Charting Diagnostic Safety: Exploring Patient-Provider Discordance in Medical Record Documentation.

BACKGROUND: The 21st Century Cures Act enables patients to access their medical records, thus providing a unique opportunity to engage patients in their diagnostic journey. OBJECTIVE: To explore the concordance between patients' self-reported diagnostic concerns and clinician-interpreted information in their electronic health records. DESIGN: We conducted a mixed-methods analysis of a cohort of 467 patients who completed a structured data collection instrument (the Safer Dx Patient) to identify diagnostic concerns while reviewing their clinician's notes. We conducted a qualitative content analysis of open-ended responses on both the tools and the case summaries. Two clinical chart reviewers, blinded to patient-reported diagnostic concerns, independently conducted chart reviews using a different structured instrument (the Revised Safer Dx Instrument) to identify diagnostic concerns and generate case summaries. The primary outcome variable was chart review-identified diagnostic concerns. Multivariate logistic regression tested whether the primary outcome was concordant with patient-reported diagnostic concerns. SETTING: Geisinger, a large integrated healthcare organization in rural and semi-urban Pennsylvania. PARTICIPANTS: Cohort of adult patients actively using patient portals and identified as "at-risk" for diagnostic concerns using an electronic trigger algorithm based on unexpected visit patterns in a primary care setting. RESULTS: In 467 cohort patients, chart review identified 31 (6.4%) diagnostic concerns, of which only 11 (21.5%) overlapped with 51 patient-reported diagnostic concerns. Content analysis revealed several areas of discordant understanding of the diagnostic process between clinicians and patients. Multivariate logistic regression analysis showed that clinician-identified diagnostic concerns were associated with patients who self-reported "I feel I was incorrectly diagnosed during my visit" (odds ratio 1.65, 95% CI 1.17-2.3, p < 0.05). CONCLUSION: Patients and clinicians appear to have certain differences in their mental models of what is considered a diagnostic concern. Efforts to integrate patient perspectives and experiences with the diagnostic process can lead to better measurement of diagnostic safety.

Rapid prototyping of perfusion cell culture devices for three-dimensional imaging of mesenchymal stem cell deposition and proliferation.

Perfusion of porous scaffolds transports cells to the surface to yield cellular constructs for 3D models of disease and for tissue engineering applications. While ceramic scaffolds mimic the structure and composition of trabecular bone, their opacity and tortuous pores limit the penetration of light into the interior. Scaffolds that are both perfusable and amenable to fluorescence microscopy are therefore needed to visualize the spatiotemporal dynamics of cells in the bone microenvironment. In this study, a hybrid injection molding approach was designed to enable rapid prototyping of collector arrays with variable configurations that are amenable to longitudinal imaging of attached human mesenchymal stem cells (hMSCs) using fluorescence microscopy. Cylindrical collectors were arranged in an array that is permeable to perfusion in the xy-plane and to light in the z-direction for imaging from below. The effects of the collector radius, number, and spacing on the collection efficiency of perfused hMSCs was simulated using computational fluid dynamics (CFD) and measured experimentally using fluorescence microscopy. The effect of collector diameter on simulated and experimental cell collection efficiencies followed a trend similar to that predicted by interception theory corrected for intermolecular and hydrodynamic forces for the arrays with constant collector spacing. In contrast, arrays designed with constant collector number yielded collection efficiencies that poorly fit the trend with collector radius predicted by interception theory. CFD simulations of collection efficiency agreed with experimental measurements within a factor of two. These findings highlight the utility of CFD simulations and hybrid injection molding for rapid prototyping of collector arrays to optimize the longitudinal imaging of cells without the need for expensive and time-consuming tooling.

Shifting the paradigm of research-to-policy impact: Infrastructure for improving researcher engagement and collective action.

The body of scientific knowledge accumulated by the scholarly disciplines such as Developmental Psychopathology can achieve meaningful public impact if wielded and used in policy decision-making. Scientific study of how policymakers use research evidence underscores the need for researchers' policy engagement; however, barriers in the academy create conditions in which there is a need for infrastructure that increases the feasibility of researchers' partnership with policymakers. This need led to the development of the Research-to-Policy Collaboration model, a systematic approach for developing "boundary spanning" infrastructure, which has been experimentally tested and shown to improve policymakers' use of research evidence and bolster researchers' policy skills and engagement. This paper presents original research regarding the optimization of the RPC model, which sought to better serve and engage scholars across the globe. Trial findings shed light on ways to improve conditions that make good use of researchers' time for policy engagement via a virtual platform and enhanced e-communications. Future directions, implications, and practical guidelines for how scientists can engage in the political process and improve the impact of a collective discipline are also discussed.

