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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).

This randomized clinical trial uses data from the Early Venous Reflux Ablation trial to evaluate the long-term clinical and cost benefits of combined early endovenous ablation and compression compared with compression therapy alone and deferred ablation for treating superficial venous reflux of the leg., Key Points Question In patients with venous leg ulceration and superficial reflux, what is the clinical and cost-effectiveness of early endovenous ablation of reflux? Findings In this 450-patient, multicenter, randomized clinical trial, early endovenous ablation with compression accelerated venous ulcer healing, reduced the overall incidence of ulcer recurrence, and was highly cost-effective compared with compression with deferred intervention. Meaning To deliver clinical and cost benefits, leg ulcer care pathways should be revised to include early assessment and treatment of superficial venous reflux., Importance One-year outcomes from the Early Venous Reflux Ablation (EVRA) randomized trial showed accelerated venous leg ulcer healing and greater ulcer-free time for participants who are treated with early endovenous ablation of lower extremity superficial reflux. Objective To evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration. Design, Setting, and Participants Between October 24, 2013, and September 27, 2016, the EVRA randomized clinical trial enrolled 450 participants (450 legs) with venous leg ulceration of less than 6 months’ duration and superficial venous reflux. Initially, 6555 patients were assessed for eligibility, and 6105 were excluded for reasons including ulcer duration greater than 6 months, healed ulcer by the time of randomization, deep venous occlusive disease, and insufficient superficial venous reflux to warrant ablation therapy, among others. A total of 426 of 450 participants (94.7%) from the vascular surgery departments of 20 hospitals in the United Kingdom were included in the analysis for ulcer recurrence. Surgeons, participants, and follow-up assessors were not blinded to the treatment group. Data were analyzed from August 11 to November 4, 2019. Interventions Patients were randomly assigned to receive compression therapy with early endovenous ablation within 2 weeks of randomization (early intervention, n = 224) or compression with deferred endovenous treatment of superficial venous reflux (deferred intervention, n = 226). Endovenous modality and strategy were left to the preference of the treating clinical team. Main Outcomes and Measures The primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost-effectiveness. Results The early-intervention group consisted of 224 participants (mean [SD] age, 67.0 [15.5] years; 127 men [56.7%]; 206 White participants [92%]). The deferred-intervention group consisted of 226 participants (mean [SD] age, 68.9 [14.0] years; 120 men [53.1%]; 208 White participants [92%]). Of the 426 participants whose leg ulcer had healed, 121 (28.4%) experienced at least 1 recurrence during follow-up. There was no clear difference in time to first ulcer recurrence between the 2 groups (hazard ratio, 0.82; 95% CI, 0.57-1.17; P = .28). Ulcers recurred at a lower rate of 0.11 per person-year in the early-intervention group compared with 0.16 per person-year in the deferred-intervention group (incidence rate ratio, 0.658; 95% CI, 0.480-0.898; P = .003). Time to ulcer healing was shorter in the early-intervention group for primary ulcers (hazard ratio, 1.36; 95% CI, 1.12-1.64; P = .002). At 3 years, early intervention was 91.6% likely to be cost-effective at a willingness to pay of £20 000 ($26 283) per quality-adjusted life year and 90.8% likely at a threshold of £35 000 ($45 995) per quality-adjusted life year. Conclusions and Relevance Early endovenous ablation of superficial venous reflux was highly likely to be cost-effective over a 3-year horizon compared with deferred intervention. Early intervention accelerated the healing of venous leg ulcers and reduced the overall incidence of ulcer recurrence. Trial Registration ClinicalTrials.gov identifier: ISRCTN02335796

