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Biomedical subjects

G Freitag

Publications and source records attributed to G Freitag.

At least 19 recordsLinked to original sources
PubMed2006

Non-parametric assessment of non-inferiority with censored data.

We suggest non-parametric tests for showing non-inferiority of a new treatment compared to a standard therapy when data are censored. To this end the difference and the odds ratio curves of the entire survivor functions over a certain time period are considered. Two asymptotic approaches for solving these testing problems are investigated, which are based on bootstrap approximations. The performance of the test procedures is investigated in a simulation study, and some guidance on which test to use in specific situations is derived. The proposed methods are applied to a trial in which two thrombolytic agents for the treatment on acute myocardial infarction were compared, and to a study on irradiation therapies for advanced non-small-cell lung cancer. Non-inferiority over a large time period of the study can be shown in both cases.

Computer Simulation↗
PubMed2005

Choice of delta: requirements and reality--results of a systematic review.

An essential problem in planning clinical non-inferiority or equivalence studies is the specification of the 'irrelevant difference' (irrelevance margin; delta). This quantifies the amount of non-inferiority or difference, respectively, between a new test therapy and an established standard treatment which is to be considered as tolerable. In the past, most recommendations and guidelines for clinical non-inferiority and equivalence studies contained only general statements and formulations concerning the specification of delta. The current unsatisfactory situation was the reason for performing a systematic review of published clinical non-inferiority and equivalence studies. It was the aim to gain an overview on the irrelevance margins used in such studies, and on reasons for choosing the particular margins. For the sake of comparability, the irrelevance margins were converted into standardized differences and odds ratios. Overall, there were 332 non-inferiority or equivalence trials obtained by means of an extensive literature search. The results of the systematic review show that current requirements on the choice of delta and the reality of recent clinical non-inferiority and equivalence trials differ substantially. In about one half of the trials a difference of 0.5 standard deviations or more was regarded as 'irrelevant' explicitly or implicitly. Estimates of standard-placebo differences formed the basis of the irrelevance margin in less than every tenth trial. Reasons for this very low proportion might be (1) the possibly resulting very small irrelevance margins, and (2) unsolved problems of the requirements themselves. Overall, it seems that a more global definition of 'irrelevance' might be warranted.

Biopharmaceutics↗
PubMed2003

[Comparison of two measurement methods with a gold standard as applied to 20-MHz-sonography and clinical palpation for ascertaining the thickness of pigmented skin tumours].

AIM: This paper focuses on different statistical methods for comparing two measurement methods with an additionally available gold standard. A given data example is used as the basis of the calculations. METHOD: We provide a complementary statistical analysis of a study presented by Hoffmann et al. on sonometric and palpatory measurements of the size of pigmented skin tumours in 681 patients. RESULTS: For comparing two measurement methods with respect to a gold standard, several statistical parameters assessing one measurement method can be used. In addition, there are further descriptive and some inference-statistical methods available. CONCLUSION: If there is a suitable categorization of the measurements, the comparison of the methods should be performed using the positive predictive values and kappa coefficients as descriptive measures. Moreover, the McNemar test can be used for comparing the differential accuracy of allocation. When investigating continuous measurements, a comparison using mere correlation analyses can lead to false conclusions. Therefore, we recommend the direct analysis of the individual measurement errors by means of numerical and graphical representations. The absolute values of the measurement errors can be compared using the sign test for paired samples.

Biometry↗
PubMed2001

Identification of radiologic healing phenomena in patients with rheumatoid arthritis.

