Quality of Life in a German Graves Orbitopathy Population

To evaluate the validity and responsiveness of a German-language version of the disease-specific Graves orbitopathy quality-of-life questionnaire (GO-QOL).Prospective cross-sectional study.At a multidisciplinary university orbital center, 310 consecutive unselected Graves orbitopathy outpatients answered the GO-QOL before undergoing complete ophthalmic and endocrine assessment. The main outcome measures were the GO-QOL and its 2 subscales, Visual Functioning and Appearance.The QOL scores for the subscales Visual Functioning and Appearance were (mean ± SE) 72.5 ± 1.4 and 71.3 ± 1.5, respectively. Visual Functioning and Appearance were higher in mild (82.2 ± 2.2 and 86.0 ± 17.6) than in moder…

Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

Plasma volume expansion of more than 1.5 1 and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (s…

Zur Wirkung gepulster elektromagnetischer Felder geringer Leistungen auf Gedächtnisprozesse

Zusammenfassung In einer Pilotstudie sollte die Wirkung elektromagnetischer Felder auf den Organismus untersucht werden. Mittels eines psychophysiologischen Tests wurde die Veranderung der Gedachtnisleistungen unter den Bedingungen mit und ohne Belastung durch gepulste Felder (GMS-Standard) an 33 Probanden uberpruft. Zur Objektivierung der kognitiven Leistungen fand das psychophysiologische Verfahren zur Bewertung der “Ordnungsschwelle” (OS) Verwendung. Die Untersuchung erfolgte in einem akustisch abgeschirmten Raum, in dem die Versuchsteilnehmer sich auf einer Liege entspannen sollten. Wahrend dieser Relaxationsphase (30 Min.) fand die Feldexposition statt. Durch Messungen vor und nach die…

Acute exposure to 50ppm toluene does not increase sleepiness

Abstract The Pupillographic Sleepiness Test (PST) is a new neurophysiological method to assess sleepiness. In an exposure study to a constant exposure level of 50 ppm toluene on 20 healthy men, our aim was to find out, if increased sleepiness could be seen with PST. PST was performed before and after 4.5 h of exposure. General complaints were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and during exposure. Values obtained during exposure were related to pre-exposure values. Parametric cross-over analysis of logarithmic Pupillary Unrest Index (PUI) values did not show an effect of toluene exposure. In a nonparametric cross-over an…

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 IR192 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 …

Public Health Relevance of Graves' Orbitopathy

Disfiguring proptosis and functional impairment in patients with Graves' orbitopathy (GO) may lead to impaired earning capacity and to considerable indirect/direct costs.The aim of the study was to investigate the public health relevance of GO.This cross-sectional study was performed between 2005 and 2009 at a multidisciplinary university orbital center.A total of 310 unselected patients with GO of various degrees of severity and activity participated in the study.We conducted an observational study.We measured work disability and sick leave as well as the resulting indirect/direct costs of GO-specific therapies.Of 215 employed patients, 47 (21.9%) were temporarily work disabled, and 12 (5.…

Plasmatic Plasminogen Activator Inhibitor Activity in Patients with Primary Breast Cancer

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 …

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 an…

Randomized trial of intravenous immunoglobulins versus prednisolone in Graves' ophthalmopathy.

Abstract Glucocorticoids are usually given for management of Graves' ophthalmopathy (GO), but they may cause side effects. By comparison, intravenous administration of immunoglobulins resulted in clinical improvement and decreased antibody titres in a large number of autoimmune diseases. Therefore, a randomized trial was done, in which 19 patients with active GO were treated with a 20-week course of oral prednisolone (P, starting dose 100 mg/day), and 21 received 1 g immunoglobulin/kg body weight for 2 consecutive days every 3 weeks. The immunoglobulin course was repeated six times. Before and at the end (20 weeks) of immunomodulating therapy, ophthalmological investigation and quantitative…

Lebensqualität nach operativer Therapie des renalen Hyperparathyreoidismus. Ergebnisse einer prospektiven Langzeitstudie / Quality of Life After Operative Therapy of Renal Hyperparathyroidism. Results of a Prospective Long-Term Follow-up Study

