The concept of attributable risk in epidemiology: yesterday, today and tomorrow.
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Confounding Factors, Epidemiologic↗
Biomedical subjects
O Gefeller
Publications and source records attributed to O Gefeller.
Partitioning methods for multifactorial risk attribution.
The epidemiological problem of risk attribution in the framework of multiple exposures has been the subject of intensive research activities in the last decade. In particular, partitioning methods have been developed to define new multidimensional measures of attributable risk putting the task of quantifying a proportion of disease events in a population that can be ascribed to the adverse health effects of certain risk factors into a multifactorial perspective. The parameters generalize the concept of attributable risk to different multifactorial frameworks in which multiple exposures might be arranged in hierarchically ordered classes or in equally ranking groups. Partitioning methods are reviewed and differences between the multifactorial variants of attributable risk are illustrated by a component causes model.
Algorithms↗
Differential expression of the lung resistance-related protein/major vault protein in the histological compartments of nephroblastomas.
Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for molecular markers of drug resistance, we investigated the expression of lung resistance protein (LRP) in tissue samples from 32 children with nephroblastoma by means of immunohistochemistry. LRP is a human major vault protein (MVP) and is associated with multidrug resistance of tumors. LRP/MVP expression was found in the blastemal and epithelial compartments but to a significantly lesser extent in the stromal compartment of Wilms' tumors. Expression was generally heterogeneous with respect to staining intensity and percentage of positive cells. We found significant relationships between LRP/MVP expression and chemotherapeutic pre-treatment of tumors and tumor stage. The immunohistochemical results were validated with a real-time RT-PCR technique and a significant association between protein and mRNA expression was observed.
Antibiotics, Antineoplastic↗
Differential expression of the multidrug resistance-related protein MRP1 in the histological compartments of nephroblastomas.
Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for prognostic markers, we investigated the expression of the multidrug resistance-related protein 1 (MRP1) in 32 nephroblastomas by means of immunohistochemistry. The immunohistochemical results were validated with a real-time RT-PCR technique. MRP1 expression was heterogeneous and predominantly found in the blastemal and epithelial compartments compared to the stromal elements of nephroblastomas. We found significant relationships of MRP1 expression to survival of patients and to expression of p53, HSP70, and LRP/MVP. The relationship between MRP1 and p53 expression is a clue that the transcriptional control of MRP1 by p53 reported for other tumor types may also take place in nephroblastomas. The correlation of MRP1 to other drug resistance genes, e.g. HSP70 and LRP/MVP in nephroblastomas indicates that the co-expression of different drug resistance genes may be under a common regulation of still unknown transcription factors.
ATP-Binding Cassette Transporters↗
More up-to-date monitoring of long-term survival rates by cancer registries: an empirical example.
A few years ago, a new method of survival analysis, denoted period analysis, has been developed to derive more up-to-date estimates of long-term survival rates of cancer patients, but this method has rarely been applied so far. Using empirical examples from the Saarland Cancer Registry, we illustrate how seriously traditional long-term survival estimates may lag behind survival expectations of newly diagnosed cancer patients in the case of recent improvement in prognosis, and to what extent this problem may be reduced by period analysis of survival. We conclude that period analysis should be more widely used for deriving more up-to-date long-term survival estimates.
Aged↗
Re: "Attributable risk in practice".
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Causality↗
[Ultraviolet exposure in childhood and in adulthood: which life period modifies the risk of melanoma more substantially?].
The paper is devoted to the analysis of the relationship between the frequency of sunburns in childhood and adulthood, respectively, and the occurrence of malignant melanoma of the skin. The analysis is based on case-control data of 603 melanoma cases and 627 population controls from 11 participating centers in seven European countries. The results confirm the increase in melanoma risk for an increasing number of sunburns during childhood and adulthood in the same magnitude of risk elevation. The maximum OR for the highest exposure category of more than five sunburns was during the childhood 2.0 (95%-CI: 1.2-3.5) and during the adulthood 2.1 (95%-CI: 1.4-3.3), respectively. The analysis of the joint effects of sunburns during child- and adulthood on melanoma development corroborated these findings. In this joint analysis an OR of 2.1 (95%-CI: 1.3-3.5) quantifies the melanoma risk of those with three or more sunburns during child- and adulthood, respectively, compared to those without any sunburns during these periods. The study does therefore provide no supporting evidence for the presence of "critical period" during childhood in which a higher melanoma risk due to sunburns has been suggested by other studies.
