Identification and weighting of the most critical "real-life” drug-drug interactions with acenocoumarol in a tertiary care hospital

Purpose: The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. Methods: We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding. Results: One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. Conclusion: Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drug

Identification and weighting of the most critical "real-life” drug-drug interactions with acenocoumarol in a tertiary care hospital

Purpose: The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. Methods: We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding. Results: One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. Conclusion: Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drug

Using ERA-Interim reanalysis for creating datasets of energy-relevant climate variables

The construction of a bias-adjusted dataset of climate variables at the near surface using ERA-Interim reanalysis is presented. A number of different, variable-dependent, bias-adjustment approaches have been proposed. Here we modify the parameters of different distributions (depending on the variable), adjusting ERA-Interim based on gridded station or direct station observations. The variables are air temperature, dewpoint temperature, precipitation (daily only), solar radiation, wind speed, and relative humidity. These are available on either 3 or 6 h timescales over the period 1979–2016. The resulting bias-adjusted dataset is available through the Climate Data Store (CDS) of the Copernicus Climate Change Data Store (C3S) and can be accessed at present from ftp://ecem.climate.copernicus.eu. The benefit of performing bias adjustment is demonstrated by comparinginitial and bias-adjusted ERA-Interim data against gridded observational fields

How Advanced Change Patterns Impact the Process of Process Modeling

Process model quality has been an area of considerable research efforts. In this context, correctness-by-construction as enabled by change patterns provides promising perspectives. While the process of process modeling (PPM) based on change primitives has been thoroughly investigated, only little is known about the PPM based on change patterns. In particular, it is unclear what set of change patterns should be provided and how the available change pattern set impacts the PPM. To obtain a better understanding of the latter as well as the (subjective) perceptions of process modelers, the arising challenges, and the pros and cons of different change pattern sets we conduct a controlled experiment. Our results indicate that process modelers face similar challenges irrespective of the used change pattern set (core pattern set versus extended pattern set, which adds two advanced change patterns to the core patterns set). An extended change pattern set, however, is perceived as more difficult to use, yielding a higher mental effort. Moreover, our results indicate that more advanced patterns were only used to a limited extent and frequently applied incorrectly, thus, lowering the potential benefits of an extended pattern set

What is the Role of Acid-Acid Interactions in Asymmetric Phosphoric Acid Organocatalysis? A Detailed Mechanistic Study using Interlocked and Non-Interlocked Catalysts

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst-catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which react mainly as phosphoric acid dimers. For acyclic phosphoric acids, we found a strongly concentration dependent behavior, involving both monomeric and dimeric catalytic pathways. Based on a detailed experimental analysis, DFT-calculations and a direct NMR-based observation of the catalyst aggregates, we could demonstrate that intermolecular acid-acid interactions have a drastic influence on the reaction rate and stereoselectivity of the asymmetric transfer-hydrogenation catalyzed by chiral phosphoric acids

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Exploring user experience and technology acceptance for a fall prevention system: results from a randomized clinical trial and a living lab

Background: Falls are common in older adults and can result in serious injuries. Due to demographic changes, falls and related healthcare costs are likely to increase over the next years. Participation and motivation of older adults in fall prevention measures remain a challenge. The iStoppFalls project developed an information and communication technology (ICT)-based system for older adults to use at home in order to reduce common fall risk factors such as impaired balance and muscle weakness. The system aims at increasing older adults’ motivation to participate in ICT-based fall prevention measures. This article reports on usability, user-experience and user-acceptance aspects affecting the use of the iStoppFalls system by older adults. Methods: In the course of a 16-week international multicenter study, 153 community-dwelling older adults aged 65+ participated in the iStoppFalls randomized controlled trial, of which half used the system in their home to exercise and assess their risk of falling. During the study, 60 participants completed questionnaires regarding the usability, user experience and user acceptance of the iStoppFalls system. Usability was measured with the System Usability Scale (SUS). For user experience the Physical Activity Enjoyment Scale (PACES) was applied. User acceptance was assessed with the Dynamic Acceptance Model for the Re-evaluation of Technologies (DART). To collect more detailed data on usability, user experience and user acceptance, additional qualitative interviews and observations were conducted with participants. Results: Participants evaluated the usability of the system with an overall score of 62 (Standard Deviation, SD 15.58) out of 100, which suggests good usability. Most users enjoyed the iStoppFalls games and assessments, as shown by the overall PACES score of 31 (SD 8.03). With a score of 0.87 (SD 0.26), user acceptance results showed that participants accepted the iStoppFalls system for use in their own home. Interview data suggested that certain factors such as motivation, complexity or graphical design were different for gender and age. Conclusions: The results suggest that the iStoppFalls system has good usability, user experience and user acceptance. It will be important to take these along with factors such as motivation, gender and age into consideration when designing and further developing ICT-based fall prevention systems

The design of a purpose-built exergame for fall prediction and prevention for older people

