[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.

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.

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.

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.

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.

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.

An exact test for meta-analysis with binary endpoints.

OBJECTIVES: We reintroduce an exact Mantel-Haenszel (MH) procedure for meta-analysis with binary endpoints which is expected to work especially well in sparse data, e.g., in meta-analyses of safety or adverse events. METHODS: The performance of the exact MH procedure in terms of empirical size and power is compared to the asymptotic MH and to the two standard procedures (fixed effects and random effects model) in a simulation study. We illustrate the methods with a meta-analysis of postoperative stroke occurrence after off-pump or on-pump surgery in coronary artery bypass grafting. RESULTS: We find that in almost all situations the asymptotic MH procedure outperforms its competitors; especially the standard methods yield poor results in terms of power and size. CONCLUSIONS: There is no need to use the reintroduced exact MH procedure; the asymptotic MH procedure will be sufficient in most practical situations. The standard methods (fixed effects and random effects model) should not be used in the sparse data situation.

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro.

OBJECTIVE AND DESIGN: Cardiopulmonary bypass (CPB) impairs monocyte and neutrophil proliferation, cytokine synthesis, and antigen presentation. This study compares in vivo data with results from an extracorporeal circulation (ECC) model, distinguishing direct effects on cytokine synthesis from regulatory mechanisms. PATIENTS AND METHODS: Whole blood from 18 patients prior to, during and after CPB was stimulated with lipopolysaccharide (LPS). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 levels were measured. Additionally, blood from 4 volunteers was circulated in an ECC model. Cytokine levels were measured before and during mock ECC. RESULTS: LPS-induced cytokine synthesis was reduced after CPB (TNF-alpha: 11 %; IL-6: 29 %; IL-8: 48 % of preoperative values, all p < 0.001). In mock ECC, cytokine production (except IL-8) was suppressed: TNF-alpha production was lowest 60 min after starting ECC, IL-6 synthesis was lowest at 90 min (33 % and 15 % vs. pre-ECC levels; both p < 0.001). Patient sera contained cytokine-inhibitory activity after CPB, an activity not found in mock ECC. CONCLUSIONS: (1) In patients, CPB induces early transient LPS hyporesponsiveness; (2) blood contact with foreign surfaces induces LPS hyporesponsiveness; (3) serum cytokine-inhibitory activities are released after CPB, but not in mock ECC. Impaired leukocyte function may explain increased susceptibility to infections after CPB.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores decreased monocyte HLA-DR expression after cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) is associated with a disturbed immune response, e.g., impaired HLA-DR expression on monocytes and the release of pro- and anti-inflammatory cytokines. Cytokine release plays a role in the pathogenesis of postoperative systemic inflammatory response syndrome (SIRS) and immune system deterioration, e.g., impaired monocyte and polymorphonuclear neutrophil (PMN) function, factors that ultimately lead to an increased susceptibility to infections. To gain a further understanding, we investigated HLA-DR expression on monocytes and on B- and T-lymphocytes. In addition, we investigated the IN VITRO effect of the immunostimulating hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) on HLA-DR expression of these cell types. Neither HLA-DR expression on B- and T-lymphocytes nor the effects of GM-CSF in cardiac surgical patients have been studied before. METHODS: In 16 patients undergoing elective cardiac surgery with CPB, counts of circulating leukocyte subsets as well as HLA-DR expression on monocytes, B- and T-lymphocytes were measured by flow cytometry before, immediately after CPB, and on the 2nd and 10th postoperative days. Treatment with GM-CSF was performed IN VITRO in whole blood cultures with 100 ng/ml recombinant human GM-CSF for 20 h. RESULTS: Monocyte HLA-DR expression was attenuated immediately after CPB (125 +/- 4 mean channel fluorescence [MCF] vs. 143 +/- 2 MCF preoperatively, mean +/- SEM, P < 0.001). HLA-DR expression further decreased on the 2nd day after CPB and did not normalize until the 10th day after the operation. In contrast, HLA-DR expression on T-cells was unchanged, whereas HLA-DR expression on B-cells did not decrease before the 2nd day after CPB (152 +/- 3 MCF vs. 170 +/- 2 MCF preoperatively, P < 0.001). IN VITRO GM-CSF treatment increased HLA-DR expression on monocytes prepared after CPB to a degree comparable to preoperative values. HLA-DR expression on B-lymphocytes could not be restored by GM-CSF. CONCLUSIONS: Immune system suppression after cardiac surgery is reflected in prolonged diminished HLA-DR expression on monocytes and B-lymphocytes. Suppression is not irreversible but can - at least IN VITRO - be overridden by the immunostimulating compound GM-CSF.

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

[Determinants of hospital admission--investigation by case vignettes]. / Determinanten der Krankenhausaufnahme--eine Untersuchung mit Fallvignetten.

