Biomedical subjects

Gerhard Hommel

Publications and source records attributed to Gerhard Hommel.

12 recordsLinked to original sources

PubMed2007

Performance of adaptive sample size adjustment with respect to stopping criteria and time of interim analysis.

The benefit of adjusting the sample size in clinical trials on the basis of treatment effects observed in interim analysis has been the subject of several recent papers. Different conclusions were drawn about the usefulness of this approach for gaining power or saving sample size, because of differences in trial design and setting. We examined the benefit of sample size adjustment in relation to trial design parameters such as 'time of interim analysis' and 'choice of stopping criteria'. We compared the adaptive weighted inverse normal method with classical group sequential methods for the most common and for optimal stopping criteria in early, half-time and late interim analyses. We found that reacting to interim data might significantly reduce average sample size in some situations, while classical approaches can out-perform the adaptive designs under other circumstances. We characterized these situations with respect to time of interim analysis and choice of stopping criteria.

Clinical Trials as Topic↗

PubMed2005

Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

CONTEXT: Glucocorticoids are effective for severe Graves' orbitopathy (GO), which causes substantial morbidity. The question at issue is how best to use them. OBJECTIVE: The objective of this study was to optimize glucocorticoid application in GO. DESIGN: The study design was a randomized trial over 12 wk with 6-month follow-up. SETTING: The study was performed at university joint thyroid and ophthalmic clinics. PATIENTS: Seventy euthyroid out-patients with untreated, active, and severe GO were studied. INTERVENTION: Patients received either once weekly iv methylprednisolone (0.5 g, then 0.25 g, 6 wk each) or oral prednisolone starting with 0.1 g/d, then tapering the dose by 0.01 g/wk. MAIN OUTCOME MEASURES: At 3 months, the primary end point was a composite of improvements in proptosis, lid fissure width, and rate of diplopia in primary gaze, visual acuity, eye muscle thickness, and patient's quality of life. RESULTS: Intravenous glucocorticoid therapy resulted in rapid, significant, and sustained improvement. At 3 months, 27 of 35 patients (77%) in the iv group had a treatment response compared with 18 of 35 (51%) in the oral group (P < 0.01). Improvements over baseline values for disease severity (e.g. visual acuity; P = 0.01) and activity (e.g. chemosis; P < 0.01) and for quality of life (P < 0.001) were greater in the iv group. TSH receptor antibody titers decreased during iv steroid administration (P < 0.001), and smoking had a strong impact on the therapy response (P < 0.001). Additional treatment was required less frequently in the iv group. Intravenous steroids were safe, with different rates of adverse events between the two groups (P < 0.001). CONCLUSIONS: In patients with active and severe GO, iv glucocorticoids were more effective and better tolerated than oral steroids.

Administration, Oral↗

PubMed2005

Subtotal or total gastrectomy for gastric cancer: impact of the surgical procedure on morbidity and prognosis--analysis of a 10-year experience.

BACKGROUND: Against the background of the continuing controversy as to the surgical procedure of choice for gastric cancer, the aim of the present study was to evaluate perioperative morbidity, prognostic factors of survival, and long-term survival after subtotal, abdominal and abdominothoracic gastrectomy in patients with gastric cancer. PATIENTS AND METHODS: Between January 1993 and December 2002, 338 consecutive patients underwent surgery for adenocarcinoma of the stomach. Subtotal gastrectomy was carried out in 80 (23.7%) patients; 240 (71.0%) patients had abdominal gastrectomy, and 18 (5.3%) underwent abdominothoracic gastrectomy. RESULTS: At an overall 30-day mortality of 3.6% (hospital mortality, 5.2%), the total complication rate was 16.3%. The estimated 5-year survival rate was 43% in patients after subtotal gastrectomy, 39% in patients with abdominal gastrectomy, and 28% in patients with abdominothoracic gastrectomy after complete tumour clearance, without significant differences between the groups. Patients who underwent left pancreatectomy and had a higher ratio of metastatic/dissected lymph nodes were characterised by a significantly poorer prognosis. CONCLUSION: The lower morbidity and mortality rate with a nearly identical long-term survival yielded by subtotal gastrectomy compared with total gastrectomy leads us to justify subtotal gastrectomy, especially in elderly patients with comorbidity and a high operative risk, on the condition that its performance is radical from an oncological point of view.