OBJECTIVE: Conventional radiographic scoring methods in rheumatoid arthritis (RA) are designed to quantify progression and disregard any improvement. Reparative changes observed during longterm followup of RA have rarely been described as healing phenomena. Healing may become increasingly important with the availability of more potent antirheumatic drugs. We investigated whether radiologic healing phenomena can be identified by different observers in a blinded fashion. METHODS: Healing phenomena were defined as (1) reappearance (and sclerosis) of the cortical plate, (2) partial or complete filling in of an erosion, or (3) subchondral bone sclerosis with osteophyte formation (secondary osteoarthritis). Pairs of radiographs of hands, wrists, and forefeet [taken 2 to 8 (mean 4.8) yrs apart] of 34 patients were selected from longterm studies: 24 sets with healing phenomena and 10 with progressive disease without healing. The radiographs were blinded and read in pairs in random order by 3 observers unaware of the patients selected for the study. One observer read the set a second time after 8 weeks, resulting in a total of 4 observations. Thirty-eight joints were rated 0 to 5 depending on the amount of surface destruction. In addition an attempt was made to identify joints with healing phenomena. The data were analyzed with help of descriptive statistics such as means, standard deviations, and frequency tables. RESULTS: Out of 1292 joints scored at the second time point, 74 had healing phenomena. These joints were identified in a mean of 89% (95/89/88/82%, respectively) in the 4 observations performed by the 3 readers. Patients without healing phenomena were correctly identified by all observers. In 54 joints less typical healing phenomena were seen in all observations. Sixty-two joints with healing in addition to the 74 joints were seen in 3 observations, 76 in 2, and 127 in one observation. All observers agreed that 1090 joints had no healing phenomenon. The 24 patients with healing had a slight reduction in the Ratingen score, while the 10 patients without healing showed a moderate progression. In the group with healing an increase and decrease in the score occurred in the same patients at different joints. CONCLUSION: In patients with RA followed for several years healing or reparative changes of erosions can be observed. These phenomena can be identified by different observers with high sensitivity even when the observers are blinded to chronological sequence of the films.

Arthritis, Rheumatoid↗
PubMed2000

Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial.

OBJECTIVE: To determine whether treatment with creatine can improve exercise intolerance in myophosphorylase deficiency (McArdle disease). DESIGN: Double-blind, placebo-controlled crossover study with oral creatine monohydrate supplementation. PATIENTS: Nine patients with biochemically and genetically proven McArdle disease were treated. INTERVENTION: Five days of daily high-dose creatine intake (150 mg/kg body weight) were followed by daily low-dose creatine intake (60 mg/kg). Each treatment phase with creatine or placebo lasted 5 weeks. MAIN OUTCOME MEASURES: The effect of treatment was estimated at the end of each treatment phase by recording clinical scores, ergometer exercise test results, phosphorus 31 nuclear magnetic resonance spectroscopy, and surface electromyography. RESULTS: Of 9 patients, 5 reported improvement of muscle complaints with creatine. Force-time integrals (P =.03) and depletion of phosphocreatine (P =.04) increased significantly during ischemic exercise with creatine. Phosphocreatine depletion also increased significantly during aerobic exercise (P =.006). The decrease of median frequency in surface electromyograms during contraction was significantly larger (P =.03) with creatine. CONCLUSION: This is the first controlled study indicating that creatine supplementation improves skeletal muscle function in McArdle disease.

Administration, Oral↗
PubMed2000

Mesalazine changes apoptosis and proliferation in normal mucosa of patients with sporadic polyps of the large bowel.

BACKGROUND AND STUDY AIMS: Regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the occurrence of colorectal adenoma and carcinoma, possibly by inducing apoptosis and/or decreasing proliferation in colorectal epithelial cells. Mesalazine is widely used in the treatment of patients with inflammatory bowel disease, and well tolerated. We investigated its effect on apoptosis and proliferation of colorectal mucosa in 21 patients with sporadic polyps of the large bowel. PATIENTS AND METHODS: In total, 17 patients with sporadic colorectal polyps (> or = 5 mm) underwent polypectomy and biopsy of uninvolved mucosa before and after treatment with 1 g/d mesalazine for 1, 3, 7 or 14 days. Four additional patients served as untreated controls. Apoptotic index (AI) was measured by terminal deoxynucleotidyl transferase-mediated d-uridine triphosphate nick-end labeling (TUNEL) assay; proliferation index (PI) was measured by immunohistochemical examination with anti-Ki67 antibody. RESULTS: AI was significantly increased 1 and 3 days after initiation of treatment with mesalazine compared with controls (P= 0.0107 for the 1-day treatment group and P=0.0142 for the 3-day treatment group), and seemed to remain largely unchanged after longer treatment duration. Proliferation appeared to be decreased by mesalazine in all treatment groups, while proliferation in controls did not change (P=0.0107 for the 1-day treatment group and P= 0.0142 for the 3-day treatment group compared with controls. CONCLUSIONS: Mesalazine significantly induces apoptosis and decreases proliferation in colorectal mucosa in patients with sporadic polyps of the large bowel. This may be clinically relevant in that it may lower the rate of polyp recurrence after polypectomy, thereby possibly contributing to the chemoprevention of sporadic colorectal carcinoma.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Practical experience with the design and analysis of a three-armed equivalence study.

