Cost-effectiveness analysis of a randomized clinical trial of early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration.

BACKGROUND: Treatment of superficial venous reflux in addition to compression therapy accelerates venous leg ulcer healing and reduces ulcer recurrence. The aim of this study was to evaluate the costs and cost-effectiveness of early versus delayed endovenous treatment of patients with venous leg ulcers. METHODS: This was a within-trial cost-utility analysis with a 1-year time horizon using data from the EVRA (Early Venous Reflux Ablation) trial. The study compared early versus deferred endovenous ablation for superficial venous truncal reflux in patients with a venous leg ulcer. The outcome measure was the cost per quality-adjusted life-year (QALY) over 1 year. Sensitivity analyses were conducted with alternative methods of handling missing data, alternative preference weights for health-related quality of life, and per protocol. RESULTS: After early intervention, the mean(s.e.m.) cost was higher (difference in cost per patient £163(318) (€184(358))) and early intervention was associated with more QALYs at 1 year (mean(s.e.m.) difference 0·041(0·017)). The incremental cost-effectiveness ratio (ICER) was £3976 (€4482) per QALY. There was an 89 per cent probability that early venous intervention is cost-effective at a threshold of £20 000 (€22 546)/QALY. Sensitivity analyses produced similar results, confirming that early treatment of superficial reflux is highly likely to be cost-effective. CONCLUSION: Early treatment of superficial reflux is highly likely to be cost-effective in patients with venous leg ulcers over 1 year. Registration number: ISRCTN02335796 (http://www.isrctn.com).

Truncal varicose vein diameter and patient-reported outcome measures.

BACKGROUND: Varicose veins and chronic venous disease are common, and some funding bodies ration treatment based on a minimum diameter of the incompetent truncal vein. This study assessed the effect of maximum vein diameter on clinical status and patient symptoms. METHODS: A prospective observational cohort study of patients presenting with symptomatic varicose veins to a tertiary referral public hospital vascular clinic between January 2011 and July 2012. Patients underwent standardized assessment with venous duplex ultrasonography, and completed questionnaires assessing quality of life (QoL) and symptoms (Aberdeen Varicose Vein Questionnaire, EuroQol Five Domain QoL assessment and EuroQol visual analogue scale). Clinical scores (Venous Clinical Severity Score (VCSS) and Clinical Etiologic Anatomic Pathophysiologic (CEAP) class) were also calculated. Regression analysis was used to investigate the relationship between QoL, symptoms and vein diameter. RESULTS: Some 330 patients were assessed before surgery. The median maximum vein diameter was 7·0 (i.q.r. 5·3-9·2) mm overall, 7·9 (6·0-9·8) mm for great saphenous vein and 6·0 (5·2-8·9) mm for small saphenous vein. In linear regression analysis, vein diameter was shown to have a significant association with VCSS (P = 0·041). For every 1-mm increase in vein diameter, there was a 2·75-fold increase in risk of being in CEAP class C4 compared with C2. No other QoL or symptom measures were related to vein diameter. CONCLUSION: Incompetent truncal vein diameter was associated with increasing VCSS, but not a variety of other varicose vein disease-specific and generic patient-reported outcome measures.

Graduated Compression Stockings as an Adjunct to Low Dose Low Molecular Weight Heparin in Venous Thromboembolism Prevention in Surgery: A Multicentre Randomised Controlled Trial.

BACKGROUND: The evidence base upon which current global venous thromboembolism (VTE) prevention recommendations have been made is not optimal. The cost of purchasing and applying graduated compression stockings (GCS) in surgical patients is considerable and has been estimated at £63.1 million per year in England alone. OBJECTIVE: The aim was to determine whether low dose low molecular weight heparin (LMWH) alone is non-inferior to a combination of GCS and low dose LMWH for the prevention of VTE. METHODS: The randomised controlled Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Trial (ISRCTN 13911492) will randomise adult elective surgical patients identified as being at moderate and high risk of VTE to receive either the current "standard" combined thromboprophylactic LMWH with GCS mechanical thromboprophylaxis, or thromboprophylactic LMWH pharmacoprophylaxis alone. To show non-inferiority (3.5% non-inferiority margin) for the primary endpoint of all VTE within 90 days, 2236 patients are required. Recruitment will be from seven UK centres. Secondary outcomes include quality of life, compliance with stockings and LMWH, overall mortality, and GCS or LMWH related complications (including bleeding). Recruitment commenced in April 2016 with the seven UK centres coming "on-line" in a staggered fashion. Recruitment will be over a total of 18 months. The GAPS trial is funded by the National Institute for Health Research Health Technology Assessment in the UK (14/140/61).

