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O Gefeller

Publications and source records attributed to O Gefeller.

At least 19 recordsLinked to original sources
PubMed1997

Conceptual aspects of attributable risk with recurrent disease events.

The concept of attributable risk is extended to cover disease events which are potentially recurrent. Whereas the conventional attributable risk parameter allows quantification of the proportion of diseased individuals due to a certain risk factor, the parameter introduced here quantifies the proportion of disease events which is attributable to a specific exposure variable. We accomplish this by taking into account not only the probability of ever being affected by the disease but also the exposure-specific number of occurrences of the disease event within a defined time period. Practical examples highlighting the relevance of the new measure are presented. Various representations of the parameter are given and methods are proposed to adjust this new measure for confounding and effect modification. Point estimates of the parameter and their asymptotic variances are derived under different distributional assumptions. Advantages and limitations of this new approach for assessing the public health impact of an exposure for recurrent disease event are discussed.

Antineoplastic Agents↗
PubMed1997

Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence.

The sensitivity, specificity and likelihood ratios of binary diagnostic tests are often thought of as being independent of disease prevalence. Empirical studies, however, have frequently revealed substantial variation of these measures for the same diagnostic test in different populations. One reason for this discrepancy is related to the fact that only few diagnostic tests are inherently dichotomous. The majority of tests are based on categorization of individuals according to one or several underlying continuous traits. For these tests, the magnitude of diagnostic misclassification depends not only on the magnitude of the measurement or perception error of the underlying trait(s), but also on the distribution of the underlying trait(s) in the population relative to the diagnostic cutpoint. Since this distribution also determines prevalence of the disease in the population, diagnostic misclassification and disease prevalence are related for this type of test. We assess the variation of various measures of validity of diagnostic tests with disease prevalence for simple models of the distribution of the underlying trait(s) and the measurement or perception error. We illustrate that variation with disease prevalence is typically strong for sensitivity and specificity, and even more so for the likelihood ratios. Although positive and negative predictive values also strongly vary with disease prevalence, this variation is usually less pronounced than one would expect if sensitivity and specificity were independent of disease prevalence.

Data Interpretation, Statistical↗
PubMed1997

Sustained elevation of vasopressin plasma levels in healthy young men, but not in abstinent alcoholics, upon expectation of novelty.

The role of vasopressin (AVP) as a stress hormone in man is still a matter of controversy. Thus, the response of plasma AVP, among other hormones, to either intravenously injected human corticotropin releasing factor (hCRF, in the absence or presence of the opioid antagonist naloxone) or a combined 5-minute stress test was compared in healthy men (n = 10) and short-term abstinent alcoholics (n = 11), a group with recognized abnormalities of humoral stress parameters. Stimuli were applied blindly and in random order, one per day, in a 3-day experimental block. A second block using the same standardized protocol was carried out 12 weeks later. Alcoholics entered block I 8 days after the last ethanol ingestion. Up to block II, they were strictly controlled for abstinence. On each experimental day, subjects remained supine from 0700h until 1500h. Stimuli were applied alternatively at 1030h each day. Fourteen blood samples were drawn per day with simultaneous fluid substitution. There were no significant changes in plasma AVP as an acute response to any of the stimuli in either group or block. However, unexpectedly, controls had significantly higher basal AVP levels throughout block I as compared with block II without concomitant changes in plasma osmolality or blood pressure. Further analysis of the data revealed that the dramatically increased AVP levels of the five younger control subjects accounted for this difference. In fact, AVP levels in the five older healthy subjects and in all alcoholics remained low throughout the two blocks. Our data suggest that plasma AVP is continuously elevated in healthy young men upon anticipation of novelty. In contrast, healthy men of the older age group and early abstinent alcoholics seem to lack such a sustained AVP response.

Adult↗
PubMed1997

Deriving more up-to-date estimates of long-term patient survival.

Statistics reflective of patient survival should be as up-to-date as possible. We illustrate that traditional methods for analysing survival have important limitations with regard to up-to-dateness of long-term cumulative survival estimates. We propose an alternative approach, denoted "period analysis," that may be used to overcome or at least substantially reduce these limitations. The conceptual background and the computational realization of the new method are outlined and its application is illustrated by an analysis of long-term survival of patients with testicular cancer in Saarland, Germany.

Cohort Studies↗
PubMed1996

An alternative approach to monitoring cancer patient survival.

