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Biomedical subjects

Olaf Gefeller

Publications and source records attributed to Olaf Gefeller.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of confidence intervals for adjusted attributable risk estimates under multinomial sampling.

The epidemiologic concept of the adjusted attributable risk is a useful approach to quantitatively describe the importance of risk factors on the population level. It measures the proportional reduction in disease probability when a risk factor is eliminated from the population, accounting for effects of confounding and effect-modification by nuisance variables. The computation of asymptotic variance estimates for estimates of the adjusted attributable risk is often done by applying the delta method. Investigations on the delta method have shown, however, that the delta method generally tends to underestimate the standard error, leading to biased confidence intervals. We compare confidence intervals for the adjusted attributable risk derived by applying computer intensive methods like the bootstrap or jackknife to confidence intervals based on asymptotic variance estimates using an extensive Monte Carlo simulation and within a real data example from a cohort study in cardiovascular disease epidemiology. Our results show that confidence intervals based on bootstrap and jackknife methods outperform intervals based on asymptotic theory. Best variants of computer intensive confidence intervals are indicated for different situations.

Adult↗
PubMed2006

Onset of action of levetiracetam: a RCT trial using therapeutic intensive seizure analysis (TISA).

OBJECTIVES: To correlate the onset of clinical effects of add-on levetiracetam (LEV) therapy with daily serum LEV concentration, in pharmaco-resistant focal epilepsies, using the TISA method. METHODS: 25 adult patients (aged>6 years) with pharmaco-resistant focal epilepsies undergoing presurgical evaluation at the Epilepsy Center Erlangen were enrolled in the study. Eligible patients on a maximum of one other antiepileptic drug (AED) were recruited into the 48-hour baseline phase. Those who had at least two seizures during this phase were randomized into the seven-day treatment phase, when they received either LEV or placebo, under continuous day-and-night video-EEG monitoring. The starting daily dose of LEV was 500 mg bid, titrated from the second treatment day to 1,000 mg bid. The peak serum concentration of LEV was monitored daily at 8:00 am (one hour after drug administration) for every patient. The number and duration of seizures per 24h (N/24h and D/24h respectively) were investigated. RESULTS: 23 patients completed the study (LEV group n=11 and placebo group n=12). Seven patients in the LEV group and two patients in the placebo group achieved seizure-freedom during the treatment phase. The intergroup comparison of the decrease in N/24h and D/24h from the baseline phase to the treatment phase was in favor of the LEV group (p<0.05). A significant effect of LEV on D/24h was seen as early as the second treatment day (p=0.013), becoming more apparent on the third treatment day (p=0.009). CONCLUSION: The present study objectively quantified the correlation between the anticonvulsant effects of LEV in focal epilepsies and the peak serum concentration of the drug. For the first time, direct measurement was used to demonstrate the onset of action of LEV to be two days after drug initiation.

Adult↗
PubMed2005

Biological monitoring of welders exposed to aluminium.

To evaluate an adequate strategy for biological monitoring of aluminium (Al), a group of 62 Al welders (age in 1999: 23-51 years, median 35 years) was surveyed annually from 1999 to 2003 by determination of pre- and post-shift Al in urine and plasma. Biomonitoring was supplemented by personal air measurements of the total dust concentration. The welders' internal exposure was compared to the exposure of 60 non-exposed assembly workers (age in 1999: 21-51 years, median: 36 years) who were surveyed in 1999, 2001 and 2003. Having a nearly constant dust exposure, median concentrations of Al in urine (Al in plasma) of the welders decreased from 40.1 microg/g to 19.8 microg/g creatinine (8.7 to 4.6 microg/l). For the control group the median levels of Al in urine (plasma) ranged from 4.8 microg/g to 5.2 microg/g creatinine (2.4-4.3 microg/l) indicating a higher sensitivity for the marker Al in urine. No systematic differences have been found between pre- and post-shift internal exposure. This might be caused by the slow elimination kinetics and low systemic bioavailability of Al. A correlation analysis did not yield close relationships between dust exposure, Al in plasma and Al in urine underlining the importance of biomonitoring for assessment of Al exposure.

Adult↗
PubMed2004

An alternative approach to age adjustment of cancer survival rates.

