NEUROD1 acts in vitro as an upstream regulator of NEUROD2 in trophoblast cells

The basic helix-loop-helix (bHLH) transcription factors NEUROD1, NEUROD2 and ATH2 are expressed during first trimester human placental development. We determined the transactivation potential of each of these factors in trophoblasts by measuring changes in the endogenous gene activity using absolute quantification by real-time quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) after transient transfection. In these assays, NEUROD1 was found to transiently transactivate NEUROD2 in trophoblast cells. Promotor truncation assays, using luciferase constructs, showed the presence of two domains in the NEUROD2 promotor, which showed increased activity after NeuroD1 transfection. Each of these NeuroD1-responsive domains contains an E-box sequence. The NEUROD2 transactivation data fit with the spatial expression pattern of NEUROD1 and NEUROD2, since they are expressed in endovascular trophoblasts. This expression pattern, as well as the present transactivation results, might suggest the presence of a NEUROD differentiation cascade during first trimester human placental development

Clinical decision trees support systematic evaluation of multidisciplinary team recommendations

Purpose: EUSOMA’s recommendation that “each patient has to be fully informed about each step in the diagnostic and therapeutic pathway” could be supported by guideline-based clinical decision trees (CDTs). The Dutch breast cancer guideline has been modeled into CDTs (www.oncoguide.nl). Prerequisites for adequate CDT usage are availability of necessary patient data at the time of decision-making and to consider all possible treatment alternatives provided in the CDT. Methods: This retrospective single-center study evaluated 394 randomly selected female patients with non-metastatic breast cancer between 2012 and 2015. Four pivotal CDTs were selected. Two researchers analyzed patient records to determine to which degree patient data required per CDT were available at the time of multidisciplinary team (MDT) meeting and how often multiple alternatives were actually reported. Results: The four selected CDTs were indication for magnetic resonance imaging (MRI) scan, preoperative and adjuvant systemic treatment, and immediate breast reconstruction. For 70%, 13%, 97% and 13% of patients, respectively, all necessary data were available. The two most frequent underreported data-items were “clinical M-stage” (87%) and “assessable mammography” (28%). Treatment alternatives were reported by MDTs in 32% of patients regarding primary treatment and in 28% regarding breast reconstruction. Conclusion: Both the availability of data in patient records essential for guideline-based recommendations and the reporting of possible treatment alternatives of the investigated CDTs were low. To meet EUSOMA’s requirements, information that is supposed to be implicitly known must be explicated by MDTs. Moreover, MDTs have to adhere to clear definitions of data-items in their reporting

Transformation of the National Breast Cancer Guideline Into Data-Driven Clinical Decision Trees

PURPOSE The essence of guideline recommendations often is intertwined in large texts. This impedes clinical implementation and evaluation and delays timely modular revisions needed to deal with an ever-growing amount of knowledge and application of personalized medicine. The aim of this project was to model guideline recommendations as data-driven clinical decision trees (CDTs) that are clinically interpretable and suitable for implementation in decision support systems. METHODS All recommendations of the Dutch national breast cancer guideline for nonmetastatic breast cancer were translated into CDTs. CDTs were constructed by nodes, branches, and leaves that represent data items (patient and tumor characteristics [eg, T stage]), data item values (eg, T2 or less), and recommendations (eg, chemotherapy), respectively. For all data items, source of origin was identified (eg, pathology), and where applicable, data item values were defined on the basis of existing classification and coding systems (eg, TNM, Breast Imaging Reporting and Data System, Systematized Nomenclature of Medicine). All unique routes through all CDTs were counted to measure the degree of data-based personalization of recommendations. RESULTS In total, 60 CDTs were necessary to cover the whole guideline and were driven by 114 data items. Data items originated from pathology (49%), radiology (27%), clinical (12%), and multidisciplinary team (12%) reports. Of all data items, 101 (89%) could be classified by existing classification and coding systems. All 60 CDTs could be integrated in an interactive decision support app that contained 376 unique patient subpopulations. CONCLUSION By defining data items unambiguously and unequivocally and coding them to an international coding system, it was possible to present a complex guideline as systematically constructed modular data-driven CDTs that are clinically interpretable and accessible in a decision support app

Conversion of a colorectal cancer guideline into clinical decision trees with assessment of validity

Objective: The interpretation and clinical application of guidelines can be challenging and time-consuming, which may result in noncompliance to guidelines. The aim of this study was to convert the Dutch guideline for colorectal cancer (CRC) into decision trees and subsequently implement decision trees in an online decision support environment to facilitate guideline application. Methods: The recommendations of the Dutch CRC guidelines (published in 2014) were translated into decision trees consisting of decision nodes, branches and leaves that represent data items, data item values and recommendations, respectively. Decision trees were discussed with experts in the field and published as interactive open access decision support software (available at www.oncoguide.nl). Decision tree validation and a concordance analysis were performed using consecutive reports (January 2016-January 2017) from CRC multidisciplinary tumour boards (MTBs) at Amsterdam University Medical Centers, location AMC. Results: In total, we developed 34 decision trees driven by 101 decision nodes based on the guideline recommendations. Decision trees represented recommendations for diagnostics (n = 1), staging (n = 10), primary treatment (colon: n = 1, rectum: n = 5, colorectal: n = 9), pathology (n = 4) and follow-up (n = 3) and included one overview decision tree for optimal navigation. We identified several guideline information gaps and areas of inconclusive evidence. A total of 158 patients' MTB reports were eligible for decision tree validation and resulted in treatment recommendations in 80% of cases. The concordance rate between decision tree treatment recommendations and MTB advices was 81%. Decision trees reported in 22 out of 24 non-concordant cases (92%) that no guideline recommendation was available. Conclusions: We successfully converted the Dutch CRC guideline into decision trees and identified several information gaps and areas of inconclusive evidence, the latter being the main cause of the observed disagreement between decision tree recommendations and MTB advices. Decision trees may contribute to future strategies to optimize quality of care for CRC patients