Both mercaptobenzothiazole and mercapto mix should be part of the standard series.
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Allergens↗
Biomedical subjects
O Gefeller
Publications and source records attributed to O Gefeller.
The attributable risk in a multifactorial situation--evaluation of different methods of partitioning.
OBJECTIVES: Different approaches to partition the attributable risk into exposure-specific components are methodologically evaluated. METHODS: Two methods of partitioning the attributable risk in a multifactorial situation have been suggested. One is based on a solution adopted from game theory, the Shapley value, whereas the other recently suggested approach uses a heuristically motivated proportional weighting scheme. These two concepts are reviewed and compared in a situation with three exposure factors. A hypothetical numerical example is discussed illustrating differences in the case of complex interaction structures. RESULTS: The two methods are found to differ in two critical features that affect the outcome of partitioning: i) including or ignoring the full interaction structure between exposure factors involved in the partitioning, ii) using an equal or proportional weighting scheme for the marginal excess risks of the exposures. As a result, not only the individual partial attributable risks for the exposure factors may be quantitatively different between the methods, but also their ranking depends on the partitioning approach. CONCLUSIONS: The epidemiologic properties of the partitioning procedure based on the Shapley value are known and fit to the needs of epidemiologic applications. The alternative approach recently suggested can lead to considerably different results. As long as its epidemiologic properties are not fully understood, the traditional partitioning method should be given preference in practical applications.
Algorithms↗
Association between split selection instability and predictive error in survival trees.
OBJECTIVES: To evaluate split selection instability in six survival tree algorithms and its relationship with predictive error by means of a bootstrap study. METHODS: We study the following algorithms: logrank statistic with multivariate p-value adjustment without pruning (LR), Kaplan-Meier distance of survival curves (KM), martingale residuals (MR), Poisson regression for censored data (PR), within-node impurity (WI), and exponential log-likelihood loss (XL). With the exception of LR, initial trees are pruned by using split-complexity, and final trees are selected by means of cross-validation. We employ a real dataset from a clinical study of patients with gallbladder stones. The predictive error is evaluated using the integrated Brier score for censored data. The relationship between split selection instability and predictive error is evaluated by means of box-percentile plots, covariate and cutpoint selection entropy, and cutpoint selection coefficients of variation, respectively, in the root node. RESULTS: We found a positive association between covariate selection instability and predictive error in the root node. LR yields the lowest predictive error, while KM and MR yield the highest predictive error. CONCLUSIONS: The predictive error of survival trees is related to split selection instability. Based on the low predictive error of LR, we recommend the use of this algorithm for the construction of survival trees. Unpruned survival trees with multivariate p-value adjustment can perform equally well compared to pruned trees. The analysis of split selection instability can be used to communicate the results of tree-based analyses to clinicians and to support the application of survival trees.
Algorithms↗
[A common and insidious side-effect: allergic contact dermatitis caused by bufexamac used in the treatment of dermatitis. Results from the Information Network of Departments of Dermatology (IDVK)].
BACKGROUND AND OBJECTIVE: Bufexamac is a non-steroidal, anti-inflammatory drug used in the topical treatment of atopic dermatitis, stasis dermatitis and perianal eczema. The substance is known to cause severe allergic contact dermatitis (ACD) as an adverse effect (AE), which may be indistinguishable from the eczema which is to be treated. Hence the diagnosis of this AE is often considerably delayed. In order to estimate the quantitative importance of ACD to bufexamac, data of the Information Network of (German) Departments of Dermatology (IVDK) from July 1999 to December 2004 were analysed. PATIENTS AND METHODS: During the study period, 39,392 unselected patients from 40 German departments of the IVDK were patch tested with bufexamac (5 % pet). The results of the reading after 72 hours were analysed. The dichotomized patch test result was further assessed for possible risk factors from the patients' history and clinical diagnosis by Poisson regression analysis. RESULTS: In 560 of 39,392 patients contact allergy to bufexamac was diagnosed, i. e. 1.4 % (95 % confidence interval: 1.3 - 1.5), standardized for sex and age. The Poisson regression analysis revealed a significantly increased risk associated with the following factors: multiple sensitization, perianal eczema, underlying atopic dermatitis, leg dermatitis, female gender and residence in areas of Germany other than Eastern Germany. The latter observation can be explained by low prescription rates in Eastern Germany. CONCLUSION: Bufexamac is an important allergen. Extrapolating the frequency of 1.4 % in our data to the whole German population by the CE-DUR approach yields an estimate of about 6000 cases per year. In view of the high frequency of sensitization, the pitfalls in diagnosis, the severity of the course of disease and the lack of efficacy of this drug, the risk to benefit ratio is obviously critical.
