Distribution de deux peptides de l'acide γ-aminobutyrique dans le liquide céphalo-rachidien et le cerveau humains

The distribution of two peptides of γ-aminobutyric acid, homocarnosine and α-(γ-aminobutyryl)-lysine, was studied in human brain and cerebrospinal fluid. Adult brain and cerebrospinal fluid α- (γ-aminobutyryl) -lysine levels and adult brain homocarnosine levels are higher than those found in children. On the other hand, it is known that the cerebrospinal fluid from children contains higher concentrations of homocarnosine than those observed in adults.     

A Markov process analysis comparing the cost effectiveness of maintenance therapy with citalopram versus standard therapy in major depression

The objective of this study was to demonstrate the cost effectiveness of long term maintenance treatment with citalopram versus standard therapy (defined as short term antidepressant treatment) in patients with major depression in Germany. We chose doxepin, amitriptyline and trimipramine as standard therapy because these drugs are the leading antidepressants in that country. A Markov process analysis was used to model health status and economic outcomes as they accrued over a 1-year follow-up period. The main outcome measures were time without depression, direct costs and indirect costs (work days lost). All costs were in 1993 Deutsche marks. The clinical data were obtained from the published literature and US clinical practice guidelines; the associated unit costs of the medical resources used were derived from official German tariff lists. The results show that, compared with standard therapy, long-term maintenance treatment with citalopram is associated with a mean increase in time without depression of 7.9% (8.2 vs 7.6 months). The total costs of maintenance treatment with citalopram were substantially lower than with standard therapy (DM7985 vs DM11,948 per patient per year. In addition, both the direct and indirect costs of maintenance treatment with citalopram (DM3764 vs DM4221 per patient, respectively) were lower than with standard therapy (DM4577 vs DM7371 per patient, respectively). In conclusion, the study demonstrates that one year's maintenance treatment with citalopram is both more effective and less costly than standard therapy in the treatment of patients with major depression.     

Methodological approaches to pharmaco-economics

Summary— Due to the increased need for cost-containment policies, most decision makers are facing the issue of the efficiency of health care strategies. In this context, economic evaluation becomes a major instrument. However, the credibility of economic data depends on a number of methodological steps: selection of strategy of economic evaluation (cost/effectiveness, cost/benefit, generation of economic hypotheses, study design (cross-sectional, prospective, naturalistic), data collection (data-base, physicians), data analysis (costing, statistics). In this respect, the conduct of proper economic evaluation relies on a combination of expertise in clinical epidemiology as well as in health economics.     

Absorption Enhancement of Rectally Infused Cefoxitin Sodium by Medium-Chain Fatty Acids in Conscious Rats: Concentration–Effect Relationship

The objective of this study was to assess the relative absorption promoting potency in terms of concentration–effect relationships of the medium-chain fatty acids hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid in conscious rats, using cefoxitin sodium as the rectally delivered model compound. Rectal uptake of cefoxitin, which was absorbed to a limited extent without enhancer (30 ± 25%), proved to be significantly enhanced by 2.0 M sodium hexanoate, 0.69 M sodium octanoate, and 0.22 M sodium decanoate, resulting in mean bioavailabilities of 102 ± 24, 68 ± 25, and 68 ± 10%, respectively. Thus, increasing fatty acid chain length results in increased enhancing potency from hexanoic acid to decanoic acid. However, using dodecanoate a statistically significant effect could not be reached, because of its limited aqueous solubility. Optimal chain length for absorption enhancement by medium-chain fatty acids is probably determined by interplay of intrinsic effects on mucosal permeability and solubility of the medium-chain fatty acid.     

Measuring sensitivity in pharmacoeconomic studies. An integration of point-sensitivity and range-sensitivity

The level of uncertainty with regard to the outcomes of pharmacoeconomic studies cannot be completely covered by the statistical methods routinely employed to handle uncertainty in clinical research. Sensitivity analysis is the most common methodology to deal with the extra uncertainty associated with pharmacoeconomics, and has also been incorporated in recent guidelines on healthcare evaluation. However, the execution of a sensitivity analysis and the interpretation of its results have not yet been standardised, which may lead to subjectivity and consequently weaken the value of economic evaluations. This article presents a method of dealing more systematically with uncertainty and eliminating potential bias in sensitivity analysis, with regard to the measurement of sensitivity and the comparison of the degree of sensitivity between variables. An assessment of the disadvantages of using slope as a measure of sensitivity leads to 2 types of sensitivity analyses (point-sensitivity and range-sensitivity), which are integrated into one method for the measurement of sensitivity.