Incidence and Outcomes of Severe Renal Impairment Following Ruptured Abdominal Aortic Aneurysm Repair.

INTRODUCTION: Acute kidney injury (AKI) following ruptured abdominal aortic aneurysm (rAAA) repair is common and multifactorial. A standard definition of AKI after endovascular repair (EVAR), the Aneurysm Renal Injury Score (ARISe), has been proposed to facilitate standardised reporting and thus improve understanding of this issue. METHODS: Data were collected retrospectively on AKI in a prospectively maintained database of all patients treated for rAAA in a single tertiary referral centre since the availability of routine out of hours emergency EVAR. The ARISe score was used to describe the degree of AKI and factors which correlated with poor renal outcomes were assessed. RESULTS: Two-hundred and five patients were treated between January 2006 and April 2014. Of these, 125 were treated with open repair (OSR) and 80 were treated with EVAR. Severe AKI (defined as ARISe score ≥3) occurred in 36% of patients. After correction for confounders, patients treated with OSR were significantly more likely to develop severe AKI (43% vs. 26%, p = .02). There was no significant difference in preoperative serum creatinine between groups, but increased preoperative serum creatinine was strongly associated with severe AKI postoperatively (p < .001). Age, sex, endograft type, and preoperative CT scanning were not associated with differences in renal outcomes. Clamp position above renal arteries was predictive of severe AKI in patients treated with OSR (p < .01). Patients suffering severe AKI had significantly higher mortality at 30 days and 12 months (28% vs. 5% and 44% vs. 13%, p < .001 for both comparisons). CONCLUSION: Severe AKI is common following successful repair of rAAA. In this large case series of high-risk patients, OSR was associated with significantly higher rates of severe AKI compared with EVAR, despite the increased dose of contrast involved in EVAR and the older age of these patients. In turn, severe AKI was associated with higher mortality rates.

Effect of frailty on short- and mid-term outcomes in vascular surgical patients.

BACKGROUND: Frailty is a multidimensional vulnerability resulting from age-associated decline. The impact of frailty on outcomes was assessed in a cohort of vascular surgical patients. METHODS: The study included patients aged over 65 years with length of hospital stay (LOS) greater than 2 days, who were admitted to a tertiary vascular unit over a single calendar year. Demographics, mode of admission, diagnosis, mortality, LOS and discharge destination were recorded, as well as a variety of frailty-specific characteristics. The impact of frailty on LOS, discharge destination, survival and readmission rate was assessed using multivariable regression techniques. The ability of the models to predict these outcomes was also assessed. RESULTS: In total, 413 patients of median age 77 years were followed for a median of 18 (range 12-24) months. The in-hospital, 3- and 12-month mortality rates were 3·6, 8·5 and 13·8 per cent respectively. Receiver operating characteristic (ROC) curve analysis revealed that frailty-based regression models were excellent predictors of 12-month mortality (area under the ROC curve (AUC) = 0·81), prolonged LOS (AUC = 0·79) and discharge to a care institution (AUC = 0·84). A simple additive frailty score using six key features retained strong predictive power for 12-month mortality (AUC = 0·83), discharge to a care institution (AUC = 0·78) and prolonged LOS (AUC = 0·74). This frailty score was also strongly associated with readmission rates (P < 0·001). CONCLUSION: Frailty in vascular surgery patients predicts a multiplicity of poorer outcomes. Optimal management should include identification of at-risk patients and treatment of modifiable risk factors.

