Quality of life assessment of treatment with dental appliance or UPPP in patients with mild to moderate obstructive sleep apnoea. A prospective randomized 1-year follow-up study.

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.

Relevance of norm values as part of the documentation of quality of life instruments for use in upper gastrointestinal disease.

This article presents the relevance of norm values to a battery of Quality of Life questionnaires for use in upper gastrointestinal disorders. The derivation of reference values offers an important contribution by confirming the ability of the questionnaires to differentiate patients from healthy controls. Two self-administered questionnaires, the Psychological General Well-being (PGWB) index and the Gastrointestinal Symptom Rating Scale (GSRS) were used. The norm values were derived in a randomly selected sample from a Swedish population consisting of 4624 individuals (reference group). The patients comprised more than 900 patients with gastroesophageal reflux disease (GORD) included in clinical trials. In the reference group, males reported significantly higher values on well-being as compared with women, whereas women reported more pronounced gastrointestinal symptoms than men. Generally, the younger persons and the group aged 60-70 years reported the highest well-being. Among gastrointestinal patients women scored lower and reported more symptoms than men. With increasing age, well-being improved and symptoms declined. Even though the well-being and symptoms scores differed between patient and the reference group similar patterns in terms of age and gender were observed. In summary, the results show that there are differences with respect to gender and age among normal controls as well as in GORD patients. These aspects have to be considered in clinical studies. The results also support the discriminative ability of the Quality of Life instruments.

Well-being and gastrointestinal symptoms among patients referred to endoscopy owing to suspected duodenal ulcer.

BACKGROUND: Few studies have evaluated quality of of life (QoL) in patients with upper gastrointestinal diseases, and there is a lack of validated measures for use in gastroenterology. METHODS: The applicability and relevance of self-administered questionnaires such as the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptoms referred to endoscopy because of suspected duodenal ulcer were evaluated. RESULTS: In total, 1526 patients with suspected duodenal ulcer were screened for inclusion in a clinical study. On the basis of medical history and endoscopy, 1424 patients who completed the questionnaire before endoscopy were classified in five diagnostic groups: oesophagitis, gastric ulcer, duodenal ulcer, negative endoscopy, and gastritis duodenitis. Irrespective of diagnosis, all patient groups reported a considerable decrease in their general well-being (mean score, 85, compared with 105 in healthy populations) with no significant differences between the groups. The results of the GSRS, however, showed statistically significant differences between the groups in dimensions depicting Abdominal pain, Reflux, Indigestion, and Diarrhoea Syndrome. CONCLUSIONS: The results of the study showed that, irrespective of endoscopic findings, patients complaining of upper gastrointestinal symptoms have a low degree of general well-being. The symptoms profiles in the different diagnostic groups vary considerably.

Migraine patients experience poorer subjective well-being/quality of life even between attacks.

The aim of the present study was to compare the general well-being of migraine patients between attacks with that of an age- and sex-matched control group. One hundred and forty-five consecutive and eligible patients at the Gothenburg Migraine Clinic were asked about their well-being and their complaints. Using three self-administered standardized questionnaires, the Minor Symptoms Evaluation Profile (MSEP), Subjective Symptoms Assessment Profile (SSAP) and the Psychological General Well-Being (PGWB) Index, evaluable responses were obtained from 138 migraine patients. Compared with control subjects, migraineurs perceived more symptoms and greater emotional distress as well as disturbed contentment, vitality and sleep. It is concluded that the general well-being of the migraine patient is impaired, even between the attacks.

Effects of 100 mg of controlled-release metoprolol and 100 mg of atenolol on blood pressure, central nervous system-related symptoms, and general well being.

Central nervous system (CNS)-related symptoms and quality of life during treatment with controlled-release (CR) metoprolol and a standard formulation of atenolol were compared in a double-blind crossover study in 60 patients with mild to moderate hypertension. After a 4-week placebo run-in period, each beta 1-adrenoceptor blocker was administered at a dosage of 100 mg once daily for 6 weeks. Quality of life was assessed regularly during the active treatment phases by use of two standardized self-administered questionnaires, the minor symptom evaluation (MSE) profile, and the psychologic general well-being (PGWB) index. Both questionnaires have previously been shown to be effective in detecting CNS symptoms and changes in well being produced by beta-blockers. Blood pressure and heart rate were monitored to assess the antihypertensive efficacy of the two drugs. Metoprolol CR and atenolol produced equivalent, clinically effective reductions in systolic and diastolic blood pressures measured 24 hours after administration. The drugs were found to exert similar effects on general well being, as assessed by the PGWB index, and there were no significant differences between the two treatments with regard to the three dimensions of the MSE profile, contentment, vitality, and sleep. Thus, at equivalent antihypertensive dosages, metoprolol CR and atenolol are clinically comparable with regard to the degree of CNS-related symptoms produced and effects on general well being. Because these agents differ markedly in lipophilicity, other factors, such as beta 1-selectivity/nonselectivity, may be more important determinants of whether these subjective symptoms occur during therapy with beta-blockers.

Quality of life in patients with upper gastrointestinal symptoms. An improved evaluation of treatment regimens?

