Decreasing Opioid Addiction and Diversion Using Behavioral Economics Applied Through a Digital Engagement Solution: Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. OBJECTIVE: Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). METHODS: A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. RESULTS: This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. CONCLUSIONS: Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. TRIAL REGISTRATION: ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52882.

Thermal Transport and Mechanical Stress Mapping of a Compression Bonded GaN/Diamond Interface for Vertical Power Devices.

Bonding diamond to the back side of gallium nitride (GaN) electronics has been shown to improve thermal management in lateral devices; however, engineering challenges remain with the bonding process and characterizing the bond quality for vertical device architectures. Here, integration of these two materials is achieved by room-temperature compression bonding centimeter-scale GaN and a diamond die via an intermetallic bonding layer of Ti/Au. Recent attempts at GaN/diamond bonding have utilized a modified surface activation bonding (SAB) method, which requires Ar fast atom bombardment immediately followed by bonding within the same tool under ultrahigh vacuum (UHV) conditions. The method presented here does not require a dedicated SAB tool yet still achieves bonding via a room-temperature metal-metal compression process. Imaging of the buried interface and the total bonding area is achieved via transmission electron microscopy (TEM) and confocal acoustic scanning microscopy (C-SAM), respectively. The thermal transport quality of the bond is extracted from spatially resolved frequency-domain thermoreflectance (FDTR) with the bonded areas boasting a thermal boundary conductance of >100 MW/m2·K. Additionally, Raman maps of GaN near the GaN-diamond interface reveal a low level of compressive stress, <80 MPa, in well-bonded regions. FDTR and Raman were coutilized to map these buried interfaces and revealed some poor thermally bonded areas bordered by high-stress regions, highlighting the importance of spatial sampling for a complete picture of bond quality. Overall, this work demonstrates a novel method for thermal management in vertical GaN devices that maintains low intrinsic stresses while boasting high thermal boundary conductances.

Inversion for Thermal Properties with Frequency Domain Thermoreflectance.

3D integration of multiple microelectronic devices improves size, weight, and power while increasing the number of interconnections between components. One integration method involves the use of metal bump bonds to connect devices and components on a common interposer platform. Significant variations in the coefficient of thermal expansion in such systems lead to stresses that can cause thermomechanical and electrical failures. More advanced characterization and failure analysis techniques are necessary to assess the bond quality between components. Frequency domain thermoreflectance (FDTR) is a nondestructive, noncontact testing method used to determine thermal properties in a sample by fitting the phase lag between an applied heat flux and the surface temperature response. The typical use of FDTR data involves fitting for thermal properties in geometries with a high degree of symmetry. In this work, finite element method simulations are performed using high performance computing codes to facilitate the modeling of samples with arbitrary geometric complexity. A gradient-based optimization technique is also presented to determine unknown thermal properties in a discretized domain. Using experimental FDTR data from a GaN-diamond sample, thermal conductivity is then determined in an unknown layer to provide a spatial map of bond quality at various points in the sample.

A novel, evidence-based, comprehensive clinical decision support system improves outcomes for patients with traumatic rib fractures.

BACKGROUND: Traumatic rib fractures are associated with high morbidity and mortality. Clinical decision support systems (CDSS) have been shown to improve adherence to evidence-based (EB) practice and improve clinical outcomes. The objective of this study was to investigate if a rib fracture CDSS reduced hospital length of stay (LOS), 90-day and 1-year mortality, unplanned ICU transfer, and the need for mechanical ventilation. The independent association of two process measures, an admission EB order set and a pain-inspiratory-cough score early warning system, with LOS were investigated. METHODS: The CDSS was scaled across nine US trauma centers. Following multiple imputation, multivariable regression models were fit to evaluate the association of the CDSS on primary and secondary outcomes. As a sensitivity analysis, propensity score matching was also performed to confirm regression findings. RESULTS: Overall, 3,279 patients met inclusion criteria. Rates of EB practices increased following implementation. On risk-adjusted analysis, in-hospital LOS preintervention versus postintervention was unchanged (incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 0.97-1.15, p = 0.2) but unplanned transfer to the ICU was reduced (odds ratio, 0.28; 95% CI, 0.09-0.84, p = 0.024), as was 1-year mortality (hazard ratio, 0.6; 95% CI, 0.4-0.89, p = 0.01). Provider utilization of the admission order bundle was 45.3%. Utilization was associated with significantly reduced LOS (IRR, 0.87; 95% CI, 0.77-0.98; p = 0.019). The early warning system triggered on 34.4% of patients; however, was not associated with a significant reduction in hospital LOS (IRR, 0.76; 95% CI, 0.55-1.06; p = 0.1). CONCLUSION: A novel, user-centered, comprehensive CDSS improves adherence to EB practice and is associated with a significant reduction in unplanned ICU admissions and possibly mortality, but not hospital LOS. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Combined Expert and User-Driven Usability Assessment of Trauma Decision Support Systems Improves User-Centered Design.

