A systematic review of frailty assessment tools used in vascular surgery research.

OBJECTIVE: Frailty is common in vascular patients and is recognized for its prognostic value. In the absence of consensus, a multitude of frailty assessment tools exist. This systematic review aimed to quantify the variety in these tools and describe their content and application to inform future research and clinical practice. METHODS: Multiple cross-disciplinary electronic literature databases were searched from inception to August 2022. Studies describing frailty assessment in a vascular surgical population were eligible. Data extraction to a validated template included patient demographics, tool content, and analysis methods. A secondary systematic search for papers describing the psychometric properties of commonly used frailty tools was then performed. RESULTS: Screening 5358 records identified 111 eligible studies, with an aggregate population of 5,418,236 patients. Forty-three differing frailty assessment tools were identified. One-third of these failed to assess frailty as a multidomain deficit and there was a reliance on assessing function and presence of comorbidity. Substantial methodological variability in data analysis and lack of methodological description was also identified. Published psychometric assessment was available for only 4 of the 10 most commonly used frailty tools. The Clinical Frailty Scale was the most studied and demonstrates good psychometric properties within a surgical population. CONCLUSIONS: Substantial heterogeneity in frailty assessment is demonstrated, precluding meaningful comparisons of services and data pooling. A uniform approach to assessment is required to guide future frailty research. Based on the literature, we make the following recommendations: frailty should be considered a continuous construct and the reporting of frailty tools' application needs standardized. In the absence of consensus, the Clinical Frailty Scale is a validated tool with good psychometric properties that demonstrates usefulness in vascular surgery.

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.).

A randomized trial comparing treatments for varicose veins.

BACKGROUND: Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. METHODS: In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. RESULTS: After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P=0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (P<0.001); the frequency of serious adverse events (approximately 3%) was similar among the groups. Measures of clinical success were similar among the groups, but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group (P<0.001). CONCLUSIONS: Quality-of-life measures were generally similar among the study groups, with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.).

Increased levels of symmetric dimethyl-arginine are associated with all-cause mortality in patients with symptomatic peripheral arterial disease.

OBJECTIVE: Recent interest has focused on the role of the methyl-arginines, endogenous inhibitors of nitric oxide, as adverse prognostic indicators. To date, few studies have assessed the role of symmetric dimethyl-arginine (SDMA) in patients with peripheral arterial disease. We aimed to determine the relationship, if any, of SDMA to all-cause mortality and disease severity as assessed by the ankle-brachial index (ABI) in patients with symptomatic peripheral arterial disease (PAD). METHODS: In 238 patients with symptomatic PAD and an ABI of <0.8, l-arginine, asymmetric dimethyl-arginine (ADMA) and SDMA levels were measured by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry. RESULTS: The median follow-up was 6 years 11 months (interquartile range [IQR], 4 years 5 months-7 years 10 months). SDMA and ADMA levels were higher in those who died compared with those who survived (0.51 [IQR, 0.44-0.66] µmol/L vs 0.46 [IQR, 0.39-0.55] µmol/L, P ≤ .001; and 0.48 [IQR, 0.41-0.55] µmol/L vs 0.45 [IQR, 0.39-0.50] µmol/L, P = .007, respectively). l-arginine levels were similar in the two groups. On multivariate analysis, SDMA and ADMA as continuous variable were significantly associated with mortality (P = .001). For SDMA and ADMA, the highest compared with the lowest quartile levels were significantly associated with mortality (SDMA: hazard ratio, 3.855; 95% confidence interval, 1.625-9.143; P = .002; ADMA: hazard ratio, 2.277; 95% confidence interval, 1.114-4.654; P = .024). ADMA and SDMA showed a negative correlation with severity of PAD as assessed by ABI (r = -0.236, N = 216, P < .001; r = -0.209, N = 208, P = .002, respectively). CONCLUSIONS: The novel finding of this study is that SDMA levels were predictive of all cause-mortality and correlated with disease severity. Further studies should assess the role of nitric oxide donors in patients with high levels of SDMA.

Frailty Assessment in Vascular OUtpatients Review (FAVOUR) protocol: single-centre prospective cohort study comparing feasibility and prognostic value of commonly used frailty assessment tools.

