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).

Optimising treatment parameters for Radiofrequency Induced Thermal Therapy (RFiTT): A comparison of the manufacturer's treatment guidance with a locally developed treatment protocol.

OBJECTIVE: Radiofrequency induced Thermal Therapy (RFiTT) is an established endovenous device for the treatment of varicose veins. Our aim was to compare the manufacturer's treatment guidance with a locally developed treatment protocol on early truncal ablation rates between two patient cohorts. METHODS: The study was a retrospective analysis of prospectively collected data from 534 patients treated for incompetent truncal saphenous veins between June 2009 and December 2012. Patients were treated either according to the manufacturer's guidance (Treatment 1), a single pullback rate of ≥1.5 s/cm, or according to local protocol (Treatment 2), repeated vein treatment to visibly occlude the vein lumen. Follow-up at 6 weeks and 12 months included duplex examination, assessment of complications, and pain scores for the first postoperative week. RESULTS: 14 patients did not attend follow-up, leaving 98 patients (142 saphenous trunk treatments) who received Treatment 1 and 422 patients (566 saphenous trunk treatments) who received Treatment 2. The two groups were well matched for age, sex, and preoperative vein parameters. Six week occlusion rates were significantly different, with more treatment failures after Treatment 1 (Treatment 1 5.6% vs. Treatment 2 0.9%; p = .0001). Treatment 1 was more likely to produce incomplete ablation (3.5% vs. 0.9%) and non-ablation (2.1% vs. 0.0%) compared with Treatment 2. No major complications occurred in either group and functional outcomes were otherwise comparable between the two treatment methods. Longer-term follow-up at 12 months in the first 100 patients undergoing Treatment 2 demonstrated maintenance of the early advantage, with partial recanalisations in 9% and 2% for Treatments 1 and 2, respectively. CONCLUSIONS: Six weeks after treatment with RFiTT, a protocol of repeated vein treatments to visibly obliterate the vein lumen produced more reliable venous occlusion compared with manufacturer's guidance. This advantage is maintained at 12 months.

Management of proximal deep vein thrombosis.

Iliofemoral DVT constitutes approximately 20-25% of lower limb DVT and represents a specific subgroup of patients at highest risk for post-thrombotic syndrome (PTS). Anticoagulation alone has no significant thrombolytic activity and has not impact on PTS prevention. Early thrombus removal has reduced PTS in uncontrolled reports and reviews but major trials are awaited. The optimal timing for treatment appear to be thrombus <2 weeks old and, methods for thrombus removal include direct open or suction thrombectomy, catheter directed thrombolysis (CDT), with or without percutaneous mechanical thrombectomy (PMT) devices. Three principle types of PMT device are in use (rotational, rheolytic and ultrasound enhanced devices) and are combined with CDT in pharmocomechanical thrombolysis (PhMT) to enhance early thrombus removal. These devices have individual device specific attributes and side effects that are additional to the bleeding complications of thrombolysis. A number of additional interventions may be utilised to the improve results of CDT and PhMT. IVC filter deployment to reduce periprocedural PE, is supported by little evidence unless an indication for its use already exists. However, balloon venoplasty and vein stents undoubtedly vein patency after treatment. Early thrombus removal comes with additional upfront costs derived from devices, imaging and critical care bed usage. However, significant potential savings from reduction in PTS and rethrombosis rates may reduce overall societal costs. This review focuses on iliofemoral thrombosis, however, the less commonly encountered but clinically important subclavian vein thrombosis is also discussed.

Can foam sclerotherapy be used to safely treat bilateral varicose veins?

OBJECTIVE: We assessed the use of ultrasound guided foam sclerotherapy (UGFS) to treat bilateral varicose veins either as synchronous or interval procedures. We specifically assessed total foam volume usage and its influence on early outcome and complications. METHODS: We reviewed our prospectively compiled computerised database of patients with bilateral varicose veins who have undergone UGFS. Duplex findings, foam volumes used and clinical outcome were assessed. RESULTS: One hundred and twelve patients had undergone UGFS for bilateral varicose veins. Sixty-one had bilateral UGFS (122 legs) and 51 had interval UGFS (102 legs). Seventy-eight percent bilateral and 60% interval procedures were for single trunk disease. Median foam volumes per treatment episode were: 17.5 mls bilateral, and 10 mls interval FS. At two weeks 81% of legs had complete occlusion after bilateral UGFS compared to 70% after interval UGFS. One patient in the bilateral UGFS developed transient visual disturbance. There was no systemic complications in the interval UGFS. CONCLUSIONS: Bilateral foam sclerotherapy treatment did not adversly affect vein occlusion rates and there was no significant difference in complication rates between the two groups. Bilateral UGFS can be safely performed in selected patient presenting with bilateral varicose veins.

