Biomedical subjects

O Gefeller

Publications and source records attributed to O Gefeller.

At least 19 recordsLinked to original sources

PubMed1999

The association between size of test chamber and patch test reaction: a statistical reanalysis.

A recent study by Brasch and co-workers reported on the association between size of test chamber and patch test reaction. The investigators interpreted their data on 495 patients as having conclusively shown that standard preparations of fragrance mix, wool wax alcohols, Kathon CG and formaldehyde led to more positive test reactions when large Finn Chambers were used for patch testing. We have scrutinized the statistical aspects of this study and conclude that the authors should have adopted a statistical approach suitable to analyse dependent samples. After explaining the correct methodological way of dealing with quadratic contingency tables formed by 2 dependent samples, we reanalyze the data accordingly and compare the results to those of the original paper. Based on this reanalysis, the conclusions are more complex: the reaction pattern for the fragrance mix and wool wax alcohols is significantly different between small and large test chambers; however, this discrepancy arises primarily from changing weak positive reactions with small chambers to strong positive reactions with large chambers. For formaldehyde, no relationship between chamber size and patch test reaction was found in the data, while for Kathon CG, statistical evidence is borderline that more positive test reactions are yielded by large test chambers than by small ones.

Adult↗

PubMed1999

Patch test reactions at D4, D5 and D6.

In this retrospective study, patch test reactions in 3 groups of patients were analysed, in order to obtain information on the best day for the 2nd patch-test reading after day 2 (D2), on the usefulness of additional readings after D3, and on the dependence of patch-test reactions at D4, D5, or D6 on allergen and/or patient characteristics. In the years 1990 to 1995, patch tests were routinely read at D3 and D4 in 1096 patients, at D3 and D5 in 1243 patients, and at D3 and D6 in 1136 patients. In all of the 3 groups, significantly more positive reactions diminished than appeared de novo from D3 to the later reading. Virtually identical results were observed in subgroups of patients formed by sex, age or atopy. However, men might possibly react more slowly than women on patch testing, showing more increasing than diminishing reactions in the D3/D4- and the D3/D5-comparison. Reactions to individual allergens showed wide differences in this connection. Neomycin sulfate, cobalt salts, and p-phenylenediamine can be characterized as slow allergens, with more reactions increasing than diminishing from D3 to the later readings. With fragrance mix and balsam of Peru, the opposite pattern occurred. In all subgroups of patients, and with most allergens, the gain in positive reactions was biggest when an additional reading was performed at D5. We conclude that for a single 2nd patch test reading after D2, D3 is the best day, and especially better than D4. If a 3rd reading is performed, it should be done at D5 to get the maximum information out of patch testing. However, this extends the test procedure to at least 1 day of the weekend.

Adult↗

PubMed1998

Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study.

OBJECTIVE: To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls. DESIGN: Prospective case-control study. SETTING: National Creutzfeldt-Jakob disease surveillance unit. SUBJECTS: 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia. MAIN OUTCOME MEASURE: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group. RESULTS: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P = 0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P = 0.023). CONCLUSION: Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy.

Biomarkers↗

PubMed1998

Detection of 14-3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease.

The analysis of 14-3-3 protein in cerebrospinal fluid (CSF) was shown to be highly sensitive and specific for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, the predictive value of this test in the clinical diagnosis of, and its relation to, sporadic, genetic, and iatrogenic CJD cases have yet to be established. CSF samples of suspect CJD cases seen in the prospective German surveillance study were tested for the presence of 14-3-3 protein by using a modified western blot (WB) technique. WB detected 14-3-3 protein in 95.4% of definite and 92.8% of probable cases. In two patients classified initially as not having CJD the test was positive, and both were later proved to have definite CJD. The positive predictive value is 94.7% and the negative predictive value is 92.4%. False-positive results in a single CSF analysis were seen in patients with herpes simplex encephalitis, hypoxic brain damage, atypical encephalitis, intracerebral metastases of a bronchial carcinoma, metabolic encephalopathy, and progressive dementia of unknown cause. WB analysis for 14-3-3 protein was positive in only 5 of 10 cases of familial forms of spongiform encephalopathies. CSF analysis for 14-3-3 protein should thus be performed in any case suspect for CJD.

14-3-3 Proteins↗

PubMed1998

Prevalence and incidence of hand dermatitis in hairdressing apprentices: results of the POSH study. Prevention of occupational skin disease in hairdressers.

