Design of a study on suboptimal cognitive acts in the diagnostic process, the effect on patient outcomes and the influence of workload, fatigue and experience of physician

BACKGROUND: Diagnostic error is an important error type since diagnostic adverse events are regularly judged as being preventable and the consequences are considered to be severe. Existing research often focuses on either diagnostic adverse events or on the errors in diagnostic reasoning. Whether and when an incorrect diagnostic process results in adverse outcomes has not been studied extensively. The present paper describes the design of a study that aims to study the relationship between a suboptimal diagnostic process and patient outcomes. In addition, the role of personal and circumstantial factors on the quality of the diagnostic process will be examined. METHODS/DESIGN: The research questions were addressed using several data sources. First, the differential diagnosis was assessed concurrently to the diagnostic process. Second, the patient records of 248 patients suffering from shortness of breath were reviewed by expert internists in order to reveal suboptimal cognitive acts and (potential) consequences for the patient. The suboptimal cognitive acts were discussed with the treating physicians and classified with the taxonomy of unsafe acts. Third, workload, fatigue and work experience were measured during the physicians work. Workload and fatigue were measured during the physicians shift using the NASA tlx questionnaire on a handheld computer. Physicians participating in the study also answered questions about their work experience. DISCUSSION: The design used in this study provides insight into the relationship between suboptimal cognitive acts in the diagnostic process and possible consequences for the patient. Suboptimal cognitive acts in the diagnostic process and its causes can be revealed. Additional measurements of workload, fatigue and experience allow examining the influence of these factors on the diagnostic process. In conclusion, the present design provides a method with which insights in weaknesses of the diagnostic process and the effect on patient outcomes can be studied and opportunities for improvement can be obtaine

Resource sharing leads to the emergence of division of labour

Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity

Interdependency of Brassinosteroid and Auxin Signaling in Arabidopsis

How growth regulators provoke context-specific signals is a fundamental question in developmental biology. In plants, both auxin and brassinosteroids (BRs) promote cell expansion, and it was thought that they activated this process through independent mechanisms. In this work, we describe a shared auxin:BR pathway required for seedling growth. Genetic, physiological, and genomic analyses demonstrate that response from one pathway requires the function of the other, and that this interdependence does not act at the level of hormone biosynthetic control. Increased auxin levels saturate the BR-stimulated growth response and greatly reduce BR effects on gene expression. Integration of these two pathways is downstream from BES1 and Aux/IAA proteins, the last known regulatory factors acting downstream of each hormone, and is likely to occur directly on the promoters of auxin:BR target genes. We have developed a new approach to identify potential regulatory elements acting in each hormone pathway, as well as in the shared auxin:BR pathway. We show that one element highly overrepresented in the promoters of auxin- and BR-induced genes is responsive to both hormones and requires BR biosynthesis for normal expression. This work fundamentally alters our view of BR and auxin signaling and describes a powerful new approach to identify regulatory elements required for response to specific stimuli

Study protocol: Cost-effectiveness of transmural nutritional support in malnourished elderly patients in comparison with usual care

BACKGROUND: Malnutrition is a common consequence of disease in older patients. Both in hospital setting and in community setting oral nutritional support has proven to be effective. However, cost-effectiveness studies are scarce. Therefore, the aim of our study is to investigate the effectiveness and cost-effectiveness of transmural nutritional support in malnourished elderly patients, starting at hospital admission until three months after discharge. METHODS: This study is a randomized controlled trial. Patients are included at hospital admission and followed until three months after discharge. Patients are eligible to be included when they are > or = 60 years old and malnourished according to the following objective standards: Body Mass Index (BMI in kg/m2) < 20 and/or > or = 5% unintentional weight loss in the previous month and/or > or = 10% unintentional weight loss in the previous six months. We will compare usual nutritional care with transmural nutritional support (energy and protein enriched diet, two additional servings of an oral nutritional supplement, vitamin D and calcium supplementation, and consultations by a dietitian). Each study arm will consist of 100 patients. The primary outcome parameters will be changes in activities of daily living (determined as functional limitations and physical activity) between intervention and control group. Secondary outcomes will be changes in body weight, body composition, quality of life, and muscle strength. An economic evaluation from a societal perspective will be conducted alongside the randomised trial to evaluate the cost-effectiveness of the intervention in comparison with usual care. CONCLUSION: In this randomized controlled trial we will evaluate the effect of transmural nutritional support in malnourished elderly patients after hospital discharge, compared to usual care. Primary endpoints of the study are changes in activities of daily living, body weight, body composition, quality of life, and muscle strength. An economic evaluation will be performed to evaluate the cost-effectiveness of the intervention in comparison with usual care. TRIAL REGISTRATION: Netherlands Trial Register (ISRCTN29617677, registered 14-Sep-2005)