In einer prospektiven Langzeituntersuchung wurde die Lebensqualitat nach operativer Therapie des renalen Hyperparathyreoidismus untersucht. Vom 1.8.1987-31.8.2000 erfolgten 186 Eingriffe. Bevorzugte Operation war die totale Parathyreoidektomie mit autologer Epithelkorperchenreplantation. Die Erfolgsrate der erstmaligen Halsexploration betrug 98,2%. Juckreiz klang bei uber 60% der betroffenen Patienten innerhalb von 4 Wochen nach dem Eingriff ab. Die Ruckbildung ossarer Symptome bedurfte langerer Zeit. Ein Jahr postoperativ waren 75% der praoperativ von Juckreiz und 79% der vom ossaren Syndrom betroffenen Patienten asymptomatisch. Patienteneigene Risikofaktoren bedingen eine niedrige Letalit…

Blood rheology during chemotherapy in patients with ovarian cancer.

The use of platinum based chemotherapy in ovarian malignancy and other cancer types is known to be associated with deep vein thrombosis. In a prospective study of 47 patients with ovarian cancer of International Federation of Gynecology and Obstetrics stage Ib-IV, serial rheological parameters were determined (plasma viscosity, red blood cell aggregation under conditions of stasis and low shear) in addition to hemoglobin, hematocrit, leukocytes, platelets, and fibrinogen. At the same time the incidence of deep vein thrombosis was recorded before, during six cycles of first line cisplatinum/epirubicin/cyclophosphamide chemotherapy, and 2 months thereafter (two-months check-up). Only six pati…

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…

Adaptive designs with correlated test statistics

In clinical trials, the collected observations such as clustered data or repeated measurements are often correlated. As a consequence, test statistics in a multistage design are correlated. Adaptive designs were originally developed for independent test statistics. We present a general framework for two-stage adaptive designs with correlated test statistics. We show that the significance level for the Bauer-Köhne design is inflated for positively correlated test statistics from a bivariate normal distribution. The decision boundary for the second stage can be modified so that type one error is controlled. This general concept is expandable to other adaptive designs. In order to use these de…

Effect of irrigation of the nose with isotonic salt solution on adult patients with chronic paranasal sinus disease

In a prospective, randomized, controlled, double-blind trial we compared the effectiveness of endonasal irrigations with Ems salt solution to that with sodium chloride solution in the treatment of adult patients with chronic paranasal sinus disease. Subjects (n = 40) were randomly allocated to treatment either with isotonic Ems salt solution or with isotonic sodium chloride solution. The treatment consisted of endonasal irrigation twice daily and additional nasal spray as required. Nasal endoscopy, plain radiography of the paranasal sinuses, olfactometry, anterior rhinomanometry, and a saccharin-clearance test were carried out on days 1 and 7. Patients recorded rating scales of general disc…

Adaptive Modifications of Hypotheses After an Interim Analysis

It is investigated how one can modify hypotheses in a trial after an interim analysis such that the type I error rate is controlled. If only a global statement is desired, a solution was given by Bauer (1989). For a general multiple testing problem, Kieser, Bauer and Lehmacher (1999) and Bauer and Kieser (1999) gave solutions, by means of which the initial set of hypotheses can be reduced after the interim analysis. The same techniques can be applied to obtain more flexible strategies, as changing weights of hypotheses, changing an a priori order, or even including new hypotheses. It is emphasized that the application of these methods requires very careful planning of a trial as well as a c…

Expression and prognostic value of the CD44 splicing variants v5 and v6 in gastric cancer

In the present study, the expression and prognostic role of the CD44 splicing variants v5 and v6 were immunohistochemically investigated in 418 curatively resected gastric carcinomas. CD44v5 was expressed in 65·3 per cent (n=273) and CD44v6 in 77·0 per cent (n=322) of the tumours. Whereas the expression of CD44v5 was correlated with advanced pT categories, with lymph node involvement, and with the presence of blood and lymphatic vessel invasion, such a correlation could not be found for the variant v6. As shown by univariate analysis, patients with CD44v5-positive tumours had a significantly shorter overall survival than patients with CD44v5-negative tumours (P=0·049). In contrast, expressi…

The value of Ems Mineral Salts in the treatment of rhinosinusitis in children

Summary The treatment of rhinosinusitis seen in the light of uncertain pathogenesis and variable symptoms is under discussion and ranges from the administration of antibiotics, decongestants and anti-allergic agents to no treatment. In this randomized, prospective, double-blind and controlled study the effect of a 14-day treatment (1–2 sprays into each nostril t.d.) with either isotonic Ems Mineral Salts (EMS) solution (Siemens & Co., Bad Ems, Germany) or xylometazoline solution (0.05%) was tested in children (n = 66) aged 2–6 years. Main outcomes: the degree of mucosal inflammation, nasal patency, general state of health, condition of the middle ear, auditory function as well as an assessm…

Wie viele Lymphknoten müssen bei gastrointestinalen Tumoren zur Beurteilung des pN Status entfernt werden?