Background Falls in older people represent a major age-related health challenge facing our society. Novel methods for delivery of falls prevention programs are required to increase effectiveness and adherence to these programs while containing costs. The primary aim of the Information and Communications Technology-based System to Predict and Prevent Falls (iStoppFalls) project was to develop innovative home-based technologies for continuous monitoring and exercise-based prevention of falls in community-dwelling older people. The aim of this paper is to describe the components of the iStoppFalls system. Methods The system comprised of 1) a TV, 2) a PC, 3) the Microsoft Kinect, 4) a wearable sensor and 5) an assessment and training software as the main components. Results The iStoppFalls system implements existing technologies to deliver a tailored home-based exercise and education program aimed at reducing fall risk in older people. A risk assessment tool was designed to identify fall risk factors. The content and progression rules of the iStoppFalls exergames were developed from evidence-based fall prevention interventions targeting muscle strength and balance in older people. Conclusions The iStoppFalls fall prevention program, used in conjunction with the multifactorial fall risk assessment tool, aims to provide a comprehensive and individualised, yet novel fall risk assessment and prevention program that is feasible for widespread use to prevent falls and fall-related injuries. This work provides a new approach to engage older people in home-based exercise programs to complement or provide a potentially motivational alternative to traditional exercise to reduce the risk of falling

Crowd-Based Mining of Reusable Process Model Patterns

Process mining is a domain where computers undoubtedly outperform humans. It is a mathematically complex and computationally demanding problem, and event logs are at too low a level of abstraction to be intelligible in large scale to humans. We demonstrate that if instead the data to mine from are models (not logs), datasets are small (in the order of dozens rather than thousands or millions), and the knowledge to be discovered is complex (reusable model patterns), humans outperform computers. We design, implement, run, and test a crowd-based pattern mining approach and demonstrate its viability compared to automated mining. We specifically mine mashup model patterns (we use them to provide interactive recommendations inside a mashup tool) and explain the analogies with mining business process models. The problem is relevant in that reusable model patterns encode valuable modeling and domain knowledge, such as best practices or organizational conventions, from which modelers can learn and benefit when designing own models. © 2014 Springer International Publishing Switzerland

Enhancing modeling and change support for process families through change patterns

