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.

A randomized placebo controlled trial of the effect of preoperative statin use on matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in areas of low and peak wall stress in patients undergoing elective open repair of abdominal aortic aneurysm.

BACKGROUND: A double-blind, randomized controlled trial was carried out to study the effects of statins on matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in areas of peak and low abdominal aortic aneurysm (AAA) wall stress. METHODS: A total of 40 patients undergoing elective open AAA repair were randomized to receive either atorvastatin 80 mg (n = 20) or placebo (n = 20) for 4 weeks preoperatively. Finite element analysis was used to determine AAA wall stress distribution. Full thickness aortic samples were obtained at surgery from areas of low and peak wall stress, snap-frozen, and stored at -80°C for subsequent MMP-2, -8, and -9 and TIMP-1 and -2 analyses. Statistical analysis was performed using SPSS 16.0 (SPSS Inc, Chicago, IL). RESULTS: Both groups were well matched (p > 0.05) regarding age, gender, comorbidities, and duration of hospital stay. There were no statistically significant differences in levels of MMPs and TIMPs between the statin and placebo group and between areas of low and peak AAA wall stress. CONCLUSION: The short-term use of statins is not associated in reducing levels of MMP 2, 8, and 9 and TIMP-1 and -2 in areas of low and peak wall stress in patients with AAA.

Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials.

OBJECTIVE: Several studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness and wave reflections as measured by pulse wave velocity (PWV) and augmentation index (AIx), respectively. We conducted a meta-analysis to investigate this effect in comparison to placebo and to other antihypertensive agents. Additionally, we investigated this effect when ACEIs are combined with other antihypertensive agents and in comparison to a combination of antihypertensive agents. METHODS: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to May 2011 on randomised controlled trials (RCTs) which assessed the effect of ACEIs on arterial stiffness vs. placebo or no treatment and ACEIs vs. angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), ß-blockers and diuretics. RCTs which assessed the effect of ACEIs combined with other antihypertensives or compared ACEIs with a combination of antihypertensives were also sought. Data from included RCTs were pooled with use of fixed and random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I(2) statistic. RESULTS: In 5 trials including 469 patients, treatment with ACEIs (n=227) vs. placebo (n=216) significantly reduced PWV (pooled mean change difference -1.69, 95% C.I. -2.05, -1.33, p<0.00001 with insignificant heterogeneity). In 9 trials which included 378 patients, treatment with ACEIs (n=178) insignificantly reduced PWV when compared with other antihypertensives (ARBs, CCBs, ß-blockers, diuretics and a combination of ACEI and ARB) (n=220) (pooled mean change difference -0.19, 95% C.I. -0.59, 0.21, p=0.36, I(2)=0%). ACEI effect on AIx in comparison to placebo was assessed in 7 trials. Treatment with ACEIs significantly reduced AIx (pooled mean change difference -3.79, 95% C.I. -5.96, -1.63, p=0.0006) with significant heterogeneity. In 7 trials, treatment with ACEIs significantly reduced AIx when compared with other antihypertensives (pooled mean change difference -1.84, 95% C.I. -3, -0.68, p=0.002, I(2)=32%, p for heterogeneity=0.11). However, this effect was only significant when compared with ß-blockers (pooled mean change difference -1.6, 95% C.I. -2.84, -0.36, p=0.01). Mean BP differences between baseline and end of treatment did not predict the treatment (ACEI) induced changes in PWV. CONCLUSIONS: ACEIs reduce PWV and AIx which are markers of arterial stiffness and wave reflections in patients with different pathological conditions. However, due to the lack of high quality and properly powered RCTs, it is not clear whether ACEIs are superior to other antihypertensive agents in their effect on arterial stiffness. The ability of ACEIs to reduce arterial stiffness (PWV) seems to be independent of its ability to reduce BP.

Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials.

