Catheter-directed thrombolysis for iliofemoral deep vein thrombosis.

BACKGROUND: Recent international guidance recommends the use of catheter-directed thrombolysis (CDT) in selected patients with symptomatic iliofemoral deep vein thrombosis (DVT). The aim of this study was to estimate the potential increase in workload as a result of this recommendation. METHODS: Using the radiology database, a review was performed of all DVTs diagnosed between August 2010 and February 2012 at a large tertiary referral hospital. The National Institute for Health and Clinical Excellence and American College of Chest Physicians guidance was applied retrospectively to this cohort, using case-note review by two independent clinicians to determine which patients would have been suitable for CDT. RESULTS: Some 563 patients had DVT confirmed radiologically over the 18-month interval. Fifty-three of the 128 patients with iliofemoral DVT would have been eligible for intervention with CDT, equivalent to 4·4 patients per 100 000 per year. Only eight (15 per cent) of the 53 were actually referred to vascular services for treatment. All eight patients had successful CDT, which involved a stay in critical care for monitoring (median 2 (range 1-3) sessions). CONCLUSION: Vascular units should be prepared for a major increase in the requirement for CDT for iliofemoral DVT. This increase will affect inpatient beds, the interventional radiology suite, critical care and interhospital referrals.

An online patient completed Aberdeen Varicose Vein Questionnaire can help to guide primary care referrals.

OBJECTIVES: To determine the feasibility and reliability of an online patient completed Aberdeen Varicose Vein Questionnaire (AVVQ) as a tool to guide specialist referral. METHODS: This was a prospective qualitative and quantitative study. One hundred and six patients completed an online questionnaire. Some 43 (40%) completed the AVVQ questionnaire at home and 63 (60%) did it immediately before their appointment. Venous Clinical Severity Score (VCSS) and CEAP grades were assigned by a consultant vascular surgeon. In 11 patients, the questionnaire was repeated at the time of surgery to assess reproducibility and bias. RESULTS: The AVVQ correlated with the specialist's VCSS scores (Spearman coefficient 0.795; p < 0.01) and similarly with CEAP grade (P < 0.01, ANOVA test). AVVQ was reproducible with close agreement (Spearman coefficient 0.89; p < 0.01) between both 1st AVVQ score of 21.61 (sd 10.26; range 6.12-40.14) and 2nd AVVQ score of 21.03 (sd 10.50 range 4.51-42.57). Patients' feedback about the online AVVQ was positive. CONCLUSIONS: An online questionnaire is acceptable to patients, correlates with clinical findings and using a threshold value could be used by healthcare Commissioners to guide varicose vein referrals.

Mid-term results of endovascular aortic aneurysm repair in the young.

OBJECTIVES: To compare the mid-term outcome and secondary intervention rate following elective open and endovascular aortic aneurysm repair (EVAR) in patients aged 65 years and younger. METHODS: A retrospective analysis of patients aged 65 years and younger who had elective abdominal aortic aneurysm repair (AAA) between 1994 and 2012. RESULTS: One hundred and sixty-five patients under the age of 65 years (mean age: 61 years ± 4; 8 women) had elective abdominal aneurysm repair (97 EVAR and 68 open). The overall 30-day mortality rate was 3.7% (2.1% EVAR and 5.9% open). Forty per cent of patients had died at a median follow up of 77 months (interquartile range, 36-140). Most deaths were not related to aneurysm. There was no difference in the long-term mortality between the EVAR and open groups (hazard ratio [HR] = 1.22; 95% confidence interval [CI] 0.75-1.98, p = .43), but there was a trend of better outcomes with the use of commercially made endografts over open repair (HR = 2.9; 95% CI 0.9-10.0, p = .08) and custom-made endografts (HR = 3.1, 95% CI 0.9-10.3; p = .07). Eleven per cent of patients who had EVAR required a further procedure compared with 13% who had open repair. All but one of the re-interventions in the EVAR group was performed on patients who had custom-made endografts. CONCLUSIONS: Young patients with AAA have significant comorbidities and do not necessarily have long lifespans. In the less fit younger patients with AAA, the results with EVAR are comparable with fit patients who had open AAA repair. The management of fitter young patients with AAA remains controversial, but improving results with EVAR over time may increase the role of EVAR in this group.

