Christopher L. Delaney

A Comparison of Flow-mediated Dilatation and Peripheral Artery Tonometry for Measurement of Endothelial Function in Healthy Individuals and Patients with Peripheral Arterial Disease

OBJECTIVE Flow-mediated dilatation (FMD) and peripheral artery tonometry (PAT) are commonly used methods for assessing endothelial function in a research setting but it is unclear how well they correlate. This study aimed to compare and correlate these methods in patients with peripheral arterial disease (PAD) and in healthy individuals. MATERIALS AND METHODS FMD and PAT measurements were obtained as samples of convenience from 26 patients with PAD and 25 healthy subjects. FMD was defined as the percentage increase in the brachial artery diameter after distal occlusion and PAT was measured using the reactive hyperaemia index (RHI). RESULTS Patients with PAD had a significantly lower FMD than healthy subjects (2.43% vs. 5.80%, p < 0.001). No difference was found in RHI between the two groups. No correlation was found between the FMD and RHI in subjects with PAD (r = 0.284, p = 0.160), in healthy subjects (r = 0.153, p = 0.464) or when both groups were combined (r = 0.174, p = 0.22). CONCLUSION The lack of change in RHI in PAD patients suggests that PAT is not a sensitive measure of endothelial function. The lack of correlation suggests that FMD and PAT are not interchangeable. PAT should not be used as a substitute for FMD as a measure of endothelial function.

A Randomised Controlled Trial of Supervised Exercise Regimens and Their Impact on Walking Performance, Skeletal Muscle Mass and Calpain Activity in Patients With Intermittent Claudication

OBJECTIVES Supervised exercise training (SET) is recommended for patients with intermittent claudication (IC). The optimal exercise programme has not been identified, and the potential adverse effects of exercise on these patients warrant consideration. Calpain proteases have been linked with tissue atrophy following ischaemia-reperfusion injury. High calpain activity may therefore cause muscle wasting in claudicants undergoing SET, and skeletal muscle mass (SMM) is integral to healthy ageing. This study assesses the impact of (1) treadmill-based SET alone; and (2) treadmill-based SET combined with resistance training on pain-free walking distance (PFWD), SMM, and calpain activity. METHODS Thirty-five patients with IC were randomised to 12 weeks of treadmill only SET (group A), or combined treadmill and lower-limb resistance SET (group B). PFWD via a 6-minute walking test, SMM via dual energy X-ray absorptiometry, and calpain activity via biopsies of gastrocnemius muscles were analysed. RESULTS Intention-to-treat analyses revealed PFWD improved within group A (160 m to 204 m, p = .03), but not group B (181 m to 188 m, p = .82). There was no between group difference (p = .42). Calpain activity increased within group A (1.62 × 10(5) fluorescent units [FU] to 2.21 × 10(5) FU, p = .05), but not group B. There was no between group difference (p = .09). SMM decreased within group A (-250 g, p = .11) and increased in group B (210 g, p = .38) (p = .10 between groups). Similar trends were evident for per protocol analyses, but, additionally, change in SMM was significantly different between groups (p = .04). CONCLUSIONS Neither exercise regimen was superior in terms of walking performance. Further work is required to investigate the impact of the calpain system on SMM in claudicants undertaking SET.

Chromium ion release from stainless steel pediatric scoliosis instrumentation.

Study Design. Case–control study. Objective. To determine whether serum metal ion levels and erythrocyte chromium levels in adolescents with stainless steel spinal instrumentation are elevated when compared with 2 control groups. Summary of Background Data. Instrumented spinal arthrodesis is a common procedure to correct scoliosis. The long-term consequences of retained implants are unclear. Possible toxic effects related to raised metal ion levels have been reported in the literature. Methods. Thirty patients who underwent posterior spinal arthrodesis with stainless steel instrumentation for scoliosis (group 1) were included. Minimum postoperative duration was 3 years. Serum chromium, molybdenum, iron, and ferritin levels were measured. Participants with elevated above normal serum chromium levels (n = 11) also underwent erythrocyte chromium analysis. Comparisons were made with 2 control groups; 10 individuals with scoliosis with no spinal surgery (group 2) and 10 volunteers without scoliosis (group 3). All control group participants underwent serum and erythrocyte analysis. Results. Elevated above normal serum chromium levels were demonstrated in 11 of 30 (37%) group 1 participants. Elevated serum chromium levels were demonstrated in 0 of 10 participants (0%) in group 2 and 1 of 10 (10%) in group 3. There was a statistically significant elevation in serum chromium levels between group 1 and group 2 participants (P = 0.001). There was no significant association between groups 1, 2, and 3 for serum molybdenum, iron, and ferritin levels. Erythrocyte chromium measurements were considered within the normal range for all participants tested (n = 31). Conclusion. Raised serum chromium levels were detected in 37% of patients following instrumented spinal arthrodesis for correction of scoliosis. This new finding has relatively unknown health implications but potential mutagenic, teratogenic and carcinogenic sequelae. This is especially concerning with most scoliosis patients being adolescent females with their reproductive years ahead.