BACKGROUND: Trauma clinical decision support systems improve adherence with evidence-based practice but suffer from poor usability and the lack of a user-centered design. The objective of this study was to compare the effectiveness of user and expert-driven usability testing methods to detect usability issues in a rib fracture clinical decision support system and identify guiding principles for trauma clinical decision support systems. METHODS: A user-driven and expert-driven usability investigation was conducted using a clinical decision support system developed for patients with rib fractures. The user-driven usability evaluation was as follows: 10 clinicians were selected for simulation-based usability testing using snowball sampling, and each clinician completed 3 simulations using a video-conferencing platform. End-users participated in a novel team-based approach that simulated realistic clinical workflows. The expert-driven heuristic evaluation was as follows: 2 usability experts conducted a heuristic evaluation of the clinical decision support system using 10 common usability heuristics. Usability issues were identified, cataloged, and ranked for severity using a 4-level ordinal scale. Thematic analysis was utilized to categorize the identified usability issues. RESULTS: Seventy-nine usability issues were identified; 63% were identified by experts and 48% by end-users. Notably, 58% of severe usability issues were identified by experts alone. Only 11% of issues were identified by both methods. Five themes were identified that could guide the design of clinical decision support systems-transparency, functionality and integration into workflow, automated and noninterruptive, flexibility, and layout and appearance. Themes were preferentially identified by different methods. CONCLUSION: We found that a dual-method usability evaluation involving usability experts and end-users drastically improved detection of usability issues over single-method alone. We identified 5 themes to guide trauma clinical decision support system design. Performing usability testing via a remote video-conferencing platform facilitated multi-site involvement despite a global pandemic.

Automated high throughput pKa and distribution coefficient measurements of pharmaceutical compounds for the SAMPL8 blind prediction challenge.

The goal of the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) challenge is to improve the accuracy of current computational models to estimate free energy of binding, deprotonation, distribution and other associated physical properties that are useful for the design of new pharmaceutical products. New experimental datasets of physicochemical properties provide opportunities for prospective evaluation of computational prediction methods. Here, aqueous pKa and a range of bi-phasic logD values for a variety of pharmaceutical compounds were determined through a streamlined automated process to be utilized in the SAMPL8 physical property challenge. The goal of this paper is to provide an in-depth review of the experimental methods utilized to create a comprehensive data set for the blind prediction challenge. The significance of this work involves the use of high throughput experimentation equipment and instrumentation to produce acid dissociation constants for twenty-three drug molecules, as well as distribution coefficients for eleven of those molecules.

Understanding the Role of Sodium Lauryl Sulfate on the Biorelevant Solubility of a Combination of Poorly Water-Soluble Drugs Using High Throughput Experimentation and Mechanistic Absorption Modeling.

This study investigates the influence of surfactant sodium lauryl sulfate (SLS) on the solubility of poorly-water soluble drug substances, model Compound X and Compound Y, used in a fixed dose combination oral solid dosage form. To determine the impact of SLS concentration on the solubility of compounds X and Y, we experimentally determined the critical micelle concentration (CMC) of SLS in water, simulated gastric fluid (SGF), and fed state simulated intestinal fluid (FeSSIF) in the presence of Compound X and Compound Y using UV/Visible spectrophotometry at 25°C. The aggregation of SLS was characterized by calculating the standard Gibbs free energy of micellization in all the media investigated.  To enhance the understanding of SLS aggregation, high throughput experiments and in-vivo mechanistic modelling were used to determine the effect of increasing levels of SLS on the solubility of compounds X and Y as both single agent and combination products to be formulated into a suitable oral solid dosage form. Micellar formation of SLS is a spontaneous process as shown by the negative values of the standard free energy of micellization. The CMC of SLS in the various media investigated in the presence of compounds X and Y decreases in the following order: water> FeSSIF> SGF. However, the aggregation of SLS in the various media is overall more spontaneous in the following order: SGF>FeSSIF>water. Using high throughput experimentation and in-vivo mechanistic modelling, it was determined that a combination oral solid product of compounds X and Y will have optimum solubility and in-vivo absorption if 2 mg of SLS was used in the oral solid dosage form.  The results obtained from this study will help broaden the understanding of the micellization process involving SLS and poorly-water soluble drugs used in combination oral solid dosage forms.

Single-Cell Analysis of Morphological and Metabolic Heterogeneity in Euglena gracilis by Fluorescence-Imaging Flow Cytometry.

Microalgal biofuels and biomass have ecofriendly advantages as feedstocks. Improved understanding and utilization of microalgae require large-scale analysis of the morphological and metabolic heterogeneity within populations. Here, with Euglena gracilis as a model microalgal species, we evaluate how fluorescence- and brightfield-derived-image-based descriptors vary during environmental stress at the single-cell level. This is achieved with a new multiparameter fluorescence-imaging cytometric technique that allows the assaying of thousands of cells per experiment. We track morphological changes, including the intensity and distribution of intracellular lipid droplets, and pigment autofluorescence. The combined fluorescence-morphological analysis identifies new metrics not accessible with traditional flow cytometry, including the lipid-to-cell-area ratio (LCAR), which shows promise as an indicator of oil productivity per biomass. Single-cell metrics of lipid productivity were highly correlated ( R2 > 0.90, p < 0.005) with bulk oil extraction. Such chemomorphological atlases of algal species can help optimize growth conditions and selection approaches for large-scale biomass production.