Onzekerheid in medisch handelen

Disciplinary law originally intends to promote quality in individual health care. One could argue on the basis of empirical data that the current practice of medical disciplinary law does not demonstrably contribute to 'defensive medicine', a putative adverse effect of this form of jurisdiction. However, the practice and perception of disciplinary law should demonstrate that the possible other side effects (e.g. time consuming, emotionally distressful, impeding transparency to patients and colleagues, increasing the burden of uncertainty in medicine) of this form of case law dwarfs the yield: this postulated quality improvement. The words 'discipline' and 'law' are in themselves barriers in catalyzing an open attitude towards discussing suboptimal processes in health care with both patients and colleagues. Further reflection on the scope of practice and the perception of disciplinary law is necessary in order to further shape a cultural shift towards such an attitude and an dialogue. We have to move from the disciplinary law to a learning portal

On the Nature of Links between Requirements and Architectures: Case Studies on User Story Utilization in Agile Development

Communication between requirements engineers and software architects is experienced as problematic. In this paper we present the Requirements Engineering for Software Architecture (RE4SA) model as a tool that supports the communication between these two roles. In the RE4SA model, requirements are expressed as epic stories and user stories, which are linked to modules and features, respectively, as their architectural counterparts. By applying the RE4SA model to a multi-case study, we investigate the nature of the relationships between the requirements and the architectural artifacts. Based on the gained experience, we put forward nine hypotheses for further research on the utilization of user stories in agile RE

Optimization of blood pressure measurement practices for pharmacodynamic analyses of tyrosine‐kinase inhibitors

Abstract Blood pressure measurements form a critical component of adverse event monitoring for tyrosine kinase inhibitors, but might also serve as a biomarker for dose titrations. This study explored the impact of various sources of within‐individual variation on blood pressure readings to improve measurement practices and evaluated the utility for individual‐ and population‐level dose selection. A pharmacokinetic–pharmacodynamic modeling framework was created to describe circadian blood pressure changes, inter‐ and intra‐day variability, changes from dipper to non‐dipper profiles, and the relationship between drug exposure and blood pressure changes over time. The framework was used to quantitatively evaluate the influence of physiological and pharmacological aspects on blood pressure measurements, as well as to compare measurement techniques, including office‐based, home‐based, and ambulatory 24‐h blood pressure readings. Circadian changes, as well as random intra‐day and inter‐day variability, were found to be the largest sources of within‐individual variation in blood pressure. Office‐based and ambulatory 24‐h measurements gave rise to potential bias (>5 mmHg), which was mitigated by model‐based estimations. Our findings suggest that 5–8 consecutive, home‐based, measurements taken at a consistent time around noon, or alternatively within a limited time frame (e.g., 8.00 a.m. to 12.00 p.m. or 12.00 p.m. to 5.00 p.m.), will give rise to the most consistent blood pressure estimates. Blood pressure measurements likely do not represent a sufficiently accurate method for individual‐level dose selection, but may be valuable for population‐level dose identification. A user‐friendly tool has been made available to allow for interactive blood pressure simulations and estimations for the investigated scenarios