Variable life adjusted display methodology for continuous performance monitoring of carotid endarterectomy.

Introduction The aim of this study was to use variable life-adjusted display (VLAD) methodology to monitor performance of six vascular surgeons undertaking carotid endarterectomy in a single institution. Materials and methods This was a prospective study with continuous analysis. A risk score model to predict 30-day stroke or death for individual patients was developed from data collected from 839 patients from 1992 to 1999. The model was used to monitor performance of six surgeons from 2000 to 2009. Individual risk factors and 30-day outcomes were analysed and VLAD plots were created for the whole unit and for each surgeon. Results Among the 941 carotid endarterectomies in the performance analysis, 28 adverse events were recorded, giving an overall stroke or death rate of 3.06%. The risk model predicted there would be 33 adverse events. There was no statistical difference between the predicted and the observed adverse events (P > 0.2, χ2 value 1.25, 4 degrees of freedom). The VLAD plot for the whole unit shows an overall net gain in operative performance, although this could have been chance variation. The individual VLAD plot showed that surgeons 1, 2, 3 and 6 to have an overall net gain in the number of successful operations. The changes observed between the surgeons was not significant (P > 0.05) suggesting chance variation only. Conclusions Performance of carotid endarterectomy can be continuously assessed using VLAD methodology for units and individual surgeons. Early identification and correction of performance variation could facilitate improved quality of care.

Prediction of organ-specific complications following abdominal aortic aneurysm repair using cardiopulmonary exercise testing.

This study aimed at assessing whether measures of aerobic fitness can predict postoperative cardiac and pulmonary complications, 30-day mortality and length of hospital stay following elective abdominal aortic aneurysm repair. We prospectively collected cardiopulmonary exercise testing data over two years for 130 patients. Upon multivariate analysis, a decreased anaerobic threshold (OR (95% CI) 0.55 (0.37-0.84); p = 0.005) and open repair (OR (95% CI) 6.99 (1.56-31.48); p = 0.011) were associated with cardiac complications. Similarly, an increased ventilatory equivalent for carbon dioxide (OR (95% CI) 1.18 (1.05-1.33); p = 0.005) and open repair (OR (95% CI) 14.29 (3.24-62.90); p < 0.001) were associated with pulmonary complications. Patients who had an endovascular repair had shorter hospital and critical care lengths of stay (p < 0.001). Measures of fitness were not associated with 30-day mortality or length of hospital stay. Cardiopulmonary exercise testing variables, therefore, seem to predict different postoperative complications following abdominal aortic aneurysm repair, which adds value to their routine use in risk stratification and optimisation of peri-operative care.

Economic analysis of a randomized trial of percutaneous angioplasty, supervised exercise or combined treatment for intermittent claudication due to femoropopliteal arterial disease.

BACKGROUND: The aim was to compare costs and utilities of percutaneous transluminal angioplasty (PTA), a supervised exercise programme (SEP) and combined treatment (PTA + SEP) in patients with intermittent claudication (IC) to establish the most cost-effective treatment. METHODS: Patients with IC due to femoropopliteal disease were randomized to receive PTA, SEP or PTA + SEP. Assessments were performed before, and at 1, 3, 6 and 12 months postintervention. Clinical and quality-of-life indicators were recorded. The SF-6D Health Utilities index was calculated from the Short Form 36, plotted, and quality-adjusted life-years (QALYs) were generated by calculating the area under the curve. Costs were calculated using National Health Service 2009-2010 payment-by-results tariffs and the National Institute for Health Research Clinical Research Network Investigation pricing index, and adjusted for reinterventions. Cost per QALY and incremental costs were calculated, and sensitivity analyses performed. RESULTS: A total of 178 patients (PTA, 60; SEP, 60; PTA + SEP, 58) were randomized. All treatments resulted in significant improvement in the SF-6D index (P < 0.001). There was no significant difference between treatments in mean QALYs gained (PTA: 0.620, 95 per cent confidence interval 0.588 to 0.652; SEP: 0.629, 0.597 to 0.660; PTA + SEP: 0.649, 0.622 to 0.675). The adjusted mean cost per procedure was significantly higher for PTA (€7301.74) compared with SEP (€3866.49) and PTA + SEP (€6911.68) (P < 0.001). The cost per QALY was significantly higher for PTA (€11,777.00) compared with SEP (€6147.04) and PTA + SEP (€10,649.74). QALYs were lost when PTA alone was used as first-line treatment in comparison with SEP or PTA + SEP. These results were robust and valid in sensitivity analyses. CONCLUSION: Supervised exercise is the most cost-effective first-line treatment for IC, and when combined with PTA is more cost-effective than PTA alone.

