A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial.

BACKGROUND: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. METHODS: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. FINDINGS: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). INTERPRETATION: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. FUNDING: UK National Institute of Health Research Health Technology Programme.

A preoperative supervised exercise program potentially improves long-term survival after elective abdominal aortic aneurysm repair.

OBJECTIVE: A preoperative supervised exercise program (SEP) improves cardiorespiratory fitness and perioperative outcomes for patients undergoing elective abdominal aortic aneurysm (AAA) repair. The aim of this study was to assess the effect of a preoperative SEP on long-term survival of these patients. A secondary aim was to consider long-term changes in cardiorespiratory fitness and quality of life. METHODS: Patients scheduled for open or endovascular AAA repair were previously randomized to either a 6-week preoperative SEP or standard management, and a significant improvement in a composite outcome of cardiac, pulmonary, and renal complications was seen following SEP. For the current analysis, patients were followed up to 5 years post-surgery. The primary outcome for this analysis was all-cause mortality. Data were analyzed on an intention to treat (ITT) and per protocol (PP) basis, with the latter meaning that patients randomized to SEP who did not attend any sessions were excluded. The PP analysis was further interrogated using a complier average causal effect (CACE) analysis on an all or nothing scale, which adjusts for compliance. Additionally, patients who agreed to follow-up attended the research center for cardiopulmonary exercise testing and/or provided quality of life measures. RESULTS: ITT analysis demonstrated that the primary endpoint occurred in 24 of the 124 participants at 5 years, with eight in the SEP group and 16 in the control group (P = .08). The PP analysis demonstrated a significant survival benefit associated with SEP attendance (4 vs 16 deaths; P = .01). CACE analysis confirmed a significant intervention effect (hazard ratio, 0.36; 95% confidence interval, 0.16-0.90; P = .02). There was no difference between groups for cardiorespiratory fitness measures and most quality of life measures. CONCLUSIONS: These novel findings suggest a long-term mortality benefit for patients attending a SEP prior to elective AAA repair. The underlying mechanism remains unknown, and this merits further investigation.

Supervised Exercise Therapy for Intermittent Claudication: A Propensity Score Matched Analysis of Retrospective Data on Long Term Cardiovascular Outcomes.

OBJECTIVE: This study aimed to explore the long term outcomes of patients with intermittent claudication (IC) who completed supervised exercise therapy (SET) vs. those who declined or prematurely discontinued SET, focusing on the incidence of chronic limb threatening ischaemia (CLTI), revascularisation, major adverse limb events (MALE), and major adverse cardiovascular events (MACE). METHODS: A retrospective registry analysis of consecutive patients with IC who were referred for SET between March 2015 and August 2016 and followed up for a minimum of five years. Serial univariable analysis and logistic regression were performed to identify the statistically significant clinical variables that were independent predictors of each outcome measure. The resulting statistically significant variables were used to guide 1:1 propensity score matching (PSM) using the nearest neighbour method with a calliper of 0.2. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between SET and the outcomes of interest. RESULTS: Two hundred and sixty-six patients were referred to SET between March 2015 and August 2016. Of these, 64 patients completed SET and 202 patients did not. After PSM, 49 patients were analysed in each cohort. The Cox proportional hazards analysis revealed a significant association between completion of SET and revascularisation requirement (HR 0.46 95% CI 0.25 - 0.84; p = .011), completion of SET and progression to CLTI (HR 0.091, 95% CI 0.04 - 0.24; p < .001), completion of SET and MACE (HR 0.52; 95% CI 0.28 - 0.99; p = .05) and completion of SET and MALE (HR 0.28, 95% CI 0.13 - 0.65; p = .003). The Harrell's C index for all of these models was greater than 0.75, indicating good predictive accuracy. CONCLUSION: Completion of SET is associated with better outcomes in patients who completed SET compared with patients who declined or discontinued SET with respect to clinically important cardiovascular outcomes over seven years.