Administration, Topical↗
The effects of joint misclassification of exposure and disease on the attributable risk.
While there is extensive methodological literature analysing the effects of misclassification on the relative risk under various misclassification scenarios, for the attributable risk only the effects of non-differential misclassification either of exposure or disease, and the effects of non-differential independent misclassification of exposure and disease have been discussed for the 2 x 2-situation. The paper investigates the effects of non-differential correlated misclassification of exposure and disease on the attributable risk taking possible correlations of both types of misclassification into account. Furthermore, a comparison with the corresponding effects on the relative risk is drawn. We propose a matrix-based approach to describe the underlying structure of non-differential misclassification. The bias arising from non-differential misclassification in the attributable risk and relative risk is evaluated in four examples assuming under- or overreporting of exposure and disease. In each of the four examples we found scenarios where pronounced differences in degree and, more importantly, in direction of bias occurred. Our results clearly demonstrate the danger lying in the stereotype transfer of findings regarding misclassification effects on the relative risk to other epidemiologic risk measures and underline the necessity of specific analyses of the effects of misclassification on the attributable risk.
Bias↗
Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients.
There is increasing evidence that infections and vaccinations play an important role in the normal maturation of the immune system. It was therefore of interest to determine whether these immune events also affect the prognosis of melanoma patients. A cohort study of 542 melanoma patients in six European countries and Israel was conducted. Patients were followed up for a mean of 5 years and overall survival was recorded. Biometric evaluations included Kaplan-Meier estimates of survival over time and Hazard Ratios (HRs), taking into account all known prognostic factors. During the follow-up between 1993 and 2002, 182 of the 542 patients (34%) died. Survival curves, related to Breslow's thickness as the most important prognostic marker, were in accordance with those observed in previous studies where the cause of death was known to be due to disseminated melanoma. In a separate analysis of patients, vaccinated with vaccinia or Bacille Calmette-Guerin (BCG), HRs and the corresponding 95% Confidence Intervals (CIs) were 0.52 (0.34-0.79) and 0.69 (0.49-0.98), respectively. Joint analyses yielded HRs (and 95% CIs) of 0.55 (0.34-0.89) for patients vaccinated with vaccinia, 0.75 (0.30-1.86) with BCG, and 0.41 (0.25-0.69) with both vaccines. In contrast, infectious diseases occurring before the excision of the tumour had little, or, at the most, a minor influence on the outcome of the melanoma patients. These data reveal, for the first time, that vaccination with vaccinia in early life significantly prolongs the survival of patients with a malignant tumour after initial surgical management. BCG vaccination seems to have a similar, although weaker, effect. The underlying immune mechanisms involved remain to be determined.
Adolescent↗
Efficiency of a minicourse in radiation reducing techniques: a pilot initiative to encourage less irradiating cardiological interventional techniques (ELICIT).
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Coronary Angiography↗
A computer program to estimate power and relative efficiency of flexibly matched case-control studies.
OBJECTIVES: We recently introduced the concept of flexible matching strategies with varying proportions of a dichotomous matching factor among controls to increase power and efficiency of case-control studies. We now present a method and a computer program to calculate power and relative efficiency compared to an unmatched design varying the proportion of the matching factor in controls over all possible values from 0 to 100 percent. METHODS: For all these values, the program calculates the expected variance of the combined Mantel-Haenszel odds ratio and determines the power using the standard error of the expected combined Mantel-Haenszel odds ratio under the null hypothesis as derived from the Mantel-Haenszel test statistic without continuity correction. RESULTS: Thereby, the program allows estimating the optimal prevalence of the matching factor in selected controls for a given scenario which often differs from the prevalence in cases. It furthermore allows to estimate loss in power and efficiency compared to optimal matching by suboptimal matching. CONCLUSIONS: Estimations like these are helpful with respect to the decision when to stop efforts to optimize the degree of matching during the recruitment of controls. Our program will strongly facilitate assessing the benefits of flexible matching strategies.