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

BACKGROUND: The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. METHODS: Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. RESULTS: There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. CONCLUSION: In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Randomized clinical trial of percutaneous transluminal angioplasty, supervised exercise and combined treatment for intermittent claudication due to femoropopliteal arterial disease.

BACKGROUND: The aim was to compare percutaneous transluminal angioplasty (PTA), a supervised exercise programme (SEP) and combined treatment (PTA plus SEP) for intermittent claudication due to femoropopliteal arterial disease. METHODS: Consenting patients with femoropopliteal arterial lesions were randomized to one of three treatment arms: PTA, SEP, or PTA plus SEP. All patients received optimal medical treatment. Patients were assessed at baseline and 1, 3, 6 and 12 months after intervention. Clinical (ankle pressures, walking distances, symptoms) and quality-of-life (QoL) outcomes (Short Form 36, VascuQol) were analysed. RESULTS: A total of 178 patients (108 men, median age 70 years) were included. All three treatment groups demonstrated significant clinical and QoL improvements. One year after PTA (60 patients, 8 withdrew), 37 patients (71 per cent) had improved (16 mild, 16 moderate, 5 marked), nine (17 per cent) showed no improvement and six (12 per cent) had deteriorated. After SEP (60 patients, 14 withdrew), 32 patients (70 per cent) had improved (19 mild, 10 moderate, 3 marked), six (13 per cent) showed no improvement and eight (17 per cent) had deteriorated. After PTA plus SEP (58 patients, 11 withdrew), 40 patients (85 per cent) had improved (18 mild, 20 moderate, 2 marked), seven (15 per cent) showed no improvement and none had deteriorated. On intergroup analysis, PTA and SEP alone were equally effective in improving clinical outcomes, although the effect was short-lived. PTA plus SEP produced a more sustained clinical improvement, but there was no significant QoL advantage. CONCLUSION: For patients with intermittent claudication due to femoropopliteal disease, PTA, SEP, and PTA plus SEP were all equally effective in improving walking distance and QoL after 12 months. REGISTRATION NUMBER: NCT00798850 (http://www.clinicaltrials.gov).

Randomized phase II clinical trial of avotermin versus placebo for scar improvement.

BACKGROUND: Scarring is a major problem following skin injury. In early clinical trials, transforming growth factor ß3 (avotermin) improved scar appearance. The aim of this study was to determine whether an injection of avotermin at the time of wound closure is effective in improving scar appearance. METHODS: Study RN1001-0042, a double-blind, randomized, within-patient, placebo-controlled trial, investigated the efficacy and safety of four doses of avotermin given once. Patients undergoing bilateral surgery to remove varicose leg veins by saphenofemoral ligation and long saphenous vein stripping were enrolled at 20 European centres. A total of 156 patients were randomized to receive one of four doses of avotermin (5, 50, 200 or 500 ng per 100 µl, at 100 µl per linear cm of wound margin), administered by intradermal injection to the groin and distal wound margins of one leg; placebo was administered to the other leg. Scar appearance was evaluated by an independent panel of lay people (lay panel), investigators and patients. The primary efficacy variable was lay panel Total Scar Score (ToScar), derived from visual analogue scale scores for groin scars between 6 weeks and 7 months. RESULTS: Avotermin 500 ng significantly improved groin scar appearance compared with placebo (mean lay panel ToScar difference 16·49 mm; P = 0·036). CONCLUSION: Avotermin 500 ng per 100 µl per linear cm of wound margin given once is well tolerated and significantly improves scar appearance.

Randomized clinical trial of co-amoxiclav versus no antibiotic prophylaxis in varicose vein surgery.