Leg ulceration: the importance of treating the underlying pathophysiology.

The last 20 years have seen considerable advances in the management of vascular diseases both in non-invasive imaging and minimally invasive surgical interventions. Colour duplex ultrasonography provides non-invasive and increasingly high-resolution anatomic and haemodynamic vascular information. This has been complimented by the development of minimally invasive interventional procedures such as subintimal angioplasty and endovenous treatments, all of which can be performed under local anaesthesia. These advances can now be utilized to improve both the assessment and management of patients with chronic leg ulceration where the aetiology is usually vascular and mostly primary venous insufficiency. Using non-invasive Doppler pressures and colour duplex imaging, the anatomic and haemodynamic pattern of the underlying vascular disease (and consequently the pathophysiology) can be precisely determined. This enables appropriate planning and targeting of effective management from an early stage in the history of any particular ulcer. This paper highlights the importance of achieving accurate diagnosis and instituting effective treatments that are appropriately targeted at the underlying pathophysiology, in patients with chronic leg ulceration, and describes how recent advances in technology and interventions have substantially increased the tools available to the vascular specialist. Thus allowing safe and effective management of what can otherwise become a prolonged or recurrent disease process.

Is the retrojugular approach safer than the conventional approach for carotid endarterectomy?

BACKGROUND: The retrojugular approach is promoted as an alternative to traditional antejugular carotid endarterectomy. Absence of named posterior venous branches and ease of distal internal carotid dissection reduce time for carotid exposure together with improved distal exposure. However, a higher incidence of local nerve injury and persistent hoarse voice has been reported. We compare the incidence of these and other complications for the antejugular and retrojugular approaches. DESIGN: This is a nonrandomised retrospective review of prospectively collected data on consecutive patients undergoing carotid endarterectomy. RESULTS: Our 178 patients formed two groups who were homogeneous in terms of sex and age. Mean operative times, patch usage, and general/local anaesthesia did not differ significantly for the two groups. Postoperative complications including transient ischemic attack (TIA), major stroke, or death; hypertension; miosis; and hypoglossal injury were similar for the two groups. However, there was a significantly increased incidence of persistent hoarse voice (p < 0.05) in the retrojugular group. CONCLUSIONS: Reports of increased incidence of persistent hoarse voice associated with the retrojugular approach to carotid endarterectomy are supported by our findings, which point to a learning curve effect. A randomized controlled trial would be necessary before any strong recommendation could be made for or against the retrojugular approach.

Durability of botulinum toxin treatment for axillary hyperhidrosis.

OBJECTIVES: Botulinum toxin injection effectively treats axillary hyperhidrosis. Durability estimates of 3-14 months, based on self re-referral may overestimate duration. Our objective was to determine treatment durability by active follow-up of patients. DESIGN: Audit of current practice. MATERIALS AND METHODS: Patients presenting with severe primary axillary hyperhidrosis were actively followed up for 24 months after intradermal injections of Botulinum Toxin A (Dysport 120 units/axilla). A 10-point Likert Scale (1=worst imaginable symptoms, 10=absolute resolution) and the Hyperhidrosis Disease Severity Score (HDSS) were used at 1 day and 3, 6, 12 and 24 months. We offered re-treatment when symptoms returned to the pre-intervention state. RESULTS: We treated 45 patients with a mean age of 29 (15-49) years of whom 36 (78%) were women. The median pre-treatment Likert score (i.q.r.) of 3 (2-3) improved to 10 (10-10) on day 1. Scores at 3 (n=44), 6 (n=43) and 12 (n=39) months were 10 (10-10), 8 (7.5-10), and 7 (5-8) respectively. The median 24-month score was 3 (3-6) for 35 patients, including 11 patients with scores >/=6 who have not required re-treatment. HDSS scores followed a similar pattern. CONCLUSIONS: Axillary botulinum toxin treatment is durable. Patients experience gradual return of symptoms between 6 and 24 months. A minority do not require re-treatment at this time.

Fatal haemorrhage from varicose veins: is the correct advice being given?

A case report is presented illustrating the occasional sinister nature of varicose veins, revealing the need for assessment of haemorrhage risk of the patient and appropriate advice.

Should all patients undergo postoperative duplex imaging to detect a deep vein thrombosis after varicose vein surgery?