BACKGROUND: Monitoring patient survival, a practice routinely employed by many cancer registries, is an essential component of the evaluation of progress against cancer. However, changes in prognosis over time are disclosed with considerable delay, with traditional methods of monitoring cumulative survival. METHODS: This article introduces an alternative approach, denoted "period monitoring." which aims at more timely detection of such changes. The conceptual background and the computational realization of the proposed method are outlined, and its application is illustrated by an empirical example from the population-based cancer registry of Saarland, Germany. RESULTS: The principle of period monitoring is shown to be analogous to the well established use of period life tables in the field of demography. Computational realization of period monitoring can be achieved with simple modifications of standard survival analysis techniques. Compared with traditional methods of monitoring survival, period monitoring can advance detection of changes in cumulative survival considerably. CONCLUSION: Despite some limitations with respect to the ease of data interpretation. period monitoring offers a useful supplement to existing methods of monitoring patient survival.

Humans↗
PubMed1996

Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid.

BACKGROUND: The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on clinical and electroencephalographic criteria which do not allow a reliable diagnosis to be made during life. METHODS: Serum and cerebrospinal fluid (CSF) samples were obtained after informed consent from relatives of suspected cases of CJD referred to the German CJD surveillance unit. CSF samples from 58 definite (neuropathologically verified), 46 probable, and 34 possible CJD cases, and from 44 patients without CJD were analysed by two-dimensional gel electrophoresis (2-DE). Two investigators blinded to clinical findings recorded the presence of two proteins, p130/131. The kappa value for the level of agreement between these investigators was calculated. Results obtained were compared with the determination of neuron-specific enolase (NSE) in CSF. NSE concentrations of more than 35 ng/mL were considered indicative of CJD. FINDINGS: p130/131 was detected in 81% of definite (47/58), 80% of probable (37/46), 68% of possible (23/34) CJD cases, and in none of the other 44 cases. NSE concentrations of more than 35 ng/mL were seen in 79% of definite (46/58), 80% of probable (37/46), 59% of possible (20/34) CJD cases, and 9% of other cases (4/43). The positive predictive value for 2-DE of CSF is 100% and the negative predictive value is 69%. The level of agreement for the detection of p130/131 by two evaluators in a subset of 141 2-DE gels was a kappa of 0.93 (95% CI 0.86-0.99). Of 13 cases initially classified as possible and later reclassified as definite, ten cases were identified correctly by the 2-DE analysis, indicating a better diagnostic accuracy of this test compared with the current clinical classification. None of nine cases classified as other by neuropathology had p130/131 in 2-DE. INTERPRETATION: 2-DE for p130/131 is a specific test for the diagnosis of CJD. These data suggest including detection of p130/131 as a criterion for the diagnosis of probable CJD in addition to the currently accepted criteria of a rapidly progressive dementia of less than 2 years duration, typical neurological signs, and periodic sharp-wave complexes in the EEG.

Adult↗
PubMed1996

A novelty-related sustained elevation of vasopressin plasma levels in young men is not associated with an enhanced response of adrenocorticotropic hormone (ACTH) to human corticotropin releasing factor (hCRF).

A comparative study of the effects of intravenously administered corticotropin releasing factor (i.e. exogenous CRF), in the absence or presence of simultaneous opioid receptor blockade, versus stress (i.e. endogenous CRF) on plasma adrenocorticotropic hormone (ACTH), cortisol and vasopressin (AVP) was carried out in ten healthy men (mean age 35.6 +/- 9.5 years) using an intra-individual repeat setting. Three different stimuli were applied blindly and in random order, one per day, in a 3-day experimental block: (1) human (h) CRF; (2) hCRF/naloxone; and (3) a combined multifaceted 5-min stress test. A second block, following the same protocol, was carried out 12 weeks later. Each experimental day lasted from 0700 to 1500 hours, with subjects remaining supine throughout. ACTH and cortisol levels each responded with significant peaks to all three stimulating conditions in both blocks while AVP levels remained unaffected by any of these stimuli. Unexpectedly, in five of the ten subjects significantly elevated AVP basal concentrations were measured throughout the first block. This phenomenon appeared to be age-related, being observed in younger men only (29.6 +/- 5.2 vs 41.6 +/- 9.2 years; p = 0.03) and was not paralleled by changes in plasma osmolality or blood pressure. In the second block, AVP levels were low and no longer different between younger and older subjects. ACTH and cortisol curves did not differ among subgroups nor between blocks. In conclusion, plasma AVP, in contrast to ACTH, is not acutely influenced by either endogenous or exogenous CRF. However, anticipation of novelty seems to be a human-specific, stress-related stimulus for a sustained elevation of plasma AVP in young men. This novelty-related continuous elevation of AVP levels reported here neither affected basal plasma ACTH nor acted synergistically with exogenous hCRF to increase circulating ACTH.

Adrenocorticotropic Hormone↗
PubMed1996

Induction of heat shock protein 70 genes in human lymphocytes during fever therapy.

