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Gernot Wassmer

Publications and source records attributed to Gernot Wassmer.

16 recordsLinked to original sources
PubMed2006

Planning and analyzing adaptive group sequential survival trials.

The use of adaptive methods has experienced increasing interest in the current literature on group sequential designs. Group sequential analysis in survival trials usually apply the error spending function approach due to the unpredictable amount of information available in an interim analysis. An alternative way is to apply adaptive methods where additionally the maximum amount of information and other designing parameters can be changed based on the information available at the interim stage. In this paper, it is shown how the inverse normal method can be used within a survival design using the log-rank test for comparing two survival functions. This method allows for many kinds of design modifications. In case of no modifications, the inverse normal method coincides with the commonly used analysis strategy. It is straightforward to specify effect estimates. Confidence intervals for the hazard ratio that can be calculated at each stage of the trial and intervals that can only be computed by the end of the trial are proposed. The latter also enables the calculation of median unbiased estimates. Overall p-values can be defined analogously. Properties of the analyses techniques are investigated and compared with alternative approaches. It is shown that the proposed analysis technique might help to rescue an underpowered study and opens the way to other types of changes in design. The proposed technique is implemented in the software ADDPLAN Adaptive Design, Plans and Analyses (http://www.addplan.com).

Biometry↗
PubMed2006

A brief review on software developments for group sequential and adaptive designs.

In this paper the currently available software we know for group sequential and adaptive designs is briefly reviewed. Stand-alone packages as well as modules within software packages or programming languages exist. New software developments for adaptive designs enable the user to perform data dependent design adaptations while controlling the Type I error rate.

Biometry↗
PubMed2005

Improved lipid profiles and maintenance of virologic control in heavily pretreated HIV-infected patients who switched from stavudine to tenofovir treatment.

A retrospective chart analysis of 66 human immunodeficiency virus type 1 (HIV-1)-infected patients whose treatment was switched from stavudine to tenofovir without any other treatment changes was conducted. The mean total cholesterol values decreased significantly within 3 months after the tenofovir substitution and remained significantly less than baseline values during 18 months of follow-up (mean decrease, 36 mg/dL; P = .002). Regimens containing tenofovir provided effective control of HIV-1 infection, with stable CD4+ cell counts and continued suppression of plasma HIV-1 level following the treatment switch from stavudine.

Adenine↗
PubMed2004

Perioperative granulocyte colony-stimulating factor does not prevent severe infections in patients undergoing esophagectomy for esophageal cancer: a randomized placebo-controlled clinical trial.

OBJECTIVE: Esophagectomy for esophageal cancer is associated with substantial postoperative morbidity as a result of infectious complications. In a prior phase II study, granulocyte colony-stimulating factor (G-CSF) was shown to improve leukocyte function and to reduce infection rates after esophagectomy. The aim of the current randomized, placebo-controlled, multicenter phase III trial was to investigate the clinical efficacy of perioperative G-CSF administration in reducing infection and mortality after esophagectomy for esophageal cancer. PATIENTS AND METHODS: One hundred fifty five patients with resectable esophageal cancer were randomly assigned to perioperative G-CSF at standard doses (77 patients) or placebo (76 patients), administered from 2 days before until day 7 after esophagectomy. The G-CSF and placebo groups were comparable as regards age, gender, risk, cancer stage, frequency of neoadjuvant radiochemotherapy, and type of esophagectomy (transthoracic or transhiatal esophageal resection). RESULTS: Of 155 randomized patients, 153 were eligible for the intention-to-treat analysis. The rate of infection occurring within the first 10 days after esophagectomy was 43.4% (confidence interval 32.8-55.9%) in the placebo and 44.2% (confidence interval 32.1-55.3%) in the G-CSF group (P = 0.927). 30-day mortality amounted to 5.2% in the G-CSF group versus 5.3% in the placebo group (P = 0.985). Similar results were found in the per-protocol analysis. CONCLUSION: Perioperative administration of G-CSF failed to reduce postoperative morbidity, infection rate, or mortality in patients with esophageal cancer who underwent esophagectomy.

Adult↗
PubMed2004

Comparison of magnetic resonance imaging and computed tomography of 8 aortic stent-graft models.

