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.

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.

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.

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.

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.

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.

A Randomized Controlled Trial of Endovenous Laser Ablation Versus Mechanochemical Ablation With ClariVein in the Management of Superficial Venous Incompetence (LAMA Trial).

OBJECTIVE: This RCT compares the clinical, technical and quality of life outcomes after EVLA and MOCA. SUMMARY OF BACKGROUND DATA: Thermal ablation is the current mainstay treatment for SVI. Newer nonthermal methods of treatment have been developed which do not require the use of tumescent anesthesia. The potential advantages of these newer methods should be tested in RCTs to ascertain their role in the future treatments of SVI. METHODS: This single-center RCT enrolled patients with symptomatic, unilateral, single-axis SVI. Eligible patients were equally randomized to either EVLA or MOCA, both with concomitant phlebectomy when necessary. The joint primary outcomes were intraprocedural axial ablation pain scores and anatomical occlusion at 1 year. Secondary outcomes included postprocedural pain, venous clinical severity score (VCSS), quality of life (Aberdeen varicose veins questionnaire and EuroQol 5-domain utility index), patient satisfaction and complication rates. RESULTS: One hundred fifty patients were randomized equally between the 2 interventions. Both groups reported low intraprocedural pain scores; on a 100 mm visual analog scale, pain during axial EVLA was 22 (9-44) compared to 15 (9-29) during MOCA; P = 0.210. At 1 year, duplex derived anatomical occlusion rates after EVLA were 63/69 (91%) compared to 53/69 (77%) in the MOCA group; P = 0.020. Both groups experienced significant improvement in VCSS and AVVQ after treatment, without a significant difference between groups. Median VCSS improved from 6 (5-8) to 0 (0-1) at one year; P < 0.001. Median AVVQ improved from 13.8 (10.0-17.7) to 2.0 (0.0-4.9); P < 0.001. One patient in the MOCA group experienced DVT. CONCLUSIONS: Both EVLA and MOCA were highly efficacious in treating SVI; patients improved significantly in terms of disease severity, symptoms, and QoL. Both resulted in low procedural pain with a short recovery time. Axial occlusion rates were higher after EVLA. Long term follow-up is warranted to assess the effect of recanalization on the rate of clinical recurrence.

Through-knee versus above-knee amputation for vascular and non-vascular major lower limb amputations.

BACKGROUND: Diabetes and vascular disease are the leading causes of lower limb amputation. Currently, 463 million adults are living with diabetes, and 202 million with peripheral vascular disease, worldwide. When a lower limb amputation is considered, preservation of the knee in a below-knee amputation allows for superior functional recovery when compared with amputation at a higher level. When a below-knee amputation is not feasible, the most common alternative performed is an above-knee amputation. Another possible option, which is less commonly performed, is a through-knee amputation which may offer some potential functional benefits over an above-knee amputation. OBJECTIVES: To assess the effects of through-knee amputation compared to above-knee amputation on clinical and rehabilitation outcomes and complication rates for all patients undergoing vascular and non-vascular major lower limb amputation. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases; the World Health Organization International Clinical Trials Registry Platform; and the ClinicalTrials.gov trials register to 17 February 2021. We undertook reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: Published and unpublished randomised controlled trials (RCTs) comparing through-knee amputation and above-knee amputation were eligible for inclusion in this study. Primary outcomes were uncomplicated primary wound healing and prosthetic limb fitting. Secondary outcomes included time taken to achieve independent mobility with a prosthesis, health-related quality of life, walking speed, pain, and 30-day survival. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all records identified by the search. Data collection and extraction were planned in line with recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We planned to assess the certainty of evidence using the GRADE approach. MAIN RESULTS: We did not identify RCTs that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: No RCTs have been conducted to determine comparative clinical or rehabilitation outcomes of through-knee amputation and above-knee amputation, or complication rates. It is unknown whether either of these approaches offers improved outcomes for patients. RCTs are needed to guide practice and to ensure the best outcomes for this patient group.

Cardiovascular and musculoskeletal response to supervised exercise in patients with intermittent claudication.

