Associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes: analysis at the municipality level in North Rhine-Westphalia, Germany.

AIM: To analyse the associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes in the German federal state of North Rhine-Westphalia. METHODS: Data of incident type 1 diabetes cases in children and adolescents aged <20 years between 2007 and 2014 were extracted from a population-based diabetes register. Population data, indicators of area deprivation and urban/rural traits at the municipality level (396 entities) were obtained from official statistics. Area deprivation was assessed in five groups based on quintiles of an index of multiple deprivation and its seven deprivation domains. Poisson regression accounting for spatial dependence was applied to investigate associations of area deprivation and urban/rural traits with type 1 diabetes incidence. RESULTS: Between 2007 and 2014, 6143 incident cases were reported (99% completeness); the crude incidence was 22.3 cases per 100 000 person-years. The incidence decreased with increasing employment and environmental deprivation (relative risk of the most vs. the least deprived municipalities: 0.905 [95% CI: 0.813, 1.007] and 0.839 [0.752, 0.937], respectively) but was not associated with the composite deprivation index. The incidence was higher in more peripheral, rural, smaller and less densely populated municipalities, and the strongest association was estimated for the location trait (relative risk of peripheral/very peripheral compared with very central location: 1.231 [1.044, 1.452]). CONCLUSIONS: The results suggest that the type 1 diabetes risk is higher in more remote, more rural, less densely populated and less deprived areas. Urban/rural traits were stronger predictors of type 1 diabetes risk than area deprivation indicators.

Age at diagnosis of Type 2 diabetes in Germany: a nationwide analysis based on claims data from 69 million people.

AIM: For many European countries, including Germany, no valid estimates are available on age at diagnosis of Type 2 diabetes. Thus, we aimed to estimate the age at diagnosis in Germany. METHODS: Age at diagnosis of Type 2 diabetes in Germany was estimated based on Type 2 diabetes prevalence and incidence and the age distribution of the German population. Age- and sex-specific incidence and prevalence in 2014/2015, based on claims data from statutory health insurance (n= 69 000 000, ~85% of the German population), and the age pyramid for Germany in 2015 were used for the calculation. Age at Type 2 diabetes diagnosis was stratified by sex. CIs were estimated using bootstrap methods. In addition, the age range in which 50% of the population received a diagnosis of Type 2 diabetes was calculated (the interquartile range). RESULTS: The mean ± sd age at Type 2 diabetes diagnosis in 2015 was 61.0 ± 13.4 years (95% CI 60.9-61.0) in men. Women were diagnosed ~2 years later than men (mean age 63.4 ± 14.9 years; 95% CI 63.4-63.5). The age range in which 50% of the population was diagnosed with diabetes was 53-72 years for men and 54-76 years for women. CONCLUSIONS: The sex differences are mainly attributable to a higher incidence of Type 2 diabetes in men than women during middle age and the higher absolute number of women in the older ages. The early age at diabetes diagnosis compared to average life expectancy means that the risk of diabetes-related complications is increased.

Distinct trajectories of HbA1c in newly diagnosed Type 2 diabetes from the DPV registry using a longitudinal group-based modelling approach.

AIM: To identify groups of heterogeneous HbA1c trajectories over time in newly diagnosed Type 2 diabetes. METHODS: The study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/m2 ) from the Diabetes Patienten Verlaufsdokumentation (DPV) prospective multicentre diabetes registry (Germany, Austria). Individuals were assessed during the first 5 years after diabetes diagnosis if they had ≥ 3 aggregated HbA1c measurements during follow-up. Latent class growth modelling was used to determine distinct subgroups that followed similar longitudinal HbA1c patterns (SAS: Proc Traj). Multinomial logistic regression models were used to investigate which variables were associated with the respective HbA1c trajectory groups. RESULTS: Four distinct longitudinal HbA1c trajectory (glycaemic control) groups were found. The largest group (56% of participants) maintained stable good glycaemic control (HbA1c 42-45 mmol/mol). Twenty-six percent maintained stable moderate glycaemic control (HbA1c 57-62 mmol/mol). A third group (12%) initially showed severe hyperglycaemia (HbA1c 97 mmol/mol) but reached good glycaemic control within 1 year. The smallest group (6%) showed stable poor glycaemic control (HbA1c 79-88 mmol/mol). Younger age at diabetes diagnosis, male sex, and higher BMI were associated with the stable moderate or poor glycaemic control groups. Insulin therapy was strongly associated with the highly improved glycaemic control group. CONCLUSIONS: Four subgroups with distinct HbA1c trajectories were determined in newly diagnosed Type 2 diabetes using a group-based modelling approach. Approximately one-third of people with newly diagnosed Type 2 diabetes need either better medication adherence or earlier intensification of glucose-lowering therapy.