Case-Control Studies↗
A computer program to estimate power and relative efficiency to assess multiplicative interactions in flexibly matched case-control studies.
Matching on one of two possibly interacting exposures can increase power and efficiency to estimate multiplicative interactions in case-control studies. We recently introduced the concept of flexible matching strategies with varying proportions of a dichotomous matching factor among controls to further increase power and efficiency. In order to facilitate the application of this concept, we developed a computer program which provides estimates of power and efficiency varying the proportion of the matching factor in controls over all possible values from 1 to 99%. The program allows one to estimate the effect of frequency matching on power and efficiency to study multiplicative interactions and to assess the optimal prevalence of the matching factor in selected controls for a given scenario which often differs from the prevalence in cases (aimed at in traditional 'fixed' frequency matching). Our program will strongly facilitate assessing the benefits of matching and flexible matching strategies in case-control studies addressing multiplicative interactions, including gene-environment interactions.
Case-Control Studies↗
Period analysis for 'up-to-date' cancer survival data: theory, empirical evaluation, computational realisation and applications.
Long-term survival rates are the most commonly used outcome measures for patients with cancer. However, traditional long-term survival statistics, which are derived by cohort-based types of analysis, essentially reflect the survival expectations of patients diagnosed many years ago. They are therefore often severely outdated at the time they become available. A couple of years ago, a new method of survival analysis, denoted period analysis, has been introduced to derive more 'up-to-date' estimates of long-term survival rates. We give a comprehensive review of the new methodology, its statistical background, empirical evaluation, computational realisation and applications. We conclude that period analysis is a powerful tool to provide more 'up-to-date' cancer survival rates. More widespread use by cancer registries should help to increase the use of cancer survival statistics for patients, clinicians, and public health authorities.
Cohort Studies↗
Modification of SAS macros for a more efficient analysis of relative survival rates.
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Humans↗
Monitoring of nevus density in children as a method to detect shifts in melanoma risk in the population.
BACKGROUND: Nevus density in children, a well-known risk factor for malignant melanoma, depends both on constitutional factors and on previous ultraviolet (UV) exposure. Secular trends of childhood UV exposure could thus be indirectly monitored by repeated standardized surveys assessing nevus density in children, such as the "childhood monitoring of nevus density (CMONDE-Study)". METHODS: Two complete surveys comprising all children at the time of school enrolment were performed in the city and county of Göttingen, Germany, during the years 1999 and 2000. A total of 4252 children with a median age of 6.25 years were examined as part of the mandatory school enrolment health assessment, and complete data were available for 3881 children. RESULTS: Median nevus density was 5.8/m(2) in the entire study group. The subgroup-specific median increased from "Fitzpatrick skin type" IV to II, but the density was not increased for the type I subgroup. Similarly, nevus density rose with increasing lightness of hair color, but was very low in red-haired individuals. While the number of freckles was also strongly associated with nevus density, the association between iris color and skin reflectance, respectively, was weak. The duration of the additional examination for CMONDE was on average 3-5 min per child. CONCLUSION: We regard CMONDE as a highly feasible surveillance instrument, which should be implemented as an important addition to regular regional or national health reporting.
Child↗
Inter-relation between variables determining constitutional UV sensitivity in Caucasian children.
BACKGROUND/PURPOSE: Sensitivity to ultraviolet (UV) light is associated with phenotypic variables like iris or hair colour or freckling, which are all strongly inter-related. We assessed the pattern of association among these factors to construct a summary measure reflecting constitutional UV sensitivity in a simple one-dimensional score with sufficient discriminating power. METHODS: Information on iris and hair colour (3 and 4 categories, respectively), freckling (none vs. any) and the reaction to mid-day summer sunlight as an outcome (dichotomized into 'burn' and 'tan') was collected in a cross-sectional study among children at school enrollment in 1999 and 2000 in Göttingen, Germany (n=3765 with complete data). Chi-squared automatic interaction detector (CHAID) analysis and log-linear modelling was used to assess the pattern of mutual inter-relations. RESULTS: Hair colour turned out to be the factor most strongly associated with UV sensitivity. In case of blonde or brown hair (the most common phenotypes in our sample), the consideration of freckling further refined the classification system, whereas iris colour did not contribute additional information. The results of the CHAID and log-linear analyses suggest a simple five-point score capturing constitutional UV sensitivity. The discriminating power of this score was high in our sample, with the proportion of persons who burned ranging from 7.7 (lowest category) to 73% (highest category). CONCLUSION: The new scoring system summarized efficiently relevant information on individual constitutional UV sensitivity in our sample. Its further validation in independent studies comprising Caucasian children or adults is necessary to assess objectively its properties for future applications.
