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The objectives of this study were: to evaluate the change in the three quality of life (QOL) dimensions of vitality, contentment and sleep before intervention and 1 year after treatment with a dental appliance or uvulopalatopharyngoplasty (UPPP); to compare the effect of treatment between these two treatment groups on these three dimensions; and to determine the relation between the QOL scores and somnographic values. Ninety-five patients with mild to moderate obstructive sleep apnoea (OSA) (AI > 5) were randomly allocated to either a dental appliance or UPPP treatment group. Seven patients withdrew after randomization but before treatment, leaving 88 patients eligible for treatment. The patients were examined using somnography and administered the Minor Symptoms Evaluation-Profile (MSE-P), a QOL questionnaire, before and 1 year after intervention. Thirty-seven patients in the dental appliance group and 43 in the UPPP group completed the 1-year follow-up. The mean values for the three dimensions vitality, contentment and sleep improved significantly 1 year after intervention in the dental appliance and UPPP groups. No difference in the QOL scores at baseline was noted between the groups. One year after intervention the UPPP group showed significantly more contentment than the dental appliance group. In contrast, vitality and sleep dimensions did not differ between the two treatment groups. No significant correlations were observed between the QOL scores and somnographic values. In conclusion, quality of life improved significantly in the dental appliance and UPPP groups 1 year after intervention. However, the dental appliance group showed a lower level of contentment than the UPPP group, even though the somnographic values were superior in the former group.

There is a growing interest in including Quality of Life (QOL) in gastroenterology. Along with objective variables such as healing rate, as recorded with endoscopy, QOL may give a better basis for evaluating medical treatment regimens. However, although QOL is an important aspect to consider, few studies in patients with upper gastrointestinal diseases have evaluated these aspects. The methods for assessing QOL may offer improved possibilities with which to evaluate the impact of therapies but also raise a number of questions concerning how to select, utilize and interpret the results obtained. This work is aimed at exploring some of the possibilities, but also challenges, in the evaluation of Quality of Life in patients with upper gastrointestinal diagnosis.

In this article, the issues involved in the measurements of quality of life in clinical trials of cardiovascular drugs are discussed with emphasis on beta-blocker treatment. The extensive documentation available for beta-blockers makes it possible to evaluate different aspects of this class of drugs. Generally, beta-blockers have been shown to be safe with a low frequency of serious side effects. However, results of different studies have shown that this class of drugs affects various aspects of well-being and psychomotor tests both negatively and positively. Adverse effects often associated with beta-blockers are the subjective symptoms that are considered to be related to the central nervous system. Today there is increasing evidence that these can be quantitatively as well as qualitatively reduced by using beta-blockers in a low dose and avoiding high plasma peak concentrations. Considering effects on well-being and psychomotor tests, there seems to be no clinical difference between hydrophilic and lipophilic beta-blockers, when administered in comparable therapeutic dosages, whereas beta 1-selective blockers in clinically relevant doses seem to produce fewer and less severe adverse effects than nonselective blockers. Compared with other classes of cardiovascular drugs, there is no clear evidence of differences in well-being between selective beta-blockers and angiotensin converting enzyme inhibitors or calcium antagonists.

Quality of life (QoL) has during recent years become recognized as an important outcome in clinical trials. But it is not sufficient just to incorporate QoL measures in a trial. Several factors have important repercussions on the results of clinical trials using QoL as an outcome measure. Unless more attention is directed towards factors that may be important when evaluating QoL, the value of including these measurements in clinical trials will be minimized. Important issues pertain to trial design, duration of follow-up, the role of placebo effects, side effects, and confounding variables.

During the last decade beta-adrenoceptor antagonists have become one of the first-line treatments for hypertension. Generally, they have been shown to be safe with a low frequency of serious side effects. However, minor subjective symptoms, usually considered to be CNS-related, have been reported for all beta-blockers used. Thus, all beta-blockers on the market seem to have a high benefit:risk ratio; independent of their physicochemical properties and pharmacodynamic profile, however, they seem to cause CNS-related side effects to about the same extent. These minor side effects, the mechanisms of which are unclear, consist of subtle effects on general well being, decreased initiative, a depressed frame of mind, and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. The results so far available have been obtained primarily by using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect. Rather, the plasma concentration of the beta-blocking drug (degree of beta-blockade) seems to be the major determinant of whether or not CNS-related symptoms appear in susceptible patients.