Quantitation of strain-specific hemagglutinin trimers in mosaic quadrivalent influenza nanoparticle vaccine by ELISA.

An enzyme linked immunosorbent assay (ELISA) method was developed to analyze the assembly of a tetravalent mosaic influenza nanoparticle (NP) vaccine, Flumos-v1, consisting of hemagglutinin trimers (HAT) from H1 (A/Idaho/07/2018), H3 (A/Perth/1008/2019), HBV (Vic-B/Colorado/06/2017) and HBY (Yam-B/Phuket/3073/2013) strains. The sandwich ELISA assay used lectin from Galanthus nivalis as a universal capture reagent for all HAT strains and specific monoclonal antibody (mAb) to detect corresponding hemagglutinin antigen. The mAb binding of HATs incorporated into NPs diverged from those for single HAT solutions, resulting in inaccurate quantitation of assembled HATs. An optimized zwittergent treatment was used to fully dissociate the influenza NP and aligned binding activities in each pair of single HAT and dissociated HAT from NP. The dissociated HATs were then quantified against their corresponding HAT standard solutions for three development lots of FluMos-v1 vaccine and the assembly ratio of all four HATs was calculated. The molar ratio of different HATs incorporated into this quadrivalent NP vaccine was consistent and determined as H3:H1: HBV: HBY âˆ¼ 1.00:0.92:0.96:0.87, which was close the expected 1:1:1:1 ratio and confirmed a proper assembling of multivalent NP.

Strain-dependent differences in coordination of yeast signalling networks.

The yeast mitogen-activated protein kinase pathways serve as a model system for understanding how network interactions affect the way in which cells coordinate the response to multiple signals. We have quantitatively compared two yeast strain backgrounds YPH499 and ∑1278b (both of which have previously been used to study these pathways) and found several important differences in how they coordinate the interaction between the high osmolarity glycerol (HOG) and mating pathways. In the ∑1278b background, in response to simultaneous stimulus, mating pathway activation is dampened and delayed in a dose-dependent manner. In the YPH499 background, only dampening is dose-dependent. Furthermore, leakage from the HOG pathway into the mating pathway (crosstalk) occurs during osmostress alone in the ∑1278b background only. The mitogen-activated protein kinase Hog1p suppresses crosstalk late in an induction time course in both strains but does not affect the early crosstalk seen in the ∑1278b background. Finally, the kinase Rck2p plays a greater role suppressing late crosstalk in the ∑1278b background than in the YPH499 background. Our results demonstrate that comparisons between laboratory yeast strains provide an important resource for understanding how signalling network interactions are tuned by genetic variation without significant alteration to network structure.

COVID-19 Information Sources for Black and Latine Communities: A Community Co-created Survey.

BACKGROUND: To ensure equity in coronavirus disease 2019 (COVID-19) vaccine access, it is critical that Black and Latine communities receive trustworthy COVID-19 information. This study uses community-based participatory research to understand sources of COVID-19 information for Black and Latine adults, how trustworthy that information is, and relationships between information sources and COVID-19 vaccine intention. METHODS: We co-created a survey in Spanish and English and distributed it to Black and Latine adults residing in the Pittsburgh area. Data were analyzed using descriptive statistics and multivariate logistic regression. RESULTS: There were 574 participants who completed the survey. Participants reported accessing a variety of COVID-19 information sources and generally trusted these sources. Few sources of information were associated with COVID-19 vaccine intention. We also review lessons learned from our community-academic collaboration. CONCLUSIONS: Trustworthy COVID-19 information sources may not be sufficient for increasing vaccine intention. Results can help other community-academic partnerships working to improve COVID-19 vaccine equity.

Inviting patients to identify diagnostic concerns through structured evaluation of their online visit notes.