BACKGROUND: Wound infection rates of up to 16 per cent are reported following varicose vein surgery and the value of antibiotic prophylaxis in clean surgery remains unclear. METHODS: Some 443 patients undergoing varicose vein surgery randomly received a single prophylactic dose of 1.2 g co-amoxiclav (219 patients) or no antibiotic (224). Patients completed a wound diary on postoperative days 3, 5, 7, 9 and 10 using an adapted ASEPSIS method of wound assessment, and were reviewed after 14 days. RESULTS: Patients who had prophylaxis had lower ASEPSIS wound scores on days 3, 5 and 7 (P = 0.043, P = 0.032 and P = 0.003 respectively), and lower total ASEPSIS scores (median (interquartile range) 3 (0-9) versus 6 (0-15); P = 0.013). They were less likely to consult their general practitioner (16.0 versus 24.3 per cent; P = 0.040) or to receive postoperative antibiotics (4.7 versus 13.5 per cent; P = 0.002) for wound-related problems. Wound outcomes were worse with higher body mass index (odds ratio (OR) 0.92 (95 per cent confidence interval (c.i.) 0.87 to 0.97); P = 0.005) and current smoking (OR 0.5 (0.3 to 0.9); P = 0.033). Prophylactic antibiotics conferred satisfactory wound healing (OR 2.2 (95 per cent c.i. 1.3 to 3.6); P = 0.003). CONCLUSION: Antibiotic prophylaxis reduced wound-related problems after varicose vein surgery. Registration number ISRCTN12467340 (http://www.controlled-trials.com).

Early outcomes from a randomized, controlled trial of supervised exercise, angioplasty, and combined therapy in intermittent claudication.

BACKGROUND: To compare angioplasty (PTA), supervised exercise (SEP) and PTA + SEP in the treatment of intermittent claudication (IC) due to femoropopliteal disease. METHODS: Over a 6-year period, 178 patients (108 men; median age, 70 years) with femoropopliteal lesions suitable for angioplasty were randomized to PTA, SEP, or PTA + SEP. Patients were assessed prior to and at 1 and 3 months post treatment. ISCVS outcome criteria (ankle pressures, treadmill walking distances) and quality of life (QoL) questionnaires (SF-36 and VascuQoL) were analyzed. RESULTS: All groups were well matched at baseline. Twenty-one patients withdrew. Results are as follows: Intragroup analysis: All groups demonstrated significant clinical and QoL improvements (Friedman test, p < 0.05). SEP (60 patients, 8 withdrew)-62.7% of patients (n = 32) improved following treatment [20 mild, 9 moderate, 3 marked], 27.4% (n = 14) demonstrated no improvement, and 9.8% (n = 5) deteriorated. PTA (60 patients, 3 withdrew)-66.6% patients (n = 38) improved following treatment [19 mild, 10 moderate, 9 marked], 22.8% (n = 13) demonstrated no improvement, and 10.5% (n = 6) deteriorated. PTA + SEP (58 patients, 10 withdrew)-81.6% of patients (n = 40) improved following treatment [10 mild, 17 moderate, 3 marked], 14.2% (n = 7) demonstrated no improvement, and 4.0% (n = 2) deteriorated. Intergroup analysis: PTA + SEP produce a much greater improvement in clinical outcome measures than PTA or SEP alone, but there was no significant QoL advantage (Kruskal-Wallis test, p > 0.05). CONCLUSION: SEP should be the primary treatment for the patients with claudication and PTA should be supplemented by an SEP.

Plasma tissue factor is a predictor for restenosis after femoropopliteal angioplasty.

BACKGROUND: In vitro studies suggest an association between raised levels of tissue factor and restenosis after coronary percutaneous transluminal angioplasty (PTA). This prospective, controlled study examined the association between plasma tissue factor concentrations and restenosis after femoropopliteal PTA. METHODS: Plasma samples from ten healthy controls and 36 patients with unilateral claudication undergoing femoropopliteal PTA were collected at baseline and, in the patients with claudication, at 24 h and 1, 3 and 6 months after PTA. Clinical assessment and arterial duplex imaging were performed before and at the same time points after PTA to identify restenosis. Plasma tissue factor was measured using a specific enzyme-linked immunosorbent assay. RESULTS: Baseline plasma tissue factor concentrations were significantly higher in patients with claudication (median 3.4 (interquartile range (i.q.r.) 1.3-7.4) ng/ml) than in controls (median 1.2 (i.q.r. 0.5-1.8) ng/ml) (P < 0.050). Baseline tissue factor concentrations were significantly higher in the ten patients with claudication who developed restenosis after PTA (median 7.0 (i.q.r. 3.4-183.5) ng/ml) than in those who did not (median 1.7 (i.q.r. 1.3-7.2) ng/ml) (P < 0.050). In addition, plasma tissue factor levels increased significantly over time in the patients who developed restenosis after PTA. CONCLUSION: High baseline and progressive increases in the plasma tissue factor concentration were useful predictors of restenosis after femoropopliteal angioplasty.

A non-randomised controlled trial of the clinical and cost effectiveness of a Supervised Exercise Programme for claudication.