Audit of the utilization of time in an orthopaedic trauma theatre

Background:  The efficient use of operating theatres is important to ensure optimum cost–benefit for the hospital and to clear waiting lists. This audit uses the orthopaedic trauma theatre as a model to assess the theatre efficiency at our institution.

A systematic review to evaluate the effectiveness of carnitine supplementation in improving walking performance among individuals with intermittent claudication

OBJECTIVE To evaluate the evidence for the use of carnitine supplementation in improving walking performance among individuals with intermittent claudication. DESIGN Systematic review. METHODS An electronic search of the literature was performed using MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled Trials and The Cochrane Library from inception through to November 2012. Search terms included peripheral arterial disease, intermittent claudication and carnitine. Reference lists of review articles and primary studies were also examined. Full reports of published experimental studies including randomized controlled trials and pre-test/post-test trials were selected for inclusion. A quality assessment was undertaken according to the Jadad scale. RESULTS A total of 40 articles were retrieved, of which 23 did not meet the inclusion criteria. The 17 included articles reported on a total of 18 experimental studies of carnitine supplementation (5 pre-test/post-test; 8 parallel RCT; 5 cross-over RCT) for improving walking performance in adults with intermittent claudication. For pre-test/post-test studies, 300-2000 mg propionyl-L-carnitine (PLC) was administered orally or intravenously for a maximum of 90 days (7-42 participants) with statistically significant improvements of between 74 m and 157 m in pain free walking distance and between 71 m and 135 m in maximal walking distance across 3 out of 5 studies. Similarly, PLC (600 mg-3000 mg) was administered orally in 7 out of 8 parallel RCTs (22-485 participants), the longest duration being 12 months. All but one of the smallest trials demonstrated statistically significant improvements in walking performance between 31 and 54 m greater than placebo for pain free walking distance and between 9 and 86 m greater than placebo for maximal walking distance. A double-blind parallel RCT of cilostazol plus 2000 mg oral L-carnitine or placebo for 180 days (145 participants) did not demonstrate any significant improvement in walking performance. Of 5 cross-over RCTs (8-20 participants), 4 demonstrated significant improvements in walking performance following administration of 300-6000 mg L-carnitine or PLC. Compared to placebo, pain free walking distance and maximal walking distance improved by 23-132 m and 104 m respectively following carnitine intervention. CONCLUSIONS Most trials demonstrated a small or modest improvement in walking performance with administration of PLC or L-carnitine. These findings were largely independent of level or quality of evidence, while there was some evidence that intravenous administration was more effective than oral administration and those with severe claudication may achieve greater benefits than those with moderate claudication. Routine carnitine supplementation in the form of PLC may therefore be a useful adjunct therapy for management of intermittent claudication. Further research is warranted to determine the optimal form, duration, dose and safety of carnitine supplementation across the spectrum of peripheral arterial disease severity and its effect with concurrent supervised exercise programs and best medical therapy. These studies should be supplemented with cost effectiveness studies to ensure that the return on the investment is acceptable.

