Carotid stenting is equivalent to CEA in reducing carotid stenosis without increased risk for major complications of death/stroke. Because of shortened hospitalization and convalescence, CAS challenges CEA as the preferred treatment of symptomatic carotid stenosis if a reduction in costs can be achieved.

Background: Poor glycemic control is a risk factor for microvascular complications in patients with type 2 diabetes mellitus. Achieving glycemic control safely with insulin therapy can be challenging.Methods: A prospective, 16-week, multicenter, randomized, double-blind, placebo-controlled, parallelgroup study conducted at 50 sites in the United States and 1 site in Mexico between August 12, 2004, and December 28, 2005. Subjects had type 2 diabetes mellitus that was not adequately controlled (glycated hemoglobin level, 7.5%-9.5%, inclusive) receiving insulin therapy alone or in combination with oral antidiabetes agents. In total 287 subjects (52% men; mean age, 57 years; with a mean baseline glycated hemoglobin level of 8.3%) were randomized: 147 to receive colesevelam hydrochloride, 3.75 g/d, and 140 to receive placebo.Results: Using the least squares method, the mean (SE) change in glycated hemoglobin level from baseline to week 16 was −0.41% (0.07%) for the colesevelam-treated group and 0.09% (0.07%) for the placebo group (treatment difference, −0.50% [0.09%]; 95% confidence interval, −0.68% to −0.32%; P Ͻ .001). Consistent reductions in fasting plasma glucose and fructosamine levels, glycemic-control response rate, and lipid control measures were observed with colesevelam. As expected, the colesevelam-treated group had a 12.8% reduction in low-density lipoprotein cholesterol concentration relative to placebo (PϽ.001). Of recipients of colesevelam and placebo, respectively, 30 and 26 discontinued the study prematurely; 7 and 9 withdrew because of protocol-specified hyperglycemia, and 10 and 4 withdrew because of adverse events. Both treatments were generally well tolerated.Conclusions: Colesevelam treatment seems to be safe and effective for improving glycemic control and lipid management in patients with type 2 diabetes mellitus receiving insulin-based therapy, and it may provide a novel treatment for improving dual cardiovascular risk factors.

Background: Bile acid sequestrants are a wellaccepted class of cholesterol-lowering drugs. Over the last decade, small studies have indicated that these agents may also lower glucose levels in patients with type 2 diabetes mellitus (T2DM).Methods: This 26-week, randomized, double-blind, placebo-controlled, parallel-group study was conducted between August 2004 and July 2006 at 54 sites in the United States and 2 in Mexico to determine the effects of colesevelam hydrochloride, a bile acid sequestrant, in patients with inadequately controlled T2DM (hemoglobin A 1c [HbA 1c ] level, 7.5%-9.5% [baseline HbA 1c level, 8.1%]), who were receiving metformin monotherapy or metformin combined with additional oral anti-diabetes mellitus drugs. In total, 316 subjects were randomized (159 to colesevelam hydrochloride, 3.75 g/d, and 157 to matching placebo). The primary efficacy parameter was mean placebo-corrected change in HbA 1c level from baseline to week 26 (analysis was on an intent-to-treat population using a last-observation-carried-forward approach).Results: Colesevelam lowered the mean HbA 1c level compared with placebo at week 26 (−0.54%; PϽ.001). Simi-lar results were observed in the metformin monotherapy (−0.47%; P = .002) and combination therapy cohorts (−0.62%; PϽ.001). In addition, colesevelam significantly (1) lowered fasting plasma glucose (−13.9 mg/dL P = .01), fructosamine (−23.2 µmol/L; P Ͻ .001), total cholesterol (TC) (−7.2%; PϽ.001), low-density lipoprotein cholesterol (LDL-C) (−15.9%; P Ͻ .001), apolipoprotein B (−7.9%; P Ͻ .001), non-high-density lipoprotein cholesterol (HDL-C) (−10.3%; P Ͻ .001), and high-sensitivity C-reactive protein (−14.4%; P=.02) levels and (2) improved other measures of glycemic response, as well as TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C, and apolipoprotein B/apolipoprotein A-I ratios (P Ͻ.003 for all). Triglyceride, HDL-C, and apolipoprotein A-I levels were not statistically significantly increased. Conclusion:Colesevelam improves glycemic and lipid parameters in patients with T2DM inadequately controlled with metformin-based therapy.