The measures of cancer prognosis most commonly reported by cancer registries are 5- or 10-year absolute or relative survival rates. Because cancer survival rates often vary by the age of cancer patients, and because the age structure of cancer patients often varies between populations, age adjustment is crucial for comparative analyses of cancer survival rates. However, traditional age adjustment often breaks down for long-term survival rates, particularly for sparse data, and it may provide inconsistent results for relative survival rates, even if age adjustment is made to the study population's own age distribution. In this manuscript, we propose an alternative approach to age adjustment of both absolute and relative survival rates to overcome both the practical and conceptual problems inherent in traditional age adjustment. We outline the computational realisation of this approach, and we give an empirical illustration of its application using data from the nationwide Finnish Cancer Registry.

Adolescent↗
PubMed2004

Contact allergy in construction workers: results of a multifactorial analysis.

OBJECTIVES: To quantify the risk of contact allergy (CA) to important ubiquitous allergens associated with certain occupations, in particular the construction industry, and to identify possible time trends, controlling for potential confounding variables. METHODS: Bivariate as well as Poisson regression analysis of standardized anamnestic and patch test data comprising 82,561 patients assessed in the 33 German and Austrian contact dermatitis units of the Information Network of Departments of Dermatology (IVDK) between 1992 and 2000. RESULTS: CA to five of the 18 (groups of) allergens considered here were observed significantly more often in construction workers: dichromate, epoxy resin (BADGE), cobalt, thiurams and N-isopropyl-p-phenylenediamine (IPPD). Multifactorial analysis confirmed an increased risk of CA to these allergens in construction workers, compared with other occupations. A very strong association between cobalt and chromate allergy was found in construction workers (OR 39.1, 95% CI 21.1-79.6). CONCLUSIONS: Dichromate is still an prominent allergen in construction workers; as yet, there is only weak evidence of a decrease in Germany. Therefore, the addition of ferrous sulphate to cement, which has been a successful intervention in other countries, should be promoted further. Although CA to other important occupational allergens like thiurams, IPPD and epoxy resin or cobalt (very often associated with dichromate CA) is less frequent, prevention should address these allergens, too. The use of protective gloves with minimal intrinsic CA risk, e.g. due to thiurams in (synthetic) rubber or chromate in leather gloves, should be promoted.

Adult↗
PubMed2004

Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin.

Mutations of mitochondrial (mt) DNA such as the 4977 base-pair large-scale deletion, also called common deletion, are increased in photoaged skin. Direct evidence for their induction by chronic exposure to ultraviolet (UV) radiation in vivo in human skin has remained elusive however. Furthermore, their fate after induction is unclear. Previously unirradiated skin of 52 normal human individuals was repetitively exposed to physiological doses of UVA light. Skin and blood specimens were investigated for the presence of mtDNA mutations employing semiquantitative nested PCR, as well as real-time PCR, after 2 weeks of UV exposure and the content of the common deletion was followed up for up to 16 mo after cessation of irradiation. As assessed by both methods, repetitive UV exposure led to an approximately 40% increase in the levels of the common deletion in normal human skin. The majority of deletions were detectable in the dermis also showing the biggest increase, whereas in the epidermis only residual levels and no increase were found. Nine individuals were examined up to 16 mo after cessation of UV exposure and some showed accumulation up to 32-fold. Thus, mtDNA mutations are induced in the human skin by repetitive UV exposure. In addition, these mutations seem to represent long-term in-vivo biomarkers for actinic damage in the human skin.

Adolescent↗
PubMed2004

Guidelines for the descriptive presentation and statistical analysis of contact allergy data.

The present guidelines aim to support clinical researchers in adequately presenting data on contact allergy, and to use statistical tests appropriate for their data. A description of the mode of selection of patients, and of their relevant demographic details, is an essential prerequisite for the correct interpretation of study results. Proportions and rates, if regarded as estimate of these parameters of a target populations, should normally be supplemented with confidence intervals to address precision. Concordance, i.e., agreement between two ratings in a dependent sample, must be quantified with a chance-corrected measure such as Cohen's kappa coefficient. If the diagnostic quality of an outcome is being assessed, standard measures like sensitivity and specificity, as well as the prevalence-dependent positive and negative predictive values should be calculated. Often, contact allergy to a certain substance depends on several factors. In this situation, depending on the research question, techniques like stratification, standardization or multifactorial analysis should be employed. With increasing complexity of statistical description and analysis, consulting with a biostatistician is often mandatory.