Adenocarcinoma↗

PubMed2005

Tests for differentiation in gene expression using a data-driven order or weights for hypotheses.

In the analysis of gene expression by microarrays there are usually few subjects, but high-dimensional data. By means of techniques, such as the theory of spherical tests or with suitable permutation tests, it is possible to sort the endpoints or to give weights to them according to specific criteria determined by the data while controlling the multiple type I error rate. The procedures developed so far are based on a sequential analysis of weighted p-values (corresponding to the endpoints), including the most extreme situation of weighting leading to a complete order of p-values. When the data for the endpoints have approximately equal variances, these procedures show good power properties. In this paper, we consider an alternative procedure, which is based on completely sorting the endpoints, but smoothed in the sense that some perturbations in the sequence of the p-values are allowed. The procedure is relatively easy to perform, but has high power under the same restrictions as for the weight-based procedures.

Algorithms↗

PubMed2005

Two-stage adaptive designs with correlated test statistics.

When performing a trial using an adaptive sequential design, it is usually assumed that the data for each stage come from different units; for example, patients. However, sometimes it is not possible to satisfy this condition or to check whether it is satisfied. In these cases, the test statistics and p-values of each stage may be dependent. In this paper we investigate the type I error of two-stage adaptive designs when the test statistics from the stages are assumed to be bivariate normal. Analytical considerations are performed under the restriction that the conditional error function is constant in the continuation region. We show that the decisions can become conservative as well as anticonservative, depending on the design parameters and on the sign of the correlation coefficient. Further, we discuss properties and advantages of this design and compare it with the Bauer-Köhne method.

Algorithms↗

PubMed2004

[The effects of pulsed low-level EM fields on memory processes].

This pilot study examined the effects of pulsed electromagnetic fields on the organism in humans. Using a psychophysiological test, the changes in memory performance were tested in 33 volunteers both at rest and upon exposure to pulsed fields (GSM standard). To evaluate the cognition performance, we applied a psycho-physiological test paradigm (auditory discrimination task) based on the "Order Threshold". The investigation took place in an acoustically-shielded room, and the volunteers were requested to relax on a stretcher. The exposure to electromagnetic fields took place during this relaxation time (30 minutes). Measurements were performed before and after the exposure phase, and compared to a reference situation of change in vigilance. Exposure to pulsed fields resulted in reduced mental-regeneration performance in 21 of the 33 test participants, as reflected by an increase of order threshold.

Adolescent↗

PubMed2004

Monitoring of rheologic variables during postoperative high-dose brachytherapy for uterine cancer.

Oxygenation of tumor tissue has recently been assed an important prerequisite for the effectiveness of radiotherapy in cervical cancer. Hyperviscosity is a common phenomenon in malignancy and a cause of reduced oxygen transport capacity that would favour tissue hypoxia. Hemorheological variables were serially tested preoperatively, during four cycles of fractionated adjuvant IR(192) HDR after loading radiation (HDR-AL) of the vaginal vault (weekly intervals), and 6 months postoperatively in patients with cervical (n=12) and endometrial cancer (n=26). Women who were scheduled for benign tumor surgery served as controls (n=29). Preoperatively, in cervical and endometrial cancer patients, mean plasma viscosity (PV: 1.31+/-0.1 mPa s; p<0.05; 1.35+/-0.13 mPa s; p<0.001) and fibrinogen levels (383+/-46 mg/dL; p<0.05; 379+/-117 mg/dL; p<0.05) were higher as compared to the controls (1.25+/-0.07 mPa s; 314+/-89 mg/dL). Red blood cell aggregation at low shear and stasis (RBC agg.: 15.7+/-5.6; p<0.05; 29.6+/-9.1; p<0.05) was higher in endometrial cancer patients as compared to the controls (13.7+/-3.4; 25.3+/-5.6). Postoperatively PV decreased in endometrial cancer patients and transiently increased in cervical cancer patients. After the third session of irradiation in both cancer groups, PV regained and at the 6-month checkup, levels were higher as compared to the values before surgery. Postoperatively fibrinogen levels increased and remained higher throughout HDR-AL and 6 months postoperatively. After surgery and during irradiation, anemia persisted in both cancer groups while hematocrit recovered after 6 months in endometrial cancer patients. Thrombosis was diagnosed in three patients postoperatively (7.9 %) but in none during HDR-AL. While a temporary reduction of hyperviscosity is found postoperatively and during HDR-AL in uterine cancer patients, 6 months after surgery RBC aggregation, PV, and hematocrit returned to the pretreatment range.