The increasing adoption of process-aware information systems (PAISs), together with the variability of business processes (BPs), has resulted in large collections of related process model variants (i.e., process families). To effectively deal with process families, several proposals (e.g., C-EPC, Provop) exist that extend BP modeling languages with variability-specific constructs. While fostering reuse and reducing modeling efforts, respective constructs imply additional complexity and demand proper support for process designers when creating and modifying process families. Recently, generic and language independent adaptation patterns were successfully introduced for creating and evolving single BP models. However, they are not sufficient to cope with the specific needs for modeling and evolving process families. This paper suggests a complementary set of generic and language-independent change patterns specifically tailored to the needs of process families. When used in combination with existing adaptation patterns, change patterns for process families will enable the modeling and evolution of process families at a high-level of abstraction. Further, they will serve as reference for implementing tools or comparing proposals managing process families. © 2013 Springer-Verlag.This work has been developed with the support of MICINN under the Project EVERYWARE TIN2010-18011.Ayora Esteras, C.; Torres Bosch, MV.; Weber, B.; Reichert, M.; Pelechano Ferragud, V. (2013). Enhancing modeling and change support for process families through change patterns. En Enterprise, Business-Process and Information Systems Modeling, BPMDS 2013. Springer Verlag. 246-260. https://doi.org/10.1007/978-3-642-38484-4_18S246260van der Aalst, W.M.P., ter Hofstede, A.H.M., Barros, B.: Workflow Patterns. Distributed and Parallel Databases 14(1), 5–51 (2003)Aghakasiri, Z., Mirian-Hosseinabadi, S.H.: Workflow change patterns: Opportunities for extension and reuse. In: Proc. SERA 2009, pp. 265–275 (2009)Ayora, C., Torres, V., Reichert, M., Weber, B., Pelechano, V.: Towards run-time flexibility for process families: Open issues and research challenges. In: La Rosa, M., Soffer, P. (eds.) BPM 2012 Workshops. LNBIP, vol. 132, pp. 477–488. Springer, Heidelberg (2013)Ayora, C., Torres, V., Weber, B., Reichert, M., Pelechano, V.: Change patterns for process families. Technical Report, PROS-TR-2012-06, http://www.pros.upv.es/technicalreports/PROS-TR-2012-06.pdfDadam, P., Reichert, M.: The ADEPT project: a decade of research and development for robust and flexible process support. Com. Sci. - R&D 23, 81–97 (2009)Dijkman, R., La Rosa, M., Reijers, H.A.: Managing large collections of business process models - Current techniques and challenges. Comp. in Ind. 63(2), 91–97 (2012)Döhring, M., Zimmermann, B., Karg, L.: Flexible workflows at design- and runtime using BPMN2 adaptation patterns. In: Abramowicz, W. (ed.) BIS 2011. LNBIP, vol. 87, pp. 25–36. Springer, Heidelberg (2011)Gottschalk, F.: Configurable process models. Ph.D. thesis, Eindhoven University of Technology, The Netherlands (2009)Grambow, G., Oberhauser, R., Reichert, M.: Contextual injection of quality measures into software engineering processes. Intl. J. Adv. in Software 4, 76–99 (2011)Gschwind, T., Koehler, J., Wong, J.: Applying patterns during business process modeling. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 4–19. Springer, Heidelberg (2008)Günther, C.W., Rinderle, S., Reichert, M., van der Aalst, W.M.P.: Change mining in adaptive process management systems. In: Meersman, R., Tari, Z. (eds.) OTM 2006. LNCS, vol. 4275, pp. 309–326. Springer, Heidelberg (2006)Hallerbach, A., Bauer, T., Reichert, M.: Context-based configuration of process variants. In: Proc. TCoB 2008, pp. 31–40 (2008)Hallerbach, A., Bauer, T., Reichert, M.: Capturing variability in business process models: the Provop approach. J. of Software Maintenance 22(6-7), 519–546 (2010)Kitchenham, B., Charters, S.: Guidelines for performing Systematic Literature Reviews in Software Engineering, Technical Report EBSE/EPIC–2007–01 (2007)Kulkarni, V., Barat, S., Roychoudhury, S.: Towards business application product lines. In: France, R.B., Kazmeier, J., Breu, R., Atkinson, C. (eds.) MODELS 2012. LNCS, vol. 7590, pp. 285–301. Springer, Heidelberg (2012)Küster, J.M., Gerth, C., Förster, A., Engels, G.: Detecting and resolving process model differences in the absence of a change log. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 244–260. Springer, Heidelberg (2008)Küster, J.M., Gerth, C., Engels, G.: Dynamic computation of change operations in version management of business process models. In: Kühne, T., Selic, B., Gervais, M.-P., Terrier, F. (eds.) ECMFA 2010. LNCS, vol. 6138, pp. 201–216. Springer, Heidelberg (2010)Lanz, A., Weber, B., Reichert, M.: Time patterns for process-aware information systems. Requirements Engineering, 1–29 (2012)La Rosa, M., van der Aalst, W.M.P., Dumas, M., ter Hofstede, A.H.M.: Questionnaire-based variability modeling for system configuration. Software and System Modeling 8(2), 251–274 (2009)Lerner, B.S., Christov, S., Osterweil, L.J., Bendraou, R., Kannengiesser, U., Wise, A.: Exception Handling Patterns for Process Modeling. IEEE Transactions on Software Engineering 36(2), 162–183 (2010)Li, C., Reichert, M., Wombacher, A.: Mining business process variants: Challenges, scenarios, algorithms. Data Knowledge & Engineering 70(5), 409–434 (2011)Marrella, A., Mecella, M., Russo, A.: Featuring automatic adaptivity through workflow enactment and planning. In: Proc. CollaborateCom 2011, pp. 372–381 (2011)Müller, D., Herbst, J., Hammori, M., Reichert, M.: IT support for release management processes in the automotive industry. In: Dustdar, S., Fiadeiro, J.L., Sheth, A.P. (eds.) BPM 2006. LNCS, vol. 4102, pp. 368–377. Springer, Heidelberg (2006)Reichert, M., Weber, B.: Enabling flexibility in process-aware information systems: challenges, methods, technologies. Springer (2012)Reinhartz-Berger, I., Soffer, P., Sturm, A.: Organizational reference models: supporting an adequate design of local business processes. IBPIM 4(2), 134–149 (2009)Rosemann, M., van der Aalst, W.M.P.: A configurable reference modeling language. Information Systems 32(1), 1–23 (2007)Russell, N., ter Hofstede, A.H.M., Edmond, D., van der Aalst, W.M.P.: Workflow data patterns. Technical Report FIT-TR-2004-01, Queensland Univ. of Technology (2004)Russell, N., ter Hofstede, A.H.M., Edmond, D., van der Aalst, W.M.P.: Workflow resource patterns. Technical Report WP 127, Eindhoven Univ. of Technology (2004)Russell, N., van der Aalst, W.M.P., ter Hofstede, A.H.M.: Workflow Exception Patterns. In: Martinez, F.H., Pohl, K. (eds.) CAiSE 2006. LNCS, vol. 4001, pp. 288–302. Springer, Heidelberg (2006)Smirnov, S., Weidlich, M., Mendling, J., Weske, M.: Object-sensitive action patterns in process model repositories. In: Muehlen, M.z., Su, J. (eds.) BPM 2010 Workshops. LNBIP, vol. 66, pp. 251–263. Springer, Heidelberg (2011)Weber, B., Reichert, M., Rinderle-Ma, S.: Change patterns and change support features - Enhancing flexibility in process-aware information systems. Data Knowledge & Engineering 66, 438–466 (2008)Weber, B., Sadiq, S., Reichert, M.: Beyond rigidity - dynamic process lifecycle support. Computer Science 23, 47–65 (2009)Weber, B., Reichert, M., Reijers, H.A., Mendling, J.: Refactoring large process model repositories. Computers in Industry 62(5), 467–486 (2011