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M Kieser

Publications and source records attributed to M Kieser.

33 records · Page 2Linked to original sources
PubMed1999

Approximate sample sizes for testing hypotheses about the ratio and difference of two means.

This article deals with a unifying approach to approximate sample size determination for different types of hypotheses formulated in terms of two means of normally distributed data. A simple approximation is given to the sample size required for testing hypotheses about the ratio of the means. The formula includes the situations of testing noninferiority, superiority, or equivalence. We present a more general formula that also covers hypotheses formulated in terms of the difference of means. We show that over a wide range of parameter values the approximation provides reliable sample sizes.

Controlled Clinical Trials as Topic↗
PubMed1998

St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy.

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female outpatients suffering from mild or moderate depression according to DSM-IV criteria. Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3 x 1 tablets of either placebo, Hypericum extract WS 5573 (300 mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for the two Hypericum preparations was identical, so that they differed only in their hyperforin content. Efficacy regarding depressive symptoms was assessed on days 0, 7, 14, 28, and 42, using the Hamilton Rating Scale for Depression (HAMD, 17-item version) and the Depression Self-Rating Scale (D-S) according to von Zerssen. In addition, the severity of illness was also rated by the investigators on days 0 and 42 using the Clinical Global Impression (CGI) scale. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 +/- 4.6 points; mean +/- SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 +/- 6.1 points) and the placebo group (7.9 +/- 5.2 points). As regards the change in the HAMD total score between day 0 and treatment end and its relationship to the hyperforin dose, a significant monotonic trend was demonstrated in the Jonckheere-Terpstra test (p = 0.017). In pairwise comparisons, WS 5572 (5% hyperforin) was superior to placebo in alleviating depressive symptoms according to HAMD reduction (Mann-Whitney U-test: p = 0.004), whereas the clinical effects of WS 5573 (0.5% hyperforin) and placebo were descriptively comparable. These results show that the therapeutic effect of St. John's Wort in mild to moderate depression depends on its hyperforin content.

Antidepressive Agents↗
PubMed1998

Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication--a placebo-controlled, double-blind multicenter trial.

BACKGROUND: A multicentric, randomized, placebo-controlled double-blind study on ginkgo biloba special extract EGb 761 (Tebonin forte) in patients suffering from peripheral occlusive arterial disease (POAD) in Fontaine stage II b was carried out in order to prove its clinical efficacy in this indication according to guidelines of European Community authorities and the German Angiological Society and to confirm the results of former clinical studies with EGb 761. PATIENTS AND METHODS: In total, 111 patients with angiographically proven POAD in Fontaine stage II b and intermittent claudication (pain-free walking distance < 150 m on the treadmill) were recruited in 5 centers and treated with either EGb 761 or placebo at a daily dose of 3 times 1 film-coated tablet over a duration of 24 weeks following a 2-week placebo run-in period. The primary response variable was the difference of the pain-free walking distance between the start of treatment and after 8, 16 and 24 weeks as measured on the treadmill (walking speed 3 km/h and slope of 12%) under standardized conditions. RESULTS: At the start of the treatment period, the mean pain-free walking distances were very similar with 108.5 m in the EGb 761 group and 105.2 m in the placebo group. At the end of the treatment period these values increased to 153.2 m and 126.6 m, respectively. The group differences were statistically significant at all three control visits with p = 0.017, p = 0.007, and p = 0.016. The differences for the maximum walking distance and the relative increases of the pain-free walking distance and the maximum distance were also significantly higher in the EGb 761 group with p-values < 0.05 each. In both groups Doppler indices remained nearly unchanged during therapy. The subjective assessment of the patients demonstrated an amelioration of complaints in both groups. Tolerability was very good with no adverse events under EGb 761 and one case of heartburn and gastric pain in the placebo group. CONCLUSIONS: It can be concluded from the results of this study that treatment with EGb 761 in POAD patients with Fontaine stage II b is very safe and causes a significant and therapeutically relevant prolongation of the patients' walking distance.

Aged↗
PubMed1997

Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial.

101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines.

Anti-Anxiety Agents↗
PubMed1996

[Placebo-controlled double-blind study of the effectiveness of Ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication].