Aged↗

PubMed2003

Urinary tetrahydroaldosterone as a screening method for primary aldosteronism: a comparative study.

BACKGROUND: The major aldosterone metabolite 3 alpha,5 beta tetrahydroaldosterone reflects up to 45% of the aldosterone secretion. Its 24-h urinary excretion is likely to provide an accurate index of the daily aldosterone production and to be an indicator for primary aldosteronism (PA). METHODS: In a prospective study, the validity of tetrahydroaldosterone as a screening test for PA was evaluated in comparison to serum potassium, plasma aldosterone, plasma renin activity, plasma aldosterone/renin activity ratio (PARR), as well as 24-h urinary aldosterone-18-glucuronide and free aldosterone. A total of 111 normotensive individuals, 412 PA patients and 1453 essential hypertensive patients, were studied. The effect of blood sampling technique on potassium level was also investigated. RESULTS: Tetrahydroaldosterone differentiated PA from essential hypertension with a sensitivity of 96% and a specificity of 95%. The sensitivity was 89% for plasma aldosterone, 87% for free aldosterone, 85% for PARR, 71% for aldosterone-18-glucuronide and 51% for renin activity. Specificities varied between 91% and 85%. The combined use of the parameters plasma aldosterone > or =9.0 ng/dL and PARR > or =25 resulted in a sensitivity of 82% and specificity of 95%. Forearm exercise proved to be a source of erroneous elevations of potassium sufficient to obscure the suspicion of PA. CONCLUSION: The data suggest that tetrahydroaldosterone is the most reliable screening test for PA. Tetrahydroaldosterone determination in combination with aldosterone-18-glucuronide and free aldosterone increases diagnostic specificity for PA. Potassium, renin, plasma aldosterone, and basal PARR are inadequate screening procedures because they are subject to high rates of false-positive and false-negative results.

Adolescent↗

PubMed2003

Impact of rheological variables in cancer.

Rheological alterations are commonly found in malignant disease and are most pronounced in advanced-stage cancer. Although most of these changes are caused by cancer-unspecific mechanisms, it has been shown that the extent of these changes in some cancer types is related with the stage of cancer, prognosis of disease, and the patient's risk for thrombosis. Monitoring of rheological variables during follow-up of patients has been useful in gynecologic cancer; a significant increase in the main determinants of blood viscosity was found when metastasis became clinically apparent. The most frequent constellation in newly diagnosed cancer is an increase in plasma viscosity (PV) and red blood cell (RBC) aggregation that produces hyperviscosity and is compensated for by anemia. Unconditional elevation of the hematocrit in cancer can deteriorate microcirculatory flow properties and may plunge the patient into an undesirable hemorheological condition that limits effectiveness of cytoreductive treatment and favors dissemination of cancer cells and the development of thrombosis. Modification of hyperviscosity, most likely at the plasma level, may represent a concept for cancer treatment and prevention of thrombosis. Anticoagulants and anti-inflammatory substances seem most suitable at this point, because high fibrinogen turnover is an important determinant of hyperviscosity in malignancy.

Antineoplastic Agents↗

PubMed2002

Quantification of shunt volumes in congenital heart diseases using a breath-hold MR phase contrast technique--comparison with oximetry.