OBJECTIVE: Occupational skin changes in hairdressers are very common. Morbidity, however, has not yet been quantified precisely. METHODS: A cohort of 2,352 hairdressing apprentices (of the 2,570 invited to participate, i.e., 91.5% response) was prospectively followed for the duration of their vocational training (3 years) by three examinations. Three waves (years) were recruited in 1992, 1993, and 1994 from 15 vocational training schools in northwestern Germany. RESULTS: The point prevalence of (mostly slight) irritant skin changes of the hands increased from 35.4% in the initial examination to 47.5% in the intermediate examination and to 55.1% in the final examination. Given a more conservative definition of a case of "hand dermatitis," these estimates were 12.9%, 23.5%, and 23.9%, respectively. Altogether, 34.3 and 15.2 cases of "skin changes (any degree)" and "hand dermatitis," respectively, in 100 person-years were observed during the study period. The incidence rate, i.e., the number of newly diseased study participants in relation to the person-time at risk contributed, decreased in the course of the study. The proportion of dropouts until final follow-up was 51.8%. CONCLUSION: The present results appear to lie in a range with those found in other, much smaller cohort studies. However, comparison of the results is hampered either by the lack of a clear definition or by a different definition of "person-time at risk" or "a case of hand dermatitis." As compared with an external control group of office apprentices, the incidence was several times higher in hairdressing apprentices, which points to the high risk for skin damage in this occupation.

Beauty Culture↗

PubMed1998

Averaging attributable fractions in the multifactorial situation: assumptions and interpretation.

In multifactorial situations, the concept of attributable fraction quantifying the population impact of exposure factors on the disease load needs special methodologic care to take the interrelationship between exposures into account. Recently, new epidemiologic parameters have been introduced to address this issue. These approaches are reconsidered here from a game-theoretical perspective. The derivation of game-theoretical properties of these parameters provides additional motivation for their use in epidemiologic practice and offers new insights into their interpretation in epidemiologic studies. The nontechnical description of the results is illustrated by examples from the Hordaland study on obstructive lung disease.

Causality↗

PubMed1998

An empirical investigation on matching in published case-control studies.

The methodological discussion about matching when recruiting controls in case-control studies has been controversial for a long time. To delineate the impact of this discussion on the practice of matching we reviewed 266 case-control studies published in nine yearly volumes of three major epidemiological journals within the period 1955-1994. Among studies published until 1980 71.7% of the control groups were recruited by individual matching compared to 46.4% in 1994. This decline is paralleled by an increase in the application of frequency matching (from 5.0% to 26.2%). As the issue of matching is closely connected with methodological questions of the statistical analysis we also examined the type of analysis applied to the data. We found that the use of logistic regression modeling has dramatically increased during this period (from 18.4% up to 87.2%), whereas application of the traditional Mantel-Haenszel technique for estimating summary odds ratios has nearly vanished. The correct approach for individually matched data in the logistic modeling framework, the conditional likelihood technique, has been unknown in the early part of the time window of our investigation, but is even nowadays applied by only three quarters of the corresponding studies. Our literature-based investigation provides thus compelling evidence that the type of control selection and statistical analysis used in case-control studies have changed substantially during recent years.

Case-Control Studies↗

PubMed1998

Cutaneous malignant melanoma in women and the role of oral contraceptives.

The role of oral contraceptives (OC) in the aetiology of cutaneous malignant melanoma (CMM) has been controversially discussed over the last two decades. In an extensive literature search we identified 18 case-control studies, published between 1977 and 1996, offering information on this relationship. Using a meta-analytical approach we combined the study-specific risk estimates and derived a summary odds ratio of 0.95 (95% confidence interval: 0.87-1.04). Based on the data of 3796 cases and 9442 controls, we thus found no evidence for an aetiological role of OC use in the development of CMM.

Case-Control Studies↗

PubMed1998

An epidemiological study of the influence of season (cold and dry air) on the occurrence of irritant skin changes of the hands.

In the course of an ongoing cohort study on constitutional and occupational risk factors for the development of irritant hand dermatitis in hairdressing apprentices, an increased prevalence of irritant skin changes was noted in a subgroup examined during particularly cold winter months. Prompted by this observation, the importance of several meteorological factors (day means of temperature, relative and absolute humidity) was assessed in extensive statistical analyses based on data of 742 participants, supplemented by meteorological information obtained from the German Meteorological Service (DWD). There were significant associations of existing hand dermatitis with low temperature and low absolute humidity (Mann-Whitney U-test, P < 0.0001), but not with relative humidity (P = 0.38). Logistic regression analysis, including known determinants of irritant hand dermatitis in this setting, showed that low temperature and low relative humidity tended to be risk factors (OR = 1.66 and 1.57, respectively, for the lower quartiles, P = 0.07 in both cases), and confirmed that absolute humidity significantly influenced the occurrence of irritant hand dermatitis (OR = 2.06 for < 4.8 mg/L, P < 0.01). Thus, these environmental factors must be regarded as possible confounders in the analysis of future epidemiological studies on irritant hand dermatitis and should be considered in multifactorial analyses.

Adolescent↗

PubMed1998

Hand eczema in a prospectively-followed cohort of office-workers.

A cohort of initially 111 office apprentices was prospectively followed for the duration of their training (2 and 3 years, respectively). The point prevalence of (slight) irritant or atopic hand eczema was 18.9% in the initial and 25.0% in the final examinations. Altogether, 37 cases of (slight) hand eczema were noted within the study period; of these, 10 qualified for a more conservative definition of "hand eczema". Expressed in a person-time-model, the incidence rates were 18.4 and 4.1 cases per 100 persons per year, respectively. The only significant risk factor for the development of (slight) irritant or atopic hand eczema within the study period was previous hand eczema--partly as a child, partly during a preceding occupation (e.g. hairdressing). Compared to one retrospective study in a cohort of older office employees and to a study sampling the general population, incidence rates were slightly higher in this study. Such differences may partly be due to different definitions of what has to be considered "a case of hand eczema". The necessity to (i) communicate on the method of case definition and (ii) develop guidelines for case definition in epidemiological studies is emphasised.