[Impact of national cardiac, cardiac surgery, and intensive care conferences on cardiovascular mortality in Germany]. / Einfluss der nationalen kardiologischen, herzchirurgischen und intensivmedizinischen Konferenzen auf die kardiovaskuläre Mortalität in Deutschland.

BACKGROUND: Thousands of physicians and other employees of the health system participate in major national congresses of German cardiologists, cardiac surgeons, and intensive care physicians and are, thus, key players in the treatment of acute cardiovascular events. While differences in mortality during such congress days were described in the USA, Germany-wide data are missing. METHODS: In order to study the effect of congresses on cardiovascular mortality, the numbers of daily cardiovascular deaths (ICD-10 codes: I01-I15, I20-I25, I30-I52) in Germany from 1997-2011 from the data of the Federal Statistical Office were used for the most important cardiac, intensive medical, and cardiac surgery congresses (DGAI, DGIIN, DGK, DGTHG, DIVI). For comparison, numbers of cardiovascular deaths at a defined time interval before and after the respective Congress were defined. RESULTS: Over the 15-year study period, a total of 701,272 cardiovascular deaths (conference days: 233,456, nonconference days: 467,816) were observed during 89 conferences with 318 congress days and 638 control days. The relative risks of increased mortality on congresses were inconspicuous for the entire population (relative risk [RR] 0.998, confidence interval [CI] 0.994; 1.004), even after adjustment for gender, age group, professional, and ICD codes (RR 1.005, CI 0.951; 1.063). CONCLUSION: National congresses of cardiologists, intensive care physicians and cardiac surgeons have no influence on the cardiovascular mortality in Germany.

Utility of HbA1c and fasting plasma glucose for screening of Type 2 diabetes: a meta-analysis of full ROC curves.

AIMS: There is still debate on the optimal threshold for population-based screening of diabetes (diagnosed by the oral glucose tolerance test) using tests like HbA1c or fasting plasma glucose. Meta-analyses provide meaningful input in such situations. The aim of this article is to perform a meta-analysis that includes the complete information reported in the individual studies of two existing systematic reviews. METHODS: We screened the individual studies from two systematic reviews and reconstructed the full four-fold tables for every reported threshold. Using a recently proposed meta-analysis model for the comparison of two diagnostic tests, we compared HbA1c with fasting plasma glucose, and estimated meta-analytic receiver operating characteristic curves for both tests using the 11.1 mmol/l threshold of the 2-h post-challenge glucose level (2 h-PG) as the gold standard. RESULTS: We included nine studies from two existing systematic reviews in our analysis. Based on our data set, the optimal threshold lies between 42 and 44 mmol/mol (6.0-6.2%) for HbA1c , and 6.2-6.4 mmol/l for fasting plasma glucose choosing the Youden index as the technical criterion. In addition, we found that there is no relevant difference in the performance of HbA1c and fasting plasma glucose. CONCLUSIONS: In our meta-analysis, we found that the optimal threshold with reference to the 2 h-PG should be chosen between 42 and 44 mmol/mol (6.0-6.2%) for HbA1c , and 6.2-6.4 mmol/l for fasting plasma glucose on the basis of maximal sensitivity and specificity.

Healthcare costs of Type 2 diabetes in Germany.