INTRODUCTION: Frailty has consistently demonstrated associations with poorer healthcare outcomes. Vascular guidelines have recognised the importance of frailty assessment. However, an abundance of frailty tools and a lack of prospective studies confirming suitability of routine frailty assessment in clinical practice has delayed the uptake of these guidelines. The Frailty Assessment in Vascular OUtpatients Review study speaks to this evidence gap. The primary aim is to assess feasibility of implementing routine frailty assessment in a reproducible outpatient setting. Secondary objectives include comparing prognostic values and interuser agreement across five frailty assessment tools. METHODS AND ANALYSIS: This single-centre prospective cohort study of feasibility is conducted in a rapid-referral vascular surgery clinic, serving a population of 2 million. Adults with capacity (>18 years), attending a clinic for any reason, are eligible for inclusion. Five assessments are completed by patient (Rockwood Clinical Frailty Scale (CFS) and Frail NonDisabled Questionnaire), clinician (CFS, Healthcare Improvement Scotland FRAIL tool and 'Initial Clinical Evaluation') and researcher (11-item modified Frailty Index). Consistent with feasibility objectives, outcome measures include recruitment rates, frailty assessment completion rates, time-to-complete assessments and interuser variability. Electronic follow-up at 30 days and 1 year will assess home-time and mortality as prognostic indicators. Patients treated surgically/endovascularly will undergo additional 30-day and 1-year postoperative follow-up, outcome measures include: surgical procedure, mortality, complications (according to Clavien-Dindo Classification), length of stay, readmission rates, non-home discharge, home-time, higher social care requirements on discharge and amputation-free survival. Prognostic value will be compared by area under receiver operating characteristic curves. Continuous outcome variables will be analysed using Spearman's rank correlation coefficient. Interuser agreement will be compared by percentage agreement in Cohen's kappa coefficient.  ETHICS AND DISSEMINATION: The study is sponsored by National Health Service Greater Glasgow and Clyde (R&IUGN23CE014). London-Riverside REC (23/PR/0062) granted ethical approval. Results will be disseminated through publication in peer-reviewed vascular surgery and geriatric medicine themed journals and presentation at similar scientific conferences. TRIALS REGISTRATION NUMBER: NCT06040658. Stage of study: pre-results.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

INTRODUCTION: Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. METHODS: This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. RESULTS: A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. CONCLUSIONS: Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. TRIAL REGISTRATION: Prospective Clinical Trials, ISRCTN32188676.

Exercise therapy in routine management of peripheral arterial disease and intermittent claudication: a scoping review.

BACKGROUND: Little is known about the extent to which routine care management of peripheral arterial disease (PAD) and intermittent claudication (IC) align with best practice recommendations on exercise therapy. We conducted a scoping review to examine the published literature on the availability and workings of exercise therapy in the routine management of patients with PAD and IC, and the attitude and practice of health professionals and patients. METHODS: A systematic search was conducted in February 2018. The Cumulative Index of Nursing and Allied Health Literature, Ovid MEDLINE, Allied and Complementary Medicine Database, ScienceDirect, Web of Science and the Directory of Open Access Repositories were searched. Hand searching of reference lists of identified studies was also performed. Inclusion criteria were based on study aim, and included studies that reported on the perceptions, practices, and workings of routine exercise programs for patients with IC, their availability, access, and perceived barriers. RESULTS: Eight studies met the eligibility criteria and were included in the review. Studies conducted within Europe were included. Findings indicated that vascular surgeons in parts of Europe generally recognize supervised exercise therapy as a best practice treatment for IC, but do not often refer their patients for supervised exercise therapy due to the unavailability of, or lack of access to supervised exercise therapy programs. Available supervised exercise therapy programs do not implement best practice recommendations, and in the majority, patients only undergo one session per week. Some challenges were cited as the cause of the suboptimal program implementation. These included issues related to patients' engagement and adherence as well as resource constraints. CONCLUSION: There is a dearth of published research on exercise therapy in the routine management of PAD and IC. Available data from a few countries within Europe indicated that supervised exercise is underutilized despite health professionals recognizing the benefits. Research is needed to understand how to improve the availability, access, uptake, and adherence to the best exercise recommendations in the routine management of people with PAD and IC.