High INtensity Interval Training in pATiEnts with Intermittent Claudication: A Qualitative Acceptability Study.

BACKGROUND: A novel high-intensity interval training (HIIT) program has demonstrated feasibility for patients with intermittent claudication (IC). The aim of this study was to explore patient perspectives of the HIIT program to inform refinement and future research. METHODS: All patients screened and eligible for the 'high intensity interval training in patients with intermittent claudication (INITIATE)' study were eligible to take part in a semistructured interview. A convenience subsample of patients was selected from 3 distinct groups: 1) those who completed the HIIT program, 2) those who prematurely discontinued the HIIT program, and 3) those who declined the HIIT program. Interviews considered patients views of the program and experiences of undertaking and/or being invited to undertake it. Interviews were audio recorded, transcribed verbatim, and analyzed via thematic analysis. RESULTS: Eleven out of 31 participants who completed the program and 12 out of 38 decliners were interviewed. No participants who withdrew from the program agreed to interview. The 3 key themes were; personal reflections of the program; program facilitators and barriers; and perceived benefits. Completers enjoyed taking part, reported symptomatic improvement and would complete it again. Practical and psychological barriers exist, such as transport and motivation. Changes to the program were suggested. CONCLUSIONS: Findings support the acceptability of this novel HIIT program, which in combination with the feasibility findings, suggest that a fully powered randomized controlled trial, comparing HIIT to usual-care supervised exercise programs is warranted.

The incidence of surgical site infection following major lower limb amputation: A systematic review.

Surgical site infections (SSIs) following major lower limb amputation (MLLA) in vascular patients are a major source of morbidity. The objective of this systematic review was to determine the incidence of SSI following MLLA in vascular patients. This review was prospectively registered with the International Prospective Register of Systematic Reviews (CRD42023460645). Databases were searched without date restriction using a pre-defined search strategy. The search identified 1427 articles. Four RCTs and 21 observational studies, reporting on 50 370 MLLAs, were included. Overall SSI incidence per MLLA incision was 7.2% (3628/50370). The incidence of SSI in patients undergoing through-knee amputation (12.9%) and below-knee amputation (7.5%) was higher than the incidence of SSI in patients undergoing above-knee amputation, (3.9%), p < 0.001. The incidence of SSI in studies focusing on patients with peripheral arterial disease (PAD), diabetes or including patients with both was 8.9%, 6.8% and 7.2%, respectively. SSI is a common complication following MLLA in vascular patients. There is a higher incidence of SSI associated with more distal amputation levels. The reported SSI incidence is similar between patients with underlying PAD and diabetes. Further studies are needed to understand the exact incidence of SSI in vascular patients and the factors which influence this.

Molecular mechanisms of action of negative pressure wound therapy: a systematic review.

Negative pressure wound therapy (NPWT) has significantly advanced wound care and continues to find new applications. Its effects at a molecular level however, remain a subject of debate. The aim of this systematic review is to summarize the current evidence regarding the molecular mechanisms of action of NPWT. Medline, Embase, EBSCO databases and clinical trial registries were searched from inception to January 2023. Clinical studies, animal models or in-vitro studies that quantitatively or semi-quantitatively evaluated the influence of NPWT on growth factors, cytokine or gene-expression in the circulation or wound-bed were included. Risk of Bias assessment was performed using the RoBANS tool for non-randomized studies, the COCHRANE's Risk of Bias 2(ROB-2) tool for randomized clinical studies, OHAT tool for in-vitro studies or the SYRCLE tool for animal model studies. A descriptive summary was collated and the aggregated data is presented as a narrative synthesis. This review included 19 clinical studies, 11 animal studies and 3 in-vitro studies. The effects of NPWT on 43 biomarkers and 17 gene expressions were studied across included studies. NPWT stimulates modulation of numerous local and circulating cytokines and growth factor expressions to promote an anti-inflammatory profile. This is most likely achieved by downregulation of TNFα, upregulation of VEGF, TGF-ß and fibronectin.