AIM: To describe for the first time the direct costs of Type 2 diabetes treatment by analysing nationwide routine data from statutory health insurance in Germany. METHODS: This cost-of-illness-study was based on a 6.8% random sample of all German people with statutory health insurance (4.3 out of 70 million people). The healthcare expenses show direct per capita costs from the payer perspective. Healthcare expenses for physicians, dentists, pharmacies, hospitals, sick benefits and other healthcare costs were considered. Per capita costs, cost ratios for people with Type 2 diabetes and without diabetes as well as diabetes-attributable costs were calculated. RESULTS: Per capita costs for people with Type 2 diabetes amounted to €4,957 in 2009 and €5,146 in 2010. People with Type 2 diabetes had 1.7-fold higher health expenses than people without diabetes. The largest differences in health expenses were found for prescribed medication from pharmacies (cost ratio diabetes/no diabetes: 2.2) and inpatient treatment (1.8). Ten percent of the total statutory health insurance expense, in total €16.1 billion, was attributable to the medical care of people with Type 2 diabetes. CONCLUSIONS: This nationwide study indicates that one in 10 Euros of healthcare expenses is spent on people with Type 2 diabetes in Germany. In the future, national statutory health insurance data can be used to quantify time trends of costs in the healthcare system.

Interdisciplinary care programme to improve self-management for cancer patients undergoing stem cell transplantation: a prospective non-randomised intervention study.

The purpose of this single-centre prospective non-randomised study was to evaluate the effectiveness of an interdisciplinary care programme to enhance self-management in patients with haematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT, aged >14 years with informed consent were recruited (n = 79). Patients in the intervention group (IG) received standard care plus the SCION-HSCT intervention to counteract three problems after HSCT: muscle weakness, oral mucositis and malnutrition. Control group patients received standard care. Primary endpoint was global health-related quality of life (HRQoL) at discharge (EORTC QLQ C30 v. 3.0). Baseline characteristics were balanced between both groups, except physical performance (ECOG) being significantly lower for patients of the IG. At discharge, no group differences could be seen regarding HRQoL. Non-confirmatory post hoc analyses showed for patients of the IG a shorter duration of hospitalisation (MD -10.90; 95% CI -18.05 to -3.75) and increased activity during hospitalisation (MD 2.44; 95% CI 1.27-3.61). In conclusion, clinical effectiveness of the intervention could not be proven with respect to the aspired improvement of HRQoL. However, the nurse-led interdisciplinary caring programme could be carried out in every day ward routine. Further research should focus on working mechanisms of complex interventions aiming to improve HRQoL of patients undergoing HSCT.

Meta-analysis of diagnostic tests accounting for disease prevalence: a new model using trivariate copulas.

In real life and somewhat contrary to biostatistical textbook knowledge, sensitivity and specificity (and not only predictive values) of diagnostic tests can vary with the underlying prevalence of disease. In meta-analysis of diagnostic studies, accounting for this fact naturally leads to a trivariate expansion of the traditional bivariate logistic regression model with random study effects. In this paper, a new model is proposed using trivariate copulas and beta-binomial marginal distributions for sensitivity, specificity, and prevalence as an expansion of the bivariate model. Two different copulas are used, the trivariate Gaussian copula and a trivariate vine copula based on the bivariate Plackett copula. This model has a closed-form likelihood, so standard software (e.g., SAS PROC NLMIXED) can be used. The results of a simulation study have shown that the copula models perform at least as good but frequently better than the standard model. The methods are illustrated by two examples.

Statistical methods for meta-analyses including information from studies without any events-add nothing to nothing and succeed nevertheless.

Meta-analyses with rare events, especially those that include studies with no event in one ('single-zero') or even both ('double-zero') treatment arms, are still a statistical challenge. In the case of double-zero studies, researchers in general delete these studies or use continuity corrections to avoid them. A number of arguments against both options has been given, and statistical methods that use the information from double-zero studies without using continuity corrections have been proposed. In this paper, we collect them and compare them by simulation. This simulation study tries to mirror real-life situations as completely as possible by deriving true underlying parameters from empirical data on actually performed meta-analyses. It is shown that for each of the commonly encountered effect estimators valid statistical methods are available that use the information from double-zero studies without using continuity corrections. Interestingly, all of them are truly random effects models, and so also the current standard method for very sparse data as recommended from the Cochrane collaboration, the Yusuf-Peto odds ratio, can be improved on. For actual analysis, we recommend to use beta-binomial regression methods to arrive at summary estimates for the odds ratio, the relative risk, or the risk difference. Methods that ignore information from double-zero studies or use continuity corrections should no longer be used. We illustrate the situation with an example where the original analysis ignores 35 double-zero studies, and a superior analysis discovers a clinically relevant advantage of off-pump surgery in coronary artery bypass grafting.