OBJECTIVES: The main aims of treatment in patients with intermittent claudication (IC) are to improve the clinical indicators of lower limb ischaemia and patients' quality of life (QoL). The aims of this study were assess the clinical and cost effectiveness of a supervised exercise programme (SEP) in patients with IC. DESIGN: Non-randomised, controlled trial. SETTING: University teaching hospital. PATIENTS AND METHODS: Two groups of patients with IC were studied. Seventy patients were sequentially recruited before and after the establishment of a Supervised Exercise Programme at our unit. Thirty-seven patients (median age 69 years, 26 men) received conservative medical therapy (CMT) and 33 patients (median age 67 years, 22 men) received CMT plus a 3 month SEP of graduated physical exercise for sixty minutes, three times each week. Patients were assessed prior to and at 6 months following treatment. At each assessment patient reported walking distances (PRWD), treadmill claudication and maximal distances (ICD and MWD), ankle brachial pressure indices (ABPI) pre & post exercise and patient reported QoL using the SF36 questionnaire were assessed. RESULTS: Prior to intervention the two groups were well matched. Following treatment, CMT patients demonstrated no significant change in PRWD or ICD but did record a small but significant improvement in MWD. CMT was also associated with a negative effect size in the SF36 index and in 7 of the 8 SF36 QoL domains, effect size >-0.5 for the domains of Physical Function and Emotional Role. SEP patients demonstrated significant improvement in PRWD, ICD and MWD. SEP was associated with a positive effect size in the SF36 index and in 2 SF36 QoL domains but a negative effect size in a further 2 domains. However, all QoL effect sizes following SEP were < +/-0.5. Intergroup differences in effect sizes were >0.5 for the SF36 domains of Physical Function, Physical Role, Emotion Role and SF36 index. SEP resulted in a 0.027 quality adjusted life year (QALY) gain over CMT in the first year post-treatment thus the cost/QALY gained of SEP is pound1780 at 1 year. CONCLUSIONS: Compared to CMT, SEP increases walking distances, improves QoL and is a highly cost-effective treatment for IC.

Heat shock proteins in vascular disease--a review.

INTRODUCTION: There is growing evidence that heat shock proteins (HSPs), a family of stress-inducible proteins may be involved in the pathogenesis of atherosclerotic vascular diseases. Here, we systematically review the evidence behind this notion. METHODS: A detailed literature search and extensive bibliographic review of literature relating to HSPs and atherosclerotic vascular disease. RESULTS: Atherosclerotic vascular disease is classified into four main areas of presentation: carotid, coronary, aortic and peripheral vascular disease, for consideration in this review. In each of these vascular diseases, the evidence linking HSPs and atherosclerosis is outlined in a systematic manner. Current evidence suggests that components of the immune system may be involved in the pathogenesis of atherosclerosis, with HSPs acting as auto-antigens in the immune response. HSPs are detected in atherosclerotic lesions and antibodies to HSPs are increased in patients with vascular disease; the rise often correlating with the severity of atherosclerosis. The levels of anti-HSP antibodies have been shown to be independent predictors of risk and have prognostic value. CONCLUSION: There is a strong link between heat shock protein expression and the principal manifestations of atherosclerotic vascular diseases. A better understanding of this involvement could lead to the development of new and improved treatment strategies.

A comparative study of aortic wall stress using finite element analysis for ruptured and non-ruptured abdominal aortic aneurysms.

BACKGROUND: The decision to repair an asymptomatic abdominal aortic aneurysm (AAA) is currently based on diameter (> or =5.5 cm) alone. However, aneurysms less than 5.5 cm do rupture while some reach greater than 5.5 cm without rupturing. Hence the need to predict the risk of rupture on an individual patient basis is important. This study aims to calculate and compare wall stress in ruptured and non-ruptured AAA. METHODS: The 3D geometries of AAA were derived from CT scans of 27 patients (12 ruptured and 15 non-ruptured). AAA geometry, systolic blood pressure and literature derived material properties, were utilised to calculate wall stress for individual AAA using finite element analysis. RESULTS: Peak wall stress was significantly higher in the ruptured AAA (mean 1.02 MPa) than the non-ruptured AAA (mean 0.62 MPa). In patients with an identifiable site of rupture on CT scan, the area of peak wall stress correlated with rupture site. CONCLUSIONS: Peak wall stress can be calculated from routinely performed CT scans and may be a better predictor of risk of rupture than AAA diameter on an individual patient basis.