This monocenter, randomized, placebo-controlled double-blind study with parallel-group comparison was carried out in order to demonstrate the efficacy of Ginkgo biloba special extract EGb 761 on objective and subjective parameters of the walking performance in trained patients suffering from peripheral arterial occlusive disease in Fontaine stage IIb. In total 60 patients were recruited (42 men; aged 47-82 years) with angiographically proven peripheral arterial occlusive disease of the lower extremities and an intermittent claudication existing for at least 6 months. No improvement had been shown despite consistent walking training and a maximum pain-free walking distance on the treadmill of less than 150 m was recorded at the beginning of the study. The therapeutic groups were treated with either Ginkgo biloba special extract EGb 761 at a dose of 3 times 1 film-coated tablet of 40 mg per day by oral route or placebo over a duration of 24 weeks following a two-week placebo run-in phase. The main outcome measure was the difference of the walking distance between the start of treatment and after 8, 16 and 24 weeks of treatment as measured on the treadmill (walking speed 3 km/h and slope of 12%). As secondary parameters the corresponding differences for the maximum walking distance, the relative increase of the pain-free walking distance, the Doppler index and the subjective evaluation of the patients were analyzed. The absolute changes in the pain-free walking distance in treatment weeks 8, 16 and 24 as against the treatment beginning (median values with 95% confidence interval) led to the following values for the patients treated with Ginkgo biloba special extract EGb 761:19 m (14, 33), 34 m (18, 50) and 41 m (26, 64). The corresponding values in the placebo group were as follows: 7 m (-4, 12), 12 m (5, 22) and 8 m (-1, 21). The advantage of the EGb 761-treated group as compared to the placebo group could be verified statistically at the 3 time points with p < 0.0001, p = 0.0003 and p < 0.0001. The test for the presence of a clinically relevant difference of 20% between EGb 761 and placebo also produced a statistically significant result (p = 0.008). The Doppler index remained unchanged in both therapeutic groups: A corresponding statistically significant advantage for the EGb 761 group was observed on a descriptive level for the other parameters tested. The tolerance of the treatment was very good. The results of this placebo-controlled study show that treatment with Ginkgo biloba special extract EGb 761 produces a statistically highly significant and clinically relevant improvement of the walking performance in trained patients suffering from intermittent claudication with very good tolerance of the study preparation.

Aged↗
PubMed1996

Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia.

The efficacy and safety of the standardized herbal combination preparation of Enteroplant, consisting of peppermint oil (90 mg) and caraway (50 mg) in an enteric coated capsule, have been studied in a double-blind, placebo-controlled multicentre trial in patients with non-ulcer dyspepsia. A total of 45 patients were included in the trial after thorough physical and gastro-enterological examination. The primary outcome variables were the change in the intensity of pain and the global clinical impression (Clinical Global Impression [CGI], Item 2), which were evaluated for 39 patients (test preparation: 19, placebo: 20). After four weeks of treatment both target parameters were significantly improved for the group of patients treated with the peppermint oil/caraway oil combination compared to the placebo group (p = 0.015 and 0.008, respectively). Before the start of treatment all patients in the test preparation group reported moderate to severe pain, while by the end of the study 63.2% of these patients were free of pain. The pain symptoms had improved in a total of 89.5% of the patients in the active treatment group. After 4 weeks the Clinical Global Impressions were improved for 94.5% of the patients treated with the peppermint oil/caraway oil combination. The trial medication was also superior to placebo with respect to pain frequency, medical prognosis, the severity of the disorder and the efficacy index (CGI, Items 1 and 3), which were adopted as secondary end-points for evaluation of efficacy. There were similarly favourable findings for the herbal combination, compared with placebo, with respect to the reduction of other gastrointestinal symptoms. The combination preparation was found to be excellently tolerated. There was a total of 7 adverse events (test preparation: 4, placebo: 3), with a causal association with the treatment being ascribed in one case for the test preparation group and one case for the placebo group.

Adult↗
PubMed1995

A confirmatory strategy for therapeutic equivalence trials.

In the planning phase of a therapeutic equivalence trial, a range has to be specified that defines the parameter region within which the treatments to be compared are considered equal for practical purposes. It is current practice in equivalence assessment to fix some value for limiting the equivalence range and to test the corresponding null hypothesis in confirmatory analysis. This procedure is unsatisfactory, if, for example, the drug to be investigated is not only equivalent but turns out to be even superior to standard. In this situation it would be desirable to test not only for equivalence but also for superiority. The paper presents an alternative approach that allows for a flexible handling of the problem. If therapeutic equivalence can be established the method additionally allows, under maintenance of the multiple level, for testing all null hypotheses that correspond to acceptable equivalence ranges and even of superiority. Because of the special structure of the hypotheses no alpha-adjustment is needed for these additional confirmatory analyses.

Antihypertensive Agents↗
PubMed1994

[New approaches to evaluation of nonspecific inhalation provocation (dose-response relationship) in the comparative evaluation of bronchial hyperreactivity within the scope of clinical trials].

For the performance of clinical drug trials in the therapy for bronchial hyperresponsiveness, unspecific inhalatory provocation tests are generally employed to judge therapeutic success. In particular, the parameter-specific provocation doses are considered to be the main target values. However, it must be considered that these provocation doses are not equally calculable for every patient in the same way and at any examination time. This leads to the fact that the number of evaluable case studies is often appreciably lower than the number of test participants and that a meaningful therapy group comparison may even not be possible under certain circumstances. An evaluation model is presented here in order to fully exploit the obtained data; in this the percentile changes of the function parameters (estimated by linear regression) at a defined dose of the provocation substance are analyzed. In analogy, a survival time model and, as a supplement, a best case/worst case analysis are performed for further statistical evaluation. With the present procedure, an evaluation with inclusion of all test participants is possible. In contrast to the previously used evaluation procedures, this allows a reliable statistical confirmation of the results of clinical tests in the therapy for bronchial hyperresponsiveness.