Confounding Factors, Epidemiologic↗
PubMed2004

Lung function among workers in the soft tissue paper-producing industry.

OBJECTIVES: To describe lung function in correlation with information on exposure to dust and fibers in soft tissue paper-producing factories in Germany. METHODS: Ambient monitoring was performed for inhalable, respirable dust and fibers in nine soft tissue paper-producing factories. In a study group of 1,047 workers (189 control subjects, 240 workers with moderate exposure, and 618 workers with high exposure), spirometry (FVC, FEV(1)) was performed. Information on occupational history, duration of exposure, workshop within the company, former occupational exposures, and smoking habits were collected. By employing multiple linear regression modeling, the potentially confounding effects of age, sex, body mass index, smoking habits, and factory were incorporated into the analysis of FVC, FEV(1), and FEV(1) in percent of FVC (FEV(1)%FVC). By employing a logistic regression model, odds ratios were calculated for FVC < 80% predicted in different exposure subgroups. RESULTS: The mean concentrations for inhalable, respirable, and fibrous dusts were 12.4 mg/m(3), 0.28 mg/m(3), and 420,000 fibers per cubic meter. With relation to cumulative dust and fiber exposure, a decrease of FVC from 105.4% predicted to 96.9% predicted (dust) and 97.1% predicted (fibers) in the subgroup with highest cumulative exposure was observed. For FEV(1), a decrease from 107.3% predicted to 103.0% predicted (dust) and 102.8% predicted (fibers) was found. The parameter estimates show dose-response relationships that are more pronounced for FVC compared to FEV(1). FEV(1)%FVC did not change significantly with increasing cumulative exposure, indicating a restrictive pattern of the findings. CONCLUSIONS: Due to high ambient dust concentrations and the observed adverse effects on lung function, a reduction of dust exposure and secondary preventive measures is advised.

Adult↗
PubMed2003

Predicting mortality in patients with rheumatoid arthritis.

OBJECTIVE: A number of different variables have been proposed as risk factors for mortality in patients with rheumatoid arthritis (RA), but limited prospective information on the magnitude of their effects is available. This study was undertaken to evaluate the relative predictive strength and usefulness of a wide range of variables on the risk of mortality in a large, long-term, prospectively studied cohort of patients with RA. METHODS: Over a 20-year period of followup beginning in 1981, 1387 consecutive RA patients were seen in a single clinic. A wide range of clinical and demographic assessments were recorded and entered into a computer database at the time of each clinical assessment. Assessment of predictive strength included determination of standardized and fourth-versus-first-quartile odds ratios (ORs), goodness-of-fit measures, and contributing fraction. RESULTS: The Health Assessment Questionnaire (HAQ) disability index was the strongest clinical predictor of mortality. A 1-SD change in the HAQ resulted in a much larger increase in the odds ratio for mortality compared with a 1-SD change in global disease severity, the next most powerful predictor of mortality (OR 2.31 versus 1.83). Considering the contributing fraction, mortality would be reduced by 50% for the HAQ and by 33% for global disease severity if patients in the fourth quartile for these variables could be switched to the first quartile. Global disease severity, pain, depression, anxiety, and laboratory and radiographic features were significantly weaker predictors. Disease duration, nodules, and tender joint count were clinical variables that provided very little predictive information. In multivariable analyses, HAQ and other patient self-report measures were significantly better predictors than were radiographic and laboratory variables. A single baseline observation provided the least information, with substantially increasing predictive ability associated with 1-year, 2-year, and all-time point followup observations (time-varying covariates). CONCLUSION: In this large 20-year study from routine clinical practice, the HAQ was the most powerful predictor of mortality, followed by other patient self-report variables. Laboratory, radiographic, and physical examination data were substantially weaker in predicting mortality. We recommend that clinicians collect patient self-report data, since they produce more useful clinical outcome information than other available clinical measures.

Actuarial Analysis↗
PubMed2003

The association between ambient air conditions (temperature and absolute humidity), irritant sodium lauryl sulfate patch test reactions and patch test reactivity to standard allergens.