The value of abdominal examination in the diagnosis of abdominal aortic aneurysm.

BACKGROUND: There is considerable variability in the reported value of clinical examination in the diagnosis of abdominal aortic aneurysms (AAA). This study aims to assess accuracy of abdominal examination by a doctor, a nurse and the patient in the diagnosis of AAA and whether this accuracy is related to the size of the aneurysm and/or the BMI of the patient. METHODS: 164 patients, 138 men and 26 women, median age 71 years, consented to participate in this prospective, single blind, controlled study. Thirty-nine patients attending for carotid duplex were used as controls. Abdominal examination was performed by a doctor and a nurse. Patients then performed self-examination. RESULTS: Examination by a doctor, a nurse and the patient were similar in accuracy in diagnosing/excluding AAA which was directly related to AAA size and patient BMI. The Negative Predicted Value of abdominal examination exceeds 0.9 with AAA diameters > or =4 cm and the Positive Predictive Value exceeds 0.8 with AAA diameters > or =5 cm. CONCLUSIONS: Abdominal examination by a doctor, a nurse and the patient is of value in the exclusion and diagnosis of significant AAA. It should be promoted and may represent a useful adjunct to population screening with ultrasound.

The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial.

OBJECTIVE: ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications. The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers. METHOD: eighteen diabetic patients with ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind study. Patients were randomly assigned either to receive 100% oxygen (treatment group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min daily (total of 30 treatments). RESULTS: healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group. The median decrease of the wound areas in the treatment group was 100% and in the control group was 52% (p=0.027). Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen, there was a potential saving in the total cost of treatment for each patient during the study. CONCLUSION: hyperbaric oxygen enhanced the healing of ischaemic, non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible.

Fluvastatin induces apoptosis of vascular endothelial cells: blockade by glucocorticoids.

Statins block de novo synthesis of cholesterol by inhibiting the enzyme, HMG CoA reductase. The product of this reaction, mevalonic acid, is also a precursor of isoprenoids, molecules required for the activation of signaling G-proteins, such as Ras. Signal transduction pathways involving Ras are important for cell survival and this may be why statins induce apoptotic death of several cell types. Given that statins are used to treat vascular disease, surprisingly no studies have been conducted on vascular endothelial cells. Here we show that fluvastatin (FS), at concentrations from 1-2 microM, blocks growth and induces apoptosis of the endothelial cell line, EA.hy 926. Considerable redundancy is known to exist in cell signaling and in vivo toxicity of FS might be prevented by other signaling pathways, like those activated by adrenal or sex steroids. RT-PCR analysis revealed the expression of the androgen and glucocorticoid receptor in EA.hy 926 cells. Although the androgen, dihydrotestesterone (DHT) had no effect, the glucocorticoid, dexamethasone (Dex), blocked FS-induced apoptosis. Cell cycle analysis revealed that 24 h exposure to FS prevented cells from leaving G(1) and 24-48 h later a marked sub-G(1) peak was observed. Dex was able to reduce the sub-G(1) peak, but it failed to block accumulation of cells in G(1), indicating that it's effect was specific for blockade of apoptosis, and not specific to an effect on FS alone. This study strongly suggests that glucocorticoids have a role to play in preventing vascular injury and they may provide the reason why statins are not inherently toxic to vascular endothelial cells, in vivo.

A Bayesian hierarchical approach to comparative audit for carotid surgery.

OBJECTIVES: the aim of this study was to illustrate how a Bayesian hierarchical modelling approach can aid the reliable comparison of outcome rates between surgeons. DESIGN: retrospective analysis of prospective and retrospective data. MATERIALS: binary outcome data (death/stroke within 30 days), together with information on 15 possible risk factors specific for CEA were available on 836 CEAs performed by four vascular surgeons from 1992-99. The median patient age was 68 (range 38-86) years and 60% were men. METHODS: the model was developed using the WinBUGS software. After adjusting for patient-level risk factors, a cross-validatory approach was adopted to identify "divergent" performance. A ranking exercise was also carried out. RESULTS: the overall observed 30-day stroke/death rate was 3.9% (33/836). The model found diabetes, stroke and heart disease to be significant risk factors. There was no significant difference between the predicted and observed outcome rates for any surgeon (Bayesian p -value>0.05). Each surgeon had a median rank of 3 with associated 95% CI 1.0-5.0, despite the variability of observed stroke/death rate from 2.9-4.4%. After risk adjustment, there was very little residual between-surgeon variability in outcome rate. CONCLUSIONS: Bayesian hierarchical models can help to accurately quantify the uncertainty associated with surgeons' performance and rank.