OBJECTIVES: Deep vein thrombosis (DVT) is a serious complication of varicose vein surgery, with attendant risks of pulmonary embolization. Prospective duplex screening identifies DVT in 5% of patients compared to clinical incidence of approximately 1%. Universal duplex screening is costly, and the benefits of diagnosing subclinical DVT are unproven. This study evaluates whether a policy of using clinical indications (leg swelling) to determine the need for duplex imaging is safe after varicose vein surgery. METHODS: Patients undergoing varicose vein surgery over a 4-year period were studied. Postoperative venous duplex imaging was performed if leg swelling occurred within 6 weeks of surgery. Long-term follow-up was performed to detect any missed occurrence of clinical DVT or pulmonary embolism. RESULTS: A total of 411 patients had 491 leg operations with 80 bilateral procedures (27%); 29 patients with leg swelling underwent duplex imaging, 5 of whom had duplex-proven DVT. No patient without early clinical signs went on to develop clinical DVT on long-term follow-up. CONCLUSION: A policy of using clinical signs as a triage for duplex imaging detected all clinically significant DVTs and generated manageable workloads for our vascular laboratory.

Current therapeutic options for treating primary hyperhidrosis.

Severe hyperhidrosis can cause extreme embarrassment that may lead to social and professional isolation. Therapeutic strategies to hyperhidrosis should employ the least invasive treatment that provides effective symptom control. The treatment options available for control of hyperhidrosis, non-surgical or surgical, differ in their invasiveness and efficacy. Mechanisms of action of antiperspirants, iontophoresis, cholinergic inhibitor drugs, botulinum toxin, and surgical sympathectomy are reviewed. There is little published evidence in the form of comparative randomised trials to support the use of one treatment over another. However, authors have tended to recommend those therapies that are available to their speciality. Specific therapies should be tailored to the patient's symptoms to gain maximum symptomatic improvement with minimum invasiveness and side-effects. To achieve this, the full range of treatment options should be available to, or accessible by the consulting doctor in order for the patient to have a meaningful choice.

Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty.

BACKGROUND: Photodynamic therapy (PDT) reduces neointimal hyperplasia and negative remodelling following balloon injury in small and large animal models. This clinical study investigated the role of adjuvant PDT following femoral percutaneous transluminal angioplasty (PTA). METHODS: Eight PTAs in seven patients (two women) with a median age of 70 (range 59-86) years were performed with adjuvant PDT. All patients had previously undergone conventional angioplasty at the same site which resulted in symptomatic restenosis or occlusion between 2 and 6 months. Each was sensitized with oral 5-aminolaevulinic acid 60 mg/kg, 5-7 h before the procedure. Following a second femoral angioplasty, up to 50 J/cm2 red light (635 nm) was delivered to the angioplasty site via a laser fibre within the angioplasty balloon. Patients were kept in subdued light overnight and discharged the following day. Outcome was assessed by duplex imaging at 24 h, 1, 3 and 6 months and by intravenous digital subtraction angiography at 6 months. A peak systolic velocity ratio (PSVR) of more than 2.0 at the angioplasty site was taken to represent restenosis. RESULTS: All patients tolerated the procedure well without adverse complications or death. All were rendered asymptomatic which was sustained throughout the study interval. All vessels remained patent and no lesion attained the duplex definition of restenosis. Median (interquartile range) PSVR across stenotic segments was 4.7 (3.7-5.7) before angioplasty, 1.1 (0.9-1.3) at 24 h and 1.4 (1.0-1.8) at 6 months after intervention (P = 0.04 compared with preoperative value). CONCLUSION: This pilot study suggests that endovascular PDT is safe and may reduce restenosis follow- ing angioplasty. The data justify a randomized controlled trial.

The diagnosis and management of mixed arterial/venous leg ulcers in community-based clinics.

OBJECTIVES: To assess a management protocol for mixed arterial/venous leg ulcers in a community service. DESIGN: Two-year prospective study of outcome with intention of assessing limbs with mixed arterial/venous ulcers when managed by a new protocol. METHOD: Limbs were assessed for venous reflux by duplex and arterial insufficiency by ankle-brachial pressure index (ABPI) and defined into three categories: ABPI > 0.85, 0.5 > ABPI < or = 0.85 (moderate), ABPI < or = 0.5 (severe). Four-layer compression was applied to limbs with normal arteries. Modified compression was applied to limbs with venous and moderate arterial disease with treatment failure triggering arterial imaging and revascularisation. Limbs with venous and severe arterial disease were investigated for revascularisation. RESULTS: Of 267 consecutive limbs, 221 had pure chronic venous ulcers and 46 had mixed arterial/venous ulcers with 33 having moderate and 13 having severe arterial disease. Thirty-six week healing rates for chronic venous, moderate arterial/venous and severe arterial/venous ulcers were 70%, 64% and 23%, respectively. CONCLUSION: Limbs with mixed moderate arterial/venous ulcers achieved rates comparable with venous ulcers with this protocol although nurse-led surveillance was required. Limbs with mixed severe arterial/venous ulcers healed slowly despite an aggressive approach to correct arterial disease.

Influence of a specialised leg ulcer service and venous surgery on the outcome of venous leg ulcers.

