Tailored risk assessment and forecasting in intermittent claudication.

BACKGROUND: Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the first line of treatment in intermittent claudication, but implementation challenges and poor patient compliance lead to significant variation in management and therefore outcomes. The development of a precise risk stratification tool is proposed through a machine-learning algorithm that aims to provide personalized outcome predictions for different management strategies. METHODS: Feature selection was performed using the least absolute shrinkage and selection operator method. The model was developed using a bootstrapped sample based on patients with intermittent claudication from a vascular centre to predict chronic limb-threatening ischaemia, two or more revascularization procedures, major adverse cardiovascular events, and major adverse limb events. Algorithm performance was evaluated using the area under the receiver operating characteristic curve. Calibration curves were generated to assess the consistency between predicted and actual outcomes. Decision curve analysis was employed to evaluate the clinical utility. Validation was performed using a similar dataset. RESULTS: The bootstrapped sample of 10 000 patients was based on 255 patients. The model was validated using a similar sample of 254 patients. The area under the receiver operating characteristic curves for risk of progression to chronic limb-threatening ischaemia at 2 years (0.892), risk of progression to chronic limb-threatening ischaemia at 5 years (0.866), likelihood of major adverse cardiovascular events within 5 years (0.836), likelihood of major adverse limb events within 5 years (0.891), and likelihood of two or more revascularization procedures within 5 years (0.896) demonstrated excellent discrimination. Calibration curves demonstrated good consistency between predicted and actual outcomes and decision curve analysis confirmed clinical utility. Logistic regression yielded slightly lower area under the receiver operating characteristic curves for these outcomes compared with the least absolute shrinkage and selection operator algorithm (0.728, 0.717, 0.746, 0.756, and 0.733 respectively). External calibration curve and decision curve analysis confirmed the reliability and clinical utility of the model, surpassing traditional logistic regression. CONCLUSION: The machine-learning algorithm successfully predicts outcomes for patients with intermittent claudication across various initial treatment strategies, offering potential for improved risk stratification and patient outcomes.

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.

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.

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.

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.

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.

A pilot feasibility randomised clinical trial comparing dialkylcarbamoylchloride-coated dressings versus standard care for the primary prevention of surgical site infection.

A surgical site infection (SSI) may occur in up to 30% of procedures and results in significant morbidity and mortality. We aimed to assess the feasibility of conducting a randomised controlled trial (RCT) examining the use of dialkylcarbamoylchloride (DACC)-impregnated dressings, which bind bacteria at the wound bed, in the prevention of SSI in primarily closed incisional wounds. This pilot RCT recruited patients undergoing clean or clean-contaminated vascular surgery. Participants were randomised intraoperatively on a 1:1 basis to either a DACC-coated dressing or a control dressing. Outcomes were divided into feasibility and clinical outcomes. The primary clinical outcome was SSI at 30 days (assessed using Centers for Disease Control criteria and Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of the deep tissues, Isolation of bacteria and duration of inpatient Stay scoring methods). This study recruited 144 patients in 12 months at a median rate of 10 per month. Eligibility was 73% and recruitment 60%. At 30 days, there was a 36.9% relative risk reduction in the DACC-coated arm (16.22% versus 25.71%, odds ratio 0.559, P = 0.161). The number needed to treat was 11 patients. A large-scale RCT is both achievable and desirable given the relative risk reduction shown in this study. Further work is needed to improve the study protocol and involve more centres in a full-scale RCT.

Assessing the effectiveness of dialkylcarbamoylchloride (DACC)-coated post-operative dressings versus standard care in the prevention of surgical site infection in clean or clean-contaminated, vascular surgery (the DRESSINg trial): study protocol for a pilot feasibility randomised controlled trial.

BACKGROUND: Surgical site infection in vascular surgery has a reported incidence of up to 19%. A novel method of reducing this rate of infection is dressings coated with dialkylcarbamoylchloride (DACC), a hydrophobic wound contact layer that binds bacteria and removes them from the wound bed. Early research has suggested that DACC-coated wound dressings are effective in reducing surgical site infection when applied to wounds healing by primary intention post-operatively, therefore this trial aims to assess the feasibility of producing high-quality evidence assessing this theory. METHODS: Patients undergoing clean or clean-contaminated vascular surgery will be randomised to have their surgical wounds dressed with a DACC-coated dressing or a non-coated occlusive absorbent post-operative dressing. All other aspects of their peri-operative care will be standardised or carried out in line with hospital policy. Wound assessments will be carried out between day 5-7, day 30 (± 3 days) and 6 months post-operatively (± 7 days) by a blinded assessor using the ASEPSIS scoring tool. Quality of life data using EQ-5D and SF-36, resource use and mortality data will also be collected. This feasibility trial will dictate the conduct of a full-scale trial through the collection of data on recruitment and retention rates, and fitness-for-purpose of the follow-up arrangements. DISCUSSION: Surgical site infections are now the second most common hospital acquired infections with a significant cost implication. The aim of the DRESSINg trial is to investigate the effectiveness of a novel preventative measure at reducing wound infections post-surgery and will provide robust evidence to support or deny its use. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02992951, Registered 12/12/16. REC Reference: 16/LO/2135.