The induction of heat shock protein 70 (HSP70) genes has been studied in peripheral blood mononuclear cells of individuals undergoing fever therapy because of metastatic malignant melanoma. Induction of HSP70 was assessed at the protein level by metabolic labelling or, for the HLA-linked HSP70-1 and HSP70-2 genes, at the RNA level by in situ hybridization. However, de novo expression of HSP70 could be observed during fever (usually above 39 degrees C) in only about half of the cases. No simple threshold model for inducibility of HSP70 in vivo could be applied. The HSP70-1 gene was induced more easily than HSP70-2. Thus, heat-inducible HSP70 genes, including HLA-linked HSP70 genes, become expressed in human lymphocytes during fever, but not regularly.

Adult↗
PubMed1996

Dynamic patterns of allergic patch test reactions to 10 European standard allergens. An analysis of data recorded by the Information Network of Departments of Dermatology (IVDK).

Insight into the dynamic time courses of patch test reactions may be useful for patch test evaluation. To put this to the proof, we have analysed the time courses of allergic patch test reactions that were filed between 1990 and 1994 by the Information Network of Departments of Dermatology in Germany (IVDK). Based on reaction strength at days 1 to 3, each allergic patch test was assigned to 1 of 5 distinct dynamic reaction patterns: crescendo, plateau, decrescendo, crescendo/decrescendo, or decrescendo/ crescendo. The frequencies of these patterns were determined for those 10 standard allergens yielding the highest numbers of allergic reactions (n between 180 and 1240), and dynamic patterns were classified as type 1 (crescendo or plateau patterns) or type 2 (other patterns). Influences of population characteristics upon the classification of patterns were evaluated by logistic regression analyses. Different frequencies of reaction patterns were found for distinct allergens. For all 10 allergens, type-1 patterns were significantly more often observed for allergic reactions assessed as clinically relevant. For 5 allergens, female sex of patients was associated with a lower frequency of type-2 patterns. A history of atopic dermatitis and the age of patients were only weakly associated with a certain classification of reaction patterns in some of the allergens. In a comparison of reaction patterns obtained with different allergens in the same population, we found that nickel sulfate elicited type 1 reaction patterns more often than fragrance mix. We conclude that the dynamic reaction patterns should be taken into account in the evaluation of patch tests. The relation of type-1 patterns to clinical relevance of the reaction needs further attention.

Adult↗
PubMed1996

Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function.

Using sufficiently sensitive and precise assays, we systematically investigated the correlation between thyrotropin, thyroglobulin, index of free thyroxine and index of free triiodothyronine after different doses of thyroxine (25, 50, 100, 150 micrograms), which were administered daily for 10 days to individuals with normal thyroid function and in a control group. Analysis of the data using relative median values expressing changes to basal values before administration of thyroxine yielded the following results: (i) thyrotropin and thyroglobulin decreased monoexponentially, depending on the doses of thyroxine administered; (ii) the extent of their decrease showed a linear correlation with the dose of thyroxine administered and was greater for thyrotropin than for thyroglobulin; (iii) the relative velocity of their decrease increased monoexponentially with the dose of thyroxine and did not differ between thyrotropin and thyroglobulin. These results provide strong evidence for a clear quantitative reaction of the feedback mechanism and confirm that the secretion of thyroglobulin is a physiological process dependent on thyrotropin. The high intra-individual variations obtained for thyrotropin were probably due to its pulsatile secretion.

Adolescent↗
PubMed1995

Melanoma and use of sunscreens: an Eortc case-control study in Germany, Belgium and France. The EORTC Melanoma Cooperative Group.

Use of sunscreens is widely advocated as a preventive measure against sun-induced skin cancers. However, to date, no epidemiologic study has reported a decreased melanoma risk associated with sunscreen use. We have conducted a case-control study aimed at evaluating the influence of sunscreen use on the occurrence of cutaneous malignant melanoma. In 1991 and 1992, 418 melanoma cases and 438 healthy controls were interviewed in Germany, France and Belgium. The questionnaire used differentiated between regular sunscreens, psoralen sunscreen (prepared with 5-methoxypsoralen, a tanning activator and photocarcinogen), and self-tanning cosmetics (which produce a tan without ultraviolet radiation). After adjusting for age, sex, hair colour and holiday weeks spent each year in sunny resorts, the melanoma risk was of 1.50 (95% Cl:1.09-2.06) for regular sunscreens, and of 2.28 (95% Cl: 1.28-4.04) for psoralen sunscreens. No melanoma risk was associated with use of self-tanning cosmetics. Among subjects with a poor ability to tan, psoralen sunscreen users displayed a melanoma risk of 4.45 (95% Cl: 1.25-15.8) when compared with regular sunscreen users. There was a significant negative interaction between regular sunscreen use and sunburns experienced in adulthood. Use of sunscreens, especially psoralen sunscreen, was associated with higher density of pigmented lesions of the skin. Although we cannot exclude the presence of an unknown confounding factor, our results support the hypothesis that sunscreens do not protect against melanoma, probably because of their ability to delay or avoid sunburn episodes, which may allow prolonged exposure to unfiltered ultraviolet radiation. Serious doubts are raised regarding the safety of sunscreens containing psoralens.