A systematic review and meta-analysis on the role of varicosity treatment in the context of truncal vein ablation.

BACKGROUND: With the advent of endovenous truncal ablation under local anaesthetic for the treatment of varicose veins, the fate of varicosed tributaries has become controversial, with centres offering different timings of treatment, if offered at all. This study aims to review the literature assessing delayed and simultaneous varicosity treatment during truncal ablation. METHODS: Randomised trials and cohort studies concerning varicosity treatment timing were identified through a systematic literature search. Requirements for further treatment, quality of life and rate of venous thrombotic events were assessed for meta-analysis. RESULTS: Four studies were identified assessing need for further varicosity procedure, with no significant difference seen between simultaneous or delayed treatment (p = 0.339). Two studies assessed quality of life, with simultaneous treatment providing significantly improved outcomes at six weeks (p = 0.029) but not at 12 weeks (p = 0.283). Studies examining venous thrombotic events showed no difference in venous thromboembolism rate between simultaneous or delayed treatment approaches (p = 0.078). CONCLUSION: The evidence base regarding timing of varicosity treatment is sparse; however, it does show that simultaneous treatment of varicosities leads to early gains in quality of life, with a non-significant trend for fewer further procedures but more venous thrombotic events.

Design and validation of an error capture tool for quality evaluation in the vascular and endovascular surgical theatre.

BACKGROUND: The unique and complex vascular and endovascular theatre environment is associated with significant risks of patient harm and procedural inefficiency. Accurate evaluation is crucial to improve quality. This pilot study attempted to design a valid, reproducible tool for observers and teams to identify and categorise errors. METHODS: Relevant published literature and previously collected ethnographic field notes from over 250 h of arterial surgery were analysed. A comprehensive log of vascular procedural errors was compiled and twelve vascular experts graded each error for the potential to disrupt procedural flow and cause harm. Using this multimodal approach, the Imperial College Error CAPture (ICECAP) tool was developed. The tool was validated during 21 consecutive arterial cases (52 h operating-time) as an observer-led error capture record and as a prompt for surgical teams to determine the feasibility of error self-reporting. RESULTS: Six primary categories (communication, equipment, procedure independent pressures, technical, safety awareness and patient related) and 20 error sub-categories were determined as the most frequent and important vascular procedural errors. Using the ICECAP, the number of errors detected correlated well between two observers (Spearman rho = 0.984, p < 0.001). Both observers identified all moderate or severe errors similarly and categorised all but 4/139 (2.9%) of the total errors in an identical fashion. Self-reporting of errors without prompting identified a mean of 24.4% (range 0-50%) of all recorded errors, whereas surgical teams reported a mean of 69.7% (range 50-100%) of errors when ICECAP error-category prompts were used. CONCLUSION: The ICECAP tool may be useful for capturing and categorising errors that occur during vascular/endovascular procedures. ICECAP may also have a role as an error recall prompt for self-reporting purposes by vascular surgical teams.

The effect of pressure-induced mechanical stretch on vascular wall differential gene expression.

High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.

Identification of patient safety improvement targets in successful vascular and endovascular procedures: analysis of 251 hours of complex arterial surgery.