OBJECTIVE: Intermittent claudication occurs in 20% of the population older than 70 years, and treatment includes a supervised exercise program (SEP). Whereas there is evidence demonstrating walking improvements after an SEP, there are conflicting data on the physiologic changes behind this. This study aimed to explore and to identify the potential cardiovascular and musculoskeletal changes with exercise. METHODS: This was a single-center study at a vascular unit in England. Following written informed consent, 109 patients were recruited for an SEP, three times per week for 12 weeks. Outcome measures included walking distances, quality of life, cardiorespiratory fitness, flow-mediated dilation, and muscle strength and endurance. For normal data, paired sample t-tests were performed to compare baseline data to all time points for significance. For nonparametric data, Wilcoxon signed rank tests were performed. Significance was set at P < .05. The association between functional improvement (ie, walking distance at 3 months after the SEP) and metabolic response and patients' characteristics was determined by multivariable regressions. RESULTS: Maximum walking distance significantly improved from baseline by 117% at 1 week, 143% at 4 weeks, and 143% at 12 weeks after exercise. Claudication distance also significantly improved from baseline by 222% at week 1, 393% at week 4, and 452% at week 12. Quality of life significantly improved at all time points in seven of nine domains of the 36-Item Short Form Health Survey and two of five domains of the Vascular Quality of Life questionnaire. Markers of cardiorespiratory fitness significantly improved at all time points. Flow-mediated dilation demonstrated a 50% improvement, but this was not statistically significant. Muscle strength and muscle endurance significantly improved at all time points. Multivariate regression demonstrated that the ventilatory anaerobic threshold and the physical component summary score for quality of life predicted improvements in 12-week walking distance. CONCLUSIONS: This study identified that the ventilatory anaerobic threshold and physical component summary scores from quality of life were the best predictors of improvement in an SEP. Future studies should prioritize these outcomes and assess whether different SEPs have similar effects. Cardiorespiratory fitness was also a predictor of outcome and should be prioritized in future studies alongside traditional measures.

The Intrarater and Interrater Reliability of Measures Derived from Cardiopulmonary Exercise Testing in Patients with Abdominal Aortic Aneurysms.

BACKGROUND: Patients with abdominal aortic aneurysms (AAAs) often have low exercise tolerance due to comorbidities and advanced age. Cardiopulmonary exercise testing (CPET) is predictive of postoperative morbidity and mortality in patients with AAA. We aimed to assess the intrarater and interrater reliability of both treadmill-based and cycle ergometer-based CPET variables. METHODS: Patients with an AAA (>3.5 cm) were randomized to a treadmill or bike CPET. Patients were asked to perform two separate CPETs seven days apart after a familiarization protocol. All CPETs were carried out using a ramp cycle or modified Bruce treadmill protocol with breath-by-breath gas analysis. RESULTS: Twenty-two male and 2 female patients, aged 73.6 ± 6.0 years, completed the study. Intrarater analysis (intraclass correlation coefficients) demonstrated high reliability on both the treadmill and bike for ventilatory anaerobic threshold (r = 0.834 and r = 0.975, respectively). All other CPET variables demonstrated high intrarater reliability on both modalities, bar the highest point for the ventilatory slope of oxygen (VE/VO2) on the treadmill (substantial agreement r = 0.755). Furthermore, interrater reliability demonstrated high agreement for ventilatory anaerobic threshold on both the treadmill and cycle (r = 0.983 and r = 0.905, respectively). All other CPET variables demonstrated high intrarater reliability on both modalities, with the exception of VO2Peak on the cycle ergometer (fair agreement r = 0.400). CONCLUSION: CPET in patients with AAAs is a reliable tool test and among CPET test reviewers for common testing modalities/protocols. These findings provide further support for the use of CPET, especially treadmill walking, as a clinical measure of perioperative cardiorespiratory fitness in patients with AAAs.