To support the decision as to whether erythematous patch test reactions to allergens are irritant or allergic, sodium lauryl sulfate (SLS, 0.5% in water) has been added to the standard patch tests since July 1996 in the Dortmund Department of Dermatology. Data on 1600 patients patch tested up until June 2001, as well as standardized data on ambient temperature and humidity obtained by the German Meteorological Service, were included in a logistic regression analysis taking age, sex and atopy as potential confounders into account. The pattern of association was heterogeneous: while doubtful reactions to nickel sulfate were significantly associated with dry/cold weather conditions, but not with SLS reactivity, the opposite was observed for lanolin alcohol, benzocaine and Myroxylon pereirae resin (balsam of Peru). Doubtful reactions to other allergens, namely formaldehyde, fragrance mix or p-phenylenediamine, were associated with both factors. For several other allergens of the standard series, no distinct, significant pattern could be discerned. In conclusion, meteorological conditions and SLS reactivity independently contribute information on individual irritability at the time of patch testing, and both should be considered.

Allergens↗
PubMed2002

Patch tests with thiurams at 0.25% pet. and 1% pet. are of equal diagnostic value.

Thiuram mix is tested in the standard series at a test concentration of 1% pet. The single thiurams (DPTD, TMTD, TMTM, TETD), however, are usually tested at 0.25% pet. in Germany. In other countries, the individual components of thiuram mix are tested at 1% pet. The German Contact Dermatitis Research Group (DKG) compared both patch test concentrations in 530 patients in order to find out if (i) a significant number of positive patch tests are missed by testing at the lower concentration, (ii) problems with irritant test reactions occur by increasing the test concentration to 1%, and (iii) the sensitivity of the thiuram mix rises when the breakdown test is done with the higher concentration. Slightly more positive reactions were seen with the higher concentration, but this increase did not reach statistical significance. The reaction index, as a measure for the relation of positive to irritant and/or questionable reactions, remained unchanged for the individual thiurams. The sensitivity of the mix also did not change when the breakdown test was performed with 1% pet. instead of 0.25% pet. Thus, we conclude that both concentrations are of equal diagnostic value in patch testing.

Dermatitis, Allergic Contact↗
PubMed2002

Sunscreen use and melanoma: a case of evidence-based prevention?

BACKGROUND: A preventive effect of sunscreens on melanoma development is still subject of intense discussion. The practical consequences for changes in public health campaigns are neglected in this debate. METHODS: An extensive literature search for studies on the association between sunscreen use and melanoma occurrence was performed. The principles of evidence-based medicine (EBM) are applied to the issue to derive at recommendations for an evidence-based prevention of melanoma. RESULTS: We identified 17 case-control studies providing risk estimates for the relationship under study. These risk estimates are too heterogeneous to allow a reasonable conclusion by summarizing the evidence. The application of the EBM approach yields therefore an inconclusive result: the melanoma protective potential of sunscreens cannot be proven using the existing evidence. The information necessary to fully assess the effect of sunscreen use on melanoma development is not currently available. CONCLUSION: Based on the current evidence the focus of recommendations for melanoma prevention in public awareness campaigns has to be changed. It should be much more emphasized to minimize exposure to ultraviolet (UV) radiation during peak hours, wear protective clothing, hats and UV-opaque sunglasses, seek shade and protect infants and children against too much UV radiation exposure at all than to use sunscreens.

Evidence-Based Medicine↗
PubMed2002

Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: results of the FEBIM study.

Various forms of immunotherapy utilizing bacille Calmette-Guérin vaccine or vaccinia vaccine have been evaluated in clinical trials on melanoma patients. The effect of the "natural" application of these vaccinations, administered to provide protection against tuberculosis and smallpox, has, however, never been studied in epidemiologic investigations on risk factors for melanoma. In a case-control study comprising 11 institutions in seven countries we recruited 603 incident melanoma cases and 627 population controls frequency matched to the cases with respect to sex, age, and ethnic origin within each center to assess this relationship to obtain insights into the prevention of melanoma. Exposure information, incorporating also detailed ascertainment of potential confounding variables, was obtained in standardized personal interviews at the study subject's home. We found an inverse association between melanoma risk and previous bacille Calmette-Guérin vaccine/vaccinia vaccination depicted by an adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those vaccinated against tuberculosis and smallpox compared with subjects without a positive history of either vaccination. A variety of subgroup analyses showing a consistent pattern of results make it unlikely that the observed inverse association is a spurious finding. We conclude that bacille Calmette-Guérin vaccination and vaccinia vaccination may lower melanoma risk. Current immunologic theory of melanoma development provides a sound basis for understanding the biologic plausibility of the findings that have to be confirmed in future studies.

BCG Vaccine↗