Unexplained differences in the density of in-patient management in one federal state in Germany led to a regional survey of physicians in independent and hospital practice, which aimed to describe more precisely the determinants of referral and admission behaviour. Brief typical case descriptions (vignettes) were designed, as an instrument of data collection, dealing with two examples of management problems: upper and lower abdominal pain. The urgency of inpatient treatment was ranked using clinical scores and guidelines. Social characteristics for the patient (age, gender, social situation, preference for/against hospitalisation, day of the week on which the patient presented) were randomly assigned to the case vignettes. Each physician was asked by mail to decide on the management of 10 upper and 10 lower abdominal vignettes each. The physicians were also asked to provide additional information on the characteristics of their practice or hospital. The data were analysed using multivariate hierarchical models. A 28 % response rate meant that vignettes were available from 455 general practitioners and internal medicine specialists in independent practice, as well as 261 hospital surgeons and internal medicine specialists, together with responses from 31 physicians from the medical service of the German statutory health insurance (MDK). 7376 upper abdominal and 7335 lower abdominal vignettes were analysed. Admission rates reflected the graded severity of the symptoms built into the vignettes. Hospital physicians wanted to admit the vignette patients much more frequently than physicians in independent practice wished to refer them. Older patients, independent of symptoms, were more frequently referred or admitted than younger patients. In the case of acute symptoms it is the day of the week when the patient consulted the physician and in the case of elective surgery the patient's preference that are important for hospitalisation. The results show that medical decisions on case management are made using reasonable problem-specific preferences. The probability of actually instigating admission was, other things being equal, much higher in hospital physicians than in office-based physicians. As an instrument of comparative research into medical care, case vignettes have practical advantages in relation to medical audits and standardised patients. They can also be used for teaching, examining, documenting and quality assurance purposes.

[New dermatologist's procedure. Research plans for improving secondary prevention of occupational dermatoses]. / Das neue Hautarztverfahren. Forschungsvorhaben zur Verbesserung der Sekundärprävention von Berufsdermatosen.

The dermatologist's procedure was introduced in 1972 by employers' liability insurance funds in the industrial, agricultural, and public sectors of Germany's statutory occupational accident insurance as a "procedure for early detection of occupational skin diseases." So far, it is still the most relevant tool for secondary prevention in occupational dermatology in Germany. According to the intention of this procedure, insured persons with a skin disease in which an occupational etiology is suspected must be offered preventive measures and, if necessary, given appropriate treatment to avoid job-loss. To improve the efficiency of the "classic" dermatologist's procedure, in 1999, on the initiative of the Central Federation of Industrial Professional Associations, a study group was founded in cooperation with the Task Force on Occupational and Environmental Dermatology of the German Dermatological Society and the Professional Organisation of German Dermatologists. In October 2002, a controlled intervention study started in North-western Germany to scientifically evaluate the "optimised" dermatologist's procedure, which was proposed by the study group and compare it to the standard ("classic") procedure. The study results should allow detailed suggestions for an improved dermatologist's procedure before it is introduced nationwide.

Early secondary prevention of occupational skin disease in Germany: the dermatologist's procedure in perspective.

The dermatologist's procedure was introduced in 1972 as a "procedure of early detection of occupational skin disease" by industrial, agricultural and public-sector employers' liability insurance funds of Germany's statutory occupational accident insurance. To date, it represents the most relevant tool for secondary prevention in industrial dermatology in Germany. According to the intention of this procedure, insured parties who are likely to have an occupational skin disease have to be offered preventive measures and, if necessary, given appropriate treatment to avoid job-loss. In co-operation with the Central Federation of the Industrial Professional Associations, the Task Force on Occupational and Environmental Dermatology of the German Dermatological Society, and the Professional Organisation of German Dermatologists, a study group was constituted in 1999 to improve the traditional dermatologist's procedure. In October 2002 a controlled intervention study was started in North-western Germany to establish the definitive value of the "optimised" dermatologist's procedure. Past, present, and future of this specific procedure are discussed.

Tumor necrosis factor-alpha production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities.