There is growing interest in measuring quality of life (QoL) in medicine. Together with objective variables such as healing rate, as recorded with endoscopy, this is believed to give a better basis for evaluation of treatment regimens in patients with upper gastrointestinal diseases. A strategy for the assessment of QoL in patients with upper gastrointestinal symptoms is presented here. The QoL evaluation was based on a battery of questionnaires, covering both general and specific aspects of life. General well-being was evaluated with the Psychological General Well-being Index (PGWB), and subjective symptoms with two specific questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS) and the Ulcus Esophagitis Subjective Symptoms Scale (UESS). This new strategy was applied clinically in a study including 146 outpatients with suspected peptic ulcer. Initially, the patients reported a low degree of general well-being as evaluated with the PGWB, but the values returned to those found in normal populations within 4 weeks. Evaluation of the GSRS and UESS with regard to internal consistency, construct validity, and the ability to detect changes showed them to be satisfactory. The psychometric documentation of the measures indicates that they may give reliable and clinically valid information when used for evaluation of medical treatments in upper gastrointestinal disease. Further documentation of the methods is, however, needed to establish a generally acceptable QoL assessment in gastroenterology.

Methodological aspects of evaluation of Quality of Life in upper gastrointestinal diseases.

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.

General well-being during treatment with different ACE-inhibitors: two double-blind placebo-controlled cross-over studies in healthy volunteers.

Two randomised, double-blind, cross-over studies in healthy volunteers given captopril 50 mg b.d. (n = 37; Study I) or enalapril 20 mg o.d. (n = 40; Study 2) and placebo for 2 weeks have been done to examine general well-being. Subjective experiences were evaluated using the standardised, Minor Symptoms Evaluation-profile (MSEP), which was completed during Run-in and on Days 1, 4, 7 and 14 in the morning. In comparison to placebo and the Run-in period, neither captopril nor enalapril affected the MSEP dimensions of Vitality, Contentment and Sleep. Captopril treatment was also assessed by applying the Quality of Life Clinical Questionnaire during Run-in and on Days 7 and 14. No improvement in the quality of life was demonstrated during treatment in comparison with the placebo or the Run-in period. Thus, no mood elevating effect of the ACE-inhibitors captopril and enalapril was demonstrated in healthy volunteers. Cough, which is believed to be a common adverse effect of ACE-inhibitors, was no more frequent during the treatment with captopril or enalapril than with placebo. It is concluded, that short-term treatment with captopril or enalapril is not perceived differently by healthy volunteers than placebo or no treatment at all. Furthermore, the cough associated with ACE-inhibition may be dependent on the duration of treatment, and two weeks was apparently too short for it to emerge.

Quality of life in cardiovascular diseases. Emphasis on beta-blocker treatment.

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.

The relationship between exercise tolerance and quality of life in angina pectoris.

The relationship between exercise tolerance assessed by a conventional exercise stress test using a standard Bruce protocol and quality of life (QoL) was studied in 50 patients with stable angina pectoris (AP). Before the exercise test, patients completed three self-administered QoL questionnaires, the Psychological General Well-Being Index, an Angina-Specific QoL Questionnaire, and Jenkins' Sleep Dysfunction Scale. Total exercise time (r = -0.40) and time until onset of pain (r = -0.44) were significantly correlated with perceived physical limitations. Somatic symptoms were related to total time (r = -0.38). Apart from a significant correlation between depressed mood and total exercise time (r = 0.36), there was no corresponding correlation with well-being and sleep disturbance. These results suggest that exercise stress tests do not reflect quality of life in patients with AP.

Aspects of quality of life on treatment with felodipine.

Quality of life has been assessed in a double-blind four week study comparing felodipine 5, 10, 20 mg and placebo added to metoprolol by adding two self-administered questionnaires to the conventional procedure for the evaluation of adverse events. None of the aspects related to general well-being was affected by felodipine. The subjective symptoms reported were mostly dose-related and so here mainly observed at the highest dose. Some of them, e.g. headache, were transient. It is concluded that felodipine in combination with metoprolol CR did not negatively influence the feeling of well-being of the patients. When the drug was given in low, individually adjusted doses, the symptoms normally associated with Ca antagonists were likely to be minimised.

Evaluation of three methods of symptom reporting in a clinical trial of felodipine.

251 patients from 23 primary health care centres were recruited to a clinical trial in which either felodipine or placebo was added to baseline metoprolol treatment. Three methods of symptom reporting were used in 191 patients, namely two previously documented self-administered questionnaires and an adverse event monitoring system (spontaneous reports to treating physician). Higher frequencies of symptoms were seen with the questionnaires compared to spontaneous reporting. However, the overlap between the methods was moderate and they were found to complement one another. The questionnaires were completed twice during the study and the adverse event monitoring system was applied on five occasions. The rate of application had consequences for the ability of each method to detect transient, dose-related symptoms, e.g. headache and dizziness. Regardless of method, the possibility of detecting dose-related symptoms was enhanced when symptoms were measured not only during active treatment but also during a run-in or other baseline period, and both phases were considered in the analyses.

Factors of importance when evaluating quality of life in clinical trials.

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.

Side effects of beta-blocker treatments as related to the central nervous system.

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.

Comparison of CNS-related subjective symptoms in hypertensive patients treated with either a new controlled release (CR/ZOK) formulation of metoprolol or atenolol.

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.

Tolerability and well-being with metoprolol in a controlled release (CR/ZOK) formulation: a review article.

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.

Beta-adrenoceptor blockade and CNS-related subjective symptoms: a randomized, double-blind, placebo-controlled comparison of metoprolol CR/ZOK, atenolol and propranolol LA in healthy subjects.

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.

Subjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects--a comparison with atenolol.

In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2-4 h. All three active treatments produced significant beta 1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of beta 1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.