The relationships between dose and antihypertensive effect of the first four available AT 1 -receptor blockers, i.e. losartan, valsartan, irbesartan and candesartan, were assessed based on data ...obtained from the FDA's evaluation reports of the respective New Drug Application files. All available randomized, double-blind, placebo-controlled, parallel-group studies in adult men and women with mild to moderate primary diastolic hypertension were included, provided that the reduction in trough (24 h post-dose) supine or sitting diastolic blood pressure (DBP) had been assessed using the intention-to-treat approach. All studies had an initial single-blind placebo run-in period followed by at least 4 weeks double-blind treatment. The selected studies were included in a meta-analysis of the dose-response relationship for each drug. The dose-response relationship was estimated by fitting the placebo-adjusted, weighted mean reductions in DBP for each dose of the drug to an E max model. The E max (maximal effect at an infinitely large dose) for the reduction in DBP, with corresponding 95% confidence intervals in brackets, were found to be 5.6 (3.6-7.5) mmHg for losartan, 5.8 (5.0-6.6) mmHg for valsartan, 6.9 (5.9-7.9) mmHg for irbesartan and 7.5 (6.1-8.9) mmHg for candesartan ( p = 0.014, candesartan vs valsartan). In conclusion, this investigation demonstrates that candesartan can reduce DBP significantly more than valsartan, and is supportive of previous head-to-head comparisons, which have proven candesartan to have a greater antihypertensive effect than losartan at recommended doses. Thus, differences in efficacy between different AT 1 -receptor blockers do exist, and should have implications for the choice of AT 1 -receptor blocker when treating patients with hypertension, considering the importance of good blood pressure control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Study on COgnition and Prognosis in the Elderly (SCOPE) study is a multi-centre, prospective, randomized, double-blind, and parallel-group study aiming at comparing the effects of candesartan ...cilexetil and placebo on cardiovascular events and cognitive function in elderly patients with hypertension. The aim of this sub-analysis was to present data on cognitive function and health-related quality of life (HRQL) at baseline (randomization), and to investigate whether cognitive function was related to HRQL. More specifically, the main aim was to investigate the possible relationship between the Mini-Mental State Examination on one hand, and the Psychological General Well-Being (PGWB) index, the Subjective Symptom Assessment (SSA-P) Profile and the EuroQoL Health Utility Index (EQ-5D) on the other. All the instruments are extensively validated. A general finding was that cognitive function was positively associated with higher well-being (PGWB total score and self-control) and higher utility value (EQ-5D current health) but was unrelated to the occurrence of subjective adverse symptoms (SSA-P). Age and the use of psychotropic drugs, but not gender and education level, influenced this relationship significantly.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
The kinetics of chemical changes are usually described as being zero order, first order, and so forth. A common and generally accepted description of fat oxidation in foods is that the ...reaction has an initial linear phase which gradually changes to an exponential phase. In the present investigation a generalized mathematical model was developed for the overall characterization of the formation of volatile fat oxidation products. The model is continuous, and describes the rate of the oxidation during both the linear phase (zero order) and the exponential phase (first order). The break point at which the oxidation changes from zero to first order was determined by a stepwise procedure. The zero order and first order models are special cases of the generalized model.
Zero order, first order, and generalized mixed models were used to describe the formation of straight chain aldehydes, methyl ketones, Strecker aldehydes, alkyl furans, sulfur compounds, and hydrocarbons in spray dried, whole milk powder during storage. The milk powder was prepared without and with additions of either a mixture of the antioxidants BHA and BHT or an antioxidative mixture of Maillard reaction products. The milk powder was stored in either air or nitrogen for 84 weeks.
The formation of volatile compounds was analyzed using gas chromatographic headspace methods. A static equilibrium sampling method was used for the most volatile compounds and a dynamic sampling method for the less volatile compounds.
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