The well-being model: a new drug interaction model for positive and negative effects

BACKGROUND: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account. METHODS: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs. RESULTS: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed. CONCLUSIONS: The model is consistent with clinical knowledge and supports previously published experimental results on optimal drug combinations. This new framework improves understanding of the characteristics of drug combinations used in clinical practice and can be used in clinical research to identify optimal drug dosing.

UMTS base station-like exposure, well-being, and cognitive performance

BACKGROUND: Radio-frequency electromagnetic fields (RF EMF) of mobile communication systems are widespread in the living environment, yet their effects on humans are uncertain despite a growing body of literature. OBJECTIVES: We investigated the influence of a Universal Mobile Telecommunications System (UMTS) base station-like signal on well-being and cognitive performance in subjects with and without self-reported sensitivity to RF EMF. METHODS: We performed a controlled exposure experiment (45 min at an electric field strength of 0, 1, or 10 V/m, incident with a polarization of 45 degrees from the left back side of the subject, weekly intervals) in a randomized, double-blind crossover design. A total of 117 healthy subjects (33 self-reported sensitive, 84 nonsensitive subjects) participated in the study. We assessed well-being, perceived field strength, and cognitive performance with questionnaires and cognitive tasks and conducted statistical analyses using linear mixed models. Organ-specific and brain tissue-specific dosimetry including uncertainty and variation analysis was performed. RESULTS: In both groups, well-being and perceived field strength were not associated with actual exposure levels. We observed no consistent condition-induced changes in cognitive performance except for two marginal effects. At 10 V/m we observed a slight effect on speed in one of six tasks in the sensitive subjects and an effect on accuracy in another task in nonsensitive subjects. Both effects disappeared after multiple end point adjustment. CONCLUSIONS: In contrast to a recent Dutch study, we could not confirm a short-term effect of UMTS base station-like exposure on well-being. The reported effects on brain functioning were marginal and may have occurred by chance. Peak spatial absorption in brain tissue was considerably smaller than during use of a mobile phone. No conclusions can be drawn regarding short-term effects of cell phone exposure or the effects of long-term base station-like exposure on human health.

Effects of expectation and caffeine on arousal, well-being, and reaction time

The objective of this study is to determine the impact of expectation associated with placebo and caffeine ingestion. We used a three-armed, randomized, double-blind design. Two three-armed experiments varying instruction (true, false, control) investigated the role of expectations of changes in arousal (blood pressure, heart rate), subjective well-being, and reaction time (RT). In Experiment 1 (N = 45), decaffeinated coffee was administered, and expectations were produced in one group by making them believe they had ingested caffeinated coffee. In Experiment 2 (N = 45), caffeinated orange juice was given in both experimental groups, but only one was informed about the true content. In Experiment 1, a significant effect for subjective alertness was found in the placebo treatment compared to the control group. However, for RT and well-being no significant effects were found. In Experiment 2, no significant expectancy effects were found. Caffeine produced large effects for blood pressure in both treatments compared to the control group, but the effects were larger for the false information group. For subjective well-being (alertness, calmness), considerable but nonsignificant changes were found for correctly informed participants, indicating possible additivity of pharmacologic effect and expectations. The results tentatively indicate that placebo and expectancy effects primarily show through introspection.

Long-term effects of heart transplantation: the gap between physical performance and emotional well-being

The purpose of our study was to assess physical and emotional factors in heart transplant patients. A prospective design was used to compare patients' physical symptoms, emotional complaints, and restrictions at admission to the waiting list, immediately after, and 1 and 5 years after heart transplantation. Thirty-three patients were included (30 male, 3 female) in the study. Their mean age at admission was 48 +/- 10.2 years. Of these, 23 suffered from cardiomyopathy, 8 from coronary heart disease, and 2 from valvular insufficiency. At admission, the patients suffered from symptoms of cardiac insufficiency, and were restricted in sports, gardening, hobbies, sexual life, job, food-intake, and mobility. More than three-fourths rated their physical and emotional status as moderate to poor. Emotionally, they suffered from irritability, restlessness, depression, psychic lability, lowered drive, lack of social contact, low self-esteem, and anxiety. At the end of rehabilitation (4-8 weeks after the operation), all physical and emotional complaints, as well as restrictions had significantly decreased (p < 0.0001 to p < 0.001), except for trembling, numbness of hands/feet, and food-intake. One year postoperatively, patients reported even fewer physical complaints (p < 0.01). Three-fourths rated their physical and emotional status good or excellent. Five years postoperatively--in contrast to physical status, restrictions, and physical complaints--the emotional complaints had increased significantly (p < 0.0001). Patients reported excellent physical performance up to 5 years postoperatively. On the other hand, the study revealed that their emotional well-being had significantly deteriorated from 1 to 5 years postoperatively. Attention should, therefore, not only be paid to the good physical health of the survivors, but also to the worsening of their emotional status.