PURPOSE: To report the systematic comparison of magnetic resonance imaging (MRI) with contrast-enhanced computed tomography (CT) for evaluating 8 different aortic stent-graft models. METHODS: MR angiography (MRA) was performed using a 1.5-T whole body system within 2 days of a CT examination (4 detector row scanner) on 8 patients with one of these stent-graft models: AneuRx, Endofit, PowerLink, Excluder, LifePath, Talent, Vanguard, or Zenith. Using a 4-point scale (maximum score 112 points), 4 independent readers (1 vascular surgeon and 3 radiologists) rated the impact of stent-related artifacts on the diagnostic quality of each imaging method for 28 parameters: length, diameter, collateral aortic side branches, stent-graft prostheses, and contrast. Each examiner also scored his personal diagnostic confidence with each stent-graft model. RESULTS: The scores for diagnostic confidence in the CT imaging were 4 points for each stent-graft, with the exception of the LifePath (3 points). The diagnostic confidence in the MR images was mainly poor, with a median score of only 1; however, 3 stent-grafts (AneuRx, Excluder, and Vanguard) received > or =3 points. The total scores for comparative assessment were significantly different (p<0.05) between CT imaging (111.5) and MR (58.5). CT studies of all stent-grafts received >101 points, while only 3 devices acquired >80 points (AneuRx, Excluder, and Vanguard). Bland-Altman analysis showed that the reliability of the 4 readers was higher using the CT method. The total assessment scores of the stent-graft systems were related only on the different imaging methods (p<0.0001) and not to the different readers (p=0.983). CONCLUSIONS: CT and MRI are fast, reliable means of providing all relevant information for stent-graft surveillance. Of 8 different stent-graft models, only 3 could be adequately assessed by MRA. Therefore, the potential advantages of the MR technique (e.g., use of minimally nephrotoxic contrast media, lack of ionizing radiation) are available only to a small proportion of patients.

Analysis of Variance↗
PubMed2003

Randomized comparison of mounted versus unmounted stents: the multicenter COMUS trial.

BACKGROUND: Although the use of premounted stents on a delivery balloon has almost completely eliminated the initially used hand-crimping procedure, no data are available that prove the superiority of one or the other approach on a randomized basis. Therefore, this study was designed to examine whether the use of premounted stents is comparable with the hand-crimping procedure. METHODS: A total of 123 patients (64 treated with unmounted stents, 59 treated with premounted stents) were examined in a multicenter, randomized, prospective study. There were no significant differences in patient characteristics between groups. RESULTS: Primary end points (acute, postinterventional [within 72 hours], and late complications related to the stenting procedure) were reached in 1 patient treated with an unmounted stent versus 2 patients with mounted stents (P = not significant). In patients with angiographic follow up (n = 84, mean follow-up period 6 +/- 1 months), the total rate of restenosis was 27% (unmounted 12, mounted 11, P = not significant). Secondary end points were procedural success of stenting and maximal balloon inflation pressure needed for optimal stenting results by use of angiography. There were no differences in secondary end points for both techniques. The mean balloon pressure was 12.56 +/- 2.1 atmospheres (unmounted) and 12.12 +/- 1.92 atmospheres (mounted, P = not significant). CONCLUSION: Stenting with premounted devices was demonstrated to have a similar clinical and angiographic outcome as the hand-crimping approach for maximal inflation pressure, procedural success, major cardiac events, and rate of restenosis after 6 months of follow up. Thus, the more convenient use of a premounted stent provides procedural safety and efficacy comparable with a hand-crimped system.

Angioplasty, Balloon, Coronary↗
PubMed2003

Analyzing randomized dose finding studies with a primary and a secondary endpoint.

The identification of the minimum effective dose for both the primary and secondary endpoint under a priori importance ordering assumption is described. Stepwise testing procedures, which conditionally test each elementary hypotheses at level alpha, but control the experimentwise Type I error rate, can be used.

Dose-Response Relationship, Drug↗
PubMed2003

Data-driven analysis strategies for proportion studies in adaptive group sequential test designs.

Using multistage adaptive group sequential test designs, the investigator may perform data-driven changes in the design during the course of the trial without inflation of the Type I error rate. This is possible, for example, through the use of the inverse normal method of combining the p-values from the separate stages of the trial. Generally, conditional error functions are useful instruments for midtrial design modifications of clinical trials. Particularly, it is worthwhile to consider sample size reassessment strategies based on conditional power arguments. In this paper, approximate techniques will be proposed for the application of the inverse normal combination testing principle in superiority and noninferiority proportion studies. Planning facilities and the adaptive analysis strategies will be discussed in terms of the Type I error rate, the necessary sample size, and the power within the adaptive design. Furthermore, how to calculate confidence intervals and overall p-values will be shown.