High-intensity interval training in patients with intermittent claudication.

OBJECTIVE: Provision, uptake, adherence, and completion rates for supervised exercise programs (SEP) for intermittent claudication (IC) are low. A shorter, more time-efficient, 6-week, high-intensity interval training (HIIT) program may be an effective alternative that is more acceptable to patients and easier to deliver. The aim of this study was to determine the feasibility of HIIT for patients with IC. METHODS: A single arm proof-of-concept study, performed in secondary care, recruiting patients with IC referred to usual-care SEPs. Supervised HIIT was performed three times per week for 6 weeks. The primary outcome was feasibility and tolerability. Potential efficacy and potential safety were considered, and an integrated qualitative study was undertaken to consider acceptability. RESULTS: A total of 280 patients were screened: 165 (59%) were eligible, and 40 (25%) were recruited. The majority (n = 31; 78%) of participants completed the HIIT program. The remaining nine patients were withdrawn or chose to withdraw. Completers attended 99% of training sessions, completed 85% of sessions in full, and performed 84% of completed intervals at the required intensity. There were no related serious adverse events. Maximum walking distance (+94 m; 95% confidence interval, 66.6-120.8 m) and the SF-36 physical component summary (+2.2; 95% confidence interval, 0.3-4.1) were improved following completion of the program. CONCLUSIONS: Uptake to HIIT was comparable to SEPs in patients with IC, but completion rates were higher. HIIT appears feasible, tolerable, and potentially safe and beneficial for patients with IC. It may provide a more readily deliverable, acceptable form of SEP. Research comparing HIIT with usual-care SEPs appears warranted.

Provision of NICE-recommended varicose vein treatment in the NHS.

BACKGROUND: Standardization of access to treatment and compliance with clinical guidelines are important to ensure the delivery of high-quality care to people with varicose veins. In the National Health Service (NHS) in England, commissioning of care for people with varicose veins is performed by Clinical Commissioning Groups (CCGs) and clinical guidelines have been developed by the National Institute for Health and Care Excellence (NICE CG168). The Evidence-Based Intervention (EBI) programme was introduced in the NHS with the aim of improving care quality and supporting implementation of NICE CG168. The aim of this study was to assess access to varicose vein treatments in the NHS and the impact of EBI. METHODS: CCG policies for the delivery of varicose vein treatments in the NHS in England were obtained from 2017 (before EBI introduction) and 2019 (after EBI introduction) and categorized by two independent reviewers into levels of compliance with NICE CG168. Hospital Episode Statistics data were compared with the NICE commissioning model predictions. A quality-adjusted life-year was valued at £20 000 (Euro 23 000 15 November 2022). RESULTS: Despite the introduction of the EBI programme, CCG compliance with NICE CG168 fell from 34.0 per cent (64 of 191) to 29.0 per cent (55 of 191). Some 33.0 per cent of CCG policies (63 of 191) became less compliant and only 7.3 per cent (14 of 191) changed to become fully compliant. Overall, 66.5 per cent of CCGs (127 of 191) provided less than the recommended intervention rate before EBI and this increased to 73.3 per cent (140 of191) after EBI. The overall proportion of patients estimated to require treatment annually who received treatment fell from 44.0 to 37.0 per cent. The associated estimated loss in net health benefit was between £164 and 174 million (Euro 188 million and 199 million 15 November 2022) over 3 years. A compliant policy was associated with a higher intervention rate; however, commissioning policy was associated with only 16.8 per cent of the variation in intervention rate (R2 = 0.168, P < 0.001). CONCLUSION: Many local varicose vein commissioning policies in the NHS are not compliant with NICE CG168. More than half of patients who should be offered varicose vein treatment are not receiving it, and there is widespread geographical variation. The EBI programme has not been associated with any improvement in commissioning or access to varicose vein treatment.

Clinical outcomes following mechanochemical ablation of superficial venous incompetence compared with endothermal ablation: meta-analysis.