OBJECTIVE: Several studies have assessed the effect of angiotensin converting enzyme inhibitors (ACEIs) on endothelial dysfunction as measured by brachial flow-mediated vasodilatation (FMD). We conducted a meta-analysis to investigate this effect in comparison to placebo or no treatment and to other antihypertensive agents. METHODS: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1996 to October 2010 on randomised controlled trials (RCTs) that assessed the effect of ACEIs on brachial FMD versus placebo or no treatment and ACEIs versus angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and ß-blockers. Data from included studies were pooled with use of random effects meta-analysis of the weighted mean change differences between the comparator groups. Heterogeneity across studies was assessed with the I(2) statistic. RESULTS: In 10 trials including 1129 patients, treatment with ACEIs (n = 498) versus placebo or no treatment (n = 503) significantly improved brachial FMD (pooled mean change difference 1.26%, 95% C.I. 0.46-2.07, p = 0.002 with significant heterogeneity). In 11 trials which included 805 patients, treatment with ACEIs (n = 264) had a significant effect on brachial FMD when compared with other antihypertensives (ARBs, CCBs and ß-blockers) (n = 420) (pooled mean change difference 0.89%, 95% C.I. 0.22-1.56, p = 0.009, I(2) = 83%, p for heterogeneity < 0.00001). In 7 trials, treatment with ACEIs had no significant effect on FMD when compared with ARBs (pooled mean change difference = 0.21%, 95% C.I. -0.24 to 0.66, p = 0.36, I(2) = 0%). However, in 4 trials ACEIs significantly improved FMD when compared with CCBs (pooled mean change difference 2.15%, 95% C.I. 0.55-3.75, p = 0.009, I(2) = 90%, p for heterogeneity < 0.00001). When compared with ß-blockers in 4 trials, ACEIs also had a significant effect on FMD (pooled mean change difference = 0.59%, 95% C.I. 0.05-1.13, p = 0.03, I(2) = 34%, p for heterogeneity = 0.21). CONCLUSIONS: This study shows that ACEIs improve brachial FMD which is a marker of endothelial function in patients with endothelial dysfunction caused by various conditions and are superior to CCBs and ß-blockers. There was no significant difference between ACEIs and ARBs effect on brachial FMD.

Diffuse large B-cell lymphoma presenting as a chronic leg ulcer: the importance of repeat tissue biopsy.

Ulceration of the leg is often associated with significant consequences for both the individual and society. The diagnosis of chronic leg ulcer is not appropriate. Primary cutaneous diffuse large B-cell lymphoma (PCLBCL), leg type, is a distinct clinicopathological entity. Chemotherapy in the form of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) is considered to be the first line of treatment for these lymphomas. We report a 69-year-old man who presented with chronic leg ulcer with a first negative biopsy and a diagnosis of PCLBCL, leg type, verified on the subsequent biopsy. This case report emphasises the importance of differential diagnosis of lymphoma in non-healing ulcers and also the value of repeat tissue biopsy in cases with a negative initial result but strong clinical suspicion.

Gender disparity in patients undergoing percutaneous coronary intervention for acute coronary syndromes - does it still exist in contemporary practice?

INTRODUCTION: Prior studies have demonstrated evidence of a disparity in the treatment and outcome of male compared to female patients undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: From a dedicated database, we retrospectively analysed all consecutive patients with acute coronary syndrome (ACS) admitted to our institution for PCI in 2008. Baseline and procedural characteristics as well as complications were then evaluated for male patients (n = 331) as compared with female patients (n = 137). RESULTS: Women were noted to be older at the time of presentation (66.1 +/- 10.0 vs 60.7 +/- 11.6 years, P <0.00001), the groups were otherwise well matched in terms of baseline characteristics. Female patients were treated with significantly smaller diameter stents (2.86 +/- 0.44 vs 2.96 +/- 0.50 mm, P = 0.04), though the proportion of drug-eluting stents was similar (53.7% vs 50.5%, P = 0.5). Female patients were significantly less likely to receive optimal medical therapy with lesser use of glycoprotein IIb/IIIa inhibitor (26.3% vs 55.3%, P <0.0000001), and beta-blockers (83.9% vs 90.9%, P = 0.04). At 30 days, there were no differences in the rate of major adverse cerebrovascular or cardiac events (2.9% vs 3.9%, P = 0.8), though females had a significantly higher rate of femoral access site pseudoaneurysm (4.4% vs 0.9%, P = 0.02). CONCLUSIONS: There remains evidence for continued gender disparity in contemporary practice; despite evidence for efficacy in ACS patients, females received a notably lower use of glycoprotein IIb/IIIa inhibitors and beta-blockers. Women are also significantly more likely to develop femoral access site complications with pseudoaneurysm development; it is important therefore to optimise procedures for sheath removal in female patients or give strong consideration to the use of radial access site.