Improving Provider Adoption With Adaptive Clinical Decision Support Surveillance: An Observational Study.

BACKGROUND: Successful clinical decision support (CDS) tools can help use evidence-based medicine to effectively improve patient outcomes. However, the impact of these tools has been limited by low provider adoption due to overtriggering, leading to alert fatigue. We developed a tracking mechanism for monitoring trigger (percent of total visits for which the tool triggers) and adoption (percent of completed tools) rates of a complex CDS tool based on the Wells criteria for pulmonary embolism (PE). OBJECTIVE: We aimed to monitor and evaluate the adoption and trigger rates of the tool and assess whether ongoing tool modifications would improve adoption rates. METHODS: As part of a larger clinical trial, a CDS tool was developed using the Wells criteria to calculate pretest probability for PE at 2 tertiary centers' emergency departments (EDs). The tool had multiple triggers: any order for D-dimer, computed tomography (CT) of the chest with intravenous contrast, CT pulmonary angiography (CTPA), ventilation-perfusion scan, or lower extremity Doppler ultrasound. A tracking dashboard was developed using Tableau to monitor real-time trigger and adoption rates. Based on initial low provider adoption rates of the tool, we conducted small focus groups with key ED providers to elicit barriers to tool use. We identified overtriggering of the tool for non-PE-related evaluations and inability to order CT testing for intermediate-risk patients. Thus, the tool was modified to allow CT testing for the intermediate-risk group and not to trigger for CT chest with intravenous contrast orders. A dialogue box, "Are you considering PE for this patient?" was added before the tool triggered to account for CTPAs ordered for aortic dissection evaluation. RESULTS: In the ED of tertiary center 1, 95,295 patients visited during the academic year. The tool triggered for an average of 509 patients per month (average trigger rate 2036/30,234, 6.73%) before the modifications, reducing to 423 patients per month (average trigger rate 1629/31,361, 5.22%). In the ED of tertiary center 2, 88,956 patients visited during the academic year, with the tool triggering for about 473 patients per month (average trigger rate 1892/29,706, 6.37%) before the modifications and for about 400 per month (average trigger rate 1534/30,006, 5.12%) afterward. The modifications resulted in a significant 4.5- and 3-fold increase in provider adoption rates in tertiary centers 1 and 2, respectively. The modifications increased the average monthly adoption rate from 23.20/360 (6.5%) tools to 81.60/280.20 (29.3%) tools and 46.60/318.80 (14.7%) tools to 111.20/263.40 (42.6%) tools in centers 1 and 2, respectively. CONCLUSIONS: Close postimplementation monitoring of CDS tools may help improve provider adoption. Adaptive modifications based on user feedback may increase targeted CDS with lower trigger rates, reducing alert fatigue and increasing provider adoption. Iterative improvements and a postimplementation monitoring dashboard can significantly improve adoption rates.

Segmentation and tracking of adherens junctions in 3D for the analysis of epithelial tissue morphogenesis.

Epithelial morphogenesis generates the shape of tissues, organs and embryos and is fundamental for their proper function. It is a dynamic process that occurs at multiple spatial scales from macromolecular dynamics, to cell deformations, mitosis and apoptosis, to coordinated cell rearrangements that lead to global changes of tissue shape. Using time lapse imaging, it is possible to observe these events at a system level. However, to investigate morphogenetic events it is necessary to develop computational tools to extract quantitative information from the time lapse data. Toward this goal, we developed an image-based computational pipeline to preprocess, segment and track epithelial cells in 4D confocal microscopy data. The computational pipeline we developed, for the first time, detects the adherens junctions of epithelial cells in 3D, without the need to first detect cell nuclei. We accentuate and detect cell outlines in a series of steps, symbolically describe the cells and their connectivity, and employ this information to track the cells. We validated the performance of the pipeline for its ability to detect vertices and cell-cell contacts, track cells, and identify mitosis and apoptosis in surface epithelia of Drosophila imaginal discs. We demonstrate the utility of the pipeline to extract key quantitative features of cell behavior with which to elucidate the dynamics and biomechanical control of epithelial tissue morphogenesis. We have made our methods and data available as an open-source multiplatform software tool called TTT (http://github.com/morganrcu/TTT).

Complete RNA inverse folding: computational design of functional hammerhead ribozymes.

Nanotechnology and synthetic biology currently constitute one of the most innovative, interdisciplinary fields of research, poised to radically transform society in the 21st century. This paper concerns the synthetic design of ribonucleic acid molecules, using our recent algorithm, RNAiFold, which can determine all RNA sequences whose minimum free energy secondary structure is a user-specified target structure. Using RNAiFold, we design ten cis-cleaving hammerhead ribozymes, all of which are shown to be functional by a cleavage assay. We additionally use RNAiFold to design a functional cis-cleaving hammerhead as a modular unit of a synthetic larger RNA. Analysis of kinetics on this small set of hammerheads suggests that cleavage rate of computationally designed ribozymes may be correlated with positional entropy, ensemble defect, structural flexibility/rigidity and related measures. Artificial ribozymes have been designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential Enrichment); however, this appears to be the first purely computational design and experimental validation of novel functional ribozymes. RNAiFold is available at http://bioinformatics.bc.edu/clotelab/RNAiFold/.

Energy parameters and novel algorithms for an extended nearest neighbor energy model of RNA.

We describe the first algorithm and software, RNAenn, to compute the partition function and minimum free energy secondary structure for RNA with respect to an extended nearest neighbor energy model. Our next-nearest-neighbor triplet energy model appears to lead to somewhat more cooperative folding than does the nearest neighbor energy model, as judged by melting curves computed with RNAenn and with two popular software implementations for the nearest-neighbor energy model. A web server is available at http://bioinformatics.bc.edu/clotelab/RNAenn/.