OBJECTIVE -Hyperglycemia is a risk factor for microvascular complications and may increase the risk of cardiovascular disease in patients with type 2 diabetes. This study tested the LDL cholesterol-lowering agent colesevelam HCl (colesevelam) as a potential novel treatment for improving glycemic control in patients with type 2 diabetes on sulfonylurea-based therapy. RESEARCH DESIGN AND METHODS-A 26-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study was carried out between August 2004 and August 2006 to evaluate the efficacy and safety of colesevelam for reducing A1C in adults with type 2 diabetes whose glycemic control was inadequate (A1C 7.5-9.5%) with existing sulfonylurea monotherapy or sulfonylurea in combination with additional oral antidiabetes agents. In total, 461 patients were randomized (230 given colesevelam 3.75 g/day and 231 given placebo). The primary efficacy measurement was mean placebo-corrected change in A1C from baseline to week 26 in the intent-to-treat population (last observation carried forward).RESULTS -The least squares (LS) mean change in A1C from baseline to week 26 was Ϫ0.32% in the colesevelam group and ϩ0.23% in the placebo group, resulting in a treatment difference of Ϫ0.54% (P Ͻ 0.001). The LS mean percent change in LDL cholesterol from baseline to week 26 was Ϫ16.1% in the colesevelam group and ϩ0.6% in the placebo group, resulting in a treatment difference of Ϫ16.7% (P Ͻ 0.001). Furthermore, significant reductions in fasting plasma glucose, fructosamine, total cholesterol, non-HDL cholesterol, and apolipoprotein B were demonstrated in the colesevelam relative to placebo group at week 26.CONCLUSIONS -Colesevelam improved glycemic control and reduced LDL cholesterol levels in patients with type 2 diabetes receiving sulfonylurea-based therapy.

Background and Purpose-We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for retrospective use in clinical, health services, and quality of care outcome studies. The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings. Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians. However, the investigators cautioned that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible. Methods-In preparation for a study of outcomes and management practices for patients with ischemic stroke within Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first retrospectively classified a series of 14 randomly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement. A 2-phase process was then used to improve the reliability of subtype assignment. In the first phase, a computerized algorithm was developed to assign the TOAST diagnostic category. The reliability of the computerized algorithm was tested with a series of synthetic cases designed to provide data fitting each of the 11 definitions. In the second phase, critical disagreements in the data abstraction process were identified and remaining variability was reduced by the development of standardized procedures for retrieving relevant information from the medical record. Results-The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of the 14 cases (29%) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings (ϭ0.42; 95% CI, 0.32 to 0.53). There was 100% agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases. The algorithm was then applied to the original 14 cases, and the diagnostic categorization was compared with each of the 4 physicians' baseline assignments. For the 5 collapsed subtypes, the algorithm-based and physician-assigned diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the abstracted data and/or its interpretation. The use of an operations manual designed to guide data abstraction improved the reliability subtype assignment (ϭ0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data were identified, and the manual was revised accordingly. Reliability with the use of the 5 collapsed groupings then improved for both interrater (ϭ0.68; 95% CI, 0.44 to 0.91) and intrarater (ϭ0.74; 95% CI, 0.61 to 0.87) agreement. Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstraction. Concl...

CAS and CEA may be equally effective and safe in treating individuals with asymptomatic carotid stenosis.

The losses of protein into dialysate have been considered a major limitation of maintenance peritoneal dialysis. We, therefore, undertook a comprehensive evaluation of protein losses in 30 patients undergoing maintenance intermittent peritoneal dialysis (IPD), 12 patients undergoing acute IPD, and 8 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The weekly loss of protein based upon the usual treatments per week was relatively similar with the three modes of dialysis. Protein losses during repeated dialyses were similar for a given patient, but there was repeated dialyses were similar for a given patient, but there was marked interpatient variation. During maintenance IPD, protein loss was 12.9 +/- (SD) 4.4 g per 10 hours of dialysis; albumin loss was 8.5 g, and IgG loss was 1.3 g. Approximately 50% of the protein loss was from the ascitic fluid accumulated during the interdialytic interval, and concentrations of most proteins in the ascitic fluid correlated with their serum levels. Serum protein concentrations were in the low, normal range and did not change during dialysis. The development of peritonitis markedly increased protein losses. During acute IPD, 23.3 +/- 16.5 g of protein were lost per 36 hours of dialysis, lower losses than those previously reported. With CAPD, 8.8 +/- 1.7 g of protein were removed per 24 hours; also immunoglobulin losses correlated with their serum concentrations. The results of these studies suggest that, in the absence of peritonitis, dialysate protein losses do not appear to limit the usefulness of peritoneal dialysis.

Nineteen malnourished chronic peritoneal dialysis patients who were ingesting a low protein intake underwent metabolic balance studies to test whether a dialysate that contained amino acids would improve their protein nutrition. Patients lived in the hospital for 35 days while they ate a constant diet and underwent their usual regimen of continuous ambulatory peritoneal dialysis (CAPD). The first 15 days served as a Baseline Phase. For the last 20 days, the usual dialysate was substituted with a dialysate of essentially the same composition except that it contained 1.1% essential and nonessential amino acids and no glucose. Patients received one or two dialysate exchanges with amino acids each day depending on the amount necessary to bring the individual's dietary protein plus dialysate amino acid intake to 1.1 to 1.3 g/kg body weight/day. During Baseline, patients were in neutral nitrogen balance; net protein anabolism was positive, as determined from 15N-glycine studies. After commencing intraperitoneal amino acid therapy, nitrogen balance became significantly positive, there was a significant increase in net protein anabolism, the fasting morning plasma amino acid pattern became more normal, and serum total protein and transferrin concentrations rose. Patients generally tolerated the treatment well, although some patients developed mild metabolic acidemia. These findings indicate that a dialysate containing amino acids may improve protein malnutrition in CAPD patients ingesting low protein intakes.