Die von der UICC vorgegebene Anzahl der zu resezierenden Lymphknoten zur korrekten Festlegung des pN Status von gastrointestinalen Tumoren beruht auf empirischen Werten. Beim Oesophaguskarzinom wird eine Lymphknotenanzahl von mindestens 6 LK empfohlen [1], bem Kolon- und Rektumkarzinom liegt die Richtzahl der zu resezierenden Lymphknoten bei 12 LK [1]. Bei Uberschreiten dieser Richtzahl wird im Umkehrschlus angenommen, das die Wahrscheinlichkeit einer Anderung des Lymphknotenstatus (pN) gering ist, auch im Falle einer ausgedehnteren Lymphknotendissektion. Hier besteht oft eine Diskrepanz zwischen Pathologen und Chirurgen. Von Interesse ist daher, ob diese Vorgaben mittels eines mathematisch…

Residuenanalyse des Unabhängigkeitsmodells Zweier Kategorialer Variablen

For the ‘cellwise’ analysis of independence of two categorial variables, Haberman (1973) proposes the method of ‘adjusted residuals’. Fuchs and Kenett (1980) use (the absolute value of) the maximal adjusted residual as a measure for the deviation from the null hypothesis.

Hyperviscosity syndrome in patients with ovarian carcinoma

BACKGROUND In patients with ovarian carcinoma, an hematocrit-independent hyperviscosity syndrome is often present. The syndrome is characterized by normal or low hematocrit and hemoglobin concentration, an elevated platelet count, and an increase in clotting factor turnover. Because deep vein thrombosis (DVT) often complicates the course of ovarian carcinoma, the aim of this study was to investigate the possible association of hyperviscosity syndrome with the development of DVT. METHODS Rheologic estimations of the blood included red blood cell (RBC) aggregation (stasis and low shear), plasma viscosity (pv), blood cell count, and fibrinogen, which were performed before primary surgery and t…

Multiple Hypotheses Testing

The paper is mainly concerned with multiple testing procedures which control a given multiple level α. General concepts for this purpose are the closure test and a modification which is independent of the special structure of hypotheses and tests. We consider improvements of this modification using information about the logical dependences (redundancies) within the system of hypotheses and present an efficient algorithm. Finally, we discuss some problems which are specific for hierarchical systems of hypotheses, e.g. in model search.

Multiple testing in candidate gene situations: a comparison of classical, discrete, and resampling-based procedures.

In candidate gene association studies, usually several elementary hypotheses are tested simultaneously using one particular set of data. The data normally consist of partly correlated SNP information. Every SNP can be tested for association with the disease, e.g., using the Cochran-Armitage test for trend. To account for the multiplicity of the test situation, different types of multiple testing procedures have been proposed. The question arises whether procedures taking into account the discreteness of the situation show a benefit especially in case of correlated data. We empirically evaluate several different multiple testing procedures via simulation studies using simulated correlated SN…

Human papillomavirus (HPV) DNA in primary cervical cancer and in cancer free pelvic lymph nodes--correlation with clinico-pathological parameters and prognostic significance.

OBJECTIVE To assess whether the presence of human papilloma virus (HPV) DNA and/or several genotypes of HPV DNA in primary cervical cancer and cancer free pelvic lymph nodes are correlated with several clinicopathological parameters of well-defined prognostic significance and whether virological parameters are predictors of long-term survival in cancer patients. PATIENTS AND METHODS 223 cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the high sensitive polymerase chain reaction (PCR) method followed by …

Prospektive Beobachtungsstudie zur operativen Therapie des renalen Hyperparathyreoidismus