Adolescent↗
Positive nickel patch tests do not intensify positive reactions to adjacent patch tests with dichromate. Results from a double-blind multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).
The possible interference of neighbouring allergic patch-test reactions is still an open question. In this study, we investigated whether there is a distance-related mutual modification of neighbouring allergic patch-test reactions to nickel sulfate and potassium dichromate. We used a double-blind multicentre study design with randomized attachment of special TRUE Tests with 1, 3 and 7 cm distance between nickel sulfate and potassium dichromate patches. 589 patients with a history of nickel allergy (523 female, 66 male) were tested, with a mean age of 35 years. A log-linear modelling approach was used for statistical assessment of the relation between the distance separating neighbouring patch tests with nickel and dichromate and the reactions to the allergens. Non-reproducibility coefficients were compared by the generalized version of Fisher's exact test for arbitrary 2-dimensional contingency tables. For the left side of the back, virtually no differences (p=0.70) were found in the reaction patterns obtained for the 3 distances separating nickel and dichromate patch tests. On the right side of the back, the number of reactions to dichromate patches with only 1 cm distance from moderate/strong nickel reactions was lower than the number of positive dichromate tests at larger distances from nickel tests (on the border of statistical significance: p= 0.05). Corresponding side-related results were obtained for subgroups of patients with and without a history of atopic dermatitis. The non-reproducibility of reactions to dichromate was not significantly related to the distance between neighbouring tests. Our data argue against a "spillover" effect of strong/moderate nickel reactions, but indicate that such reactions may, under certain conditions, attenuate adjacent reactions to an unrelated allergen. In the case of future verification, this will have implications for the interpretation of patch tests.
Adolescent↗
Patch testing with methyldibromoglutaronitrile.
BACKGROUND: The combination of methyldibromoglutaronitrile (MDBGN) and phenoxyethanol (PE) is widely used as a preservative in body care products. Sensitization rates to MDBGN have increased parallel to its increasing use in cosmetics, skin care products, and moist toilet paper since the early 1990s, whereas PE is obviously not a sensitizer. The optimum patch preparation for diagnosing a contact allergy to MDBGN is still a matter of debate. OBJECTIVE: This study was performed to assess an adequate patch test concentration for MDBGN/PE and MDBGN. METHODS: Based on previous results from other countries, the German Contact Dermatitis Research Group (DKG) performed parallel patch tests with MDBGN/PE 0.5% in petrolatum (pet.) and 1% pet. in 4,615 patients and with MDBGN 0.1% pet. and 0.3% pet. in 988 patients. The results of these tests, performed in routine patch testing, were collected and analyzed be the Information Network of Departments of Dermatology (IVDK). RESULTS: Comparing MDBGN/PE 0.5% pet. with 1.0% pet., the percentage of patients showing a positive test reaction increased from 2.3% to 3. 5% (P <.001), mainly because of an increase in weak positive reactions. The reaction index remained stable at 0.54. Comparing MDBGN 0.1% pet. with 0.3% pet., the percentage of patients with positive reactions increased from 1.4% to 3.3% (P <.001), and the reaction index decreased from 0.33 to -0.10. With the lower test concentration, 79% of the positive reactions were only +, with the greater concentration, this was true of 64%. CONCLUSION: Testing MDBGN/PE 1.0% pet. shows additional cases of contact allergy to MDBGN that would have remained undetected with MDBGN 0.5% pet. The greater test concentration seems to have no disadvantages in quality. The DKG decided to keep MDBGN/PE 1.0% pet. in the standard series. MDBGN 0.3% pet. leads to far more doubtful or irritant test reactions than MDBGN 0.1% and may produce false-positive patch test results. Therefore, the DKG recommends testing MDBGN 0.3% pet only in special cases.
Cosmetics↗
Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Members of the Collaborative European Multicenter Study Group.
OBJECTIVE: Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction. We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS). DESIGN/METHODS: The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results. They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987-1993) and prospectively from the same units in the following years. A nonrandomized control group of 236 noninfected infants was selected from the same database. The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications. RESULTS: Median birth weight in the GBS study group was 1468 g (25th-75th percentiles: 1015-2170), and median gestational age was 30 (27-33) weeks. Thirty-one percent of the infants weighed >2000 g. Median age at surfactant treatment was 6 hours. The mean initial surfactant dose was 142 mg/kg (standard deviation: 53). Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany). Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th-75th percentiles:.63-1.0) to.50 (.35-.80). The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS. CONCLUSIONS: Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia. The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed. The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.