BACKGROUND: Mechanochemical ablation (MOCA) is an alternative method to endovenous thermal ablation (EVTA) for the treatment of superficial venous incompetence that does not require tumescent anaesthesia. The aim of this study was to compare the outcomes from RCTs of MOCA versus EVTA. METHODS: A search was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). Meta-analysis inclusion was restricted to RCTs comparing MOCA against EVTA. Outcomes included anatomical occlusion rate, disease-specific quality of life using the Aberdeen Varicose Vein Questionnaire, procedural and postprocedural pain, and rates of venous thromboembolism. RESULTS: Four RCTs were included in the meta-analysis comprising 654 patients. The anatomical occlusion rate at 1 year was lower after MOCA than EVTA (risk ratio 0.85, 95 per cent c.i. 0.78 to 0.91; P < 0.001). No significant differences were detected in procedural pain (mean difference -3.25, -14.25 to 7.74; P = 0.560) or postprocedural pain (mean difference -0.63, -2.15 to 0.89; P = 0.420). There were no significant differences in Aberdeen Varicose Vein Questionnaire score at 1 year (mean difference 0.06, -0.50 to 0.62; P = 0.830) or in incidence of venous thromboembolism (risk ratio 0.72, 95 per cent c.i. 0.14 to 3.61; P = 0.690). CONCLUSION: The rate of successful anatomical occlusion after MOCA is significantly lower than that after EVTA, but there is no difference in procedural and postprocedural pain between the two interventions. Long-term data are required to assess the impact of the reduced vein occlusion rate on clinical outcomes such as quality of life and reintervention.

The current first-line treatment for varicose veins uses heat to block the diseased veins and is called endovenous thermal ablation (EVTA). Mechanochemical ablation (MOCA) is an alternative method of treatment using a chemical and a fast-spinning wire to block the veins instead. The potential benefits of MOCA include less pain and fewer complications. The aim of this study was to identify high-quality clinical trials comparing MOCA with EVTA, and to assess any differences in the results of treatment. The results showed that MOCA was less successful in blocking the diseased veins than EVTA. There were no differences in the amount of pain or discomfort during or after the procedures (which was low). At 1 year, those treated with both techniques reported the same quality of life. Both techniques were effective over 1 year in terms of improving quality of life; however, the potential benefits of MOCA were not clearly proven in the trials, and the poorer rates of successfully blocking the veins may cause the varicose veins to come back sooner, or the quality-of-life improvement to be shorter lived. There was no evidence to support MOCA replacing EVTA as the first-line treatment in the majority of patients, but it is a viable treatment for selected people.

Outcomes after minor lower limb amputation for peripheral arterial disease and diabetes: population-based cohort study.

BACKGROUND: Patients with diabetes and peripheral arterial disease are at increased risk of minor amputation. The aim of study was to assess the rate of re-amputations and death after an initial minor amputation, and to identify associated risk factors. METHODS: Data on all patients aged 40 years and over with diabetes and/or peripheral arterial disease, who underwent minor amputation between January 2014 and December 2018, were extracted from Hospital Episode Statistics. Patients who had bilateral index procedures or an amputation in the 3 years before the study were excluded. Primary outcomes were ipsilateral major amputation and death after the index minor amputation. Secondary outcomes were ipsilateral minor re-amputations, and contralateral minor and major amputations. RESULTS: In this study of 22 118 patients, 16 808 (76.0 per cent) were men and 18 473 (83.5 per cent) had diabetes. At 1 year after minor amputation, the estimated ipsilateral major amputation rate was 10.7 (95 per cent c.i. 10.3 to 11.1) per cent. Factors associated with a higher risk of ipsilateral major amputation included male sex, severe frailty, diagnosis of gangrene, emergency admission, foot amputation (compared with toe amputation), and previous or concurrent revascularization. The estimated mortality rate was 17.2 (16.7 to 17.7) per cent at 1 year and 49.4 (48.6 to 50.1) per cent at 5 years after minor amputation. Older age, severe frailty, comorbidity, gangrene, and emergency admission were associated with a significantly higher mortality risk. CONCLUSION: Minor amputations were associated with a high risk of major amputation and death. One in 10 patients had an ipsilateral major amputation within the first year after minor amputation and half had died by 5 years.