Child↗
Longitudinal study examining the neurotoxicity of occupational exposure to aluminium-containing welding fumes.
OBJECTIVES: The neurotoxicity of occupational exposure to aluminium (Al)-containing welding fumes has been discussed with controversial results. The aim of the longitudinal study was to examine a group of Al welders for significant central nervous changes in comparison with a non-exposed cohort. METHODS: A group of 98 Al welders (mean age 37 years) in the car-body construction industry, with a median of 6 years of occupational exposure to Al welding fumes, and an education-matched, gender-matched, age-matched control group of 50 car-production workers (mean age 36 years) at the same plant, were included in this longitudinal study. Two cross-sectional studies were done in 1999 and 2001. In the second cross-sectional study 97 welders and 50 controls could be examined. The examination programme consisted, for example, of a standardised anamnesis, focussing on occupational history, education, illnesses, medication, accidents and current alcohol consumption, a physical examination that included neurological status, and the assessment of Al concentration in plasma and urine. The neurobehavioral methods included a symptom questionnaire, modified Q16, and computerised and non-computerised tests: psychomotor performance (steadiness, line tracing, aiming, tapping), verbal intelligence (WST), simple reaction time, digit span, block design (HAWIE), symbol-digit substitution, digit span, switching attention (European neurobehavioral evaluation system, EURO-NES), and standard progressive matrices. The data were analysed by multivariate analysis of covariance (MANCOVA) for repeated measurements with covariates age, education, and carbohydrate-deficient transferrin in plasma (CDT). RESULTS. The median Al urine concentration (mean preshift/postshift) was 52.4 microg/g creatinine (2001) and 57.6 microg/g creatinine (1999). Median respirable air dust was 0.67 mg/m(3) (2001) and 0.47 mg/m(3) (1999). Welders and controls did not report significantly more symptoms in the modified Q16. Furthermore, no significant differences in psychomotor performance and other neurobehavioral tasks, except for reaction time, were seen between welders and non-welders. Regression analyses reveal a significant relationship between reaction time and Al excretion in urine that was confounded by other factors. CONCLUSIONS: At present the outcome for reaction time has to be interpreted as a single result. However, as the modified Q16 questionnaire and the rest of the psychomotor performance showed no significant changes, the next cross-sectional study, in 2003, will provide further information on which a final conclusion can be based.
Adult↗
Impact of vaccinations and infectious diseases on the risk of melanoma--evaluation of an EORTC case-control study.
A significant correlation between a reduced risk of melanoma and BCG and vaccinia vaccination in early childhood or infectious diseases later in life has already been reported from the FEBrile Infections and Melanoma (FEBIM) multicentre case-control study. This correlation is further evaluated in this study based on 603 incident cases of malignant melanoma and 627 population controls in six European countries and Israel by means of a joint analysis of the influence of vaccinations and infectious diseases. In addition, the previously unconsidered impact of influenza vaccinations is evaluated for the whole study population. The strong effects of the frequently given BCG and vaccinia vaccinations in early childhood, as well as of uncommon previous severe infectious diseases, were apparently not cumulative. With the Odds Ratio (OR) being set at 1 in the absence of vaccinations and infectious diseases, the OR dropped to 0.37 (95% Confidence Interval (CI): 0.10-1.42) when subjects had experienced one or more severe infectious diseases, associated with a fever of > 38.5 degrees C, and had not been vaccinated with BCG or vaccinia. The OR was 0.29 (CI: 0.15-0.57) in those who had had a severe infectious disease and were vaccinated with either BCG or vaccinia and 0.33 (CI: 0.17-0.65) for those with 1 or more severe infectious diseases and who had received both vaccinations. We conclude that both vaccinations as well as previous episodes of having a severe infectious disease induced the same protective mechanism with regards to the risk of melanoma. Because of a 'masking effect' by the vaccinia vaccination, the protective effect of the BCG vaccination and of certain infectious diseases against cancer has remained undetected. The vaccinations contributed more to the protection of the population than a previous episode of having an infectious disease. In view of the termination of vaccinations with vaccinia in all countries and of BCG in many of them, these findings call for a re-evaluation of vaccination strategies.