Risk assessments and structured care interventions for prevention of foot ulceration in diabetes: development and validation of a prognostic model.

BACKGROUND: Diabetes-related foot ulcers give rise to considerable morbidity, generate a high monetary cost for health and social care services and precede the majority of diabetes-related lower extremity amputations. There are many clinical prediction rules in existence to assess risk of foot ulceration but few have been subject to validation. OBJECTIVES: Our objectives were to produce an evidence-based clinical pathway for risk assessment and management of the foot in people with diabetes mellitus to estimate cost-effective monitoring intervals and to perform cost-effectiveness analyses and a value-of-information analysis. DESIGN: We developed and validated a prognostic model using predictive modelling, calibration and discrimination techniques. An overview of systematic reviews already completed was followed by a review of randomised controlled trials of interventions to prevent foot ulceration in diabetes mellitus. A review of the health economic literature was followed by the construction of an economic model, an analysis of the transitional probability of moving from one foot risk state to another, an assessment of cost-effectiveness and a value-of-information analysis. INTERVENTIONS: The effects of simple and complex interventions and different monitoring intervals for the clinical prediction rules were evaluated. MAIN OUTCOME MEASURE: The main outcome was the incidence of foot ulceration. We compared the new clinical prediction rules in conjunction with the most effective preventative interventions at different monitoring intervals with a 'treat-all' strategy. DATA SOURCES: Data from an electronic health record for 26,154 people with diabetes mellitus in one Scottish health board were used to estimate the monitoring interval. The Prediction Of Diabetic foot UlcerationS (PODUS) data set was used to develop and validate the clinical prediction rule. REVIEW METHODS: We searched for eligible randomised controlled trials of interventions using search strategies created for Ovid® (Wolters Kluwer, Alphen aan den Rijn, the Netherlands), MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Randomised controlled trials in progress were identified via the International Standard Randomised Controlled Trial Number Registry and systematic reviews were identified via PROSPERO. Databases were searched from inception to February 2019. RESULTS: The clinical prediction rule was found to accurately assess the risk of foot ulceration. Digital infrared thermometry, complex interventions and therapeutic footwear with offloading devices were found to be effective in preventing foot ulcers. The risk of developing a foot ulcer did not change over time for most people. We found that interventions to prevent foot ulceration may be cost-effective but there is uncertainty about this. Digital infrared thermometry and therapeutic footwear with offloading devices may be cost-effective when used to treat all people with diabetes mellitus regardless of their ulcer risk. LIMITATIONS: The threats to the validity of the results in some randomised controlled trials in the review and the large number of missing data in the electronic health record mean that there is uncertainty in our estimates. CONCLUSIONS: There is evidence that interventions to prevent foot ulceration are effective but it is not clear who would benefit most from receiving the interventions. The ulceration risk does not change over an 8-year period for most people with diabetes mellitus. A change in the monitoring interval from annually to every 2 years for those at low risk would be acceptable. FUTURE WORK RECOMMENDATIONS: Improving the completeness of electronic health records and sharing data would help improve our knowledge about the most clinically effective and cost-effective approaches to prevent foot ulceration in diabetes mellitus. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016052324. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 62. See the NIHR Journals Library website for further project information.

People with diabetes sometimes have problems with their feet that can become serious and make getting around harder and life less enjoyable. We have developed a test based on a simple score to find out a person's risk of getting a foot ulcer. We also wanted to know how often the test needs to be done. People who have been tested and learn that they might go on to have foot problems rightly expect to be given treatment that stops the problem happening in the first place. In this project, we read many written reports about the best treatments to prevent foot ulcers. We found that some things can prevent foot ulcers, such as wearing special shoes and insoles, taking the temperature of the skin of the foot and resting when the temperature rises, and receiving specialist care from diabetes foot care teams. However, we also looked at the costs of the test and treatments and found that some treatments are better value for money than others. By using people's health data from NHS computers, we discovered that very few people with diabetes develop a worse risk score for foot ulcers as time goes on, and it seems that being tested every year is not necessary for everyone. New clinical trials might help to improve foot health for people with diabetes, but if all of the researchers who have collected data from people in clinical trials shared their data it would be possible to find out more about who will gain most from these treatments without spending a lot on new research. It is clear that better input of patients' health data into NHS computers will benefit diabetes research in the future.