Drug Administration Schedule↗
Current clinical diagnosis in Creutzfeldt-Jakob disease: identification of uncommon variants.
According to the recently established molecular basis for phenotypic heterogeneity of sporadic Creutzfeldt-Jakob disease (CJD), six different phenotypes are characterized by the size of the protease-resistant fragment of the pathological prion protein (types 1 and 2) and homozygosity or heterozygosity for methionine or valine at codon 129 of the prion protein gene (designated by MM1, MM2, MV1, MV2, W1, and W2). In the present investigation, we analyzed the value of commonly used clinical tests (electroencephalogram [EEG], detection of 14-3-3 protein in cerebrospinal fluid [CSF], and hyperintensity of the basal ganglia in magnetic resonance imaging) for the clinical diagnosis in each CJD phenotype. The detection of periodic sharp and slow wave complexes in the EEG is reliable in the clinical diagnosis of MM1 and MV1 patients only. The CSF analysis for 14-3-3 protein showed high sensitivity in all analyzed subgroups with the exception of MV2 patients. Valine-homozygous patients had a negative EEG, but most had detectable levels of neuronal proteins in the CSF. The sensitivity of the magnetic resonance imaging was 70%, irrespective of the subgroup, but was particularly reliable in the clinical diagnosis of MV2 patients. The widening spectrum of diagnostic techniques in CJD is not only useful in the increased accuracy of the clinical diagnosis but should also lead to the identification of more atypical cases of sporadic CJD.
14-3-3 Proteins↗
The effect of stress on the onset and progression of Creutzfeldt-Jakob disease: results of a German pilot case-control study.
The association between Creutzfeldt-Jakob disease (CJD) and stressful life events was examined in a pilot case-control study in Germany. The study sample consisted of 37 CJD cases and 37 controls, both groups were frequency-matched for age and sex. In standardised interviews of close relatives of the cases and the controls, all stressful life events were assessed and subsequently grouped into one of the following three subgroups: psychosocial stress events, medical operations with hospitalisation, and other serious medical examinations. A significantly higher proportion of CJD cases experienced stressful life events during the last six months before disease onset than controls (65% vs. 32%, p = 0.01), yielding an odds ratio (OR) of 3.85 (95% confidence interval (CI): 1.33-11.30). We found the clearest distinction between cases and controls for the subgroup of medical operations where an OR of 6.97 (95% CI: 0.76-329.20) was observed. Further data indicated that stressful events seem to influence not only the onset of CJD but also the progression of the disease. Although based on a rather small study sample, this pilot case-control investigation suggests evidence that stressful life events in the last six months before disease onset may influence CJD occurrence and may modify the course of disease. This 'stress hypothesis', which is in line with findings from other epidemiological and experimental studies in CJD, is thus a promising direction for future CJD research as it could enlighten the pathophysiological mechanisms and point towards strategies for the prevention and therapy of CJD.
Age Distribution↗
Kinetics of serum neuron-specific enolase and prolactin in patients after single epileptic seizures.
PURPOSE: To investigate and compare the temporal profile of serial levels of neuron-specific enolase (NSE) and prolactin in serum from patients after single epileptic seizures. METHODS: Measurement of NSE and prolactin by sensitive immunoassays in 21 patients with complex partial seizure (CPSs: n = 11) and secondarily generalized tonic-clonic seizures (SGTCSs; n = 10) during continuous video-EEG monitoring at four different time points (1, 3, 6, and 24 h after ictal event). Statistical analysis was performed by using a repeated-measures analysis of variance (ANOVA) model. RESULTS: Mean+/-SD values for NSE levels (ng/ml) were 12.5 +/-4.4 (1 h), 10.8+/-3.8 (3 h), 11.1+/-4.9 (6 h), and 8.2+/-1.9 (24 h). The corresponding prolactin levels (mU/L) were 1,311+/-1,034, 232+/-158, 237+/-175, and 251+/-98. There was a significant decrease of NSE and prolactin levels over time (p < 0.001). The pair-wise comparison of NSE levels showed significant differences between the time points 1 vs. 24 h (p < 0.001), 3 vs. 24 h (p = 0.007), and 6 vs. 24 h (p = 0.009). In contrast, serum prolactin levels showed a significant difference between 1 vs. 3 h (p < 0.001) only. Most of the NSE levels remained normal after CPSs and SGTCSs. At 1 h after the seizure, only 33% of the subjects had increased NSE, whereas abnormal prolactin levels occurred with a sensitivity of 80%. CONCLUSIONS: In contrast to prolactin, serum NSE is not a sensitive marker of individual seizures. Only some individuals showed an increase of NSE beyond the prolactin-sensitive time frame after a single seizure, and mean NSE levels were not significantly increased compared with those of normal controls.