OBJECTIVES: Cardiopulmonary bypass is associated with the release of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta(1)). On the one hand this cytokine release is related to the postoperative systemic inflammatory response syndrome, and on the other hand it is related to deterioration of the immune system, for example in monocyte or polymorphonuclear neutrophil function, leading to an increased susceptibility to infections. To gain further insight into the alterations of immune cell reactivity and possible regulatory mechanisms, we studied lipopolysaccharide-induced tumor necrosis factor alpha synthesis in whole blood from cardiac surgical patients. METHODS: Fifteen patients undergoing elective heart surgery with cardiopulmonary bypass were included in the study. Ex vivo lipopolysaccharide-induced tumor necrosis factor alpha synthesis was measured in a whole blood assay before, during, and after bypass. Corresponding tumor necrosis factor alpha messenger RNA levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction. In addition, the influence of patient serum on whole blood responsiveness and its relationship to anti-inflammatory cytokines were evaluated in vitro. RESULTS: Tumor necrosis factor alpha synthesis was significantly reduced after 30 minutes of cardiopulmonary bypass and showed the lowest values at the end of bypass (mean +/- SD 0.109 +/- 0.105 ng/10(6) white blood cells after 30 minutes of bypass and 0.050 +/- 0.065 ng/10(6) white blood cells at the end of bypass, vs 0.450 +/- 0.159 ng/10(6) white blood cells preoperatively, P <.001). As a further indication of reduced cytokine biosynthesis, diminished messenger RNA levels for tumor necrosis factor alpha were detected. Serum withdrawn from patients at the end of cardiopulmonary bypass reduced tumor necrosis factor alpha synthesis in heterologous blood from healthy volunteers highly significantly to 39.93% +/- 23.18% relative to control serum (P =.005) and preoperatively drawn serum (P =.024). This effect was dose dependent and was not specific for lipopolysaccharide-induced tumor necrosis factor alpha synthesis. Anesthesia and heparin administration did not influence tumor necrosis factor alpha production significantly. Ex vivo tumor necrosis factor alpha synthesis was negatively related to interleukin 10 serum levels, positively but weakly related to interleukin 4, and was not related to transforming growth factor beta(1) (Spearman correlation coefficients -0.565, P <.001, 0.362, P <.001, and -0.062, P =.460, respectively). However, interleukin 10 levels in patient serum after cardiopulmonary bypass were 300-fold below the quantities needed for half-maximal inhibition of tumor necrosis factor alpha synthesis in vitro. Moreover, the inhibitory activity could not be removed by immune absorption of interleukin 10. CONCLUSIONS: These results suggest that during cardiac operations cytokine-inhibitory serum activities are released or newly formed. These activities could not be explained by the actions of interleukins 4 and 10 or transforming growth factor beta(1). Although their exact nature remains undetermined, these substances may contribute to the diminished immune cell functions after cardiopulmonary bypass and thus need further characterization.

Occupational relevance of positive standard patch-test results in employed persons with an initial report of an occupational skin disease.

OBJECTIVES: It is commonly accepted that the standard screening tray is an essential diagnostic test in patch testing supporting the diagnosis of contact dermatitis, the most common type of occupational skin disease (OSD). In this study standard patch-test results of employed persons with an initial report of an OSD were analyzed within 24 occupational groups. METHODS: An evaluation was made of employed persons recorded in the Register of Occupational Skin Diseases in Northern Bavaria (Berufskrankheitenregister Haut-Nordbayern; BKH-N) between 1990 and 1999, catering for those standard screening tray allergens tested over the 10-year period. RESULTS: Nickel sulfate was the most common sensitizer (29.5%), showing occupational relevance in only 11% of the cases sensitized. Other common sensitizers were cobalt chloride (13.5%), p-phenylenediamine free base (10.7%), potassium dichromate (9.8%), fragrance mix (5.4%), thiuram mix (4.2%), balsam of Peru (4.0%), chloromethylisothiazolinone/methylisothiazolinone (4.0%), and formaldehyde (4.0%). The most occupationally relevant sensitizers were thiuram mix (71%), epoxy resin (67%), p-phenylenediamine free base (59%), p-phenylenediamine-black-rubber mix/ N-isopropyl- N'-phenyl- p-phenylenediamine (53%), potassium dichromate (48%), formaldehyde (38%), chloromethylisothiazolinone/methylisothiazolinone (37%), and mercapto-mix/mercaptobenzothiazole (35%). Occupational groups at risk of acquiring delayed-type sensitization were, in particular, electroplaters, tile setters and terrazzo workers, construction and cement workers, solderers, wood processors, and leather and fur processors. CONCLUSIONS: The standard series contributes valuable information and asserts its position in clarifying the causes of OSDs. Based on the study results, the rate of occupationally relevant sensitization to each single allergen is demonstrated, and the difficulties in verifying the occupational relevance are discussed.

Occupational skin diseases in Northern Bavaria between 1990 and 1999: a population-based study.

BACKGROUND: Occupational skin diseases (OSDs) account for a large portion of occupational diseases in Europe, but population-based epidemiological studies are missing. OBJECTIVES: We analysed the initial reports of OSDs in our register of OSDs in Northern Bavaria (BKH-N). METHODS: A total of 5285 cases were assessed prospectively and registered from 1990 to 1999. As the German Federal Employment Office provides specific occupational data in relation to the total employed population of Northern Bavaria, it was possible to conduct a population-based study that investigated the trend in incidence rates between two study periods (1990-92 and 1993-99) in 24 different occupational groups. RESULTS: A total of 3097 cases of OSD (median age 25 years) were recorded in the 24 occupational groups. There was a significant decline (P < 0.001) in the overall incidence rate of OSD with 10.7 cases per 10,000 workers per year for the first study period and 4.9 cases per 10,000 workers per year for the second study period. This general trend in incidence rates was also significant for hairdressers and barbers, bakers, health-care workers, cooks and metal processors. CONCLUSIONS: The BKH-N provides national data based on the notification of OSDs in Germany. The results demonstrate the rank of occupations hazardous for the skin and are helpful for defining target groups for prevention.