Randomized controlled trial of aspirin and clopidogrel versus aspirin and placebo on markers of smooth muscle proliferation before and after peripheral angioplasty.

OBJECTIVE: In peripheral arterial disease (PAD) patients, a limiting factor in the success of percutaneous transluminal angioplasty (PTA) is the development of restenosis secondary to vascular smooth muscle cell (SMC) proliferation. Following endothelial damage and platelet activation, there is release of factors and adhesion molecules which affect SMC proliferation. The aim of this study was to determine the effect of combination antiplatelet therapy (clopidogrel and aspirin compared with aspirin and placebo) on the ability of plasma from PAD patients undergoing PTA to stimulate SMCs in vitro. We further aimed to investigate the effect of combination treatment on the levels of circulating adhesion molecules and factors, which are known to mediate SMC proliferation in experimental models. METHODS: Fifty patients were randomized to receive blinded clopidogrel or placebo, for thirty days, in addition to their daily 75 mg aspirin. To measure proliferative capacity, diluted plasma was incubated for 15 minutes with 24 hour-growth-arrested rat vascular smooth muscle cells, and extracellular regulated kinase (ERK)1/2 activation was analyzed by Western blotting at baseline, one hour pre-PTA, one hour, 24 hours and 30 days post-PTA. Plasma platelet-derived growth factor (PDGF), sE-selectin, intracellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) were measured by ELISA, at the same five timepoints. Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and one hour post-PTA. RESULTS: ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel before and after PTA. ERK 1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups (P < .001). There was a statistically significant decrease in PDGF (P = .004), and increase in vWF (P = .026), following loading with clopidogrel. sICAM-1 levels significantly decreased (P = .016) in the aspirin/placebo group following PTA. There were no other significant changes and also there was no statistically significant difference between the two treatment groups for each of ERK 1/2, sICAM-1, sE-selectin, or vWF. CONCLUSIONS: This is the first study to show in-vitro ERK 1/2 activation (a surrogate marker of SMC proliferation) increases post-PTA. Combination antiplatelet therapy had no significant effect on this, although it did reduce PDGF. Further work is required to evaluate potential therapeutic treatments, which may reduce peripheral PTA-induced smooth muscle cell activation. CLINICAL RELEVANCE: High rates of restenosis remain the major limitation of peripheral arterial angioplasty and stenting.The restenotic lesion occurs secondary to platelet activation, released circulating factors, and subsequent smooth musclecell proliferation and migration into the intima. Methods to limit the restenotic lesion are poorly understood. This paperinvestigates the effect of PTA on smooth muscle cell activation and the release of factors in plasma which mediate SMCproliferation. It also examines the effect of combination antiplatelet therapy as a potential therapeutic strategy.

Efficacy and Feasibility of Pain management and Patient Education for Physical Activity in Intermittent claudication (PrEPAID): protocol for a randomised controlled trial.

BACKGROUND: Physical activity (PA) improves functional capacity and quality of life and provides secondary prevention benefits in individuals with peripheral arterial disease (PAD) and intermittent claudication (IC). However, pain and patient lack of knowledge are key barriers to the uptake of, and adherence to, PA recommendations. This trial will test the efficacy and feasibility of a non-invasive pain management intervention with and without patient education to improve PA in individuals with PAD and IC. METHODS: This is a randomised, controlled assessor-blinded feasibility trial with four parallel groups. Eighty adults with PAD and IC will be randomly assigned 1:1:1:1 to Active TENS (transcutaneous electrical nerve stimulation), Placebo TENS, Active TENS + Patient education or Placebo TENS + Patient education groups. All groups will continue to receive usual care over the intervention period. Participants randomised to Active TENS will receive a TENS device (preset at 120 Hz, 200 µs) and will be instructed to use the device daily at home or elsewhere for 6 weeks with a patient-determined intensity of "strong but comfortable". Placebo TENS group participants will receive the same model of TENS device and instructions for use as those in the active group, except that the stimulation dose will be safely altered to produce non-therapeutic, ineffective stimulation. Participants randomised to patient education will receive a one-off 3-h workshop of structured group education (four to five persons in each group) and three sets of twice-weekly phone calls. Efficacy outcomes will be assessed at baseline, after 6 weeks of intervention and at 3 months follow-up. Absolute claudication distance using the Gardner treadmill protocol will be assessed as the primary outcome. Secondary outcomes will assess initial claudication distance, daily PA and patient-reported outcomes including quality of life, pain self-efficacy, depression, disease perception and walking impairment pain intensity and quality. Feasibility outcomes will assess rates of recruitment, retention and adherence. Focus groups with participants at the end of the trial will explore the acceptability of the interventions. DISCUSSION: This trial will determine the efficacy and feasibility of using a low-cost, CE-marked non-invasive pain management modality delivered with or without a patient-centred education intervention to improve PA in individuals with PAD and IC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03204825 . Registered on 2 July 2017.