OBJECTIVE: While there is a lot of experience with the design, conduct and interpretation of bioequivalence studies, the methodology of trials concerning therapeutic equivalence is still at an early stage of development. Two-armed equivalence studies involve special problems of interpretation, which can be partly solved by the introduction of a third (placebo) arm. We describe a trial in which the therapeutic equivalence of horse chestnut seed extract (HCSE) and compression treatment was to be demonstrated in patients with chronic venous insufficiency (CVI). Compression is regarded as the standard therapy in this field. However, the efficacy of compression in terms of the variable of primary interest, namely oedema reduction, has never been demonstrated according to current methodological rules. Thus, the 'standard' had to be established in the trial itself. This can be achieved by demonstration of relevant superiority in comparison with placebo. METHODS: Two hypotheses had to be tested: (1) the relevant superiority of compression compared with placebo as a precondition for (2) the at most irrelevant inferiority of HCSE in comparison with compression ('equivalence'). For both corresponding statistical tests, the irrelevance criterion -- formulated as standardized difference -- was set to 0.5. RESULTS: Therapeutic equivalence could not be demonstrated following this design, because compression failed to be relevantly superior compared with placebo, even though HCSE was shown to be at most irrelevantly inferior compared with compression. Explorative analyses show that it is not possible to reject simultaneously both null hypotheses with the obtained data when using equal irrelevance limits for both tests. CONCLUSION: Although the primary objective of the trial could not be achieved, the results were encouraging. Thus, a new study was planned and started based on the observed data. The concept of a shifted null hypothesis may be applied to 'routine' clinical trials too; using 'no difference' as the null hypothesis in a trial does not seem to be meaningful when in fact an at least relevant difference is required.

Clinical Trials as Topic↗
PubMed1997

Results of a postmarketing drug monitoring survey with a polidocanol-urea preparation for dry, itching skin.

In an open multicentre drug monitoring survey, 1611 patients with atopic dermatitis, contact eczema, dry eczema, psoriasis and pruritus were treated with a preparation containing 5% urea and 3% polidocanol (laurylmacrogol). To monitor the course of treatment, three examinations were performed, one at the start of therapy and two more at intervals of approximately two weeks. A marked improvement in the status of the skin was observed during treatment. A marked regression occurred in the principal signs of dry skin--scaling, dryness and roughness. Troublesome itching was also greatly reduced. Almost half of the patients (48.9%) were free of itching at the end of the observation period. Adverse drug effects arose in only 2.8% of cases, and were mostly smarting, itching and irritation. No intolerance reactions were observed in children under six years. At the end of the observation period the skin status was judged, by both the doctors and the patients as 'good' or 'very good' in almost 90% of cases. Furthermore, the assessment with regard to the regression of itching was almost identical.

Adolescent↗
PubMed1994

Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

BACKGROUND: Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. OBJECTIVE: We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. METHODS: Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). RESULTS: SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. CONCLUSION: We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

Adult↗
PubMed1994

Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

BACKGROUND: Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. OBJECTIVE: Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. METHODS: Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. RESULTS: TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. CONCLUSION: This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of diverse surfactants depended significantly on the feature evaluated (erythema vs electrical capacitance and TEWL), on the mode of application (acute vs cumulative), and, in the cumulative model, on the point of observation.