Statin-induced apoptosis of vascular endothelial cells is blocked by dexamethasone.

Statins block de novo synthesis of cholesterol by inhibiting the enzyme, HMG CoA reductase. The product of this reaction, mevalonic acid, is also a precursor of isoprenoids, molecules required for the activation of signalling G-proteins, such as Ras. Signal transduction pathways involving Ras are important for cell survival and this may be why statins induce apoptotic death of several cell types. Given that statins are used to treat vascular disease, it is surprising that no studies have been conducted on vascular endothelial cells. For this reason, we have tested the effect of fluvastatin (FS) on the endothelial cell line EA.hy 926. Here we show that FS, at concentrations from 1 to 2 microM, blocks growth and induces apoptosis of the endothelial cell line, EA.hy 926. As considerable redundancy exists in cell signalling pathways for cell survival, toxicity of FS under more physiological conditions might be prevented by pathways that do not require Ras, such as those activated by adrenal or sex steroids. To test this hypothesis, first RT-PCR analysis was performed for nuclear receptor mRNA expression. This revealed the presence of mRNA for the androgen receptor (AR) and glucocorticoid receptor (GR). The effect of the AR agonist, dihydrotestosterone (DHT), and the GR agonist, dexamethasone (Dex), was then tested. Whilst DHT (100 nM) had no effect on FS-induced cell death, Dex (1 microM) blocked FS-induced apoptosis. Cell cycle analysis revealed that 24 h exposure to FS prevented cells from leaving G(1) and 24-48 h later a marked sub-G(1) peak was observed. Dex was able to reduce the sub-G(1) peak, but it failed to reduce accumulation of cells in G(1). Further studies revealed that, in addition to blocking FS-induced apoptosis, Dex was able to block apoptosis of EA.hy 926 cells induced by serum deprivation, tumour necrosis factor-alpha, oxidants, DNA damage and mitochondrial disruption. This study strongly suggests that glucocorticoids have a role to play in preventing vascular injury and they may provide a reason why statins are apparently not toxic to vascular endothelial cells in vivo.

POSSUM and P-POSSUM overpredict mortality for carotid endarterectomy.

OBJECTIVES: the aim was to test the predictive accuracy of POSSUM and P-POSSUM on patients undergoing CEA. DESIGN: retrospective and prospective study. MATERIALS: 499 CEAs performed by four vascular surgeons from a single unit from 1992-99. The median age was 68 (range 38-86) and 60% were men. METHODS: physiological parameters, operative parameters and the 30-day mortality were collected. Predicted mortality for each patient was calculated using POSSUM and P-POSSUM equations. Patients were stratified into risk groups and observed and predicted deaths were compared. Accuracy of the prediction was assessed using chi-squared analysis. RESULTS: the observed 30-day mortality was 1.8% (9/499). The predicted deaths using POSSUM and P-POSSUM analysis were 49 and 25 respectively compared to nine observed deaths. There was significant evidence of lack of fit of both models in predicting mortality (chi-squared analysis, p<0.05). CONCLUSIONS: POSSUM and P-POSSUM overpredict mortality and are unsuitable for comparative audit of CEA. Models developed specific for CEA might accurately predict mortality.

Risk modelling study for carotid endarterectomy.

BACKGROUND: The aims of this study were to identify factors that influence the risk of stroke or death following carotid endarterectomy (CEA) and to develop a model to aid in comparative audit of vascular surgeons and units. METHODS: A series of 839 CEAs performed by four vascular surgeons between 1992 and 1999 was analysed. Multiple logistic regression analysis was used to model the effect of 15 possible risk factors on the 30-day risk of stroke or death. Outcome was compared for four surgeons and two units after adjustment for the significant risk factors. RESULTS: The overall 30-day stroke or death rate was 3.9 per cent (29 of 741). Heart disease, diabetes and stroke were significant risk factors. The 30-day predicted stroke or death rates increased with increasing risk scores. The observed 30-day stroke or death rate was 3.9 per cent for both vascular units and varied from 3.0 to 4.2 per cent for the four vascular surgeons. Differences in the outcomes between the surgeons and vascular units did not reach statistical significance after risk adjustment. CONCLUSION: Diabetes, heart disease and stroke are significant risk factors for stroke or death following CEA. The risk score model identified patients at higher risk and aided in comparative audit.