Local cluster of germ cell cancer in a cohort of male automotive workers in Germany not explained by previous or concurrent activities and exposures in farming and forestry.

OBJECTIVE: To examine whether exposures or activities in farming, forestry and related occupations explain the excess incidence of germ cell cancer (GCC) observed among male employees in one of the six car-manufacturing plants that is located in a geographic area where farming is frequent. METHODS: A cohort based case-control study was conducted among workers in six car-manufacturing plants located in areas with different industrial structure. The study involved 188 cases of germ cell cancer identified through active retrieval in 38 hospitals and 1000 controls, drawn from administrative accounting files, individually matched by year of birth (± 2 years). Information regarding tasks and exposures and potential confounding variables were obtained by face-to-face or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using a conditional logistic regression model adjusted for cryptorchidism and other potential confounders. RESULTS: In this case-control study 5.3% of cases and 6.3% of controls ever worked in agriculture or livestock farming. No increased risks were observed for working in agriculture (OR=0.8 95% CI: 0.4-1.6), livestock farming (OR=0.8 95% CI: 0.4-1.6) or for exposure to pesticides (OR=0.7 95% CI: 0.3-1.7), for exposure to fertilizers (OR=0.8 95% CI: 0.4-1.8) and disinfectants (OR=1.0 95% CI: 0.3-2.8). There were no statistically significant increases in risk associated with ever exposure to salt based wood protection agents (OR=2.3 95% CI: 0.6-9.1), working with plywood (OR=1.4 95% CI: 0.6-3.2), coated wood (OR=1.4 95% CI: 0.5-3.9) or working in forestry (OR=1.7 95% CI: 0.5-6.4). Lagging of exposures did not alter the results. CONCLUSIONS: The observed excess incidence in the cohort of automotive workers can be hardly explained by previous or concurrent work in farming or forestry. Because of the small numbers of subjects ever employed in farming the statistical power in assessing associations between agricultural work and agricultural exposures was limited and does not allow final conclusions about the association of farming related exposures and GCC risk.

Occupational exposure to pesticides and bile tract carcinoma in men: results from a European multicenter case-control study.

OBJECTIVES: To estimate the associations between occupational exposure to pesticides and extrahepatic biliary tract carcinoma in men, a population-based case-control study was carried out. METHODS: Cases (n = 104), aged 35-70, diagnosed in 1995-1997, were sampled by active reporting systems from hospitals. Controls (n = 1,401) were a random sample of the general male population. Information on occupation and confounding factors was obtained by questionnaires. Exposures were quantified with respect to time, application methods, and use of personal protective equipment. Intensity was evaluated by using a published algorithm which weighted the exposure assigned according to the use of personal protective equipment and mode of application. Logistic regression analyses were conducted adjusted for gallstones, age, and country. RESULTS: Being ever exposed to pesticides resulted in an odds ratio (OR) of 1.0 [95%-confidence interval (CI) 0.6-1.6]. A modestly elevated risk was found for backpack mounted sprayers OR = 1.4 [95% CI 0.7-2.6] and vine farmers OR = 2.5 [95% CI 0.9-7.2]. Using time periods and exposure frequency as intensity measure, no elevated risks were found. The only exception was year of maximum exposure which yielded an OR of 1.6 [95% CI 0.7-3.5]. However, no clear trend was observed in this analysis. CONCLUSIONS: This study does not rule out that pesticide exposure represents an occupational risk factor for extrahepatic biliary tract carcinoma, but no indication of a strong association was observed. Some modes of exposure were weakly, albeit not significantly associated with carcinoma risk. The observed estimates of effects may be influenced by a lack of precise exposure assessment. Different chemical compositions of pesticides were utilized during a long time span of pesticide exposure, and it should be considered that the exposure is assessed with substantial uncertainty that could non-differential and bias results toward the null.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

[Hygiene provisions for the processing of food in nurseries and child care facilities. Approaching problems in practical experience]. / Hygienebestimmungen für Kinderkrippen und Kitas im Umgang mit Lebensmitteln. Probleme in der Praxis und Lösungsansätze.

In Germany more than 2 million children under the age of six attend child care institutions. Among the duties, these institutions have to provide meals to the children. Several food-borne viruses pose a particular threat to infants. In accordance with the new European Law on Food Hygiene nurseries and child care facilities are business premises as they process and dispense food. Law requires guarding all stages of food acquisition, storage, preparation and dispersal against health hazards. Furthermore, facilities are legally required to provide risk control and to ensure that food issued by their kitchen does not pose a health hazard upon consumption. Overall, child care facilities are given by far a more comprehensive responsibility under the new European Law. This article introduces a hygiene manual for child care facilities in accordance with the EU Law on Hygiene, which was field tested in more than 70 child care facilities during the course of the extensive organisational process. The manual supplies easy-tohandle instructions and form sheets for documentation and hence assists in realising legal provisions.

Comparison of social support and psychosocial stress after heart and liver transplantation.

