Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

M@X-Guide - ein wissensbasiertes System zur Unterstützung des Informed-Consents und des Shared-Decision-Makings am Beispiel der S3-Leitlinie zum metastasierten Mammakarzinom

In the last 40 years more than 40 S3 guidelines for various medical fields were placed at public disposal by the AWMF alone. Although the guidelines are of high quality, the implementation of these until now has been inadequate due to incomplete contents and faulty implementation measures, therefore the targeted aims (e.g. improvement of the quality of treatment with simultaneous increase of cost-efficiency) cannot be reached and the potential of the guidelines is not fully exploited.The first part of this doctoral thesis examines the role of the guidelines from the viewpoint of the public healthcare system.After that a detail look of the German S3-guideline Diagnostics, therapy and aftercare of breast cancer on the treatment of metastatic breast cancer follows, together with a description of the strengths and weaknesses of this specific part of the guideline.The third chapter illuminates the problem from the point of view of information technology. Different approaches for the representation of knowledge in the medical field are examined for their efficiency to represent medical guidelines. This theoretic discussion is put intopractical experience by the implementation of M@X-Guide - the knowledge-based system for the therapy of metastatic breast cancer.The thesis is rounded by a detailed discussion of M@X-Guide, the possibility of supporting the implementation of medical guidelines using knowledge based systems, and the generalization of the findings in the form of a systematicprocess which would allow the construction of such systems on the basis of narrative guidelines

M@X-Guide - a knowledge based system to support informed consent and shared decision making illustrated by a national consensus guideline for metastatic breast cancer

In the last 40 years more than 40 S3 guidelines for various medical fields were placed at public disposal by the AWMF alone. Although the guidelines are of high quality, the implementation of these until now has been inadequate due to incomplete contents and faulty implementation measures, therefore the targeted aims (e.g. improvement of the quality of treatment with simultaneous increase of cost-efficiency) cannot be reached and the potential of the guidelines is not fully exploited.The first part of this doctoral thesis examines the role of the guidelines from the viewpoint of the public healthcare system.After that a detail look of the German S3-guideline "Diagnostics, therapy and aftercare of breast cancer" on the treatment of metastatic breast cancer follows, together with a description of the strengths and weaknesses of this specific part of the guideline.The third chapter illuminates the problem from the point of view of information technology. Different approaches for the representation of knowledge in the medical field are examined for their efficiency to represent medical guidelines. This theoretic discussion is put intopractical experience by the implementation of M@X-Guide - the knowledge-based system for the therapy of metastatic breast cancer.The thesis is rounded by a detailed discussion of M@X-Guide, the possibility of supporting the implementation of medical guidelines using knowledge based systems, and the generalization of the findings in the form of a systematicprocess which would allow the construction of such systems on the basis of narrative guidelines

BRENDA-Score, a hghly significant, internally and externally validated prognostic marker for metastatic recurrence: analysis of 10,449 primary breast cancer patients

Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival

Clinical criteria replenish high-sensitive troponin and inflammatory markers in the stratification of patients with suspected acute coronary syndrome

OBJECTIVES: In patients with suspected acute coronary syndrome (ACS), rapid triage is essential. The aim of this study was to establish a tool for risk prediction of 30-day cardiac events (CE) on admission. 30-day cardiac events (CE) were defined as early coronary revascularization, subsequent myocardial infarction, or cardiovascular death within 30 days. METHODS AND RESULTS: This single-centre, prospective cohort study included 377 consecutive patients presenting to the emergency department with suspected ACS and for whom troponin T measurements were requested on clinical grounds. Fifteen biomarkers were analyzed in the admission sample, and clinical parameters were assessed by the TIMI risk score for unstable angina/Non-ST myocardial infarction and the GRACE risk score. Sixty-nine (18%) patients presented with and 308 (82%) without ST-elevations, respectively. Coronary angiography was performed in 165 (44%) patients with subsequent percutaneous coronary intervention - accounting for the majority of CE - in 123 (33%) patients, respectively. Eleven out of 15 biomarkers were elevated in patients with CE compared to those without. High-sensitive troponin T (hs-cTnT) was the best univariate biomarker to predict CE in Non-ST-elevation patients (AUC 0.80), but did not yield incremental information above clinical TIMI risk score (AUC 0.80 vs 0.82, p = 0.69). Equivalence testing of AUCs of risk models and non-inferiority testing demonstrated that the clinical TIMI risk score alone was non-inferior to its combination with hs-cTnT in predicting CE. CONCLUSIONS: In patients presenting without ST-elevations, identification of those prone to CE is best based on clinical assessment based on TIMI risk score criteria and hs-cTnT