Mortality on match days of the German national soccer team: a time series analysis from 1995 to 2009.

BACKGROUND: There is inconsistent evidence on population mortality, especially cardiovascular disease mortality, on match days of national soccer teams during particular international tournaments. This study examines the number of deaths in Germany on match days of the national soccer team during a long-term period including several tournaments. METHODS: We analysed all registered daily deaths in Germany from 1995 to 2009 (11 225 966 cases) using time series analysis methods. Following the Box/Jenkins approach, we applied a seasonal autoregressive integrated moving average model. To assess the effect of match days, we performed an intervention analysis by including a transfer function model representing match days of the national team in the statistical analyses. We conducted separate analyses for all matches and for matches during international tournaments (European and World Championships) only. Time series and results were stratified in terms of sex, age (<50 years, 50-70 years, >70 years) and cause of death (cardiovascular deaths, injuries, others). We performed a further independent analysis focusing only on the effect of match results (victory, loss, draw) and kind of tournament (international championships, qualifications, friendly matches). RESULTS: Most of the results did not indicate a distinct effect of matches of the national team on general mortality. Moreover, all null value deviations were small when compared with the average number of daily deaths (n=2270). CONCLUSIONS: There is no relevant increase or decrease in mortality on match days of the German national soccer team.

[Validity of a complex soccer-specific field test and a non-specific sprint test-assessments for test and match performance]. / Validierung eines komplexen fußballspezifischen und fußballunspezifischen Tests-Leistungsdiagnostik im Spannungsfeld von Test- und Wettkampfleistung.

BACKGROUND: Soccer assessments often lack specificity and complexity. Examinations of validity for soccer assessments, based on the relation between test and match performance, are available although they are scarce. A complex soccer-specific field test which is validated cannot be found in the literature at all. OBJECTIVE: The aim of this follow-up study was to assess the validity of a soccer-specific complexity test (FBKT) and a repeated non-specific sprint test (ST) based on three gold standards: match performance, coach ranking, and league affiliation. MATERIALS AND METHODS: A German fourth league soccer team (n = 14) was assessed using FBKT and ST in the pre-season for the second half of the 2010/2011 season. Afterwards, their performance in 17 matches was evaluated using video analysis in order to compare them with the test parameters (e. g., pass/assist ratio, goals, duelling behaviour). Eighteen months later, the league affiliation of all players was identified and the coach evaluated the tested players. RESULTS: With regard to match performance, playing time was proved to be the most suitable parameter for validating the test performance (FBKT, ST). The total and minimum times of ST were the most powerful parameters in relation to playing time and explained 50 % and 46 % of the variance, respectively. Concerning the FBKT, the parameters "sum of all linear sprints" (24 %) and "total time of all activity series with penalty time in round two" (22 %) explained the highest amount of variance. Coach ranking generated significant odds ratios for the minimum time of ST (OR = 6.5; CI: 3.2 - 5.2 × 1015; p = 0.037), and total time of speed dribbling of the FBKT (OR = 1.3; CI: 1.2 - 199.5; p = 0.036) based on a proportional-odds model. With regard to league affiliation, significant odds ratios occurred with the following parameters: minimum time of ST (OR = 15.8; CI: 2.16 - 115.4; p = 0.007); total time of ST (OR = 3.28; CI: 1.31 - 8.21; p = 0.011); and, total time of speed dribbling for the FBKT (OR = 1.3; CI: 1.01 - 1.61; p = 0.044). CONCLUSIONS: This study showed that the larger logical validity of soccer-specific complex tests does not necessarily translate to a larger construct validity, as compared to non-specific tests. However, their value is not limited to performance evaluation. The FBKT provides valuable information concerning training process control. It is possible that its low validity is caused by the poor performance of the players in soccer-specific consequences of actions (centres, goals) due to the restricted differentiation of players.