Neuromuscular Electrical Stimulation for Intermittent Claudication (NESIC): multicentre, randomized controlled trial.

METHODS: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. RESULTS: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. CONCLUSION: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.

Patients with intermittent claudication experience pain in their legs during walking or exercise which ends with rest. This severely impairs physical activity and quality of life. Treatment for such patients typically involves best medical therapy, which includes exercise advice. This study aimed to determine whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy) in a trial. Supervised exercise improved walking distances but there was no difference in those that received a device in this patient group.

Editor's Choice - Outcomes of Surgery for Patients with Peripheral Arterial Disease During the COVID-19 Pandemic in the United Kingdom: A Population Based Study.

OBJECTIVE: There is limited information on changes in the patterns of care and outcomes for patients who had vascular procedures after the first wave of the COVID-19 pandemic. The aim of this population based study was to examine the patterns of care and outcomes for vascular lower limb procedures in the UK during the COVID-19 pandemic. METHODS: Lower limb revascularisations and major amputations performed from January 2019 to April 2021 in the UK and entered in the National Vascular Registry were included in the study. The primary outcome was in hospital post-operative death and secondary outcomes were complications and re-interventions. The study was divided into Pre-pandemic (1 January 2019 - 29 February 2020), Wave 1 (1 March - 30 June 2020), Respite (1 July - 31 October 2020), Wave 2/3 (1 November 2020 - 30 April 2021). RESULTS: The study included 36 938 procedures (7 245 major amputations, 16 712 endovascular, 12 981 open revascularisations), with 15 501 procedures after March 2020, a 27.7% reduction compared with pre-pandemic. The proportion of open surgical procedures performed under general anaesthetic was lower in Wave 1 and after compared with pre-pandemic (76.7% vs. 81.9%, p < .001). Only 4.6% of patients in the cohort had SARS-CoV-2 infection (n = 708), but their in hospital post-operative mortality rate was 25.0% (n = 177), six times higher than patients without SARS-CoV-2 (adjusted odds ratio 5.88; 95% CI 4.80 - 7.21, p < .001). The in hospital mortality rate was higher during the pandemic than pre-pandemic after elective open and endovascular revascularisation (respectively 1.6% vs. 1.1%, p = .033, and 0.9% vs. 0.5%, p = .005) and after major amputations (10.4% during Wave 2/3 vs. 7.7% pre-pandemic, p = .022). CONCLUSION: There was excess post-operative mortality rate for patients undergoing lower limb vascular procedures during the pandemic, which was associated with SARS-CoV-2 infections. Further research should be conducted on long term outcomes of patients operated on during the COVID-19 pandemic period.

Endovenous ablation for venous leg ulcers.