Clinical Trials as Topic↗
PubMed2003

Association of the vitamin D receptor genotype with bone metastases in breast cancer patients.

This study was designed in order to evaluate specific vitamin D receptor (VDR) genotypes as indicators of the likelihood of developing osseous metastases in breast cancer patients. Therefore, we determined polymorphisms of the VDR gene in a study group comprising 183 breast cancer patients. Specific fragments spanning over intron 8 and exon 9 of the VDR gene were amplified by polymerase chain reaction. The fragments were then incubated with each of the specific endonucleases APAI, BSMI or TAQI, respectively. The VDR gene polymorphisms were detected by the presence or absence of the particular restriction site using agarose gel electrophoresis. Statistical analyses revealed a significant correlation between both the VDR gene polymorphisms indicated as AA (absence of the APAI restriction site in both alleles) or TT (absence of the TAQI restriction site in both alleles), respectively, and the occurrence of bone metastases. Patients with the AA genotype have a 1.7-fold increased risk of developing bone metastases, whereas patients with the TT genotype have a 0.5-fold risk. Neither other genotypes nor allelic combinations displayed any further correlation with the clinical stage. The data suggest that the AA genotype of the VDR gene might be useful to identify breast cancer patients with a high probability of forming occult bone metastases who are considered to benefit from an adjuvant bone-protective therapy.

Bone Neoplasms↗
PubMed2003

Endotension is influenced by aneurysm volume: experimental findings.

PURPOSE: To investigate in an in vitro model whether and to what extent pressure is influenced by aneurysm size. METHODS: Latex aneurysms of 3 different volumes (24, 30, and 81 mL) were inserted into an in vitro circulation model. The systemic mean pressure (SP(mean)) was varied from 50 to 120 mmHg. The aneurysms were excluded using a woven polyethylene graft. Aneurysm sac mean pressure (ASP(mean)) was measured. RESULTS: In the in vitro model, endovascular aneurysm repair created a closed chamber without endoleak but showed a relevant aneurysm sac pressure. At an SP(mean) of 80 mmHg, the ASP(mean) was 42.0+/-0.6 mmHg in the 24-mL aneurysm, 40.5+/-0.5 mmHg in the 30-mL model, and 19.3+/-0.5 mmHg in the 81-mL aneurysm (p<0.05). The ASP(mean) rose with increasing SP(mean) and was inversely dependent on the aneurysm volume. CONCLUSIONS: This in vitro model demonstrated that the sac mean pressure correlated to the systemic pressure and that a greater aneurysm volume reduced aneurysm sac pressure. These data highlight the need for further studies regarding endotension.

Analysis of Variance↗
PubMed2002

A randomized crossover trial of IV fluid replacement versus no fluid replacement in autologous blood donors with cardiovascular disease.

BACKGROUND: The aim of this study was to compare the incidence of arterial hypotension in response to autologous blood donation with and without simultaneous IV fluid replacement in 60 patients with cardiovascular disease. STUDY DESIGN AND METHODS: Each patient donated two 500 mL units of blood at an interval of 7 days. Following random allocation within a two-stage crossover design, either the first or second unit was collected with a simultaneous IV infusion of 500 mL of HES. Patients receiving IV fluid replacement during their first donation did not receive any fluid replacement during their second donation and vice versa. Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 minutes until 30 minutes after donation. Hypotension was defined as at least one decrease of more than 20 percent from baseline in systolic blood pressure. RESULTS: A decrease of more than 20 percent from baseline in systolic blood pressure occurred in 2 of the 60 patients (3%) during the donations with IV fluid replacement compared with 55 of the 60 patients (92%) during the donations without IV fluid replacement (p < 0.0001, McNemar's test). No severe reaction to blood donation was observed in any patient, regardless of whether IV fluids had been administered. CONCLUSION: Isovolemic IV fluid replacement was useful in preventing arterial hypotension in autologous blood donors with cardiovascular disease. Its effect on the safety of the autologous blood donation process remains to be established.

Adult↗
PubMed2002

Muscle analysis by measurement of maximal isometric grip force: new reference data and clinical applications in pediatrics.