Aerosols↗
PubMed1991

Affective disorders and survival after acute myocardial infarction. Results from the post-infarction late potential study.

Psychological data from 560 male survivors of acute myocardial infarction (AMI) were documented in the third week after onset of AMI. The psychodiagnostic assessment was designed to detect different forms of depression as well as hyperactive behaviour. A complete follow-up of these patients, which covers a period of 6 months, is available. Our findings indicate that affective disorders play an important role in the post-acute phase after AMI although the extent of myocardial infarction (as defined by an ECG score) and behaviour responses are not significantly related to one another. Different subforms of depression are not influenced by a history of angina pectoris, the degree and location of myocardial infarction, the occurrence of late potentials and age, whereas dyspnoea (P less than 0.001) and the recurrence of myocardial infarction (P less than 0.001) favour depressive mood states. Twelve cardiac deaths and 17 arrhythmic events occurred during the study period; they were significantly predicted by severe forms of post-AMI depression as revealed by univariate analysis. The evidence was stronger for predicting cardiac death (P less than 0.001) than for arrhythmic events (P = less than 0.035). The effect remains of borderline significance for cardiac death if all risk factors with a significant univariate influence are included in a multiple logistic regression model. The effect of depression is illustrated by Kaplan-Meier survival curves separated for patient groups with high as compared to low degrees of depression. Hyperactivity showed no impact on patient survival.

Adult↗
PubMed1982

[The effect of low-molecular hydroxyethyl starch and dextran 60 on the muscle oxygen supply in intensive care patients].

Skeletal muscle pO2 measurements were performed in two groups of critically ill patients (total n = 19) using the multiwire surface electrode (MDO) by Kessler and Lübbers to evaluate oxygen supply of the measured time. Muscle pO2 in the first group (n = 9) was recorded before and after i.v. application of 250 ml low molecular 6% hydroxyäthylstarch, Mw 40,000, in the second group (n = 10) before and after 250 ml 6% dextran 60. Both groups were tested under normoxemia and hyperoxemia respectively. It was the aim of the study, to examine if these colloidale substances may improve oxygen supply in skeletal muscle. Even the small amount of 250 ml l. m. HAS or dextran 60 respectively was able to raise the mean muscle pO2 of the measured patients significantly. The effect was similar in both groups. Since oxygen transport capacity remained uneffected, the improved oxygen supply after administration of l. m. HAS and dextran 60 must be considered as a beneficial effect of these drugs on the blood flow properties in the capillary bed.

Adolescent↗
PubMedDate not supplied

Comparative analysis of tissue fluorescence as related to capillary perfusion in random pattern skin flaps.

In random pattern skin flaps of mice, tissue fluorescence measured by means of videodensitometry at 24 h after flap elevation significantly correlates with intravital microscopically measured functional vessel density and viability of skin tissue as assessed by transmission light and electron microscopy. The correlation was found reproducible in non-ischaemic flaps (r = 0.86) and flaps being rendered ischaemic for 6 h after elevation (r = 0.98), indicating that increased microvascular permeability as a result of ischaemia/reperfusion does neither affect tissue fluorescence nor the accuracy of the fluorescein dye test. In addition, tissue fluorescence at 24 h after flap elevation accurately predicts ultimate flap survival on the 7th postoperative day with a sensitivity of 0.89 and a specificity of 0.85. These results suggest that in non-ischaemic as well as in ischaemic random pattern skin flaps tissue fluorescence can be used for assessment of nutritive blood flow, viability of skin tissue and ultimate tissue survival in these flaps.

Animals↗
PubMedDate not supplied

A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia.

This intent-to-treat (ITT) analysis was performed to provide a realistic image of the efficacy that could be expected after 26 weeks treatment with a 120-mg dose (40 mg t.i.d.) of EGb 761 (EGb). The data were collected during a 52-week, double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study. Patients were mildly to severely impaired and diagnosed with uncomplicated Alzheimer's disease or multi-infarct dementia according to ICD-10 and DSM-III-R criteria. The primary outcome measures included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI) and Clinical Global Impression of Change. From 309 patients included in the ITT analysis, 244 patients (76% for placebo and 73% for EGb) actually reached the 26th week visit. In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS-Cog (p = 0.04) and the GERRI (p = 0.007). In the group receiving EGb, 26% of the patients achieved at least a 4-point improvement on the ADAS-Cog, compared to 17% with placebo (p = 0.04). On the GERRI, 30% of the EGb group improved and 17% worsened, while the placebo group showed an opposite trend with 37% of patients worsening for 25% improved (p = 0.006). Regarding safety, no differences between EGb and placebo were observed.

Aged↗