Adolescent↗

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

[Prevention of melanoma by sun protective measures in childhood. Temporal changes in awareness of parents].

Numerous epidemiological studies on risk factors of malignant melanoma confirm the etiologic role of excessive UV-exposure especially in childhood. Preventive educational campaigns directed to parents of pre-school children have been inaugurated in several countries. In Germany the information was distributed by the "Working group for Preventive Measures in Dermatology" in cooperation with different public health institutions and the media starting in 1993. To evaluate the influence of these efforts on the knowledge and behaviour of the parents, two successive cross-sectional studies at all 56 nursery schools using the same standardised questionnaire were performed. The first interview took place in spring 1993 (before the campaign) with 1341 evaluable questionnaires', the second in fall 1994 (after the campaign) with 1150 evaluable questionnaire. The knowledge of the parents on melanoma risk factors was significantly improved in the second interview. Also the parental behavior regarding sun-protective measures when their children were outdoor at the beach or in the garden definitely changed. In 1993 the best textile sun protection was used by 21% of the parents at the beach and 36% in the garden. These numbers rose to 34% (beach) and 57% (garden) by the second interview. The percentage of children with no sunburn recorded during the preceding summer rose from 39% to 51%. According to the child's gender the parental behavior was different between the sexes; boys were always better protected than girls. The design of this study with two cross-sectional surveys in the same populations does not provide a methodologically sound basis for attributing the observed positive changes to the campaign. Without any doubt it can be stated that the parental knowledge and their attention to sun protection in their children showed substantial improvement in the second survey after the campaign. Thus, these results provide some evidence for the success of the preventive activities and confirm the necessity to continue with such activities.

Child, Preschool↗

PubMed1997

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years' duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2-117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1-19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia.

Adult↗

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↗

PubMed1997

Melanoma risk and residence in sunny areas. EORTC Melanoma Co-operative Group. European Organization for Research and Treatment of Cancer.

Melanoma risk among subjects from Germany, France and Belgium who had lived for 1 year or more in sunny climates was examined in a one-to-one unmatched case-control study conducted among white subjects 20 years old or more. A total of 412 consecutive patients with melanoma diagnosed from 1 January 1991 onwards, were derived from hospital registers; 445 controls were randomly chosen in the same municipality as the cases. After adjustment for host characteristics, melanoma risk associated with residence in a sunny area was 2.7 (95% CI: 1.4-5.2), increasing to 4.7 (95% CI: 1.4-13.5) if subjects sought a suntan when residing in sunny climates, and to 4.3 (95% CI: 1.7-11.1) if subjects arrived before the age of 10 years in the sunny area. Residence in sunny areas and recreational sun exposure seemed to combine their effects on melanoma risk. Increase in melanoma risk conveyed by deliberate sun exposure during adulthood was highest among subjects who had lived in sunny areas as a child or adolescent and lowest among subjects who had never resided in sunny areas. Our results support conclusions from migrant studies that indicated that childhood is a critical period of either vulnerability to solar radiation or more frequent exposures to melanoma risk factors. They also suggest that moderate sun exposure of an adult who was heavily sun exposed in childhood is associated with a higher melanoma risk than that of high sun exposure of an adult who was sun protected in childhood.

Adult↗

PubMed1997

Public awareness of malignant melanoma risk factors in Germany.

STUDY OBJECTIVE: To evaluate the effects of a German public education campaign which aimed to improve knowledge on risk factors for malignant melanoma. DESIGN: Comparison of data from two successive cross sectional surveys conducted before (spring 1993) and after (autumn 1994) the campaign. SETTING: All 56 nursery schools in Göttingen, the capital of southern Lower Saxony, Germany. PARTICIPANTS: Parents of children attending the nursery schools. Altogether 1341 questionnaires from parents were included in the first survey (response rate 64.9%) and 1150 questionnaires in the second survey (response rate 61.4%). MAIN RESULTS: The respondents in the second survey were much better at distinguishing true melanoma risk factors from false ones. The distribution of scores measuring the degree of accurate knowledge about melanoma risks indicated that this had improved significantly (p < 0.001). The most pronounced change with regard to knowledge of single risk factors could be observed for "sunburn during childhood," which was correctly identified by 63.1% in the first survey and by 85.6% in the second. Substantial improvement in accurate knowledge about the influence of constitutional skin factors--number of naevi, skin type etc--was also found. CONCLUSIONS: Notwithstanding the methodological problems in this analysis (non-randomised design, only before and after comparison, no control group, number of non-respondents), it is concluded that this campaign improved understanding of the risks of melanoma. Continuing public education activities should be implemented to sustain and improve further knowledge on prevention of malignant melanoma.

Adult↗