Reprinted article "Neovascularisation is the principal cause of varicose vein recurrence: results of a randomised trial of stripping the long saphenous vein".

OBJECTIVES: To determine whether routine stripping of the long saphenous vein reduces recurrence after varicose vein surgery. DESIGN: Randomised controlled trial. All operations done by a consultant vascular surgeon. Two year follow-up. MATERIALS AND METHODS: One hundred patients with primary long saphenous varicose veins (133 legs) were randomised. Two year follow-up in 81 patients (113 legs) with questionnaire, clinical examination and Duplex scanning. RESULTS: Some 89% remained satisfied with the results of their surgery, though 35% had recurrent veins on clinical examination. Recurrence was reduced from 43 to 25% in patients who had their long saphenous vein stripped (p = 0.04, χ(2)). Neovascularisation (serpentine tributaries arising from the ligated saphenofemoral junction) was detected in 52% of limbs and was the commonest cause of recurrence. Most tributaries were less than 3 mm in diameter and only caused recurrence if the long saphenous vein or a major thigh vein was intact. Twelve patients had tributaries greater than 3 mm diameter and all had recurrent varicose veins. CONCLUSIONS: Recurrence is common after varicose vein surgery and in this study was caused principally by neovascularisation at the ligated saphenofemoral junction. Clinical recurrence is reduced by routine stripping of the long saphenous vein.

Laser and radiofrequency ablation study (LARA study): a randomised study comparing radiofrequency ablation and endovenous laser ablation (810 nm).

OBJECTIVES: There have been few randomised studies comparing Radiofrequency Ablation(RFA) with other endovenous techniques. The primary aim of this study was to determine whether RFA of the great saphenous vein (GSV) was associated with less pain and bruising than endovenous laser ablation (EVLA). MATERIALS AND METHODS: This trial had two cohorts--patients with bilateral GSV incompetence causing varicose veins (VV) and those with unilateral GSV VVs. In total 87 legs were treated in this study. Limbs in the bilateral group were treated with RFA in one leg and EVLA in the other. In the unilateral group limbs were randomised to RFA or EVLA. RFA was performed using the Celon RFiTT system (Teltow, Germany). EVLA was performed using an 810nm Laser (Biolitec AG, Germany). Phlebectomies were performed as required. Primary endpoints were patient assessed pain and bruising measured by visual analogue scale (VAS). Secondary endpoints were patency assessed by duplex ultrasound at 6 weeks and 6 months. RESULTS: In the bilateral group, RFA resulted in significantly less pain than EVLA on days 2-11 postoperatively. RFA also resulted in significantly less bruising than EVLA on days 3-9. There were no significant differences in mean post operative pain, bruising and activity scores in the unilateral group. Both RFA and EVLA resulted in occlusion rates of 95% at 10 days postoperatively. CONCLUSIONS: RFA was less painful for patients than EVLA and produced less bruising in the postoperative period with comparable success rates but there was no difference in the unilateral group.

Detection of medications associated with Alzheimer's disease using ensemble methods and cooperative game theory.

OBJECTIVE: To study the feasibility of evaluating feature importance with Shapley Values and ensemble methods in the context of pharmacoepidemiology and medication safety. METHODS: We detected medications associated with Alzheimer's disease (AD) by examining the additive feature attribution with combined approach of Gradient Boosting and Shapley Values in the Medication use and Alzheimer's disease (MEDALZ) study, a nested case-control study of 70,719 verified AD cases in Finland. Our methodological approach is to do binary classification using Gradient boosting (an ensemble of weak classifiers) in a supervised learning manner. Then we apply Shapley Values (from cooperative game theory) to analyze how feature combinations affect the classification result. Medication use with a five to one year time-window before AD diagnosis was ascertained from Prescription register. RESULTS: Antipsychotics with low or medium dose, antidepressants with medium to high dose, and cardiovascular medications with medium to high dose were identified as the contributing features for separating cases with AD from controls. Medium to high amount of irregularity in the purchase pattern were an indicating feature for separating AD cases from controls. The similarity of medication purchases between AD cases and controls made the feature evaluation challenging. CONCLUSIONS: The combined approach of Gradient Boosting and feature evaluation with Shapley Values identified features that were consistent with findings from previous hypothesis-driven studies. Additionally, the results from the additive feature attribution identified new candidates for future studies on AD risk factors. Our approach also shows promise for studies based on observational studies, where feature identification and interactions in populations are of interest; and the applicability of using Shapley Values for evaluating feature relevance in pattern recognition tasks.

