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Objective: Several randomized controlled trials indicate that a low density lipoprotein cholesterol (LDL-C) target <2.0 mmol/L is appropriate for individuals at high risk of coronary artery disease (CAD). Recently released Canadian lipid management guidelines (2006) have incorporated this evidence into their recommendations. A cross-sectional study of patients treated with statins for at least 8 weeks (CALIPSO) was used as a basis to project the ability of statin monotherapy in getting high CAD-risk patients to an LDL-C level <2.0 mmol/L.Research Design and Methods: The analysis was restricted to CALIPSO patients on statin monotherapy who were at high CAD-risk (including patients with established CAD). Assuming all patients could have their statin titrated up to the maximum dose, the proportion of patients that would reach an LDL-C level of <2.0 mmol/L was projected. To do this, the additional LDL-C reduction patients would achieve with maximal titration of their statin was estimated based on a meta-analysis of clinical trials evaluating LDL-C responses to various statin regimens, and applied to patients' current LDL-C level.Results: A total of 1795 high CAD-risk patients treated with statin monotherapy were included in the analysis, of whom 69.8% had an LDL-C > or =2.0 mmol/L. Depending on the statin that was used, it was projected that between 28.2% and 62.7% of high CAD-risk patients would not attain an LDL-C of <2.0 mmol/L following statin titration to maximum dose.Conclusions: Although the accuracy of our projections may be limited by the application of clinical trials data to an external sample of patients, our results suggest that for 38% of patients at high CAD-risk, titration of statin monotherapy will not be sufficient to achieve an LDL-C target of <2.0 mmol/L. For these patients, additional treatment approaches may be needed to further reduce the risk of coronary events. [ABSTRACT FROM AUTHOR]

The car sequencing problem is the ordering of the production of a list of vehicles which are of the same type, but which may have options or variations that require higher work content and longer operation times for at least one assembly workstation. A feasible production sequence is one that does not schedule vehicles with options in such a way that one or more workstations are overloaded. In variations of the problem, other constraints may apply. We describe and compare three approaches to the modeling and solution of this problem. The first uses integer programming to model and solve the problem. The second approaches the question as a constraint satisfaction problem (CSP). The third method proposes an adaptation of the Ant Colony Optimization for the car sequencing problem. Test-problems are drawn from CSPLib, a publicly available set of problems available through the Internet. We quote results drawn both from our own work and from other research. The literature review is not intended to be exhaustive but we have sought to include representative examples and the more recent work. Our conclusions bear on likely research avenues for the solution of problems of practical size and complexity. A new set of larger benchmark problems was generated and solved. These problems are available to other researchers who may wish to solve them using their own methods. [ABSTRACT FROM AUTHOR]

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged > or =18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for > or =6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of -25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides -14.0%) compared with LDL cholesterol -3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides -2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolaemia is characterised by a decreased removal of low density lipoproteins and premature coronary artery disease. Tendinous xanthomata are a hallmark of the disease. The affected joints may also be the sites of inflammation and pain. Arthropathy has been associated mainly with the homozygous form of familial hypercholesterolaemia, but it is also known to occur in the heterozygous form. We report on the articular manifestations in 73 patients with heterozygous familial hypercholesterolaemia. About 40% of these patients had at least one episode of articular symptoms. The observed articular manifestations may be classified into four types: Achilles pain (18%), Achilles tendinitis (11%), oligoarticular arthritis (7%), polyarticular or rheumatic fever-like arthritis (4%). It is concluded that in heterozygous familial hypercholesterolaemia articular manifestations are frequent, diverse, and may be the first symptom of this metabolic disorder. [ABSTRACT FROM PUBLISHER]