A Patient-Centered Information System (myED) for Emergency Care Journeys: Design, Development, and Initial Adoption.

BACKGROUND: Medical care is highly complex in that it addresses patient-centered health goals that require the coordination of multiple care providers. Emergency department (ED) patients currently lack a sense of predictability about ED procedures. This increases frustration and aggression. Herein, we describe a system for providing real-time information to ED patients regarding the procedures in their ED medical journey. OBJECTIVE: This study aimed to develop a system that provides patients with dynamically updated information about the specific procedures and expected waiting times in their personal ED journey, and to report initial evaluations of this system. METHODS: To develop the myED system, we extracted information from hospital databases and translated it using process mining and user interface design into a language that is accessible and comprehensible to patients. We evaluated the system using a mixed methods approach that combined observations, interviews, and online records. RESULTS: Interviews with patients, accompanying family members, and health care providers (HCPs) confirmed patients' needs for information about their personal ED journey. The system developed enables patients to access this information on their personal mobile phones through a responsive website. In the third month after deployment, 492 of 1614 (30.48%) patients used myED. Patients' understanding of their ED journey improved significantly (F8,299=2.519; P=.01), and patients showed positive reactions to the system. We identified future challenges, including achieving quick engagement without delaying medical care. Salient reasons for poor system adoption were patients' medical state and technological illiteracy. HCPs confirmed the potential of myED and identified means that could improve patient experience and staff cooperation. CONCLUSIONS: Our iterative work with ED patients, HCPs, and a multidisciplinary team of developers yielded a system that provides personal information to patients about their ED journey in a secure, effective, and user-friendly way. MyED communicates this information through mobile technology. This improves health care by addressing patients' psychological needs for information and understanding, which are often overlooked. We continue to test and refine the system and expect to find positive effects of myED on patients' ED experience and hospital operations.

Structural Principles in Robo Activation and Auto-inhibition.

Proper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos' switch from "off" to "on" states remains unclear. Here, we report a 3.6 Å crystal structure of the intact human Robo2 ectodomain (domains D1-8). We demonstrate that Robo cis dimerization via D4 is conserved through hRobo1, 2, and 3 and the C. elegans homolog SAX-3 and is essential for SAX-3 function in vivo. The structure reveals two levels of auto-inhibition that prevent premature activation: (1) cis blocking of the D4 dimerization interface and (2) trans interactions between opposing Robo receptors that fasten the D4-blocked conformation. Complementary experiments in mouse primary neurons and C. elegans support the auto-inhibition model. These results suggest that Slit stimulation primarily drives the release of Robo auto-inhibition required for dimerization and activation.

The role of specialized hospital units in infection and mortality risk reduction among patients with hematological cancers.

MOTIVATION: Patients with hematological malignancies are susceptible to life-threatening infections after chemotherapy. The current study aimed to evaluate whether management of such patients in dedicated inpatient and emergency wards could provide superior infection prevention and outcome. METHODS: We have developed an approach allowing to retrieve infection-related information from unstructured electronic medical records of a tertiary center. Data on 2,330 adults receiving 13,529 chemotherapy treatments for hematological malignancies were identified and assessed. Infection and mortality hazard rates were calculated with multivariate models. Patients were randomly divided into 80:20 training and validation cohorts. To develop patient-tailored risk-prediction models, several machine-learning methods were compared using area under the curve (AUC). RESULTS: Of the tested algorithms, the probit model was found to most accurately predict the evaluated hazards and was implemented in an online calculator. The infection-prediction model identified risk factors for infection based on patient characteristics, treatment and history. Observation of patients with a high predicted infection risk in general wards appeared to increase their infection hazard (p = 0.009) compared to similar patients observed in hematology units. The mortality-risk model demonstrated that for infection events starting at home, admission through hematology services was associated with a lower mortality hazard compared to admission through the general emergency department (p = 0.007). Both models show that dedicated hematological facilities and emergency services improve patient outcome post-chemotherapy. The calculated numbers needed to treat were 30.27 and 31.08 for the dedicated emergency and observation facilities, respectively. Infection hazard risks were found to be non-monotonic in time. CONCLUSIONS: The accuracy of the proposed mortality and infection risk-prediction models was high, with the AUC of 0.74 and 0.83, respectively. Our results demonstrate that temporal assessment of patient risks is feasible. This may enable physicians to move from one-point decision-making to a continuous dynamic observation, allowing a more flexible and patient-tailored admission policy.

Approaching the Roundabout: cis and trans Robo1 Contacts Revealed.

In this issue of Structure,Aleksandrova et al. (2018) present low- and high-resolution structures of Robo1, a key player in axonal guidance. The structures shed light on the arrangement of Robo1 at the plasma membrane and provide evidence for back-to-back trans Robo1 contacts.

Robo Ig4 Is a Dimerization Domain.

Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis, angiogenesis, cell migration, and cancer progression and invasiveness. They are considered to be attractive drug targets for the treatment of cancer, ocular neovascular disorders, chronic kidney diseases, and more. Despite their great importance, the mechanisms by which Robo receptors switch from their "off" to "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer-to-monomer transition that facilitates the recruitment and activation of enzymatic effectors to instigate intracellular signaling. However, it is not known which domains mediate Robo dimerization, or the structural properties of the dimeric interactions. Here, we identify the extracellular Ig4 (D4) as a Robo dimerization domain. We have determined the crystal structure of the tandem Ig4-5 domains (D4-5) of human Robo2 and found that a hydrophobic surface on D4 mediates close homotypic contacts with a reciprocal D4. Analytical ultracentrifugation measurements of intact and mutated D4-5 shows that dimerization through the D4 interface is specific and has a dimerization dissociation constant of 16.9µM in solution. Direct fluorescence resonance energy transfer dimerization measurements in HEK293 cells corroborate the dimerization of transmembrane hRobo2 through D4, and a functional COS-7 cell collapse assay links D4-mediated dimerization with Robo intracellular signaling. The high level of conservation in the D4 dimerization interface throughout all Robo orthologs and paralogs implies that D4-mediated dimerization is a central hallmark in Robo activation and signaling.