Neutrophil-lymphocyte ratio as a prognostic marker of outcome in infrapopliteal percutaneous interventions for critical limb ischemia

BACKGROUND Endovascular intervention has become a frequently used treatment of critical limb ischemia (CLI) in recent times. The recent Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL) trial consensus recommended endovascular treatment as a first-line treatment in patients who have a life expectancy that was limited to <2 years. Despite these recommendations, there still remains limited data available to clinicians when seeking to risk stratify patients who present with CLI. The neutrophil-lymphocyte ratio (NLR) has been suggested to be a marker for predicting mortality and patency. This study aimed to investigate the use of the NLR as a prognostic marker for primary patency and mortality after an infrapopliteal endovascular intervention in patients with CLI. METHODS All patients who underwent tibial angioplasty for CLI were retrospectively analyzed. Demographics, degrees of stenosis, vessel patency rates, mortality, and comorbidities were recorded. NLRs were calculated from preoperative blood samples. Primary end points were all-cause mortality, primary patency, and amputation-free survival (AFS) within the follow-up period of 12 months. Multivariate Cox proportional hazard models were used to identify independent predictors. Overall survival, AFS, and the probability of a vessel remaining patent were evaluated by standard Kaplan-Meier survival curves and groups compared by the log-rank test. RESULTS Eighty-three patients were monitored for 12 months. Ninety limbs were identified, with 104 procedural events and 127 vessels undergoing successful angioplasty. The technical success rate was 86%, and patency at 1 year was 19%. Survival at 1 year was 76% and AFS was 61%. Patients with a NLR ≥5.25 had an increased risk of death (hazard ratio, 1.97; 95% confidence interval, 1.08-3.62; P = .03) compared with those with a NLR of <5.25. Furthermore, those with lymphocytes counts of <1.5 × 10(9)/L had higher mortality (hazard ratio, 1.88; 95% confidence interval, 1.02-3.70; P = .045) than those with lymphocyte counts >1.5 × 10(9)/L. CONCLUSIONS The NLR and absolute lymphocyte counts are potentially valuable prognostic indicators for risk stratification of patients presenting with CLI undergoing infrapopliteal angioplasty.

Is endovenous laser ablation possible while taking warfarin

Purpose The subgroup of patients with venous ulcers requiring anticoagulation for co-morbid conditions has traditionally created a therapeutic dilemma. Perioperative management of anticoagulation can be costly and increase the risk of surgical complications. This group of patients is often elderly and shows poor compliance with compression hosiery. The aim of this study was to investigate the outcome of endovenous laser ablation (EVLA) of the great saphenous vein (GSV) in patients remaining on therapeutic anticoagulation. Materials and methods Fifteen consecutive patients (CEAP [clinical, aetiological, anatomical and pathological elements] classification 5 or 6) were treated with standard GSV EVLA using tumescent anaesthesia and a diode 1470-nm radial laser fibre while maintaining international normalized ratio at therapeutic levels. Clinical and duplex follow-up at six weeks and three, six and 12 months were performed. Results The GSV was successfully occluded in 14/15 (93%) of patients. The remaining patient had a second successful treatment three months later. No significant complications requiring intervention were encountered. Conclusion EVLA using the diode 1470-nm radial fibre is efficacious with minimal complications in patients therapeutically anticoagulated. This treatment should be added to the armamentarium in this problematic patient group.

Validation of a Brief Dietary Assessment Tool for Estimating Dietary EPA and DHA Intake in Australian Adults at Risk of Cardiovascular Disease.

Background: Short food frequency questionnaires (FFQs) are powerful screening instruments for estimating nutrient intakes and play an important role in risk stratification in vulnerable populations. Omega-3 fatty acids are of increasing importance in the prevention of chronic and degenerative disease, especially in older adults who are at higher risk of these chronic conditions. A short FFQ exists to rapidly assess omega-3 intake from marine sources, however it has not previously been validated for agreement with total omega-3 intake and ability to identify suboptimal omega-3 intakes in older adults or for use in Australia. Objective: The aim of the study was to validate a 9-item marine omega-3 FFQ (MFQ) for assessment of omega-3 intake against a validated 74-item semiquantitative FFQ. Methods: One hundred and eight participants (mean age 67 ± 10 years, 47% male) completed the MFQ designed to estimate omega-3 intake from marine sources and the 74-item FFQ designed to estimate usual omega-3 and total energy intake in addition to other nutrients. To test agreement between the two questionnaires for estimating total omega-3 intake, mean bias and 95% limits of agreement (LOA) were calculated. Sensitivity and specificity were assessed using 2 × 2 contingency tables based on whether participants did or did not meet National Heart Foundation (NHF) recommendations for omega-3 intake per day. Results: Mean intake of omega-3 estimated from the MFQ was 210 ± 235 mg/day compared with 295 ± 260 mg/day as estimated by the FFQ. Mean bias (95% LOA) for omega-3 assessed by the two questionnaires was 89 mg/day (−475 mg to 653 mg). The MFQ achieved 98% sensitivity and 31% specificity for the omega-3 cut-off of 500 mg/day. When nutrient composition of the marine products were replaced with Australian data, mean intake of omega-3 was 230 ± 253 mg and the mean bias improved to 64 mg (−681 mg to 553 mg) and achieved 93% sensitivity and 40% specificity. Conclusions: The MFQ shows promise as a rapid screening tool for identifying older adults with intakes of omega-3 fatty acids likely to be below recommendations for chronic and degenerative disease risk reduction. Given the clinically meaningful mean bias and wide LOA, it cannot be recommended as an appropriate tool for the purpose of reporting average intake of individuals. Use of Australian nutrient data improved the mean bias of the tool in estimating total omega-3 intake. The values should be replaced and the MFQ could then be a useful tool for research purposes at the population level.