We studied social support, psychological symptoms, and subjective appraisal of quality of life among 233 patients at 1 to 3 years after heart (HTX) or orthotopic liver transplantation (OLT): 78 HTX in 62.8% men and 155 OLT in 51% men. Patients after OLT versus HTX were more often single or divorced (14.4% and 12.3% vs 3.9% and 7.7%), had better school education (68.4% vs 37.8%), and were more often employed (25.5% vs 11.8%). Among the HTX patients, 40.3% had more than 3 inpatient treatments due to complications after transplantation vs only 9.3% of OLT patients. HTX patients had more rejection reactions (55.4% vs 21%). Asked for their appraisal of quality of life, HTX and OLT patients gave comparably good "school grades" (2.6 vs 2.7), describing similar scores of social support in the F-SozU (4.4 vs 4.2). OLT patients, women in particular, reported a significantly higher grade of global psychological stress than HTX patients (67.4 vs 55.1; P < .001). Our results indicated that social support, employment status, and degree of somatic complications cannot sufficiently explain the degree of emotional distress after transplantation. Subjective factors such as making sense of the transplantation in terms of regarding it as a worthwhile operation within the life course are important mediators of psychological stress and perceived quality of life.

[Occupational epidemiology]. / Epidemiologie in der Arbeitswelt.

The aim of occupational epidemiology is to describe workplace-related diseases and to identify their underlying causes. Its primary goal is to protect workers from hazardous effects of the working process by applying work-related primary and secondary prevention measures. To assess health risks different study designs and a wide array of complex study instruments and methods are frequently employed that cannot be replaced by toxicological investigations. This paper primarily addresses health risks by agent exposures. In this context a central task of occupational epidemiology is careful assessment of exposure. Different data sources, such as work site measurements, register data, archive material, experts' opinion, and the workers' personal estimates of exposure may be used during this process. In addition, biological markers can complement exposure assessment. Since thorough occupational epidemiologic studies allow assessment of disease risks under realistic exposure conditions, their results should be more frequently used to derive workplace-related threshold limit values.

Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients.

This study aimed to quantify the inhibition of cytochrome P450 (CYP3A), CYP2D6, and P-glycoprotein in human immunodeficiency virus (HIV)-infected patients receiving an antiretroviral therapy (ART) containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pharmacokinetics. We measured activities of CYP3A, CYP2D6, and P-glycoprotein in 28 patients before and during ART using a cocktail phenotyping approach. Activities, demographics, and genetic polymorphisms in CYP3A, CYP2D6, and P-glycoprotein were tested as covariates. Oral midazolam clearance (overall CYP3A activity) decreased to 0.19-fold (90% confidence interval (CI), 0.15-0.23), hepatic midazolam clearance and intestinal midazolam availability changed to 0.24-fold (0.20-0.29) and 1.12-fold (1.00-1.26), respectively. In CYP2D6 extensive metabolizers, the plasma ratio AUC(dextromethorphan)/AUC(dextrorphan) increased to 2.92-fold (2.31-3.69). Digoxin area under the curve (AUC)(0-12) (P-glycoprotein activity) increased to 1.81-fold (1.56-2.09). Covariates had no major influence on lopinavir and ritonavir pharmacokinetics. In conclusion, CYP3A, CYP2D6, and P-glycoprotein are profoundly inhibited in patients receiving ritonavir boosted lopinavir. The covariates investigated are not useful for a priori dose selection.

[When is a doctor a good doctor? An analysis of the contents of statements by representatives of the medical profession ]. / Wann ist ein Arzt ein guter Arzt? Eine inhaltsanalytische Untersuchung von Aussagen medizinischer Professionsvertreter.

BACKGROUND: Several professional bodies have developed influential documents which have tried to describe the essential competences of a good doctor. Such an initiative has not been previously conducted in German-speaking countries. Differences between the published statements point towards the significance of differences in the respective sociocultural setting. METHODS: The first step was to take advantage of a series of standardized written interviews [including the item "What makes a doctor a good doctor?"], conducted with leading German physicians and published serially in the Deutsche Medizinische Wochenschrift. Responses were qualitatively analysed by three assessors in accordance with Grounded Theory. Text fragmentation and assignment of categories was built successively: it was based on the actual material and repeatedly revised. RESULTS: 261 statements were extracted from a total of 83 interviews. It was possible to assign 249 of them to one of the following nine categories: "knowledge", "empathy" and "patient orientation" and, less frequently "practical competence", "genuineness", "helper", "awareness of limits", "life-long learning" and "cooperation". Results were similar for older and younger physicians, or when comparing representatives of clinical and theoretical disciplines. CONCLUSIONS: It will be worthwhile to survey and evaluate the opinion of additional members of the medical profession and of patients and others with a stake in the health system--comparing and delineating results from different countries--so that a more comprehensive picture can be drawn of "the good doctor".

Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia.