Background Venous ulceration is a common and costly health-care issue worldwide, with poor healing rates greatly affecting patient quality of life. Compression bandaging has been shown to improve healing rates and reduce recurrence, but does not address the underlying cause, which is often superficial venous reflux. Surgical correction of the reflux reduces ulcer recurrence; however, the effect of early endovenous ablation of superficial venous reflux on ulcer healing is unclear. Objectives To determine the clinical effectiveness and cost-effectiveness of compression therapy with early endovenous ablation of superficial venous reflux compared with compression therapy with deferred endovenous ablation in patients with venous ulceration. Design A pragmatic, two-arm, multicentre, parallel-group, open randomised controlled trial with a health economic evaluation. Setting Secondary care vascular centres in England. Participants Patients aged ≥ 18 years with a venous leg ulcer of between 6 weeks’ and 6 months’ duration and an ankle–brachial pressure index of ≥ 0.8 who could tolerate compression and were deemed suitable for endovenous ablation of superficial venous reflux. Interventions Participants were randomised 1 : 1 to either early ablation (compression therapy and superficial endovenous ablation within 2 weeks of randomisation) or deferred ablation (compression therapy followed by endovenous ablation once the ulcer had healed). Main outcome measures The primary outcome measure was time from randomisation to ulcer healing, confirmed by blinded assessment. Secondary outcomes included 24-week ulcer healing rates, ulcer-free time, clinical success (in addition to quality of life), costs and quality-adjusted life-years (QALYs). All analyses were performed on an intention-to-treat basis. Results A total of 450 participants were recruited (224 to early and 226 to deferred superficial endovenous ablation). Baseline characteristics were similar between the two groups. Time to ulcer healing was shorter in participants randomised to early superficial endovenous ablation than in those randomised to deferred ablation [hazard ratio 1.38, 95% confidence interval (CI) 1.13 to 1.68; p = 0.001]. Median time to ulcer healing was 56 (95% CI 49 to 66) days in the early ablation group and 82 (95% CI 69 to 92) days in the deferred ablation group. The ulcer healing rate at 24 weeks was 85.6% in the early ablation group, compared with 76.3% in the deferred ablation group. Median ulcer-free time was 306 [interquartile range (IQR) 240–328] days in the early ablation group and 278 (IQR 175–324) days in the deferred endovenous ablation group (p = 0.002). The most common complications of superficial endovenous ablation were pain and deep-vein thrombosis. Differences in repeated measures of Aberdeen Varicose Vein Questionnaire scores (p p = 0.03) and Short Form questionnaire-36 items body pain (p = 0.05) over the follow-up period were observed, in favour of early ablation. The mean difference in total costs between the early ablation and deferred ablation groups was £163 [standard error (SE) £318; p = 0.607]; however, there was a substantial and statistically significant gain in QALY over 1 year [mean difference between groups 0.041 (SE 0.017) QALYs; p = 0.017]. The incremental cost-effectiveness ratio of early ablation at 1 year was £3976 per QALY, with a high probability (89%) of being more cost-effective than deferred ablation at conventional UK decision-making thresholds (currently £20,000 per QALY). Sensitivity analyses using alternative statistical models give qualitatively similar results. Limitations Only 7% of screened patients were recruited, treatment regimens varied significantly and technical success was assessed only in the early ablation group. Conclusions Early endovenous ablation of superficial venous reflux, in addition to compression therapy and wound dressings, reduces the time to healing of venous leg ulcers, increases ulcer-free time and is highly likely to be cost-effective. Future work Longer-term follow-up is ongoing and will determine if early ablation will affect recurrence rates in the medium and long term. Trial registration Current Controlled Trials ISRCTN02335796. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 24. See the NIHR Journals Library website for further project information.

Thrombus formation within arterial aneurysms may lead to embolisation and distal ischaemia. We have investigated the use of 111-indium labelled plate lets in the diagnosis of atherosclerotic and false aneurysms. Autologous platelets labelled with 111-indium oxine were injected into patients with eleven proven aneurysms (8 atherosclerotic, 3 false) . Gamma camera imaging performed be tween 24 and 72 hours later was positive for 10 of the aneurysms. In every case there was increased uptake of label over the aneurysm when compared to undis eased blood vessels (p < 0.05). Most aneurysms could be demonstrated within 24 hours of labelling platelets. 111-indium labelled platelets may prove useful in identifying the source of peripheral arterial emboli.

The aetiology and treatment of 35 femoral false anastomotic aneurysms in 29 patients presenting over the 4-year period 1984–88 were reviewed retrospectively. The mean interval between primary anastomosis and false aneurysm repair was 6 years (range from 2 weeks to 16 years). Twenty-two (63 per cent) false aneurysms had occurred after previous aortobifemoral bypass grafting for occlusive aortoiliac disease. Seven (20 per cent) presented as acute surgical emergencies. Review of the records of the initial operations revealed that superficial wound infections with positive bacteriological cultures had been present in eight cases (23 per cent) and a further two (6 per cent) had lymph fistulae. Thirty-two false aneurysms were repaired, by simple reanastomosis in 14 cases, interposition grafting in 17 cases and in one case by complete revision to an aortobifemoral bypass graft. The risk of a further operative repair was less (P < 0.05) following interposition grafting, than after simple revision. False aneurysm repairs, when compared with primary reconstructions done during the same period, were associated with more superficial wound infections (37 versus 10 per cent) and more explorations for haemorrhage within 30 days (19 versus 7 per cent).