The importance of anatomical suitability and fitness for the outcome of endovascular repair of ruptured abdominal aortic aneurysm.

INTRODUCTION: Endovascular repair of aortic aneurysm (EVAR) has a lower mortality than open repair. The aim of this study was to assess mortality from EVAR for emergency AAA repair and the impact of fitness for operation and adverse anatomy. METHODS: One-hundred and forty two patients who had EVAR for a ruptured AAA (80, REVAR) or a symptomatic AAA (62, SEVAR) between 1994 and 2007 in a single specialist endovascular centre were reviewed. Fitness for surgery was assessed by Hardman's index (age>76, loss of consciousness, Hb<9.0, Cr>190, ischaemic ECG). CT scans were reviewed, compared with operative images and operation notes for adverse anatomy. Details of perioperative complications, and outcome were recorded. RESULTS: Overall mortality at 24-h, 30-days and one year were, respectively: 17%, 36%, 50% for REVAR and 5%, 8%, 23% for SEVAR. Overall adverse anatomy increased 30-day mortality. Hardman's index of three or more increased mortality HR=2.59 (1.24-5.41), p=0.01. On Cox regression Univariate analysis increasing Hardman's index score and adverse anatomy increased the overall mortality over time. In multivariate Cox regression analysis (controlled for the Hardman's index) adverse anatomy was associated with significant increase in graft related mortality. CONCLUSION: The use of EVAR is feasible in patients who present with a ruptured or acutely symptomatic AAA. Care must be taken not to extend anatomical or clinical guidelines.

The Immediate Management of the Patient with Rupture: Open Versus Endovascular repair (IMPROVE) aneurysm trial--ISRCTN 48334791 IMPROVE trialists.

BACKGROUND: Systematic reviews have suggested a survival advantage for patients with ruptured abdominal aortic aneurysm (AAA), who are managed by endovascular repair. These reviews are based on single centre experiences of selected patients. OBJECTIVE: To determine whether a policy of endovascular repair improves the survival of all patients with ruptured AAA. METHODS: A randomized controlled trial, IMPROVE (ISRCTN 48334791) will randomize patients with a clinical diagnosis of rAAA, made in hospital, either to immediate CT scan and endovascular repair whenever anatomically suitable (endovascular first), or to open repair, with CT scan being optional (normal care), The trial is set on a background of guidelines for emergency care, CT scanning and anaesthesia, which incorporate the protocol of permissive hypotension. Recruitment started in October 2009 and 600 patients are required to show a 14% survival benefit at 30 days (primary outcome) for the endovascular first policy. Recruitment will be from the UK and Europe. Secondary outcomes include 24h, in-hospital and 1 year survival, complications, major morbidities, costs and quality of life. DISCUSSION: This is a "real life" trial that will answer the fundamental relevant clinical dilemma, namely, do patients who present with ruptured AAA derive benefit from treatment in a system, which offers a preferential strategy of endovascular repair? The trial addresses whether the anticipated reduced mortality and morbidity associated with endovascular repair is offset by the relatively greater ease of access and speed to conventional surgery. This issue is pivotal to future patient care and provision of services.

Computerized angiographic analysis of the outcome of peripheral thrombolysis.

BACKGROUND: Catheter-directed peripheral thrombolysis is used increasingly for the management of acute limb ischemia. The comparison of different agents and techniques has proven difficult because of the variations in patient presentation, vessel involvement, and treatment methods. METHODS: A computerized database in which angiographic information is stored on computerized arterial maps has been designed to record details of thrombolysis. RESULTS: A total of 201 patients who presented with rest pain were recorded on the database, and their angiograms were analyzed. There were 123 native-vessel and 78 graft occlusions. Immediate success of lysis and 30-day outcome were not dependent on the site of the occlusion. If an underlying stenosis was revealed, limb salvage rates were significantly greater than when none was found (82% versus 58%, P < 0.01). The presence of at least 1 run-off vessel increased limb salvage rates by 30% (P < 0.001). If more than 5 arterial segments were occluded on the prelysis angiogram, limb salvage was worse than if there were fewer than 5 (57% versus 85%, P < 0.0001). For grafts, less than 5 segments of occlusion led to limb salvage rates of 90%, and more than 5 segments of occlusion led to rates of 72% (P = 0.07). CONCLUSIONS: This simple and user-friendly system of computerized angiographic analysis will enable detailed examination of thrombolytic practice and assist in the prediction of success.