OBJECTIVES: To assess the influence of a vascular-led community service on the outcome of chronic leg ulcers. DESIGN: Before and after study. METHOD: Healing and recurrence were compared between ulcerated limbs (n = 149) from a random sample of 200 patients treated in the community and consecutive limbs (n = 200) from 180 patients treated in specialised clinics. In these clinics, vascular disease was routinely identified with venous duplex and ankle-brachial pressure index. Surgery was offered if superficial vein reflux alone was detected. Compression bandaging was applied to limbs with ABPI > 0.85. Healed limbs were treated with compression hosiery. RESULTS: After the clinics were introduced, the 12 and 24-week healing rates increased from 12 and 29 per cent to 53 and 68 per cent respectively (p < 0.01), and the 6 and 12 month recurrence rates decreased from 43 and 54 per cent to 21 and 23 per cent respectively (p < 0.01). Superficial venous surgery reduced recurrence at 1 year to 9 per cent. CONCLUSION: Outcome of leg ulcers is improved in a vascular-led community service. Routine surgical correction, in cases of reflux limited to the superficial system, may further reduce the chance of recurrence.

Clinicopathological evidence that neovascularisation is a cause of recurrent varicose veins.

OBJECTIVES: Recurrent varicose veins may result from poor initial surgical technique or progression of varicosities in collateral veins. In some cases new veins may develop at the saphenofemoral junction (neovascularisation) and cause recurrent saphenofemoral incompetence. This was a histological study of recurrent varicose veins. DESIGN: This clinicopathological study included 20 patients (median age 55 years) who had surgery for recurrent saphenofemoral incompetence. MATERIALS AND METHODS: A total of 28 legs had groin re-exploration with repeat flush saphenofemoral ligation. The venous tissue block from the saphenofemoral region (including the proximal thigh varicosity) was excised and orientated for histological analysis. Evidence of neovascularisation was sought using routine histological sections and S100 immunohistochemistry. RESULTS: At operation, thin-walled, serpentine neovascular veins were detected clinically as the principal cause of recurrence in 19 groins. In five groins recurrence was due to a residual missed vein at the saphenofemoral junction, and in four recurrence was caused by cross groin collaterals. On histological sections, evidence of neovascularisation was present in 27 of 28 groins. In eight it co-existed with the veins missed at the original operation but it was the sole identified cause of recurrent saphenofemoral incompetence in 19 (68%) groins. CONCLUSIONS: Neovascularisation was the principal cause of recurrent saphenofemoral incompetence in this series.

Quality of life after transthoracic endoscopic sympathectomy for upper limb hyperhidrosis.

OBJECTIVE: To assess the outcome after transthoracic endoscopic sympathectomy (TES) for upper limb hyperhidrosis. DESIGN: Prospective cohort study. SETTING: District general hospital. SUBJECTS: Consecutive patients undergoing TES for upper limb hyperhidrosis over a fifteen month period. INTERVENTIONS: One-stage bilateral TES. MAIN OUTCOME MEASURES: Change in quality of life as shown by the Short Form-36 health assessment questionnaire. RESULTS: Sixteen patients (11 women and 5 men, median age 26 years) underwent operation without complications. At median follow-up of 6.2 months, symptomatic improvement was found in 26 of 32 limbs treated (82%). Truncal compensatory hyperhidrosis was reported by 13 patients but was severe in only three. There were significant improvements in social function (p = 0.01) and mental health (p = 0.025) as assessed by the SF-36. CONCLUSION: Despite a high incidence of compensatory hyperhidrosis, TES improved both the symptoms and overall quality of life in patients with upper limb hyperhidrosis.

Thrombosis and restenosis after peripheral angioplasty: does acute 111indium-platelet accumulation predict angioplasty outcome?

OBJECTIVES: Use of platelet deposition to predict failure following angioplasty. DESIGN: Prospective study of angioplasty patients in a 9 months surveillance period. MATERIALS: Thirty-eight successful angioplasty patients. METHODS: Autologous 111indium-labelled platelets were re-injected immediately after angioplasty. Gamma camera and probe measures of radioactivity were obtained daily for 2-4 days and compared to a reference site to obtain a radioactivity ratio. Patient follow up was with duplex and arteriography from day 0 to 9 months or at angioplasty failure. RESULTS: Thirty-one patients remained asymptomatic; two developed acute occlusion and five developed restenosis. Platelet accumulation (increased mean radioactivity ratio) occurred at all angioplasty sites and was significantly higher after acute occlusion (camera: 2.93 and probe: 1.93) compared to asymptomatic patients (camera: 1.25 and probe: 1.15) and restenotic patients (camera: 1.31 and probe: 1.23). Radioactivity ratio was not different in patients who later developed restenosis. CONCLUSION: 111Indium platelet radioactivity effectively detected acute angioplasty reocclusions, but was unable to predict subsequent angioplasty restenosis.