In einer prospektiven Beobachtungsstudie bei Patienten mit renalem Hyperparathyreoidismus wurden nach Eingriffen an den Nebenschilddrusen der Verlauf und die Abhangigkeit der Symptomatik von praoperativ ermittelten Laborparametern analysiert. Zwischen dem 1. 8. 1987 und dem 31. 12. 1995 wurden 79 Patienten operiert. Bei 72 Patienten erfolgten erstmalige Eingriffe an den Nebenschilddrusen. Bevorzugtes Operationsverfahren war die totale Parathyreoidektomie mit autologer Epithelkorperchenreplantation (n = 67). Informationen zum postoperativen Verlauf liegen von allen Patienten vor. Bei 74 der 79 Patienten erfolgten regelmasige Nachuntersuchungen (1–9, Median = 4) mit einer Nachbeobachtungszeit…

Global and multiple test procedures using ordered p-values—a review

This paper reviews global and multiple tests for the combination ofn hypotheses using the orderedp-values of then individual tests. In 1987, Rohmel and Streitberg presented a general method to construct global level α tests based on orderedp-values when there exists no prior knowledge regarding the joint distribution of the corresponding test statistics. In the case of independent test statistics, construction of global tests is available by means of recursive formulae presented by Bicher (1989), Kornatz (1994) and Finner and Roters (1994). Multiple test procedures can be developed by applying the closed test principle using these global tests as building blocks. Liu (1996) proposed represe…

Multiple Comparisons of Treatments with Stable Multivariate Tests in a Two‐Stage Adaptive Design, Including a Test for Non‐Inferiority

The application of stabilized multivariate tests is demonstrated in the analysis of a two-stage adaptive clinical trial with three treatment arms. Due to the clinical problem, the multiple comparisons include tests of superiority as well as a test for non-inferiority, where non-inferiority is (because of missing absolute tolerance limits) expressed as linear contrast of the three treatments. Special emphasis is paid to the combination of the three sources of multiplicity - multiple endpoints, multiple treatments, and two stages of the adaptive design. Particularly, the adaptation after the first stage comprises a change of the a-priori order of hypotheses.

The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic parameters and prognostic significance: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The objective of this study was to assess whether the presence of human papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer are correlated with several clinicopathologic parameters of well-defined prognostic significance and whether virologic parameters are predictors of long-term survival in cancer patients. Two hundred twenty three cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for H…

Expression of cell-cycle regulatory proteins cyclin D1, cyclin E, and their inhibitor p21 WAF1/CIP1 in gastric cancer.

The expression and prognostic role of cyclin D1, cyclin E, and p21 (WAF1/CIP1) were immunohistochemically investigated in 413 curatively resected gastric carcinomas. p21 was expressed in 65.4 per cent (n=270), cyclin D1 in 23.7 per cent (n=98), and cyclin E in 13.6 per cent ( n=56) of the tumours. The expression of p21, cyclin D1, and cyclin E was positively associated with the papillary or tubular type of the WHO classification, as well as with the intestinal type according to the Lauren classification. No significant correlation could be found between the expression of p21, cyclin D1 and cyclin E and the parameters pT category, lymph node involvement, and blood vessel and lymphatic vessel…

Strategies for Including Patients Recruited During Interim Analysis of Clinical Trials

In clinical trials a periodical check of safety and efficacy data is often needed. For organizational reasons it is rarely desirable to stop a trial during such an interim analysis. Therefore, new study patients are included in the trial while the interim analysis is ongoing. Disregarding the additional information provided by these interim patients would be unsatisfactory, especially for an office of regulatory affairs. Consequently, the rules for group sequential or adaptive decisions must be adjusted to the recruitment of interim patients. In this paper, two strategies for modifying study designs to consider the analysis of interim patients are proposed.

Mean maternal second-trimester hemoglobin concentration and outcome of pregnancy: a population-based study.

Both anemia and the lack of physiological maternal plasma volume expansion during the second trimester are associated with higher maternal morbidity and poor fetal outcome. Mean hemoglobin levels between the 14th and 30th gestational weeks were calculated in 4985 consecutive pregnant women and were correlated with outcome data of pregnancy. It was found that 9.4% of participants (n = 3959) had normal pregnancy outcome. Mean maternal hemoglobin levels were significantly lower in women with a normal pregnancy (11.96 ± 0.94 g/dL) compared with women who had adverse outcome events (preeclampsia, n = 423, 12.5 ± 1.0 g/dL, P < .0001; early birth, n = 464, 12.2 ± 1.01 g/dL, P < .0001; low b…

Expression of nm23 in gastric carcinoma: association with tumor progression and poor prognosis.