Adolescent↗
Risk factors for contact allergy to nickel - results of a multifactorial analysis.
To quantify the independent impact of potential risk factors for nickel contact allergy (NCA), a multifactorial Poisson regression analysis of standardized anamnestic and patch test data (with nickel sulfate, 5% in petrolatum) was performed, comprising 74 940 patients assessed in the 33 German and Austrian contact dermatitis units of the Information Network of Departments of Dermatology (IVDK) between 1992 and 2000. NCA was observed in 15.5% patients. Female sex was the strongest risk factor (prevalence ratio 3.74, 95% CI: 3.51-3.98). Risk increased monotonically and significantly with decreasing age. Atopic dermatitis was not a risk factor. The year of patch test had no influence on NCA risk. Significant variation of risk between occupations was observed. In conclusion, our multifactorial analysis was able to quantify the impact of established risk factors and additionally address other, e.g. occupational, factors yet unidentified.
Adult↗
Standardization of occupational dose to patient DAP enables reliable assessment of radiation-protection devices in invasive cardiology.
PURPOSE: With the aim of assessing the effectiveness of radiation-protection devices in invasive cardiology, the goal of this study was to validate relative parameters for operator occupational exposure, standardized to the patient's primary dose. MATERIAL AND METHODS: One of these parameters was the local dose, measured in air at the operator's position per dose area product (DAP), applied to a male anthropomorphic Alderson-Rando phantom for simulation of coronary angiography. The second parameter was personal occupational dose to the operator per DAP, measured by thermoluminescence dosimeter stripes during 121 procedures in routine clinical work. RESULTS: The local and personal doses per unit DAP - using typical 0.5-mm lead overcouch and undercouch protection - were comparable (left eye 180 vs. 360, thyroid 260 vs. 260, left shoulder 280 vs. 150, chest 400 vs. 500, hands 400 vs. 550, waist 900 vs. 400 nSv/Gy x cm (2)). The results, however, were far lower than typically reported values. Our findings therefore disclose a typically inadequate use or acceptance by individual operators of available table-attached lead protection devices, and of ceiling-attached lead-glass screens. The additional use of individual 1.0-mm lead-equivalent garments reduced local doses to levels between 1. 10 %. CONCLUSIONS: DAP-standardized dose parameters - determined experimentally (phantom measurements), or in routine clinical work - are not appreciably influenced by the equipment age and type, or by the image-intensifier entrance dose rate of the respective catheterization system. They are consequently best suited for obtaining eloquent comparisons of various radiation-protection devices, and for reliable estimation of local scatter radiation exposure by simple documentation of intervention DAP.
Computer Simulation↗
Predialing the number of cinegraphic frames enables an effective patient dose due to coronary angiography of 0.8 mSv.
PURPOSE: To investigate the effect of a new device for predialing the number of cinegraphic frames before each coronary angiogaphy, with the objective of reducing the patient dose area product (DAP) from coronary angiography, which typically requires 1000 to 2350 cinegraphic frames. That DAP is high and stated to be between 15.6 to 106.3 Gy x cm (2). Applying the accepted DAP-to-ED conversion factors, for the thoracic region of approximately 0.20 mSv/Gy x cm (2), this corresponds to a mean effective dose (ED) in the range of 3.1 to 21.3 mSv. MATERIAL AND METHODS: For patients undergoing elective coronary angiography, we compared various parameters of radiation exposure obtained with judicious radiation reducing standard techniques (n = 106) and with an additional new rotary switch for predialing the number of cinegraphic frames (n = 106). RESULTS: The patient radiation dose was significantly lower with the new device, with the mean DAP reduced to 5.5 from 9.1 Gy x cm (2). The corresponding reducation of the mean DAP for left ventriculography and coronary angiography was 1.3 from 1.7, and 4.2 from 7.4 Gy x cm (2), respectively. The number of cinegraphic frames was 98 vs. 184, whereas the number of cinegraphic runs and the fluoroscopy time were comparable. CONCLUSION: Predialing the cinegraphic frame number before each cinegraphic run enables a reduction of the patients effective dose from coronary angiography to 0.8 mSv, i. e. to 57 % of the baseline value and far below typically reported values.
Aged↗