A 3-year follow-up study of inpatients with lower limb ulcers: evidence of an obesity paradox?

Objectives To determine whether body composition is related to long-term outcomes amongst vascular inpatients with lower limb ulcers. Design Prospective study with 3 years follow-up. Materials and methods Body mass index (BMI), fat, and fat-free mass were measured and associations with readmission to hospital (number, cause, length of stay) and all-cause mortality were explored. Results Thirty patients (22 men, 8 women) participated in the study. Ten patients (33%) had a BMI ≥ 30 kg/m2. 18/20 (90%) patients with a BMI < 30 kg/m2 and 9/10 (90%) patients with a BMI ≥ 30 kg/m2 were admitted to hospital in the 3 years of follow-up. Patients with a BMI < 30 kg/m2 were admitted more frequently, earlier and for longer compared to those with BMI ≥ 30 kg/m2 but these did not reach statistical significance. The 3 year mortality rate for patients with BMI ≥ 30 kg/m2 was 20% (n = 2/10) compared to 70% (n = 14/20) with a BMI < 30 kg/m2, P = 0.019. Conclusion This preliminary study suggests that higher BMI may have a protective effect against mortality in vascular patients with lower limb ulcers. These findings contradict the universal acceptance that obesity leads to poor health outcomes. Further work is required to confirm these findings and explore some of the potential mechanisms for this effect.

Pharmacist influence on prescribing in peripheral arterial disease (PIPER)

The objective of this study was to determine the association between a specialist clinical pharmacist working in collaboration with medical staff and prescribing in peripheral arterial disease (PAD). A retrospective cohort study was conducted comparing the influence of a dedicated clinical pharmacist on two samples of patients admitted to a single vascular surgery unit in either 2007 (control group) prior to implementation of a comprehensive clinical pharmacy service or 2009 (comparison group) post implementation. Data were obtained via review of medical records and electronic reports. A total of 685 patients were identified, resulting in 964 admissions. The patient to pharmacist ratio decreased from 62 to 33 patients per day in 2009. More patients were initiated on an antiplatelet (OR 4.6, 95% CI 2.26 to 9.53, p<0.001) and statin (OR 3.4, 95% CI 1.97 to 6, p<0.001) in 2009 compared to 2007. Risk factor modification increased in 2009, resulting in action being taken more often for HbA1c>7% (OR 3.45, 95% CI 1.64 to 7.27, p=0.001), total cholesterol >4 mmol/L in females (OR 14.5, 95% CI 2.67 to 78.6, p=0.002) and blood pressure above target (OR 1.9, 95% CI 1.01 to 3.73, p=0.05) when a comprehensive clinical pharmacist service was available. There was a non-significant reduction in mortality (18.7% (65) to 14.2% (46), p=0.13) and cardiovascular outcomes (5.5% (19) to 4.3% (14), p=0.44) within 12 months of discharge. In conclusion, prescribing of evidence-based medication for PAD and risk factor modification increased with a comprehensive clinical pharmacist service. This study provides important insight into optimising treatment in this patient group and how a pharmacist can be a helpful addition to the multidisciplinary team.