OBJECTIVES: To investigate failures in patient safety for patients undergoing vascular and endovascular procedures to guide future quality and safety interventions. DESIGN: Single centre prospective observational study. METHODS: 66 procedures (17 thoracoabdominal and 23 abdominal aortic aneurysms, 4 carotid and 22 limb procedures) were observed prospectively over a 9-month period (251 h operating time) by two trained observers. Event logs were recorded for each procedure. Two blinded experts identified and independently categorised failures into 22 types (using a validated category tool) and severity (5-point scale). Data are expressed as median (range). Statistical analysis was performed using Mann-Whitney U, Kruskal-Wallis and Spearman's Rank tests. RESULTS: 1145 failures were identified with good inter-assessor reliability (Cronbach's alpha 0.844). The commonest failure types related to equipment (including unavailability, configuration and other failures) (269/1145 [23.5%]) and communication (240/1145 [21.0%]). A comparatively lower number of technical and psychomotor failures were identified (103 [9.0%]). The number of failures correlated with procedure duration (rho = 0.695, p < 0.001) but not anatomical site of the procedure or pathology of the disease process. Failure rate was higher in patients undergoing combined surgical/endovascular procedures compared to open surgery (median 5.7/h [IQR 4.2-8.1] vs 3.0/h [2.5-3.5]; p < 0.001). The severity of failures was similar (1.5/5 [1-2] vs 1/5 [1-2] respectively; p = 0.095). For combined procedures, failure rates were significantly higher during the endovascular phase (9.6/h [7.5-13.7]) compared to the non-endovascular phase (3.0/h [1.0-5.0]; p < 0.001). CONCLUSIONS: Failures in patient safety are common during complex arterial procedures. Few failures were severe, although minor failures during critical stages and accumulation of multiple minor failures may potentially be important. Failures occurred especially during the endovascular phase and were often related to equipment or communication aspects. Interventions to improve procedural safety and quality of care should primarily target these specific areas.

Venous hypoxia: a poorly studied etiological factor of varicose veins.

Venous hypoxia has long been postulated as a potential cause of varicosity formation. This article aimed to review the development of this hypothesis, including evidence supporting and controversies surrounding it. Vein wall oxygenation is achieved by oxygen diffusing from luminal blood and vasa vasorum. The whole media of varicosities is oxygenated by vasa vasorum as compared to only the outer two-thirds of media of normal veins. There was no evidence that differences exist between oxygen content of blood from varicose and non-varicose veins, although the former demonstrated larger fluctuations with postural changes. Studies using cell culture and ex vivo explants demonstrated that hypoxia activated leucocytes and endothelium which released mediators regulating vein wall remodelling similar to those observed in varicosities. Venoactive drugs may improve venous oxygenation, and inhibit hypoxia activation of leucocytes and endothelium. The evidence for hypoxia as a causative factor in varicosities remains inconclusive, mainly due to heterogeneity and poor design of published in vivostudies. However, molecular studies have shown that hypoxia was able to cause inflammatory changes and vein wall remodelling similar to those observed in varicosities. Further studies are needed to improve our understanding of the role of hypoxia and help identify potential therapeutic targets.

Cost-effectiveness of traditional and endovenous treatments for varicose veins.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of traditional and endovenous treatments for patients with primary great saphenous varicose veins. METHODS: A Markov model was constructed to compare costs and quality-adjusted life years (QALYs) for great saphenous vein (GSV) reflux. Eight popular treatment strategies were compared up to 5 years. Estimates for the effectiveness of treatments were obtained from published randomized studies and cost values were obtained from published National Health Service (NHS) healthcare resource group tariffs and device manufacturers. Parameter uncertainty was tested using sensitivity analysis and Monte Carlo simulation. RESULTS: Ultrasound-guided foam sclerotherapy (UGFS) had the lowest initial cost, but a higher requirement for further interventions. Day-case surgery (with concomitant treatment of varicosities), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) performed in an outpatient or office setting (with staged treatment of varicosities) were likely to be cost-effective treatment strategies. The incremental cost-effectiveness ratio (ICER) for UGFS (versus conservative care), EVLA (versus UGFS) and RFA (versus EVLA) were £1366, £5799 and £17 350 per QALY respectively. The ICER for traditional surgery (performed on a day-case basis) was £19 012 compared with RFA. Other strategies were not cost-effective using the NHS threshold of £20 000 per QALY. CONCLUSION: Day-case surgery or endovenous ablation using EVLA or RFA performed as an outpatient are likely to be cost-effective treatment strategies for patients with primary unilateral GSV reflux requiring treatment.

Pharmacological treatment in patients with C4, C5 and C6 venous disease.