BACKGROUND Expression of nm23 has been shown to be inversely correlated with the metastatic potential of several human cancers. In the current study, the expression and prognostic impact of nm23 was immunohistochemically studied in 413 curatively resected gastric carcinomas. METHODS Tumor sections of the 413 gastric carcinomas were stained with a polyclonal antibody that was raised against the nm23-H1/NDP kinase A, which is identical to the nm23-H1 gene product. RESULTS Expression of nm23 was detected in 84.5% (n = 349) of all tumors, in the majority of cases (71.2%) causing a homogeneous staining reaction in more than 75% of tumor cells. Expression of nm23 was positively correlated with th…

Prospective evaluation of parathyroid graft function after total parathyroidectomy and heterotopic autotransplantation in renal hyperparathyroidism by bilateral determination of intact parathormone in cubital venous blood.

The value of gradients for intact parathyroid hormone (PTH) in the assessment of graft function after total parathyroidectomy/autotransplantation for renal hyperparathyroidism was evaluated in a prospective follow-up study. Altogether 99 patients who underwent operation from August 1, 1987 to December 31, 1996 were prospectively investigated and reexamined postoperatively, including analyses of serum calcium, alkaline phosphatase, and intact PTH in the antecubital venous blood of both arms. The postoperative course is known for all patients. Of the 99 patients included in the study, 95 underwent one to nine reexaminations (median three) over follow-up periods of 1 month to 5 years (median 2…

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

Abstract Background The major aldosterone metabolite 3α,5β 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…

Incidence of the Factor V Leiden-mutation, Coagulation Inhibitor Deficiency, and Elevated Antiphospholipid-antibodies in Patients with Preeclampsia or HELLP–Syndrome

LETTER TO THE EDITORS-IN-CHIEF Incidence of the Factor V Leiden-mutation, Coagulation Inhibitor Deficiency, and Elevated Antiphospholipid-antibodies in Patients with Preeclampsia or HELLP–Syndrome Georg–Friedrich von Tempelhoff1, Lothar Heilmann1, Eberhard Spanuth1, Erich Kunzmann1 and Gerhard Hommel2 1Department of Obstetrics and Gynecology, City Hospital of Ruesselsheim and 2Institute for Medical Statistic and Documentation, University of Mainz, Germany.

Prospective Study of Parathyroid Graft Function in Patients with Renal Hyperparathyroidism After Total Parathyroidectomy and Heterotopic Autotransplantation by Measurement of the Intact Parathyroid Hormone Concentrations in Both Antecubital Veins

Evaluation of the value of gradients for intact parathyroid hormone after total parathyroidectomy and heterotopic autotransplantation for renal hyperparathyroidism.Prospective long-term follow-up study.Teaching hospital, Germany.A total of 115 patients operated on for renal hyperparathyroidism between 1 August 1987 to 15 August 1997.100/115 had total parathyroidectomy with autotransplantation.Analyses of serum calcium, alkaline phosphatase, and intact parathormone in serum 1, 4, 8, 12, 18 and 24 months postoperatively and annually thereafter. Parathormone gradients were calculated as the ratio of the parathormone concentrations in the antecubital venous blood of the grafted and the non-graf…

Prospektive Evaluierung von Parathormongradienten (PTH-intakt) nach totaler Parathyreoidektomie und heterotoper Nebenschilddrüsenreplantation beim renalen Hyperparathyreoidismus

Grundlagen: In einer prospektiven Beobachtungsstudie nach totaler Parathyreoidektomie mit autologer Epithelkorperchenreplantation bei Patienten mit renalem Hyperparathyreoidismus wurden durch bilaterale Kubitalvenenblutentnahme ermittelte Parathormongradienten evaluiert.

