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Background: The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined. Methods: Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an erlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry staining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints and skin rash using a Cox regression model. Results: Fifty-five out of 153 patients were classified as pERK(low) and 98 patients as pERK(high); median overall survival (OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable, the pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients were pAKT(low) and 14/35 pAKT(high) with a corresponding median OS of 6.4 months and 6.8 months, respectively (HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression and 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a significant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of skin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with a complete loss of p53. Conclusion: pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic cancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash.

Background: The number of patients presenting with acute myocardial infarction (AMI) and being untreatable by interventional cardiologists increased during the last years. Previous experience in emergency coronary artery bypass grafting (CABG) in these patients spurred us towards a more liberal acceptance for surgery. Following a prospective protocol, patients were operated on and further analysed. Methods: Within a two year interval, 127 patients (38 female, age 68 +/- 12 years, EuroScore (ES) II 6.7 +/- 7.2%) presenting with AMI (86 non-ST-elevated myocardial infarction (NSTEMI), 41 STEMI) were immediately accepted for emergency CABG and operated on within six hours after cardiac catheterisation (77% three-vessel-disease, 47% left main stem stenosis, 11% cardiogenic shock, 21% preoperative intraaortic balloon pump (IABP), left ventricular ejection fraction 48 +/- 15%). Results: 30-day-mortality was 6% (8 patients, 2 NSTEMI (2%) 6 STEMI (15%), p=0.014). Complete revascularisation could be achieved in 80% of the patients using 2 +/- 1 grafts and 3 +/- 1 distal anastomoses. In total, 66% were supported by IABP, extracorporal life support (ECLS) systems were implanted in two patients. Logistic regression analysis revealed the ES II as an independent risk factor for mortality (p

BACKGROUND Interruptions of hospital doctors' workflow are a frequent stressor, eventually jeopardising quality of clinical performance. To enhance the safety of hospital doctors' work, it is necessary to analyse frequency and circumstances of workflow interruptions. AIM To quantify workflow interruptions among hospital doctors, identify frequent sources and relate sources to doctors' concurrent activities. METHODS Within a typical hospital, 32 participant observations of doctors' full work shifts were carried out. Time-motion information was collected on types of workflow interruption and doctors' activities and analysed with logit-linear analyses. RESULTS The frequency of workflow interruptions was high, especially on the intensive care unit and emergency ward. Telephones and bleepers were the most frequently recorded type of work interruption. The combined analysis of doctors' activities and concurrent workflow interruptions revealed that the likelihood of the occurrence of certain types of interruption depended on the tasks being carried out by the doctor. CONCLUSION The present method may be useful for quantifying and distinguishing sources of hospital doctors' workflow interruptions and useful in raising awareness of organisational circumstances.

Background Little is known about the influence of depressed patients' preferences and expectations about treatments upon treatment outcome We investigated whether better clinical outcome in depressed primary care patients is associated with receiving their preferred treatment Methods Within a randomized placebo-controlled single-centre 10-week trial with 5 arms (sertraline, placebo, cognitive-behavioral group therapy, CBT-G, moderated self-help group control, treatment with sertraline or CBT-G according to patients' choice), outcomes for 145 primary care patients with mild-to-moderate depressive disorders according to DSM-IV criteria were investigated Preference for medication versus psychotherapy was assessed at screening using a single item Post-baseline difference scores for the Hamilton Depression Rating Scale (HAMD-17) were used to assess treatment outcome (mixed-model repeated-measures regression analysis) Results Depressed patients receiving their preferred treatment (n = 63), whether sertraline or CBT-G, responded significantly better than those who did not receive their preferred therapy (n = 54, p = 0 001) The difference in outcome between both groups was 8 0 points on the HAMD-17 for psychotherapy and 2 9 points on the HAMD-17 for treatment with antidepressants Results were not explained by differences in depression severity or dropout rates Conclusions Patients' relative preference for medication versus psychotherapy should be considered when offering a treatment because receiving the preferred treatment conveys an additional and clinically relevant benefit (HAMD-17 +2 9 points for drugs, +8 0 points for CBT-G) in outcome Copyright (C) 2010 S Karger AG Basel

Background: Several studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population. Methods: Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function. Results: High blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R-2: 0.65) and forced vital capacity values (p = 0.01 respectively p = 0.05, R-2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R-2: 0.65), while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R-2: 0.73). In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too. Conclusion: Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a general adult population.

Background: Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods: Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results: The final regression equations for FEV(1) and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. Conclusions: Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

Objective: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. Methods: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m(2) twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. Results: A median of 3 treatment cycles (range 1-36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5-45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7-45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. Conclusion: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended. Copyright (C) 2008 S. Karger AG, Basel.

Background: Recent studies showed the increasing importance of depressive disorders. Despite good treatment possibilities (pharmacological treatment and psychotherapy) only a minority of patients receive adequate treatment. One of the most dramatic consequences is a big number of suicides. Methods: Within the competence network on depression and suicidality (founded by the German Ministry for Education and Research) a multi-level program was carried out in 2001 and 2002: the “Nuremberg Alliance against Depression”. In the centre of the activities was the optimisation of diagnosis and therapy in primary care. Family doctors received continuous education and different screening tools were established. Brochures and videos were produced to improve patients` knowledge of symptoms, causes and treatment possibilities. Besides that an intense information campaign was started (posters, lectures, cinema spot, leaflets etc.). Moreover a close cooperation with other community facilitators (priests, geriatric nurses, teachers etc.) should improve awareness towards depression and suicidality. Finally, special support for patients and their relatives was provided. A telephone hotline for persons after suicide attempt offered help in the case of a further suicidal crisis. Main outcome criteria of the study was the reduction of suicidal acts (suicides and suicide attempts) in comparison to a baseline-year (2000) and a control region (Wuerzburg). Results: The results for the first year of intervention (2001) show a significant decrease of suicidal acts in Nuremberg compared to the baseline and to the control region. Suicidal acts dropped from 620 cases to 500 cases (p=0.046). The decrease of persons committing a suicide attempt was 21.6% (375 vs. 475 cases) and differed significantly from the control region (p=0.008). Completed suicides decreased from 100 to 75 (-25%) which was not significant compared to the control region where a similar reduction in suicide rates was observed.