Adult↗
PubMed1995

[Early onset irritant skin damage in apprentice hair dressers].

In the course of a cohort study addressing the importance of constitutional and occupational risk factors for the development of irritant hand eczema, 859 hairdressing apprentices were examined in 14 vocational training schools in autumn 1993, after an average of 8 weeks of professional exposure. In this cross-sectional survey at the start of training, 38.2% were suffering from skin damage, in most cases mild to moderate and only rarely severe; we observed almost exclusively irritant skin damage, mostly localized interdigitally. Logistic regression analysis revealed previous hand eczema, an elevated ¿atopy score¿ (Diepgen) and, particularly, unprotected work for several hours daily with wet hands as significant risk factors for this early onset irritant damage/eczema. The high wet workload is mainly caused by very frequent shampooing and by permanent waving without wearing gloves; however, other tasks are also often performed without appropriate protective gloves. The implications of the considerable inter-observer variability are described and discussed.

Adolescent↗
PubMed1995

Sequential and average attributable fractions as aids in the selection of preventive strategies.

Methods for estimating the attributable fraction based on a multivariate model for a dichotomous response have been extensively developed in the last decade. These methods provide the means for calculating the total attributable fraction for a set of exposure variables possibly adjusted for a set of confounding variables. In this paper, a procedure for stepwise calculation of attributable fractions is outlined. The purpose is to study the effect on risk of disease of preventing several exposures, one at a time, in different orderings. This procedure introduces the concepts of sequential and average attributable fractions as aids for attributing the risk of disease to different exposures. The procedure and concepts are illustrated by analyzing data from a cross-sectional study on the prevalence of some frequent symptoms of lung disease.

Adolescent↗
PubMed1995

Randomised clinical trial of two treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome.

AIMS: To compare treatment regimens of two widely used natural surfactant preparations Curosurf and Survanta in respiratory distress syndrome (RDS). METHODS: The effects of the two treatment regimens on gas exchange, ventilatory requirements, and 28 day outcome in infants with RDS were compared. Seventy five preterm infants (birth weight 700-1500 g) with RDS requiring artificial ventilation with an FIO2 of > or = 0.4, were randomly selected at 1-24 hours of age. One group received an initial dose of Curosurf (200 mg/kg); the other group Survanta (100 mg/kg). Patients who remained dependent on artificial ventilation with an FIO2 of > or = 0.3 received up to two additional doses of Curosurf (each of 100 mg/kg) after 12 and 24 hours or up to three additional doses of Survanta (each of 100 mg/kg) between six and 48 hours after the initial dose. RESULTS: There was a rapid improvement in oxygenation and ventilatory requirements were reduced in both groups. However, infants treated with Curosurf had a higher arterial:alveolar oxygen tension ratio and required a lower peak inspiratory pressure and mean airway pressure at several time points within 24 hours of randomisation (p < 0.05-0.001). The incidences of pneumothorax in the Curosurf and Survanta groups were 6% and 12.5%, respectively; the corresponding figures for grades 3-4 intracerebral haemorrhage were 3% and 12.5%, respectively. Mortality was 3% in the Curosurf group and 12.5% in the Survanta group. However, these differences did not reach significance. CONCLUSION: The Curosurf treatment regimen resulted in a more rapid improvement in oxygenation than Survanta and reduced ventilatory requirements up to 24 hours after start of treatment. This was associated with a trend towards reduced incidence of serious pulmonary and non-pulmonary complications.

Biological Products↗
PubMed1995

Definitions of attributable risk--revisited.

BACKGROUND: The concept of attributable risk is a popular approach to describe the disease risk associated with an exposure factor on the population level. The paper reviews this epidemiologic concept. METHODS: Definitions and interpretations of four measures of association term "attributable risk" in the epidemiologic literature are compared. By introducing the notation of exposure-specific disease events, the intrinsic relationship between these definitions in unveiled from a new perspective. In addition, the terminologic confusion relating to this concept is discussed. RESULTS: It is shown that all four definitions focus on the exposure-specific disease incidence, but all in different subpopulations of the study population. Data of a German cohort study on the relationship between lipoprotein fractions and myocardial infarction further illustrate the different measures of attributable risk. DISCUSSION: It is pointed out that the evaluation of the public health impact of an exposure under study by means of attributable risk calculations should form an integral part of the epidemiologic analysis.

Adult↗