Confidence Interval or P-Value?: Part 4 of a Series on Evaluation of Scientific Publications

An understanding of p-values and confidence intervals is necessary for the evaluation of scientific articles. This article will inform the reader of the meaning and interpretation of these two statistical concepts.The uses of these two statistical concepts and the differences between them are discussed on the basis of a selective literature search concerning the methods employed in scientific articles.P-values in scientific studies are used to determine whether a null hypothesis formulated before the performance of the study is to be accepted or rejected. In exploratory studies, p-values enable the recognition of any statistically noteworthy findings. Confidence intervals provide informatio…

Multiple Vergleiche Mittels Rangtests - Alle Paarvergleiche -

Das Hauptziel der vorliegenden Arbeit ist es, zu untersuchen, wie das Prinzip des Abschlustests auf die gebrauchlichen multiplen Rangverfahren angewendet werden kann. Literatur zu diesem Thema findet sich bis jetzt nur in Tagungsberichten, so bei Ferner (1981), wo die Anwendung der Holm’schen Prozedur auch bei Rangtests vorgeschlagen wird, sowie bei Ludin (1983) und Schulz (1983, 1984).

1st die intraoperative Analyse des intakten Parathormons bei der Halsexploration wegen renalem Hyperparathyreoidismus sinnvoll? / Is Intraoperative Monitoring of Parathormone in Cervical Exploration for Renal Hyperparathyroidism Useful?

Der Wert der intraoperativen Parathormonanalyse mittels PTH-Schnell-assay wurde evaluiert. Bei 40 Patienten erfolgten Bestimmungen des PTH-intakt: Ausgangswert, 5 min nach Exstirpation der rechten, 5 min nach Exstirpation der linken Epithelkorperchen, 1. p.op. Tag. Bei 35 Patienten wurden 4 Drusen identifiziert, eine totale Parathyreoid-ektomie mit Autotransplantation durchgefuhrt. Die medianen Parathormonspiegel betrugen intraoperativ 652 pg/ml, 434 pg/ml (56%), 120 pg/ml (19%), 1. Tag 1,9 pg/ml. Bei 5 Patienten wurden 3 Drusen identifiziert, die Eingriffe ohne Replantation beendet. Die medianen Parathormonspiegel betrugen intraoperativ 987 pg/ml, 485 pg/ml (56%), 120 pg/ml (16%); 1. Tag 8…

Sequentially Rejective Test Procedures for Detecting Outlying Cells in One- and Two-Sample Multinomial Experiments

For multiple testing of multinomial models in the case of one or two samples we propose using test procedures based on the principle described by MARCUS, PERITZ and GABRIEL (1976). These methods are based in each step of the sequentially rejective strategy on tests which exhaust the full α level (i.e. which are not conservative). The tests can be performed in a finite or asymptotic version.

Quality of Life and Occupational Disability in Endocrine Orbitopathy

SUMMARY Background: In endocrine orbitopathy (EO), disfiguring proptosis and diplopia impair patients' quality of life both at home and at work. Methods: From late 2006 to the beginning of 2008, 250 outpatients in an interdisciplinary thyroid and eye clinic filled out a questionnaire about their quality of life, occupational disability, and use of psychotherapy. 400 physicians who referred their EO patients to the clinic also participated in a survey on these issues. Results: 45% of the patients complained of restrictions in their daily activities, and 38% reported impaired selfperception. 36% were on sick leave because of EO. 28% were disabled, 5% had retired early, and 3% had lost their j…

Blood Coagulation and Thrombosis in Patients with Ovarian Malignancy

SummaryOvarian cancer cells appear to be capable of both thrombin formation and induction of fibrin degradation which may be essential prerequisites for the development of deep vein thrombosis (DVT) as well as the spread of malignancy. To study further this coagulation – cancer interaction in 60 patients with untreated ovarian cancer of FIGO stage I-IV the incidence of DVT was recorded pre-operatively, postoperatively on day 1, 3, 5, 7, 10, before each of six cycles of Cisplati- num/Epirubicin/Cyclophosphamide chemotherapy, during follow-up and in the post-operative period of second look surgery. In addition, blood coagulation tests results were determined prospectively. Two patients were e…

Comparison of Unfractionated Versus Low Molecular Weight Heparin for Deep Vein Thrombosis Prophylaxis During Breast and Pelvic Cancer Surgery: Efficacy, Safety, and Follow-up

In a prospective, double-blind randomized trial the efficacy and safety of low molecular weight heparin and un fractionated heparin were compared for the prevention of post operative deep vein thrombosis in patients undergoing major surgery for breast and pelvic cancer. Three hundred fifty-eight patients were randomly allocated to the two treatment groups. Thirty-four of these were excluded from the study. Of the re maining 324 patients, 164 received 5000 IU unfractionated heparin three times daily and 160 received 3000 anti-Xa units of low molecular weight heparin once daily. Treatment was started 2 to 5 hours preoperatively and continued for 7 days. The occurrence of deep vein thrombosis…