N-terminal pro B-type natriuretic peptide is an independent predictor of postoperative myocardial injury in patients undergoing major vascular surgery.

OBJECTIVE: Myocardial ischemia and infarction after surgery remain leading causes of morbidity and mortality in patients undergoing major vascular surgery. B-type natriuretic peptide has been shown to predict early postoperative cardiac events in patients undergoing major noncardiac surgery. We aimed to determine if N-terminal pro B-type natriuretic peptide (NT-pro-BNP), with its longer half-life and greater plasma stability, can predict postoperative myocardial injury in vascular patients. METHODS: Recruited were 136 patients undergoing elective surgery for subcritical limb ischemia or abdominal aortic aneurysm (AAA) repair. Plasma NT-pro-BNP was measured preoperatively, and troponin-I was measured immediately after surgery and on postoperative days 1, 2, 3, and 5. RESULTS: Twenty-eight patients (20%) sustained postoperative myocardial injury (troponin-I rise of >0.1 ng/mL). The median NT-pro-BNP level of those with myocardial injury was significantly higher than those who did not (380 pg/mL [interquartile range (IQR), 223-967] vs 209 pg/mL [109-363]; P = .003). NT-pro-BNP predicted this outcome with an area under the receiver operating characteristic (ROC) curve of 68% (95% confidence interval [CI] 0.56%-0.78%). In a multivariate analysis, a NT-pro-BNP value of >/=308 pg/mL (the optimal ROC curve-derived cutoff) was associated with an increased incidence of myocardial injury (odds ratio, 3.4; 95% CI, 1.41-9.09, P =.01). CONCLUSION: Elevated preoperative plasma NT-pro-BNP levels independently predict postoperative myocardial injury, which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome.

Barriers and enablers to walking in individuals with intermittent claudication: A systematic review to conceptualize a relevant and patient-centered program.

BACKGROUND: Walking limitation in patients with peripheral arterial disease (PAD) and intermittent claudication (IC) contributes to poorer disease outcomes. Identifying and examining barriers to walking may be an important step in developing a comprehensive patient-centered self-management intervention to promote walking in this population. AIM: To systematically review the literature regarding barriers and enablers to walking exercise in individuals with IC. METHODS: A systematic review was conducted utilizing integrative review methodology. Five electronic databases and the reference lists of relevant studies were searched. Findings were categorized into personal, walking activity related, and environmental barriers and enablers using a social cognitive framework. RESULTS: Eighteen studies including quantitative (n = 12), qualitative (n = 5), and mixed method (n = 1) designs, and reporting data from a total of 4376 patients with IC, were included in the review. The most frequently reported barriers to engaging in walking were comorbid health concerns, walking induced pain, lack of knowledge (e.g. about the disease pathology and walking recommendations), and poor walking capacity. The most frequently reported enablers were cognitive coping strategies, good support systems, and receiving specific instructions to walk. Findings suggest additionally that wider behavioral and environmental obstacles should be addressed in a patient-centered self-management intervention. CONCLUSIONS: This review has identified multidimensional factors influencing walking in patients with IC. Within the social cognitive framework, these factors fall within patient level factors (e.g. comorbid health concerns), walking related factors (e.g. claudication pain), and environmental factors (e.g. support systems). These factors are worth considering when developing self-management interventions to increase walking in patients with IC. Systematic review registration CRD42018070418.

Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery.