BACKGROUND: Venous leg ulcers (VLUs) are a serious manifestation of chronic venous disease affecting up to 3% of the adult population. This typically recalcitrant and recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The longstanding mainstay treatment for VLUs is compression therapy. Surgical removal of incompetent veins reduces the risk of ulcer recurrence. However, open surgery is an unpopular option amongst people with VLU, and many people are unsuitable for it. The efficacy of the newer, minimally-invasive endovenous techniques has been established in uncomplicated superficial venous disease, and these techniques can also be used in the management of VLU. When used with compression, endovenous ablation aims to further reduce pressure in the veins of the leg, which may impact ulcer healing. OBJECTIVES: To determine the effects of superficial endovenous ablation on the healing and recurrence of venous leg ulcers and the quality of life of people with venous ulcer disease. SEARCH METHODS: In April 2022 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scrutinised reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions on the language of publication, but there was a restriction on publication year from 1998 to April 2022 as superficial endovenous ablation is a comparatively new technology. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing endovenous ablative techniques with compression versus compression therapy alone for the treatment of VLU were eligible for inclusion. Studies needed to have assessed at least one of the following primary review outcomes related to objective measures of ulcer healing such as: proportion of ulcers healed at a given time point; time to complete healing; change in ulcer size; proportion of ulcers recurring over a given time period or at a specific point; or ulcer-free days. Secondary outcomes of interest were patient-reported quality of life, economic data and adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for eligibility, extracted data, carried out risk of bias assessment using the Cochrane RoB 1 tool, and assessed GRADE certainty of evidence. MAIN RESULTS: The previous version of this review found no RCTs meeting the inclusion criteria. In this update, we identified two eligible RCTs and included them in a meta-analysis. There was a total of 506 participants with an active VLU, with mean durations of 3.1 months ± 1.1 months in the EVRA trial and 60.5 months ± 96.4 months in the VUERT trial. Both trials randomised participants to endovenous treatment and compression or compression alone, however the compression alone group in the EVRA trial received deferred endovenous treatment (after ulcer healing or from six months). There is high-certainty evidence that combined endovenous ablation and compression compared with compression therapy alone, or compression with deferred endovenous treatment, improves time to complete ulcer healing (pooled hazard ratio (HR) 1.41, 95% CI 1.36 to 1.47; I2 = 0%; 2 studies, 466 participants). There is moderate-certainty evidence that the proportion of ulcers healed at 90 days is probably higher with combined endovenous ablation and compression compared with compression therapy alone or compression with deferred endovenous treatment (risk ratio (RR) 1.14, 95% CI 1.00 to 1.30; I2 = 0%; 2 studies, 466 participants). There is low-certainty evidence showing an unclear effect on ulcer recurrence at one year in people with healed ulcers with combined endovenous treatment and compression when compared with compression alone or compression with deferred endovenous treatment (RR 0.29, 95% CI 0.03 to 2.48; I2 = 78%; 2 studies, 460 participants). There is also low-certainty evidence that the median number of ulcer-free days at one year may not differ (306 (interquartile range (IQR) 240 to 328) days versus 278 (IQR 175 to 324) days) following combined endovenous treatment and compression when compared with compression and deferred endovenous treatment; (1 study, 450 participants). There is low-certainty evidence of an unclear effect in rates of thromboembolism between groups (RR 2.02, 95% CI 0.51 to 7.97; I2 = 78%, 2 studies, 506 participants). The addition of endovenous ablation to compression is probably cost-effective at one year (99% probability at GBP 20,000/QALY; 1 study; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Endovenous ablation of superficial venous incompetence in combination with compression improves leg ulcer healing when compared with compression alone. This conclusion is based on high-certainty evidence. There is moderate-certainty evidence to suggest that it is probably cost-effective at one year and low certainty evidence of unclear effects on recurrence and complications. Further research is needed to explore the additional benefit of endovenous ablation in ulcers of greater than six months duration and the optimal modality of endovenous ablation.

The Edinburgh Claudication Questionnaire has poor diagnostic accuracy in people with intermittent claudication.

BACKGROUND: The screening and diagnosis of intermittent claudication is a challenging process and often relies on the expertise of specialist vascular clinicians. We sought to investigate the diagnostic performance of the Edinburgh Claudication Questionnaire (ECQ) as a screening tool for referrals of suspected intermittent claudication from primary to secondary care. METHOD: Prospectively, 100 referrals from primary care with a stated diagnosis or query regarding intermittent claudication were recruited. All participants who completed the ECQ, underwent an anklebrachial pressure index (ABPI) assessment and treadmill exercise testing. Outcomes of the ECQ were compared to clinical diagnoses of intermittent claudication. RESULTS: The ECQ had a sensitivity of 46.8% (95% CI: 27-65%), specificity of 63.2% (95% CI: 43-82%) and accuracy of 53.0% (95% CI: 43-63%). The diagnostic performance was not changed by combining the ECQ with a positive ABPI or post-exercise ABPI outcome for PAD. CONCLUSION: The ECQ had a poor diagnostic performance in this cohort. Considering the results found here and in other recent studies, the utility of the ECQ as a screening tool and epidemiological survey tool must be questioned. Novel, low-resource diagnostic tools are needed in this population.