The size of Simes’ global test for discrete test statistics

Abstract To increase the power of the Bonferroni–Holm procedure several modified Bonferroni procedures have been proposed (for example, Hochberg, 1988. Biometrika 75, 800–802; Hommel, 1988. Biometrika 75, 383–386), which are based on Simes’ global test (Simes, 1986. Biometrika 73, 751–754). By several simulation studies which, in particular, considered multinormal test statistics, it has been suggested that the Simes test is a level α test. However, an exact proof exists for only few situations one of them assuming independence of test statistics. We studied the behaviour of Simes’ test for discrete test statistics. Due to discreteness one can expect more conservative decisions whereas depe…

Interleukin-7 or Interleukin-15 Enhances Survival ofMycobacterium tuberculosis-Infected Mice

ABSTRACTBoth antigen-presenting cells and immune effector cells are required to effectively eradicate or containMycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive “cross talk” between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of α/β and γ/δ T cells. Here we show that either cytokine is able to enhance survival ofM. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival cou…

Linear Regression Analysis

SUMMARY Background: Regression analysis is an important statistical method for the analysis of medical data. It enables the identification and characterization of relationships among multiple factors. It also enables the identification of prognostically relevant risk factors and the calculation of risk scores for individual prognostication. Methods: This article is based on selected textbooks of statistics, a selective review of the literature, and our own experience. Results: After a brief introduction of the uni- and multivariable regression models, illustrative examples are given to explain what the important considerations are before a regression analysis is performed, and how the resul…

Test and power considerations for multiple endpoint analyses using sequentially rejective graphical procedures

A variety of powerful test procedures are available for the analysis of clinical trials addressing multiple objectives, such as comparing several treatments with a control, assessing the benefit of a new drug for more than one endpoint, etc. However, some of these procedures have reached a level of complexity that makes it difficult to communicate the underlying test strategies to clinical teams. Graphical approaches have been proposed instead that facilitate the derivation and communication of Bonferroni-based closed test procedures. In this paper we give a coherent description of the methodology and illustrate it with a real clinical trial example. We further discuss suitable power measur…

Powerful short-cuts for multiple testing procedures with special reference to gatekeeping strategies.

In this paper we present a general testing principle for a class of multiple testing problems based on weighted hypotheses. Under moderate conditions, this principle leads to powerful consonant multiple testing procedures. Furthermore, short-cut versions can be derived, which simplify substantially the implementation and interpretation of the related test procedures. It is shown that many well-known multiple test procedures turn out to be special cases of this general principle. Important examples include gatekeeping procedures, which are often applied in clinical trials when primary and secondary objectives are investigated, and multiple test procedures based on hypotheses which are comple…

Long term follow up after percutaneous closure of PFO in 357 patients with paradoxical embolism: Difference in occlusion systems and influence of atrial septum aneurysm

Abstract Background Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA is an alternative to medical therapy especially in patients with atrial septal aneurysm (ASA). The differences in time to complete occlusion for various closure devices in PFO alone and PFO plus ASA are of natural interest. Methods and results Between January, 1st 1998 and November, 30th 2006 percutaneous PFO closure was performed in 357 patients with a history of ≥1 paradoxical embolism using three different devices: Amplatzer PFO-( n =199), Starflex-( n =48) and Helex Occluder ( n =110). All patients were assigned to a post-interventional protocol with contrast-enhanced transe…

S36.4: Control of false discovery rate in adaptive designs

Psychosocial adjustment of children with spina bifida.