AIMS: Comparison of breath-hold MR phase contrast technique in the estimation of cardiac shunt volumes with the invasive oximetric technique. METHODS AND RESULTS: Seventeen patients with various cardiac shunts (10 ASD, 3 VSD, 1 PDA, 3 PFO) and five healthy volunteers were investigated using a 1.5 Tesla system. The mean flow velocity, the mean volume flow and the transverse area in the ascending aorta and the left and right pulmonary artery were measured using the MR phase contrast breath-hold technique (through plane, FLASH 2D-sequence, TR/TE 11/5 ms, phase length 106 ms, VENC 250 cm/s). The ratio of mean flow in the pulmonary (Qp: sum of mean flows in the left and right pulmonary arteries) and the systemic circulation (Qs: mean flow in the ascending aorta) was calculated and compared with invasively measured Qp:Qs ratios. Oximetry was performed within 24 h of the MR investigation. The non-invasive shunt measurement in the 17 patients showed a mean Qp:Qs ratio of 2.00 +/- 0.86. Comparing the MR data with the invasively measured Qp:Qs showed a correlation coefficient of r = 0.91 (p < 0.001). CONCLUSION: Cardiac shunt volumes can be measured reliably using a shorter acquisition time with breath-hold MR phase contrast technique.

Adult↗

PubMed2002

Prognostic role of plasmaviscosity in breast cancer.

Tumor growth leads to tissue hypoxia and tissue hypoxia, in turn, is a strong stimulus for expression of genes encoding factors that promote tumor growth. Likewise, hypoxia is a key condition within the vicious cycle of autogenous neoplastic dissemination. A marker of the presence of tissue hypoxia may be the presence of high blood viscosity, which is found in a number of neoplastic diseases including gynecological cancer. At the time of diagnosis of breast cancer, patients dying of this disease had had significantly higher initial pv (1.40+/-0.18 mPa s; p<0.0001) when compared to patients not dying of cancer (1.30+/-0.10 mPa s). In multivariate proportional hazard regression analysis, next to tumor size (p=0.03) and nodal status (p=0.004), pv was found an independent prognostic marker for overall survival of breast cancer patients (RR=130.2; 95% CI: 11.6-1,460.6; p<0.0001). An optimized preoperative cut-off value above 1.40 mPa s was significantly associated with poor outcome (log-rank-test) in the Kaplan-Meier survival-estimates, even in node-negative breast cancer (n=153; 54.6%). The most likely explanation for these findings is that increased fibrinogen/fibrin turnover and breakdown products characteristically associated with tumor-cell dissemination contribute to the increased plasma viscosity while the hematocrit, leukocyte count, and platelet count contributed little to the increased blood viscosity in patients with breast cancer. These findings may constitute an approach for new strategies in cancer therapy since it might be possible that reduction of plasma viscosity by treatment improves responsiveness to radio/chemotherapy and thus survival of patients.

Blood Viscosity↗

PubMedDate not supplied

How many lymph nodes are needed for an accurate pN classification in esophageal cancer? Evidence for a new threshold value.

BACKGROUND/AIMS: The UICC recommends a number of at least six lymph nodes to be examined in the surgical therapy of esophageal cancer for a reliable pN classification. The aim of this study was to evaluate this threshold by means of the data from our patients. METHODOLOGY: Following curative resection (R0) of esophageal cancer the numbers of examined tumor-free and tumor-involved lymph nodes were compared. Different statistical models of logistic regression were fitted to the data and checked for plausibility (Hosmer Lemeshow test). The sensitivity of a correct pN classification was then calculated and correlated to the total number of examined lymph nodes. RESULTS: A maximum increase of the sensitivity in classifying pN occurred from 0 to 6 examined lymph nodes. Nevertheless an additional improvement of sensitivity was continuously shown up to 100 examined nodes. An over 90% sensitivity of a correct lymph node classification was reached when more than twelve nodes were examined. Thus the results demonstrate in the case of esophageal cancer, that the suggestion by the UICC to examine at least 6 nodes for defining pN appears too low and may not represent the clinical situation. A ninety percent confidence level of a correct lymph node classification can be expected above 12 examined nodes similarly to the current recommended threshold in colorectal carcinoma. CONCLUSIONS: We suggest a new threshold for the number of examined lymph nodes of at least 12 instead of 6 nodes for accurately defining the pN category in esophageal cancer.

Abdomen↗