Validation of the German Diabetes Risk Score within a population-based representative cohort.

AIM: To validate the German Diabetes Risk Score within the population-based cohort of the Cardiovascular Disease - Living and Ageing in Halle (CARLA) study. METHODS: The sample included 582 women and 719 men, aged 45-83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow-up. Predicted probabilities and observed outcomes were compared using Hosmer-Lemeshow goodness-of-fit tests and receiver-operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses. RESULTS: We found 58 cases of incident diabetes. The median 4-year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer-Lemeshow test returned a poor correlation (chi-squared = 55.3; P = 5.8*10⁻¹²). The area under the receiver-operator characteristic curve (AUC) was 0.70 (95% CI 0.64-0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70-0.84). Consideration of glycaemic diagnostic variables, in addition to self-reported diabetes, reduced the AUC to 0.65 (95% CI 0.58-0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration (AUC 0.81; 95% CI 0.76-0.86) or HbA(1c) concentration (AUC 0.84; 95% CI 0.80-0.91) was found to peform better. CONCLUSIONS: Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes.

Treatments effects from randomized trials and propensity score analyses were similar in similar populations in an example from cardiac surgery.

OBJECTIVE: Analyses comparing randomized to nonrandomized clinical trials suffer from the fact that the study populations are usually different. We aimed for a comparison of randomized clinical trials (RCTs) and propensity score (PS) analyses in similar populations. STUDY DESIGN AND SETTING: In a systematic review, we "meta-matched" RCTs and PS analyses that compared the off- and the on-pump technique in coronary artery bypass grafting. "Meta-confounders" were summarized in a "meta-propensity score" and were used for "meta-matching." We compared treatment effects between RCTs and PS analyses for 10 previously defined binary clinical outcomes in this "meta-matched" population as differences in "meta-odds ratios." RESULTS: For all clinical outcomes, the estimated differences in "meta-odds ratios" were below an absolute value of 0.15, all confidence intervals included the null. CONCLUSIONS: In our example, treatment effects of off-pump versus on-pump surgery from RCTs and PS analyses were very similar in a "meta-matched" population of studies, indicating that only a small remaining bias is present in PS analyses.

Longevity of soccer players: an investigation of all German internationals from 1908 to 2006.

Leisure-time physical activity is associated with better health and a reduced risk of all-cause mortality. It is unclear if this association is also present with a high level of physical activity as it is found in professional athletes. In a population-based retrospective cohort study, we compared the survival experience of all soccer players participating for Germany in international matches between 1908 and 2006 to that of the general population. To summarize survival experience, we calculated cumulative relative survival ratios (RSRs) from a life table. We included data of 812 international players, of which 428 (=52.7%) died during follow-up. In all 13 intervals, cumulative observed survival was smaller than cumulative expected survival, resulting in cumulative RSRs being <1. The cumulative RSRs are statistically significantly different from 1 in all but the last interval. This impaired survival experience of the internationals translates into a loss of median residual lifetime of 1.9 years [95% confidence interval: 0.6, 3.2] years at the entry time into the cohort. This loss is mainly driven by the mortality of internationals from the earlier half of the observation period. Reasons for this might be poorer medical care in former times, internationals being killed in action during World War II, and a changing distribution of causes of death during the 20th century.

Association of CD69 up-regulation on CD4+ Cla+ T cells versus patch test, strip patch test and clinical history in nickel sensitization.