It was the aim of the present prospective study to investigate the influence of age, sex, intellectual function, and school type as well as of hydrocephalus, the level of lesion, and of the degree of handicap on the psychosocial adjustment of children with spina bifida. Seventy-five patients with spina bifida, aged 6 to 16 years were assessed concerning their psychosocial adjustment and their intellectual function by use of standardized instruments. The findings were compared with those of nondisabled controls, matched for age and sex. Children with spina bifida showed a tendency to be at an increased risk for psychosocial maladjustment. Influencing factors were age, sex, and the degree of…

Improvements and Modifications of Tarone's Multiple Test Procedure for Discrete Data

Tarone (1990, Biometrics 46, 515-522) proposed a multiple test procedure for discrete test statistics improving the usual Bonferroni procedure. However, Tarone's procedure is not monotone depending on the predetermined multiple level a. Roth (1998, Journal of Statistical Planning and Inference, in press) developed a monotone version of Tarone's procedure. We present a similar procedure that is both monotone and an improvement of Tarone's proposal. Based on this extension, we derive a step-down procedure that is a corresponding improvement of Holm's (1979, Scandinavian Journal of Statistics 6, 65-70) sequentially rejective procedure. It is shown how adjusted p-values can be computed for the …

Intricate decision making : ambivalences and barriers when fulfilling an advance directive

Lars Schröder,1 Gerhard Homme,1,2 Stephan Sahm3,4 1Department of Gynecology and Obstetrics, Center of Integrated Oncology, University Hospital Bonn, Bonn, 2Institute of Medical Biometry, Epidemiology and Informatics, Johannes Gutenberg University, Mainz, 3Department of Gastroenterology and Oncology, Ketteler Hospital, Offenbach, 4Institute for Ethics and History of Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany Background: Despite a recent statutory ruling stating the binding nature of advance directives (ADs), only a minority of the population has signed one. Yet, a majority deem it of utmost importance to ensure their wishes are followed through in case they are …

Test Procedures in Configural Frequency Analysis (CFA) Controlling the Local and Multiple Level

The test statistics used until now in the CFA have been developed under the assumption of the overall hypothesis of total independence. Therefore, the multiple test procedures based on these statistics are really only different tests of the overall hypothesis. If one likes to test a special cell hypothesis, one should only assume that this hypothesis is true and not the whole overall hypothesis. Such cell tests can then be used as elements of a multiple test procedure. In this paper it is shown that the usual test procedures can be very anticonservative (except of the two-dimensional, and, for some procedures, the three-dimensional case), and corrected test procedures are developed. Further…

Effects of intraocular cefotaxime on the human corneal endothelium

Abstract Purpose To ascertain whether 0.4 mL of cefotaxime 0.25% applied intracamerally causes toxic alteration of the human corneal endothelium. Methods In this prospective randomized masked study, 66 patients had cataract extraction using phacoemulsification, a frown incision, and implantation of a poly(methyl methacrylate) intraocular lens. This was followed by intraocular injection of 0.4 mL of cefotaxime 0.25% or balanced salt solution (BSS®). Contact specular microscopy and photography were performed preoperatively and 1 to 4 days and 3 months postoperatively. Results In the cefotaxime group, the mean endothelial cell count was 2729 cells/mm 2 ± 474 (SD) preoperatively, 2520 ± 462 cel…

Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn's disease

Abstract Background: The role of azathioprine (AZA) in the treatment of active Crohn's disease (CD) is still controversial. This study examined whether AZA combined with standard prednisolone therapy improved the therapeutic outcome compared with monotherapy with prednisolone. Methods: Forty-two patients with a Crohn's Disease Activity Index (CDAI) of > 150 were randomized into two groups. Both received 60 mg of prednisolone daily in a tapering regimen to a maintenance dose of 10 mg. In addition, group 1 received 2.5 mg AZA/kg body wt and group 2 received a placebo over the whole study period of 4 months. Results: At the end of the trial, 16 of 21 patients (76%) in group 1 were in remission…

E-Cadherin, ein neuer, unabhängiger Prognoseparameter beim Magenkarzinom

Das transmembranose Glykoprotein E-Cadherin ist in normalen Epithelien und in Tumorzellen fur die Zell-Zell-Haftung verantwortlich. In Magenkarzinomen wird E-Cadherin, dessen Gen auch als Metastasierungs- oder Invasionssuppressorgen bezeichnet wird, je nach Differenzierungsgrad unterschiedlich exprimiert. Bei einer Reihe von malignen Tumoren wie dem Mamma-, Kolon- oder Nierenkarzinom konnte eine reduzierte E-Cadherin-Expression mit einer schlechteren Prognose korreliert werden. Zum Magenkarzinom liegen derzeit nur zwei Studien an nur geringen Fallzahlen vor, die auf einen negativen prognostischen Einflus der reduzierten E-Cadherin-Expression hinweisen [4, 5].