Between January 1980 and September 1988, 34 octogenarians underwent aortic aneurysm repair. There were 26 men and eight women with a median age of 83 years (range 80–88 years). Twenty underwent ‘emergency’ repair after presenting with pain and/or collapse: 11 with a retroperitoneal rupture, three with an intraperitoneal rupture and six with an expanding aneurysm. The mortality rate for this group was 35 per cent. During the same period 14 patients had an elective repair and there were no deaths within 30 days. The mean hospital stay for the elective group was 14.2 days compared with 17.0 days for survivors in the emergency group. There was no significant difference in terms of risk factors between those who developed postoperative complications and those who did not. These mortality rates compare favourably with our overall mortality results for elective (4.6 per cent) and emergency (31 per cent) surgery. Those patients over 80 years of age with infrarenal abdominal aortic aneurysms should not be refused surgery on the basis of age alone; each patient should be judged individually.

Multiple pulmonary emboli are recognized to be the cause of progressive pulmonary failure. In these patients, the source of emboli may be difficult to detect, even by venography. The authors describe the use of autologous Indium 111-labeled platelets to locate the origin in a patient with progressing right heart failure.

Adult respiratory distress syndrome (ARDS) is a frequent cause of death in intensive care units and probably represents a collection of different conditions. In the complex issue of its aetiology the failure to define terms has led in our opinion to considerable confusion. It is doubtful whether the pulmonary failure that follows viral pneumonia or specific lung infections has the same pathophysiology as that following 3 days after massive blood transfusion, although both may share similar X-ray features and be called “ARDS”. In this chapter “shock” refers to that condition in which there is a failure of the circulation of blood to meet the metabolic needs of the tissues. “Shock lung” is defined here as pulmonary failure without left ventricular failure typified by increased pulmonary arteriovenous admixture and widespread opacification of the lung fields on X-ray, developing as a consequence of and at an interval of hours or days following an episode of shock or severe sepsis. In this way we may concentrate entirely on that variety of ARDS that almost certainly has a common, although possibly multiple, cause that was almost certainly active during the episode of shock. The delay before pulmonary failure develops is a consistent feature of great importance in understanding the pathophysiology.

Platelet inhibitory therapy has applications in vascular surgery and in patients who have coronary and cerebral vascular disease1. Screening of new products to assess their ethicacy involves measurement of platelet aggregation responses to standard aggregants2 the use of artificial circuits3 and clinical trials, which are time consuming and expensive. The frequent side-effects found with the standard platelet inhibitory therapy of aspirin combined with dipyridamole4 has led for a search for new compounds. We have developed an in vivo canine model which is used to identify effective compounds on the basis of the rate of platelet accumulation and subsequent thrombosis on artificial arterial prostheses. We describe this model and its use to evaluate a new reversible cyclo-oxygenase inhibitor, indobufen (Farmitalia Carlo Erba).

Pulmonary dysfunction frequently follows major surgery and has many features identical to ‘shock lung’. A porcine model of aortic surgery is described in which 111In-labelled platelet kinetics were related to subsequent pulmonary function. In 14 pigs, standardized aortic surgery resulted in reproducible shock and a 50 per cent mortality at 3 days. Cardiac output fell from 22.3±0.2 to 1.0±0.1 litres min−1 following removal of the aortic clamp and mean platelet and leucocyte counts fell from 437±48 to 252±39×109 litres−1 and 21.7±1.5 to 12.9±1.2×109 litres−1 respectively (P

An in vivo method of measuring thrombus deposition and pseudo-intimal thickening in prosthetic arterial grafts in an animal model is described. The effect of indobufen, a new cyclo-oxygenase inhibitor, was evaluated and compared to aspirin plus dipyridamole and placebo in 24 greyhounds. Luminal platelet accumulation expressed as thrombogenicity index was 0.33 ± 0.07 in the placebo group. This was significantly reduced to 0.14 ± 0.01 by indobufen (P

Human prosthetic vascular grafts do not sustain a growth of endothelium on the luminal surface and remain thrombogenic indefinitely1. Whilst large diameter aortic grafts develop a thin layer of platelet thrombus as pseudointima, smaller prostheses such as those in the femoro-popliteal position have a thrombosis and occlusion rate approaching 60% at 1 year after implantation2. Platelet inhibitory therapy is established in the prevention of thrombosis but the combination of aspirin plus dipyridamole produces frequent gastro-intestinal side effects. This has been shown in the recent Persantin Aspirin Re-infarction Study3 where 25% of patients had to discontinue aspirin therapy. Thromboxane A2 (TXA2) which is a product of aracidonic acid metabolism, is a powerful stimulator of platelet aggregation4. It is produced by enzymes including cyclo-oxygenase and thromboxane synthetase in platelets and the natural biological opponent of TXA2 is prostocyclin (PGI2).

Two cases of claudication of the cauda equina due to ischaemia secondary to distal aortic disease in the Small Aorta syndrome are reported. The association has not been previously reported and the appropriate management is discussed.