BACKGROUND: A range of surgical, endovenous, physical and medical treatments are available for patients with chronic venous disease. The aim of this review was to evaluate the evidence for pharmacological agents used for the treatment of chronic venous disease. METHODS: A literature search was performed using Pubmed, Embase, Cochrane and Google Scholar databases. The initial search terms 'varicose vein', 'venous ulcer', 'venous disease' and 'lipodermatosclerosis' were used to identify relevant clinical studies of pharmacotherapy in patients with chronic venous disease (C4-C6). RESULTS: A huge range of naturally occurring and synthetic drugs have been studied in patients with chronic venous disease. For patients with C4 venous disease, micronized purified flavonoid fraction (MPFF), oxerutin, rutosides and calcium dobesilate may reduce venous symptoms and oedema. MPFF and pentoxifylline have been shown to improve venous ulcer healing when used in addition to multilayer compression bandaging. The clinical benefits of other medications remain unproven. Reliability of meta-analyses was limited by study heterogeneity, small sample sizes and lack of long-term follow-up. CONCLUSIONS: In prospective randomized studies, MPFF (Daflon(®)), other flavonoid derivatives and pentoxifylline have demonstrated clinical benefits in patients with C4-C6 venous disease. Pharmacotherapy should be part of a range of treatment options in the modern management of patients with chronic venous disorders.

Heterogeneity of reporting standards in randomised clinical trials of endovenous interventions for varicose veins.

AIMS: The efficacy of endovenous treatments for venous reflux has been demonstrated in numerous randomised clinical trials, although significant heterogeneity may exist between studies. The aim of this study was to assess the heterogeneity in reporting between randomised clinical trials investigating endovenous treatments for patients with varicose veins. METHODS: A literature search of the Pubmed, Cochrane and Google Scholar databases was performed using appropriate search terms. Randomised clinical trials published between January 1968 and June 2009 evaluating endovenous interventions for varicose veins were included and relevant abstracts and full text articles were reviewed. Published study reports were evaluated against recommended reporting standards published by the American Venous Forum in 2007. RESULTS: Twenty-eight randomised trials fulfilled the inclusion criteria. Median patient age (reported in 20/28 studies) ranged from 33 to 54 years. The CEAP classification was presented in 17/28 studies and the proportion of patients with C2 disease ranged from 6.3% to 83.5%. A total of 31 different outcome measures were utilised. This included 13 different questionnaires, varicose vein recurrence at 38 time points and 30 categories of complications. Duplex ultrasonography was used in 21/28 trials to assess recurrence. Quality of life was only evaluated in 11 studies and the follow-up period ranged from 3 weeks to 10 years. CONCLUSIONS: Meaningful comparison across randomised studies of endovenous treatments is made difficult by considerable variations in study populations and outcome measures between trials. This highlights the need for the use of prospectively agreed population selection, and reporting standards for outcome measures in randomised clinical assessments of new treatments.

Secondary care treatment of patients with varicose veins in National Health Service England: at least how it appeared on a National Health Service website.

OBJECTIVES: This study aimed to assess the trends and regional variations in secondary care treatment of patients with varicose veins in National Health Service (NHS) England based on data published by the Hospital Episode Statistics which was freely and readily available to the public and health-care policy-makers. METHODS: Hospital Episode Statistics data for patients being treated for varicose veins, and UK Statistics Authority population estimates in all 28 Strategic Health Authorities (SHAs) in England from 2002 to 2006 were retrieved and analysed. RESULTS: Between 2002 and 2006 there was a 20% overall reduction (46,190-37,135) in the total number of varicose vein procedures performed in NHS England per year. The number of varicose vein procedures performed per 100,000 population per year varied significantly across the SHAs (P < 0.0001). Similarly, significant regional variations were also noted in the frequency of primary procedures of greater and small saphenous vein (P < 0.0001). During this time, injection sclerotherapy was only performed in 15 (53.6%) SHAs. The annual proportion of varicose vein procedures performed as daycases had increased from 56% to 64% during the period. CONCLUSION: From 2002 to 2006 there was an overall reduction in the total number of varicose vein procedures performed in NHS England with major regional variations.

Randomized clinical trial of VNUS ClosureFAST radiofrequency ablation versus laser for varicose veins.

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.