Skeletal muscle development is one of the key features of childhood and adolescence. Determining maximal isometric grip force (MIGF) using a hand-held Jamar dynamometer is a simple method to quantify one aspect of muscle function. Presently available reference data present MIGF as a function of chronological age. However, muscle force is largely determined by body size, and many children undergoing muscle performance tests in the clinical setting suffer from growth retardation secondary to a chronic disorder. Reference data were established from simple regressions between age or log height and log MIGF in a population of 315 healthy children and adolescents aged 6 to 19 y (157 girls). These data were used to calculate age- or height-dependent SD scores (SDS) for MIGF in three pediatric patient groups. In renal graft recipients (n = 14), the age-dependent MIGF SDS was markedly decreased (-2.5 +/- 1.9; mean +/- SD). However, these patients had short stature (height SDS, -2.5 +/- 1.2), and the height-dependent MIGF SDS was close to normal (-0.4 +/- 1.5). Similarly, in cystic fibrosis patients (n = 13) age-dependent MIGF SDS was -1.6 +/- 1.6, but height-dependent MIGF SDS was -0.5 +/- 1.1. Children with epilepsy who were taking anticonvulsant therapy (n = 34) had normal stature, and consequently age- and height-dependent MIGF SDS were similar (0.4 +/- 1.0 and 0.4 +/- 0.8, respectively). In conclusion, MIGF determination provides information on an important aspect of physical development. Height should be taken into account to avoid misinterpretation.

Adolescent↗
PubMed2002

Cardiorespiratory stability of premature and term infants carried in infant slings.

OBJECTIVE: Parents in industrialized societies make increasing use of infant slings to carry their infants. This study was conducted to determine whether infants who are carried in slings are at risk of experiencing clinically relevant changes in cardiorespiratory measurements. METHODS: In a 3-period crossover trial, 24 preterm and 12 term newborns were continually monitored while being carried horizontally or vertically in a sling or lying in a pram. Oxygen saturation, heart rate, nasal airflow, abdominal breathing, and movements were recorded. RESULTS: Infants who were carried in slings were not at risk of clinically relevant changes of oxygen saturation or heart rate. The 90% confidence interval of oxygen saturation in both infant sling positions remained within a +/-2% interval around the average oxygen saturation in the pram. However, a significant decrease of oxygen saturation was observed while infants were carried in a sling with a mean oxygen saturation of 96.3% (standard deviation [SD]: 1.8) in the vertical and 96.1% (SD: 2.0) in the horizontal sling position compared with the mean oxygen saturation in the pram (97.1%; SD: 1.5). The degree and the incidence of desaturations and bradycardia did not change while the infants were carried. Both types of episodes were seen only in preterm infants. CONCLUSION: The use of carrying slings is not associated with an increased risk of clinically relevant cardiorespiratory changes in term and preterm infants.

Bradycardia↗
PubMedDate not supplied

Efficacy of extract of Pelargonium sidoides in children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical trial data suggest that antibiotics are not indicated for the treatment of acute non-group A beta hemolytic strep (non-GABHS) tonsillopharyngitis. Nevertheless patients are symptomatic and effective alternatives for its treatment are needed that have been evaluated in clinical trials. OBJECTIVE: To confirm that treatment with an extract of Pelargonium sidoides (EPs 7630) is superior to placebo for the treatment of non-GABHS tonsillopharyngitis in children. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Six study sites in 4 pediatric and ENT primary care outpatient clinics. PATIENTS: One hundred forty-three children aged 6-10 years with non-GABHS tonsillopharyngitis present < or = 48 h, a negative rapid strep screen, a Tonsillopharyngitis Severity Score (TSS) > or = 8 points, and informed consent. INTERVENTION: EPs 7630 or placebo (20 drops tid) for 6 days. MEASUREMENT: The primary outcome criterion was the decrease of the TSS from baseline (day 0) to day 4. RESULTS: The decrease of the TSS from baseline (day 0) to day 4 was 7.1 +/- 2.1 points under EPs 7630 (n = 73), and 2.5 +/- 3.6 points under placebo (n = 70). The covariate adjusted decrease was 7.0 +/- 2.4 points under EPs 7630, and 2.9 +/- 2.4 points under placebo. The 95% RCI for the difference between the groups was [2.7; 4.9] demonstrating a significant difference in efficacy of EPs 7630 compared to placebo (P < 0.0001). Adverse events (AEs) occurred in 15/143 patients (EPs 7630: 4/73 patient, placebo: 44/70) and were not related to the investigational medication. CONCLUSIONS: EPs 7630 was superior compared to placebo for the treatment of acute non-GABHS tonsillopharyngitis in children. Treatment with EPs 7630 reduced the severity of symptoms and shortened the duration of illness by at least 2 days.

Acute Disease↗