Extracorporeal shockwave therapy for diabetic foot ulcers: a feasibility study.

OBJECTIVE: The purpose of this study was to assess the feasibility of delivering extracorporeal shockwave therapy (ESWT) to patients with diabetic foot ulcers (DFUs). It also aimed to explore any potential clinical effect of ESWT on wound healing and investigate whether ESWT offers any patient-reported benefits. METHOD: In this single-centre, mixed methods feasibility study, patients with a DFU who met the eligibility criteria underwent ESWT three times over a seven-day period. Primary outcome was feasibility of delivering the intervention. Secondary outcomes included wound size, number of DFUs healed at 12 weeks and quality of life (QoL). Semi-structured interviews explored participants' experience of undergoing ESWT. RESULTS: Of 106 patients screened, 24 (22.6%) were recruited. Following recruitment, two patients were withdrawn from the study with 22 patients included in the final analysis. The mean attendance at clinic was 90.9% and 65.1% for follow-up. The mean score for acceptability and tolerability was 9.86±0.48 (95% confidence interval (CI): 9.62-10.01) and 9.15±2.57 (95% CI: 7.87-10.42), respectively. There were no serious adverse events or side-effects. Of the DFUs, 45.5% healed during follow-up and QoL scores improved until eight weeks. Key themes identified from the qualitative interviews were: desire for fast healing; improved QoL; flexibility of new treatments; and accessibility of transport. CONCLUSION: This study has shown that it is possible to recruit and retain patents into a single-arm study of ESWT for DFUs. This study supports development of a large randomised control trial to determine the clinical and cost-effectiveness of ESWT for DFU healing.

A vascular multi-arm multi-stage trial to prevent groin wound surgical site infection: A feasibility survey.

Surgical site infection (SSI) is common following arterial surgery involving a groin incision. There is a lack of evidence regarding interventions to prevent groin wound SSI, therefore, a survey of vascular clinicians was undertaken to assess current opinion and practice, equipoise and feasibility of a randomised controlled trial (RCT). Participants at the Vascular Society of Great Britain and Ireland 2021 Annual Scientific Meeting were surveyed regarding three separate interventions designed to prevent SSI in the groin; impregnated incise drapes, diakylcarbomoyl chloride dressings and antibiotic impregnated collagen sponges. Results were collated via an online survey using the Research Electronic Data Capture platform. Seventy-five participants completed the questionnaire, most were consultant vascular surgeons (50/75, 66.7%). The majority agree that groin wound SSI is a major problem (73/75, 97.3%), and would be content using either of the three interventions (51/61, 83.6%) and had clinical equipoise to randomise patients to any of the three interventions versus standard of care (70/75, 93.3%). There was some reluctance to not use impregnated incise drapes as may be considered "standard of care". Groin wound SSI is perceived as major problem in vascular surgery, and a multicentre RCT of three preventative interventions appears acceptable to vascular surgeons.

Extracorporeal shockwave therapy compared with standard care for diabetic foot ulcer healing: An updated systematic review.