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6-8.9), pneumonia (OR, 3.6; 95%CI, 1.2-10.2), age >60 years (OR, 2.6; 95%CI, 1.5-4.5), and known source of infection (OR, 2.3; 95%CI, 1.3-4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.

Superior virological efficacy of ritonavir-boosted protease inhibitor regimens compared to single protease inhibitor therapy.

Low dose-ritonavir boosted protease inhibitors are increasingly being used for the first-line antiretroviral treatment, though their virological efficacy has just poorly been compared to alternative antiretroviral therapies. Here, we retrospectively investigated the virological responses of 316 protease inhibitor-naive HIV patients receiving highly active antiretroviral treatment based on a single (n = 256) or a ritonavir-boosted protease inhibitor (n = 60), both in the background of two nucleoside analogues. - By intent-to-treat analysis, a complete initial virological response was achieved in 71.8% of all patients in the single protease inhibitor group (indinavir: 76%, ritonavir: 67.5%, nelfinavir: 70.6%) and in 88.3% (p = 0.008) of patients treated with a boosted protease inhibitor (saquinavir/r: 71.4%, indinavir/r: 92.1%, lopinavir/r: 86.6%). The multivariate risk analysis identified boosted PI treatment as an independent predictor of a complete virological response (OR = 2.8, p=0.02). Viral rebound after an initial complete virological response was observed in 28% and 17% (p = 0.06) of patients receiving a single or a dual protease inhibitor, respectively. The rate of durable viral suppression over 12 months was 44.5% and 56.7% (p = 0.09) in the respective study cohorts. Ritonavir-boosted protease inhibitors therefore seem to induce a superior virological response rate and a higher degree of sustained virological suppression.

[Application of guidelines for the treatment of headache and cancer pain by private practitioners]. / Anwendung von Leitlinien zur Kopf-und Tumorschmerztherapie bei niedergelassenen Artzen.

In a regional pain management network in Cologne, sponsored by the German Ministry of Health, structures of outpatient pain treatment in general practice and the adherence to pain management guidelines were examined. The 3-year project was divided into a 1-year observational period to analyze the present state of outpatient pain management followed by a 2-year period of interventions such as consultations and educational training programs in pain treatment. Eighty physicians with different specializations working in general practice took part in the network. The knowledge of and adherence to the guidelines for the treatment of headache and cancer pain were examined by questionnaire surveys and six simulated patient cases. These investigations were performed yearly from 1997 to 2000. The adherence to the guidelines for the treatment of headache and cancer pain by the physicians participating in the network was low. The levels achieved for simulated cases of headache were higher than for cancer pain. The results of simulated patient cases from the beginning and the end of the project were available for comparison for 28 physicians. Evaluation of the physicians' assessment of the simulated patient cases increased only fractionally and was not significant in headache patients (median change of 0.67) and cancer pain patients (median change of 0.17). The network interventions resulted in a slight improvement in the knowledge of and attitudes to the treatment of headache and cancer pain as judged by simulated patient cases. This improvement, however, did not reach statistical significance. The small number of physicians answering at the beginning and at the end of the project made it difficult to draw a general conclusion on whether the interventions had led to an improvement in outpatient pain management in a larger group of physicians.

[Deficits in the treatment of chronic pain. 2. Possibilities for improvement through the Pain Therapy Ambulant Network (STAN)]. / Defizite in der Therapie chronischer Schmerzen (Teil 2). Möglichkeiten zur Verbesserung durch das Schmerztherapeutische ambulante Netzwerk (STAN).

In a regional pain management network in Cologne, the pain clinic of the department of anaesthesiology and the departments of psychosomatic medicine and of informatics, statistics and epidemiology have been cooperating with the regional board of physicians and more than 80 general practitioners since 1996. The program is sponsored by the German Ministry of Health. In this network, guidelines for the management of chronic pain have been implemented for outpatient care in the last three years. Results from the first year confirm the high level of distress of patients with chronic pain. Consultation and education offered by the coordinating office and in training courses were accepted by the practitioners in variable degrees. Some physicians requested consultations frequently while including only a few patients in the study documentation, while other physicians requested consultations rarely and assessed many patients. Participating physicians were also asked to provide analgesic regimens for constructed case reports with chronic headache or cancer pain. The evaluation of these prescriptions showed poor adherence to analgesic guidelines.

[Deficits in the treatment of chronic pain (I)]. / Defizite in der Therapie chronischer Schmerzen (Teil 1).

Pain management by general practitioners often is inadequate. Guidelines for pain management are either not observed or not known at all. Opioids are not prescribed adequately. Differential diagnoses influencing the therapeutic regimen such as drug-induced headache are not sufficiently known. Monotherapies with analgesic drugs are enforced for patients with chronic lower back pain in spite of low efficacy. Improving pain management can be difficult for the general practitioner having no special knowledges or support from pain specialists. However, the general practitioner should remain the patient-coordinator for the patient with chronic pain. Networks with general practitioners and specialised units in the hospital may offer possibilities for improvement of pain management deficits.