Haemostasis during carpal tunnel release under local anaesthesia: a controlled comparison of a tourniquet and adrenaline infiltration.

A randomized controlled comparison of tourniquet and local adrenaline infiltration for control of bleeding was performed in patients undergoing bilateral carpal tunnel release under local anaesthesia. Visual analogue scores for intra-operative pain were substantially greater for tourniquet (mean score 4.7) than for adrenaline (2.2). Incomplete control of bleeding was responsible for longer operating time and for the surgeons' perception of slightly greater operative difficulty with the use of adrenaline. There were no complications attributable to the use of adrenaline. The use of adrenaline-containing local anaesthesia for carpal tunnel release avoids tourniquet pain and is preferred by patients.

NATALI--a model for National Computer Databases in the investigation of new therapeutic techniques.

New medical treatments are often introduced without the benefit of randomized trials. We describe how a national computerized database was produced, by the Thrombolysis Study Group, for monitoring one such new treatment: peripheral arterial thrombolysis. A novel method for transferring angiograms to computer generated arterial maps that can help in the classification and analysis of the outcome of thrombolysis is also described. Data provided by prospective collection from 14 hospitals within the UK was entered onto the database (Auditbase for Windows), to give contributing members a continual audit of their own results and complications that can be compared with that of the group as a whole. This system may be an appropriate model for other forms of multi-centre audit and the monitoring of new treatments.

Plerixafor is superior to conventional chemotherapy for first-line stem cell mobilisation, and is effective even in heavily pretreated patients.

This study (PHANTASTIC) compares first-line plerixafor with granulocyte colony-stimulating factor (G-CSF) in 98 myeloma and lymphoma patients with 151 historic controls mobilised by conventional chemotherapy+G-CSF. Eleven patients developed mild transient symptoms possibly related to plerixafor. No serious adverse events were seen. Seventy (71%) plerixafor-mobilised patients achieved both ⩾ 4 × 10(6) CD34(+) cells/kg in ⩽ 2 aphereses and no neutropenia (<1.0 × 10(9)/l). This is significantly > 48 (32%) of 151 historical chemotherapy+G-CSF-mobilised control patients achieving this end point (P<0.001). Ninety-six (98%) plerixafor-mobilised patients achieved ⩾ 2 × 10(6) CD34(+) cells/kg within one harvest round compared with 114 (75%) of controls (P=0.001). Engraftment times and 12-month outcome were comparable in both groups. Prior treatment was summarised by two scoring systems. Controls mobilising either >2.0 or >4.0 × 10(6) CD34(+) cells/kg have significantly lower scores than mobilisation failures (P=0.002), but this relationship was not seen for plerixafor-mobilised patients. Plerixafor is a more effective and less toxic mobilising agent than conventional chemotherapy (especially in heavily pretreated patients), with comparable subsequent outcome, and merits consideration as the first-line standard of care for stem cell mobilisation.

Radiofrequency-induced thermal therapy: results of a European multicentre study of resistive ablation of incompetent truncal varicose veins.

OBJECTIVES: To investigate the effectiveness of bipolar radiofrequency-induced thermal therapy (RFITT) in a multicentre non-randomized study. METHODS: Some 672 incompetent saphenous veins (85% great saphenous varicose vein, 15% short saphenous vein) in 462 patients (56.5% CEAP [clinical, aetiological, anatomical and pathological elements] class 3 or worse) were treated in eight European centres. Patients were assessed between 180 and 360 days postoperatively. Occlusion rates were determined by duplex ultrasound and compared with the power used for treatment, pull back rate and experience of the operating surgeon. RESULTS: Complete occlusion rates of 98.4% were achieved when treatments were performed by an experienced operator (more than 20 cases), when the maximum power setting on the RFITT generator was between 18 and 20 W and the applicator was withdrawn at a rate slower than 1.5 second/cm CONCLUSIONS: RFITT is efficacious, well tolerated by patients and has a low incidence of procedure-related post-operative complications.