Adult↗
PubMed1992

[Experiences in dealing with tubal sterilization].

The political changes in the GDR and the unity of Germany give the women the possibility of deciding for tubal sterilization as a method of contraception that was restrictively used in the GDR. This investigation analysis the psychosocial and medical factors influencing the women in their decision for sterilization. 103 women were interviewed with a questionnaire before they underwent tubal sterilization in a great medical center in Sachsen-Anhalt. The findings known in the literature regarding the satisfied after sterilization were discussed. However the sterilization is an intervention that should be thought over carefully.

Abortion, Induced↗
PubMed1992

Spina bifida occulta in epilepsy syndromes.

We studied radiographs of the lumbar vertebral column and sacral region for 182 patients with epilepsy for the presence of spina bifida occulta. Spina bifida occulta was twice as common in patients with idiopathic epilepsy as in patients with symptomatic epilepsy and twice as common in patients with idiopathic epilepsy as in the general population. We discuss the relationship between spina bifida occulta and idiopathic epilepsy.

Child↗
PubMed1990

[Relation between spina bifida occulta and various epileptic syndromes].

Radiographs of the lumbar vertebral column and sacral region obtained for 182 epileptic patients after spina bifida occulta were studied. Spina bifida occulta was twice as common in patients with idiopathic epilepsy as in those with symptomatic epilepsy and twice as common as in the normal population. A relationship between spina bifida occulta and idiopathic epilepsy is discussed.

Adolescent↗
PubMed1990

[The value of diagnostic computerized tomography in tumor nephrectomy patients].

In 84 patients after nephrectomy due to renal cell carcinoma a computerized tomography was performed to evaluate local tumor recurrence. The findings are classified stage-dependent. Other metastatic lesions were found by conventional radiologic methods. Based on stage-dependent different occurrence of metastases or local recurrences recommendations are made to the use of computerized tomography in the follow-up of patients suffering from renal cell carcinoma after nephrectomy.

Adolescent↗
PubMed1989

[Surgical treatment possibilities in cerebrovascular insufficiency--status and future prospects].

After a short synopsis of the at present ascertained knowledge of the anatomy and pathophysiology of the cerebral blood supply the possibilities of the vascular-surgical treatment are discussed. The desobliteration of extracranial vessels, PTA, vascular resections and appliances of bypass are no concurrent operation techniques, but such ones which are individually to be adapted. The importance of the clinical and non-invasive diagnostics is put before the digital subtraction angiography and the direct angiography. On the basis of the experience of 461 own surgical interventions the stage-conditioned diagnosis is required. Stage II of the transitory ischaemic attack is preferred. In unilocular mediastenoses the extra-intracranial anastomosis now as ever hat its qualification.

Brain Ischemia↗
PubMed1989

[Dynamic computerized tomography in staging of urinary bladder cancer].

In 25 patients suffering from bladder cancer a dynamic computerized tomography was performed under constant conditions in a selected tumor layer level. It was the aim of this study to improve the efficacy of preoperative staging of bladder cancer. In the tumors of stages pT1 and pT2 (12 patients) different courses in the time-density-diagrams were shown in comparison with the stages pT3a + b (13 patients). Furthermore, a different intake and delivery of contrast medium was observed and differences in the vascularization of the individual tumor stages may be suspected. Thereby a separation between operable (pT1/2) and inoperable tumor (pT3a/b) seem to be possible.

Diatrizoate↗
PubMed1989

[Experiences with percutaneous drainage of abscesses and pseudocysts].

Percutaneous catheterised drainage of abscesses and pseudocysts as well as of circumscribed suppurations in soft-part tissue is considered an established therapeutic approach. Therapeutic puncture or drainage was successfully performed in 19 cases, following CT-targeted fine-needle puncture and subsequent cytological and bacteriological diagnosis. Inflammatory alterations were tackled by antibiotic therapy according to an antibiogram. Complications did not occur.

Abscess↗