Extracorporeal Shockwave Therapy for Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetes mellitus is one of the most common chronic diseases worldwide. Diabetic foot ulcers (DFUs) occur in over 10% of diabetic patients and are associated with high morbidity. Clinical trials have shown benefit from extracorporeal shockwave therapy (ESWT) in a DFU healing. This systematic review aims to assess the currently available evidence examining the efficacy of ESWT on healing of DFU. METHODS: Electronic databases including PubMed, Ovid MEDLINE, Web of Science, Embase, CINAHL Plus, Cochrane Central Registry of Controlled Trials, and Clinical Trials Registry were searched up to November 2017 for terms related to ESWT in DFU. Articles were identified, and data were extracted by 2 independent reviewers onto Review Manager 5.3 software. RESULTS: This review included 5 trials of 255 patients published between 2009 and 2016. Three studies compared ESWT to standard wound care, and 2 studies compared ESWT to hyperbaric oxygen therapy (HBOT). All studies contained unclear to high risk of bias assessed by the Cochrane Risk of Bias Tool. ESWT was superior to standard wound care at complete wound healing (odds ratio [OR] 2.66 95% confidence interval [CI] 1.03, 6.87, I2 0%) and time to healing (64.5 ± 8.06 days versus 81.17 ± 4.35 days). DFU healing improved more with ESWT than HBOT (OR 2.45 95% CI 1.07, 5.61 I2 28%). There was variable evidence of effect on the blood flow perfusion rate. Infection rate and amputation rate were not reported. CONCLUSIONS: This systematic review concludes that ESWT has the potential to improve healing in DFUs, although there is, as yet, insufficient evidence to justify its use in routine clinical practice. The meta-analysis has a high risk of bias and is unlikely to reflect true effect size because of problematic risk of bias in included studies. This review highlights the variable quality of methodology of trials and dosing of shockwave therapy and the need for robust adequately powered research into this promising therapy.

A feasibility double-blind randomized placebo-controlled trial of extracorporeal shockwave therapy as a novel treatment for intermittent claudication.

BACKGROUND: Intermittent claudication is the most common symptom of peripheral arterial disease. Previous research has suggested that extracorporeal shockwave therapy (ESWT) may induce angiogenesis in treated tissue. The objective of this feasibility pilot trial was to assess the safety, tolerability, and efficacy of ESWT as a novel treatment. METHODS: Patients with unilateral claudication were randomized to receive ESWT or sham treatment to the calf muscle three times per week for 3 weeks. Primary outcomes were pain-free walking distance (PFWD) and maximum walking distance (MWD). Secondary outcomes included safety and tolerability of ESWT treatment, ankle-brachial index before and after exercise, and quality of life assessed using generic (36-Item Short Form Health Survey, EuroQol-5 Dimension 3-Level) and disease-specific (Vascular Quality of Life) instruments. Participants were assessed at baseline and 4, 8, and 12 weeks after treatment. Feasibility outcomes included recruitment and attendance rates for treatment and follow-up. RESULTS: Thirty patients were recruited in total. Statistically significant (P < .05) improvements at all time points were observed in the active treatment group for both MWD and PFWD compared with the sham treatment group. PFWD improved by 276% in the active group and MWD improved by 167% in the active group at 12 weeks after treatment. There were no immediate or delayed treatment safety concerns or documented adverse effects of treatment with ESWT in this trial. CONCLUSIONS: ESWT is safe and well tolerated when it is applied to the calf and demonstrated significant improvements in walking distances. Current conservative management of intermittent claudication includes supervised exercise. The early results with ESWT as an alternative, noninvasive treatment option show great potential. The mechanism of action, durability of the clinical effect, and cost-effectiveness of ESWT for claudication require further investigation.

Extracorporeal shockwave therapy for intermittent claudication: Medium-term outcomes from a double-blind randomised placebo-controlled pilot trial.

Objectives Peripheral arterial disease most commonly presents as intermittent claudication (IC). Early evidence has suggested that extracorporeal shockwave therapy is efficacious in the short term for the management of intermittent claudication. The objective of this pilot trial was to evaluate the medium-term efficacy of this treatment. Methods This double-blind randomised placebo-controlled pilot trial randomised patients with unilateral intermittent claudication in a 1:1 fashion to receive extracorporeal shockwave therapy or a sham treatment for three sessions per week over three weeks. Primary outcomes were maximum walking distance and intermittent claudication distance using a fixed-load treadmill test. Secondary outcomes included pre- and post-exertional ankle-brachial pressure indices, safety and quality of life assessed using generic (SF36, EQ-5D-3L) and disease-specific (vascular quality of life) measures. All outcome measures were assessed at 12 months post-treatment. Results Thirty participants were included in the study (extracorporeal shockwave therapy, n = 15; sham, n = 15), with 26 followed up and analysed at 12 months (extracorporeal shockwave therapy, n = 13; sham, n = 13). Intragroup analysis demonstrated significant improvements in maximum walking distance, intermittent claudication distance and post-exertional ankle-brachial pressure indices ( p < 0.05) in the active treatment group, with no improvements in pre-exertional ankle-brachial pressure indices. Significant improvements in quality of life were observed in 3 out of 19 domains assessed in the active group. A re-intervention rate of 26.7% was seen in both groups. Conclusions These findings suggest that extracorporeal shockwave therapy is effective in improving walking distances at 12 months. Although this study provides important pilot data, a larger study is needed to corroborate these findings and to investigate the actions of this treatment. ISRCTN: NCT02652078.