This study was conducted to assess the ability of preoperative B-type natriuretic peptide levels to predict medium-term mortality in patients who undergo major noncardiac surgery. During a median of 654 days of follow-up, 33 patients from a total cohort of 204 patients (16%) died, 17 from cardiovascular causes. The optimal cutoff in this cohort, determined using a receiver-operating characteristic curve, was >35 pg . ml(-1). This was associated with a 3.5-fold increase in the hazard of death (p = 0.001) and a 6.9-fold increase in the hazard of cardiovascular mortality (p = 0.003). In conclusion, these findings extend recent work demonstrating that B-type natriuretic peptide levels obtained before major noncardiac surgery can be used to predict perioperative morbidity and indicate that they also forecast medium-term mortality, particularly cardiovascular death.

Targeted screening for peripheral arterial disease in general practice: a pilot study in a high risk group.

BACKGROUND: Screening of high-risk groups for peripheral arterial disease has been advocated because the condition underdiagnosed and secondary prevention can reduce cardiovascular event rates. AIM: To establish the feasibility of screening for peripheral arterial disease in people aged 60 years or over with hypertension, and to estimate the potential to improve secondary preventive treatment. DESIGN OF STUDY: Pilot study and cross-sectional survey. SETTING: Large general practice in north-east Scotland. METHOD: People aged 60 years or over with hypertension but no cardiovascular disease or diabetes were identified from computer records and invited to a screening clinic. Data were collected on ankle brachial pressure index (ABPI), preventive treatment, and risk factors. RESULTS: Of 705 potentially eligible patients, 443 (63%) agreed to participate. Sixty-four were excluded and 364 of 379 patients (96%) attended screening. Thirty patients had peripheral arterial disease (ABPI of 0.9 or less), of whom 24 (7%; 95% confidence interval [CI] = 4 to 10%) were previously undiagnosed. Fifteen (50%) patients took antiplatelets, 13 (45%) had cholesterol <5 mmol/l, and 16 (53%) had blood pressure below 140/85 mmHg. Twenty-two (73%) patients were non-smokers, 14 (47%) had low-fat diets, two (7%) were physically active, and three (10%) ate recommended amounts of fruit and vegetables. CONCLUSIONS: It is feasible to screen for peripheral arterial disease in primary care, but its prevalence is lower than anticipated. There is room for improvement in secondary preventive treatment and lifestyle, so a structured programme could still have important benefits for survival.

Haemostasis, inflammation and renal function following exercise in patients with intermittent claudication on statin and aspirin therapy.

BACKGROUND: Previous studies have suggested that exercise in patients with intermittent claudication (IC) may induce a systemic thrombo-inflammatory response. The effect of secondary prevention therapy on this response is unknown. This study aimed to investigate the effects of treadmill exercise on markers of coagulation activation, inflammation and renal function in patients with IC, receiving aspirin and statin therapy compared to healthy controls. METHODS: Samples were taken before, immediately and 1 hour after exercising on a treadmill in 20 patients with IC and 20 healthy volunteers. Interleukin-6 (IL-6), thrombin-anti-thrombin complex (TAT) and fibrin D-dimer were measured by ELISA. High sensitivity CRP (HsCRP) and urinary albumin were measured via a nephelometric technique, urinary protein via a turbidometric assay and N-acetyl-beta-D-glucosaminidase (NAG) via a colorimetric assay. RESULTS: Elevated baseline levels of Hs-CRP, IL-6, white cell counts, D-dimer and urinary NAG occurred in patients with IC compared to volunteers (p > 0.05). Following exercise there was no increase in Hs CRP or IL-6. D-dimer levels significantly increased following exercise in the patients and volunteers. TAT levels increased immediately after exercise in the patient group only and were significantly increased at 1 hour in both patients and volunteers. A transient rise in the protein creatinine ratio occurred in both groups (p < 0.007), and in albumin creatinine ratio in the patient group. There was no change in urinary NAG. CONCLUSION: Elevated markers of inflammation occurred in patients with IC on statin and aspirin therapy but these did not increase following exercise. However, acute exercise resulted in a prothrombotic state evident in both groups, although this was more prolonged in patient with IC. The clinical significance of these findings in patients who are known to be at an increased risk of cardiac and other thrombotic event are unclear.

Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.

BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. RESULTS: The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS: Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. FUTURE WORK: Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51995477. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 27. See the NIHR Journals Library website for further project information.