The effect of once daily treatment with atenolol (100 mg), metoprolol CR/ZOK (100 mg) and propranolol LA (160 mg) for one week on CNS-related subjective symptoms was compared with that of placebo using a randomised, double-blind cross-over design in 12 healthy volunteers. The symptoms were recorded using a previously documented self-administered questionnaire (MSE-profile), which included three dimensions: Contentment, Vitality and Sleep. Compared to placebo, all three beta-adrenoceptor antagonists reduced the exercise heart rate at 24 hours but a somewhat more pronounced effect was found with propranolol LA. No significant difference in any of the dimensions was detected between placebo and either metoprolol CR/ZOK or atenolol tablets. Following propranolol LA treatment a deterioration in the dimensions Vitality and Sleep was observed compared with both placebo and the beta 1-selective drugs. Difference in lipophilicity between the beta 1-selective agents metoprolol and atenolol has little bearing on the occurrence of the CNS-related symptoms, in comparison to the marked effects of the lipophilic and nonselective compound propranolol.

The present study evaluated and compared subjective symptoms in hypertensive patients (N = 83) at therapeutically comparable dosages of a new controlled release (CR/ZOK) formulation of metoprolol (100 mg od) and atenolol (50 mg od). The trial was a 4-week randomized double-blind study preceded by a placebo run-in period. Blood pressure (BP) was recorded 24 hours after intake of last dose. In subpopulations, 24-hour ambulatory BP was recorded and exercise tests performed. Subjective symptoms were evaluated with a previously documented questionnaire (MSE-profile) which has been shown to be sensitive in detecting CNS-related symptoms caused by beta blockers. The MSE-profile includes three dimensions: Contentment, Vitality and Sleep. The results showed that there were no significant differences between the groups in BP reduction either at 24 hours or over the entire 24-hour dose interval. Furthermore, the degree of beta 1-blockade (reduction in exercise-induced tachycardia) 24 hours after last dose did not differ between the groups. There were no significant differences regarding subjective symptoms (Contentment, Vitality, Sleep) between the two treatment groups. An a posteriori power analysis showed that the power to detect a true difference was of an acceptable magnitude. In conclusion, there was no difference in CNS-related symptoms between metoprolol and atenolol at therapeutically comparable dosages indicating that the degree of lipophilicity may be of minor importance for the occurrence of such symptoms.

Extensive research and clinical usage of metoprolol have shown the compound to be safe and well tolerated if the contraindications are taken into consideration. However, as with other beta-blockers, unwanted effects may occur during treatment. Although usually mild, these side effects may be of considerable clinical importance, especially since once initiated, therapy is often life-long. Results of previous studies have indicated that some of these symptoms are associated with high plasma concentrations of the drug. Theoretically, side effects may thus be reduced by administration of metoprolol in a controlled-release formulation (CR/ZOK) which yields relatively low plasma concentrations over approximately 24 hours. Using clinically relevant doses, metoprolol CR/ZOK affects beta 2-adrenoceptor-mediated functions (e.g., broncho-dilatation in asthmatics) less than tablets do. In addition, less leg fatigue during exercise has been reported. The clinical studies published so far indicate that metoprolol CR/ZOK is as well tolerated as or better tolerated than, conventional metoprolol tablets. Furthermore, metoprolol CR/ZOK is tolerated equally or better than atenolol in terms of CNS-related symptoms.

The SSA-profile is a specific, self-administered questionnaire for measurement of subjective symptoms in untreated and treated hypertensives. Forty-two of the most frequently occurring symptoms among untreated and treated hypertensives have been included. Based on factor analysis, 25 of the items combine into dimensions covering the areas Emotional distress, Gastro-intestinal symptoms, Peripheral vascular symptoms, Cardiac symptoms, Sex life and Dizziness. The reliability and circulatory of the questionnaire have been established. For improved sensitivity in detecting subjective symptoms and comparability of results obtained in different studies the use of the SSA-profile provide valuable information. The questionnaire has been shown capable of describing subjective symptoms among untreated hypertensives. Currently, the questionnaire is being used in evaluating subjective symptoms among patients treated with different classes of antihypertensive agents.

