PubMed · 15918459
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Simvastatin.. https://pubmed.ncbi.nlm.nih.gov/15918459/
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We consider the construction of efficient group sequential designs where the goal is a low expected sample size not only at the null hypothesis and the alternative (taken to be the minimal clinically meaningful effect size), but also at more optimistic anticipated effect sizes. Pre-specified Type I error rate and power requirements can be achieved both by standard group sequential tests and by more recently proposed adaptive procedures. We investigate four nested classes of designs: (A) group sequential tests with equal group sizes and stopping boundaries determined by a monomial error spending function (the 'rho-family'); (B) as A but the initial group size is allowed to be different from the others; (C) group sequential tests with arbitrary group sizes and arbitrary boundaries, fixed in advance; (D) adaptive tests-as C but at each analysis, future group sizes and critical values are updated depending on the current value of the test statistic. By examining the performance of optimal procedures within each class, we conclude that class B provides simple and efficient designs with efficiency close to that of the more complex designs of classes C and D. We provide tables and figures illustrating the performances of optimal designs within each class and defining the optimal procedures of classes A and B.
Until 2010, the Dutch ministry of Health, Welfare and Sport will fund a nationwide project to identify the approximately 40,000 patients with familial hypercholesterolaemia (FH) in the Netherlands. The Health Care Insurance Board will coordinate the project and safeguard its quality, while the 'Stichting Opsporing Erfelijke Hypercholesterolemie' [Foundation for the Detection of Hereditary Hypercholesterolaemia], with its national network of genetic fieldworkers, will search systematically within families with assessed FH-mutations. The referral of the first suspected case of FH in a family for DNA diagnosis remains a task for GPs, internists and other clinical professionals; these will also be expected to take the responsibility for treatment. The list of diagnostic criteria of the 'Dutch Lipid Clinic Network' has recently been validated and is recommended as a decision-tool for initiating DNA diagnosis. After confirmation of the DNA diagnosis, the plasma level of LDL-cholesterol remains the main criterion for pharmacotherapy; treatment with hypocholesterolaemic agents is recommended at levels above 2.5 mmol/l.
Fibrates are drugs commonly used in hypertriglyceridemias. After their absorption, fibrates are metabolized by the liver, using P450 isoenzymes not shared by statins. However, for some fibrates, such as genfibrozil, an interaction with statins can occur during their liver glucuronidation, or by displacement of free fraction of statins linked to proteins in plasma. Plasma half-life is variable among fibrates (2-80 h). Recently it has been shown that fibrates produce plasma lipid changes mainly by stimulating peroxisome-proliferation activation receptors alpha. Through this action, there is an increase in the transcription of some genes related to lipid metabolism, such as LLP, APOAI, APOAII, ABCA-1, as well as decrease in the expression of APOCIII, and many other actions.