 67.3 per cent respectively, unadjusted hazard ratio 0.90 (P = 0.139). Three-quarters of the surveillance group eventually had aneurysm repair, with a 30-day elective mortality of 6.3 per cent (versus 5.0 per cent in the early surgery group, P = 0.366). Estimates suggested that the cost of treatment was 17 per cent higher in the early surgery group, with a mean difference of 1326 pounds. The death rate in these patients was about twice that in the population matched for age and sex., Conclusion: There was no long-term survival benefit of early elective open repair of small abdominal aortic aneurysms. Even after successful aneurysm repair, the mortality among these patients was higher than in the general population., ((c) 2007 British Journal of Surgery Society Ltd.)

Context: Denileukin diftitox is a recombinant novel fusion protein of diphtheria toxin and the ligand-binding domain of human IL-2. Denileukin diftitox binds to the high-affinity IL-2 receptor on the cell surface, and it is internalized by endocytosis and enzymatically cleaved. The cytotoxic A-fragment of the toxin inhibits protein synthesis and causes cell death., Objective: The objective of this study was to recognize thyrotoxicosis in association with denileukin diftitox therapy., Design: This study was a retrospective case series., Setting: The setting of this study was a comprehensive cancer center., Patients: Eight mycosis fungoides patients who were receiving 9 or 18 microg/kg.d iv denileukin diftitox for 5 d every 3 wk were identified with thyrotoxicosis., Intervention(s): Thyroid testing was performed. Hypothyroidism after thyrotoxicosis was treated., Results: In eight mycosis fungoides patients who developed transient thyrotoxicosis during therapy, thyroid function tests were normal before onset of therapy. Clinical thyrotoxicosis developed within days of the first cycle of denileukin diftitox therapy in four patients and after the second cycle in the other four patients. Symptoms included tremors, nervousness, tachycardia, diarrhea, and weight loss. After cessation of denileukin diftitox, thyrotoxicosis resolved in all patients; two became euthyroid, and five became hypothyroid, requiring levothyroxine therapy. One patient was lost to follow-up., Conclusions: Monitoring thyroid function before and during treatment with denileukin diftitox is recommended. Symptomatic thyrotoxicosis may be missed due to other acute reactions to the drug, and subsequent hypothyroidism may develop.

Background: The elastinolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage. Cystatin C, an inhibitor of these enzymes, is expressed in arterial smooth muscle cells; an imbalance in cystatin C has been implicated in the aortic wall degeneration observed in abdominal aortic aneurysms (AAAs). The aim of the study was to investigate the impact of a polymorphism in the signal peptide of the cystatin C gene on the growth of small AAAs., Methods: Some 424 patients with a small AAA (4.0-5.5 cm) were monitored for AAA growth by ultrasonography and provided a DNA sample for analysis of the + 148 G > A polymorphism in the cystatin C signal peptide and the-82 G > C polymorphism in the gene promoter. The median length of follow-up was 2.8 years and AAA growth rates were calculated by linear regression analysis., Results: For patients of + 148 GG (n = 263), GA (n = 147) and AA (n = 20) genotypes, the mean(s.d.) AAA growth rates were 0.37(0.29), 0.37(0.23) and 0.30(0.26) cm, and initial diameters were 4.58(0.35), 4.58(0.35) and 4.62(0.36) cm, respectively. Patients of + 148 AA genotype had a slower aneurysm growth rate (unadjusted P = 0.058; after adjustment for age, sex, initial AAA diameter and smoking, P = 0.027). There also was a trend for the rare homozygotes of the-82 C allele to have slower AAA growth (adjusted P = 0.055). Smoking history had a stronger association with aneurysm growth (P = 0.003)., Conclusion: There was a weak association between variation in the cystatin C gene and AAA growth. Medical strategies to limit AAA growth might include the inhibition of cysteine proteases., (Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method has been developed for the analysis of 4,4'-diaminodiphenylmethane (DDM), 3-ethyl DDM (EDDM), and 3,3'-diethyl DDM (DEDDM) in urine. The method has been applied to the analysis of urine samples from workers exposed to a mixture of all three compounds, and the analysis has shown that EDDM and DEDDM are excreted in urine. We have also shown that there are two classes of conjugates present in urine. EDDM and DEDDM are excreted as heat labile conjugates, while DDM and EDDM are excreted, at least in part, as heat stable but alkaline hydrolyzable conjugates. It is proposed that the method described here could be used for biological monitoring of workers exposed to mixtures of DDM, EDDM, and DEDDM.