OBJECTIVE: The patch test (PT) with its modification - the strip patch test (SPT) - is the standard in vivo procedure to diagnose an allergic contact dermatitis (ACD). To date, none of the in vitro tests for the diagnosis of ACD fulfils the requirements of an easy, valid and reliable test. To investigate the prediction ability of a flow cytometric assay of CD69 up-regulation on CD4+ CLA+ T cells in nickel-sensitive and non-nickel-sensitive patients. METHODS: In a prospective, investigator-blinded, clinical study a total of 85 nickel-sensitive (n = 44; 51.8%) and non-nickel-sensitive patients (n = 41; 48.2%) were enrolled. The association between CD69 up-regulation on CD4+ CLA+ T cells on the one hand and PT, SPT, and clinical history on the other hand was measured. Association is expressed with c statistic values (receiver operating characteristic analysis) and corresponding 95% CIs. RESULTS: The associations were c = 0.57 (95% CI: 0.42-0.72) between CD69 up-regulation and PT, c = 0.49 (95% CI: 0.36-0.62) between CD69 up-regulation and SPT, and c = 0.51 (95% CI: 0.37-0.64) between CD69 up-regulation and clinical history. CONCLUSIONS: CD69 up-regulation on CD4+ CLA+ T cells in vitro could not predict neither a positive PT or SPT result nor a positive clinical history to nickel sulfate. The combination of clinical history and patch testing still remains the basis for diagnosing ACD.

Standardized tape stripping: a practical and reproducible protocol to uniformly reduce the stratum corneum.

The basic idea of the strip patch test (SPT), a modification of the conventional patch test (PT), is to increase the bioavailability of a test substance in the deeper epidermal cell layers by defined tape stripping of the test area on the back prior to a PT. In a prospective, investigator-blinded clinical study, we evaluated the variability and the interrater agreement of our proposed SPT protocol. The relative stratum corneum (SC) reduction after tape stripping was measured on 75 subjects for variability and in a subgroup of 18 subjects for interrater agreement, by performing in vivo confocal laser scanning microscopy. We found good reproducibility with an SC reduction of 31%, with 95% of the values lying between 22 and 40%, and good interrater agreement. As a result, our SPT protocol yields a clinically adequate standardization of the SC reduction and the SPT may therefore be recommended for performance in daily clinical routine.

Ignoring lack of association of heart rate variability with cardiovascular disease and risk factors: response to the manuscript "The relationship of autonomic imbalance, heart rate variability cardiovascular disease risk factors" by Julian F. Thayer, Shelby S. Yamamoto, Jos F. Brosschot.

A reduced heart rate variability (HRV) is a marker of autonomic dysfunction and has been shown to be associated with an increased risk of cardiovascular morbidity and mortality. However, especially regarding the association of HRV with cardiovascular risk factors the literature is rather inconsistent. We therefore critically discuss the review of Thayer et al. concerning the relationship between autonomic imbalance, heart rate variability and cardiovascular disease risk factors.

Dirt-binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three-step programme of occupational skin protection.

BACKGROUND: In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt-binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. OBJECTIVES: Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. METHODS: Three cleansing preparations - (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder - were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. RESULTS: After a 3-week treatment, a significant global treatment effect (P < 0.0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone. CONCLUSIONS: Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three-step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials.

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Strip patch test vs. conventional patch test: investigation of dose-dependent test sensitivities in nickel- and chromium-sensitive subjects.

BACKGROUND: Tape stripping the skin prior to patch testing (strip patch test, SPT) may enhance percutaneous penetration of test substances and increase skin reactivity to test substances. OBJECTIVE: To evaluate the test sensitivity of SPT in compliance with our recently presented practical method vs. conventional patch test (PT) in nickel- and dichromate-sensitive subjects. METHODS: Thirty subjects participated in the prospective, randomized, controlled, investigator-blind study. Serial dilution tests of nickel sulphate (10,000-50 ppm aq.) and potassium dichromate (1000-5 ppm aq.) were used. Tests were applied in duplicate to both sides of the upper back of the subject, where one, randomly chosen side was tape stripped. RESULTS: According to the estimated test sensitivities, SPT is more sensitive than PT in nickel- and dichromate-sensitive subjects, regardless of the interindividual different numbers of tape strips. The superiority of the SPT grows with diminishing concentrations of the allergens. CONCLUSION: Test sensitivity of SPT vs. PT is increased. If no positive results are obtained by PT, the SPT could help to detect hidden allergens in case of weak sensitization or low concentration and poor percutaneous penetration of the test substances.