Adult↗
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↗
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↗
Hand dermatitis in a prospectively-followed cohort of hairdressing apprentices: final results of the POSH study. Prevention of occupational skin disease in hairdressers.
The incidence of hand dermatitis is high in the hairdressing trade; the individual disease burden is substantial, as are the costs of treatment, workers compensation and retraining programs. To evaluate the risk of developing occupational irritant hand dermatitis associated with several potential risk factors, namely constitution (atopy) and occupational exposure, an observational prospective population-based cohort study set in vocational training schools in northwest Germany, recruiting 2352 hairdressing apprentices, was performed. Unprotected wet work of more than 2 h per day is the major significant risk factor; low ambient absolute humidity is equally associated with a significantly increased risk. Compared to the youngest age group, risk diminishes with increasing age. Constitutional risk factors are difficult to evaluate because of selective dropout of atopic participants. For primary prevention, a population approach, improving working conditions and skin protection for all exposed, appears to be the most beneficial.
Adolescent↗
Risk of hand dermatitis among hairdressers versus office workers.
OBJECTIVES: The risk of irritant skin damage associated with hairdressing was estimated with the individual occupational exposure and other relevant factors having been taken into consideration. METHODS: A cohort of 2352 hairdressing and 111 office apprentices was prospectively followed for the duration of their vocational training (3 years), 3 examinations having been made and 3 years of recruitment having been used [1992 (hairdressers only), 1993, 1994] in 15 vocational training schools in northwest Germany. The information of the final follow-up examination was used for the analysis. RESULTS: A multifactorial analysis taking several (constitutional) risk factors, which were unevenly distributed between the 2 groups, into account revealed a significantly increased risk for hairdressers when compared with office workers (odds ratio approximately 4.0) with a marked decline in the most recently recruited (1994) apprentice group. Other significant factors increasing the dermatitis risk were (i) low ambient absolute humidity, (ii) young age, and (iii) a certain higher range of "atopy score". If the individual profile of occupational exposure among hairdressers was also considered, unprotected wet work of more than 2 hours per day was found to be a significant risk factor. CONCLUSIONS: Good skin protection, as operationalized in the present study, can diminish, but not eliminate, the risk of occupational irritant hand dermatitis among hairdressers.
Adolescent↗
Infections and melanoma risk: results of a multicentre EORTC case-control study. European Organization for Research and Treatment of Cancer.
Immune function plays a prominent role in the defence against cutaneous malignant melanoma and the increased risk of melanoma development during immunosuppression. Since the immune system is challenged beyond its routine activity by an infection, the effect of previous infectious diseases on the risk of melanoma may also be crucial. In a European Organization for Research and Treatment of Cancer (EORTC) case-control study performed in six European countries and Israel, we compared the history of severe infections in 603 melanoma patients with that in 627 population controls. We calculated adjusted odds ratios (ORs) to estimate the effect of infectious diseases on melanoma risk. The ORs for melanoma risk were below 1 for nearly all types of infections (except two) if body temperature was not taken into consideration, and for all infections with a body temperature above 38.5 degrees C. In the latter category significantly lowered ORs were found for pulmonary tuberculosis (0.16; 95% confidence interval [CI] 0.01-0.98), Staphylococcus aureus infections (0.54; 95% CI 0.31-0.94), sepsis (0.23; 95% CI 0.06-0.70), influenza and related infections (0.65; 95% CI 0.48-0.86) and pneumonia (0.45; 95% CI 0.27-0.73). Analysis of the cumulative influence revealed a consistent pattern of results pointing to a reduction in melanoma risk with increasing numbers of recorded infections and fever height. This apparent dose-response relationship suggests a causal association. Speculations on the underlying mechanism include a Shwartzman-like phenomenon when melanoma formation precedes the infection and/or an infection-related Th1-cell activation preventing the establishment of the tumour.
Adult↗