In recent years, there has been increasing interest in incorporating the concept of "Quality of Life" in the evaluation of medical interventions. The lack of a general definition which can function as a basis for the scientific evaluation of medical treatment is, however, a problem. The definition proposed in this paper contains three main factors: Subjective well-being, Health and Welfare. "Subjective well-being" is the central component in the evaluation of Quality of Life, referring to the individual's perception of his life situation, "Health" is a subjective as well as objective evaluation of physical and mental status, while "Welfare" reflects the objective environmental factors. Thus, the evaluation of Quality of Life in medicine should ideally address these three main factors. Although the importance of any particular component may vary, subjective well-being and health should always be included.

Atenolol and metoprolol are the two most widely used beta 1-adrenoceptor antagonists in the treatment of essential hypertension. Differences in their physico-chemical properties have been the basis of a number of clinical studies whose primary or secondary objective has been to compare subjective well-being during treatment with these beta-selective blockers. The results are, however, contradictory, mainly due to factors such as open study design, different dose regimens and dissimilar study populations. The aim of the present study was to evaluate and compare subjective well-being during treatment with atenolol (50 mg o.d.) and metoprolol CR (100 mg o.d.) in a randomized double-blind, cross-over study (2 x 6 weeks) in hypertensives not previously treated with either of the drugs studied. Two self-administered questionnaires (MSE-profile and Jern quality of life questionnaire) were filled in both before randomization and before follow up visits at 1, 3 and 6 weeks in each treatment period. Furthermore, subjective symptoms, blood pressure and heart rate were monitored. At the end of the study, patients were requested to state what treatment they preferred. Atenolol and metoprolol CR were found to be equally effective in reducing blood pressure (from 159/98 to 144/87 and 144/88 mm Hg, respectively, n = 74). The MSE-profile and the Jern quality of life questionnaire could not detect any differences between the two treatments as regards general well-being. Other subjective symptoms (e.g. diarrhoea, bradycardia, cold hands and feet) were uncommon and equally distributed among atenolol and metoprolol patients. 31 of the patients preferred metoprolol CR, 23 atenolol, while 20 had no preference.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, previously untreated subjects were randomly recruited from a blood pressure screening programme. After repeated measurement of blood pressure levels, the subjects were divided into three major groups: normotensives (n = 95), borderline hypertensives (n = 69) and hypertensives (n = 30). Three self-administered standardized questionnaires were used to measure different aspects of subjective well-being and symptoms: the Nottingham Health Profile (NHP), the Subjective Symptoms Assessment Profile (SSAP) and the Minor Symptoms Evaluation Profile (MSEP). The results indicate gradual differences between the three groups, the most pronounced symptoms being seen among the hypertensives. Statistically significant differences were found for cardiac and gastrointestinal symptoms as well as for emotional reactions, home life, social life, sex life and sleep. The differences in well-being and subjective symptoms noted between the groups are important in the evaluation of new antihypertensive agents. Self-administered questionnaires of the type used in this study could also be valuable in identifying symptoms and disturbances in subjective well-being related to the antihypertensive medication per se.

1. Whilst a number of studies have investigated whether metoprolol and atenolol, the most widely used beta 1-adrenoceptor antagonists, differ with regard to CNS-related subjective symptoms, few placebo-controlled studies using standardised questionnaires have been performed. 2. In the present report, the findings of two randomised, double-blind, cross-over studies in healthy volunteers are presented. The subjects were treated with placebo and atenolol (100 mg once daily) (Study 1) and metoprolol (100 mg once daily) and placebo (Study 2). 3. Subjective experiences were evaluated using a standardised instrument, the Minor Symptoms Evaluation-profile (MSE-profile), which was filled in 4, 8 and 24 h after intake of the tablets. A Type A questionnaire was also completed by the subjects. 4. At 4 h both metoprolol and atenolol were found to affect negatively vitality and contentment, but these effects had declined after 8 h. A significant adverse effect on sleep was shown for atenolol compared with placebo, while no negative effect was observed for metoprolol. No significant differences were found in relation to Type A behaviour and beta-adrenoceptor blockade. The number of subjects with Type A personality was, however, low. 5. The results of the studies indicate that the subjective symptoms of the beta 1-adrenoceptor blockers are mild, and that the effects appear consistently with the recognised pharmacokinetic profiles of the two drugs.