Dialkylcarbamoyl Chloride Dressings in the Prevention of Surgical Site Infections after Nonimplant Vascular Surgery.

BACKGROUND: Dressings coated with dialkylcarbamoyl chloride (DACC) are highly hydrophobic and irreversibly bind multiple types of bacteria, trapping them in the dressing and reducing the number of organisms at the wound surface. We aimed to assess the impact of DACC-coated postoperative dressings on the incidence of surgical site infection (SSI) in nonimplant vascular surgery patients. METHODS: Two hundred patients undergoing nonimplant vascular surgery were prospectively recruited at a single vascular center. The initial 100 patients had their operative wounds dressed with conventional dressings followed by 100 patients who received DACC-coated postoperative dressings. Wounds were reviewed at day 5 and day 30 to determine the presence of SSI using the ASEPSIS scoring system. The variation in outcomes between groups was assessed using chi-squared test and logistic regression analysis to assess the effects of other variables, which may affect healing. RESULTS: Between August 1, 2015 and February 29, 2016, a total of 120 men and 80 women were recruited. The mean age was 63 (range 27-97) years, 92% were current or ex-smokers and 45.5% were diabetic. Rate of SSI at 5 days was significantly lower in the DACC group compared with standard dressings (1% vs. 10%, P < 0.05). There was no difference in the rates of SSI at 30 days. Logistic regression suggested that the type of dressing used was the most prominent predictor variable for the presence of early SSI (P = 0.028, odds ratio = 0.09, 95% confidence interval: 0.01-0.77). CONCLUSIONS: DACC-coated dressings were associated with a significant reduction in SSI rates in the early postoperative period.

Comparison of Use of Short Form-36 Domain Scores and Patient Responses for Derivation of Preference-Based SF6D Index to Calculate Quality-Adjusted Life Years in Patients with Intermittent Claudication.

BACKGROUND: The short form 36 (SF36) questionnaire is used for assessment of generic quality of life. Responses to the individual question in SF36 are also used for calculation of the SF6D index score. This score is used for calculation of quality adjusted-life years (QALYs) in economical analyses. As the individual patient questionnaires are not always available for performing systematic reviews and meta-analyses, a new formula has been developed for derivation of SF6D index score from the reported SF36-domain scores. This study aimed to evaluate the validity of this formula for use in patients with intermittent claudication. METHODS: A retrospective review of a prospectively collected database of a randomized controlled trial was performed. A total of 178 patients were recruited. Clinical indicators of ischemia were recorded. All patients completed SF36 questionnaires. Response and domain-based SF6D scores (R-SF6D and D-SF6D) and QALYs were calculated. Correlation and agreement analysis were performed. RESULTS: Response rate was 88% (n = 781) over a 1-year follow-up period. Domain-based SF6D score (mean, 0.684; standard deviation [SD] 0.110) was significantly higher (paired t-test, P = 0.001) than the response-based score (mean, 0.627; SD, 0.110) with a mean difference of 0.056 (95% confidence interval, 0.053-0.060). Mean QALY calculated using D-SF6D score (0.503; SD, 0.116) was also significantly higher than the QALY calculated from the R-SF6D score (0.467; SD, 0.121). Bland-Altman comparison showed strong agreement (limit of agreement -0.167 to 0.054) between the 2 methods with equal variances (Pitman's test, P = 0.629). D-SF6D scores showed stronger correlation with clinical indicators of ischemia (r = 0.246-0.602) compared with that of R-SF6D scores (r = 0.233-0.549). CONCLUSIONS: Domain-based estimation of SF6D score is a valid and reliable method with strong agreement to the gold standard response-based scores in claudicants. However, adjustments may be required in studies using a mixture of D-SF6D and R-SF6D scores for QALY calculation.