Emerging evidence suggests that extracorporeal shockwave therapy (ESWT) may improve time to DFU healing. The aim of this review was to appraise the evidence on role of ESWT in DFU healing and impact of different ESWT doses. Databases were searched for trials comparing ESWT plus standard care to standard care alone in participants with DFUs. Search results were reviewed by two independent reviewers. The Cochrane Risk of Bias 2 tool and GRADE approach was used to assess bias and certainty. The primary outcome was time to healing. The search identified 345 papers after duplicates removed. Six trials consisting of 471 participants were included. There was unclear or high risk of bias across all domains. Time to ulcer healing was probably shorter in patients treated with ESWT compared with standard ulcer care alone (GRADE: low certainty). Patients treated with ESWT were more likely to heal at 20 weeks post-ESWT compared with those treated with standard ulcer care alone (GRADE: low certainty). There was significant heterogeneity. ESWT remains a promising new treatment but the translation into routine clinical practice is still limited by the low certainty of evidence surrounding its effectiveness, case selection and optimum dose.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

Extended-course antibiotic prophylaxis in lower limb amputation: randomized clinical trial.

BACKGROUND: Lower limb amputation (LLA) is typically described as 'clean surgery', but surgical-site infection (SSI) rates are high and there is significant variation in antibiotic prophylaxis practice. This study aimed to determine whether an extended period of antibiotic prophylaxis (5-day course) is superior to a short course (24 h) in preventing SSI in patients undergoing minor and major LLA. METHODS: Patients undergoing minor and major amputation from a single vascular unit were recruited and randomized to receive either a 5-day or a 24-h prophylactic course of antibiotics. Patients with significant baseline infection were excluded. Outcomes included the incidence of SSI and impaired wound healing (IWH), both measured using ASEPSIS criteria, the need for further surgery, duration of hospital stay, and mortality up to 1 year. RESULTS: Some 161 patients were recruited to the study, and 152 were included in the analysis. A 5-day course of antibiotics was associated with a lower incidence of SSI (11.8 versus 39.5 per cent; P < 0.001) and lower incidence of IWH (22.4 versus 58 per cent; P < 0.001). Fewer patients receiving the 5-day course required amputation revisional surgery (6.6 versus 21 per cent; P = 0.010). Duration of hospital stay and mortality rates were similar. The presence of SSI (odds ratio (OR) 5.14, 95 per cent c.i. 1.96 to 13.45; P < 0.001) and IWH (OR 4.62, 1.68 to 12.72; P = 0.003) increased the need for revisional surgery. SSI increased the duration of hospital stay: median 28 (i.q.r. 16-40) versus 14 (9-21) days (P = 0.045). CONCLUSION: SSI and IWH are common after LLA and have a significant impact on outcome. A 5-day course of antibiotic prophylaxis was associated with a reduction in both SSI and IWH compared with a 24-h course, and this reduced the need for further surgery. Registration number: NCT02018094 (http://www.clinicaltrials.gov); EudraCT 2012-003146-32 (https://www.clinicaltrialsregister.eu).

Compression following treatment of superficial venous incompetence: systematic review.

BACKGROUND: International guidelines recommend postprocedural compression when treating symptomatic superficial venous incompetence (SVI). This updated review of RCTs investigated the requirement for postprocedural compression and how it can be applied optimally. METHODS: The National Institute for Health and Care Excellence's Healthcare Databases Advanced Search engine was used to identify all English-language RCTs of compression following treatment for SVI. Outcomes of interest included postprocedural pain, venous thromboembolism, health-related quality of life (HRQoL), and anatomical occlusion. RESULTS: A total of 18 studies were included comprising some 2584 treated limbs. Compression was compared with no compression in four studies, nine studies compared different durations of compression, and a further five compared different types of compression. A 1-2-week period of compression was associated with a mean reduction of 11 (95 per cent c.i. 8 to 13) points in pain score on a 100-mm visual analogue scale compared with a shorter duration (P < 0.001). This was associated with improved HRQoL and patient satisfaction. Longer durations of compression did not add further benefit. There was low-quality evidence suggesting that 35-mmHg compression with eccentric thigh compression achieved lower pain scores than lower interface pressures. There were no significant differences in venous thromboembolism rates or technical success in any group, including no compression. CONCLUSION: Postprocedural compression of 1-2 weeks after SVI treatment is associated with reduced pain compared with a shorter duration. The optimal interface pressure and type of compression, and the impact on venous thromboembolism risk, remain to be determined.