BACKGROUND: The 21st Century Cures Act mandates patients' access to their electronic health record (EHR) notes. To our knowledge, no previous work has systematically invited patients to proactively report diagnostic concerns while documenting and tracking their diagnostic experiences through EHR-based clinician note review. OBJECTIVE: To test if patients can identify concerns about their diagnosis through structured evaluation of their online visit notes. METHODS: In a large integrated health system, patients aged 18-85 years actively using the patient portal and seen between October 2019 and February 2020 were invited to respond to an online questionnaire if an EHR algorithm detected any recent unexpected return visit following an initial primary care consultation ("at-risk" visit). We developed and tested an instrument (Safer Dx Patient Instrument) to help patients identify concerns related to several dimensions of the diagnostic process based on notes review and recall of recent "at-risk" visits. Additional questions assessed patients' trust in their providers and their general feelings about the visit. The primary outcome was a self-reported diagnostic concern. Multivariate logistic regression tested whether the primary outcome was predicted by instrument variables. RESULTS: Of 293 566 visits, the algorithm identified 1282 eligible patients, of whom 486 responded. After applying exclusion criteria, 418 patients were included in the analysis. Fifty-one patients (12.2%) identified a diagnostic concern. Patients were more likely to report a concern if they disagreed with statements "the care plan the provider developed for me addressed all my medical concerns" [odds ratio (OR), 2.65; 95% confidence interval [CI], 1.45-4.87) and "I trust the provider that I saw during my visit" (OR, 2.10; 95% CI, 1.19-3.71) and agreed with the statement "I did not have a good feeling about my visit" (OR, 1.48; 95% CI, 1.09-2.01). CONCLUSION: Patients can identify diagnostic concerns based on a proactive online structured evaluation of visit notes. This surveillance strategy could potentially improve transparency in the diagnostic process.

A Perfusion Bioreactor Model of Tumor-Induced Bone Disease Using Human Cells.

Advanced solid tumors often metastasize to bone. Once established in bone, these tumors can induce bone destruction resulting in decreased quality of life and increased mortality. Neither 2D in vitro models nor 3D animal models sufficiently recapitulate the human bone-tumor microenvironment needed to fully understand the complexities of bone metastasis, highlighting the need for new models. A 3D in vitro humanized model of tumor-induced bone disease was developed by dynamically culturing human osteoblast, osteoclast, and metastatic cancer cells together within tissue-engineered bone constructs. Cell-mediated resorption can be observed by micro-computed tomography and can be quantified by change in mass. Taken together, these data can be used to investigate whether the metastatic cancer cells included in the model have the potential to drive osteoclastogenesis and cell-mediated resorption in vitro. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Fabricating bone-like scaffolds Basic Protocol 2: Preparing cells for the humanized model of TIBD Basic Protocol 3: Crafting a 3D in vitro humanized model of TIBD.

Legislating to Prevent Adverse Childhood Experiences: Growth and Opportunities for Evidence-Based Policymaking and Prevention.

Since the landmark study of Adverse Childhood Experiences (ACEs; Felitti et al., American Journal of Preventive Medicine, 14(4):245-258, 1998), there has been a significant growth in efforts to address ACEs and their impact on individual health and well-being. Despite this growing awareness, there has been little systematic review of state legislative action regarding variation in focus or scope or of the broader context impacting the introduction and enactment of ACE-related policy efforts. To inform the role of psychologists and related professionals to contribute to these legislative efforts, we conduct a comprehensive mixed-method analysis of all state bills introduced over the past two decades to investigate the use and impact of ACE research in introduced and enacted state legislative language (51 states, NTotal Bills = 1,212,048, NACE Bills = 425). In addition, these analyses examine congressional office communications (N = 14,916,546 public statements) and voting records (N = 1,163,463 votes) to understand the relationship between legislative members' public discussion of ACEs and their voting behavior on these bills. We find that legislators' public discourse is significantly related to ACE-related policymaking above and beyond political affiliation or demographic characteristics. Furthermore, key legislative language related to domestic violence, evidence-based practice, and prevention were significant predictors of whether an ACE-related bill becomes law-above and beyond the political party in power. These analyses highlight the ways in which ACE-related research has informed state policy. Based upon this work, we offer recommendations for researchers and policymakers.

Acceptability of an mHealth App for Youth With Substance Use and Mental Health Needs: Iterative, Mixed Methods Design.

BACKGROUND: Treating substance use disorders (SUDs) during adolescence can prevent adult addiction and improve youth outcomes. However, it can be challenging to keep adolescents with SUDs engaged in ongoing services, thus limiting potential benefits. Developmentally appropriate tools are needed to improve treatment engagement during and between sessions for youth with SUDs and mental health disorders. Mobile health apps may augment or replace psychotherapy components; however, few have been developed specifically for youth with SUDs following user-guided design principles, which may limit their appropriateness and utility. Formative research on acceptability to intended end users is needed before the efficacy of such tools can be examined. OBJECTIVE: This study involves user-centered, iterative development and initial user testing of a web-based app for adolescents with SUDs and mental health concerns. METHODS: Adolescents aged 14 to 17 years with past-year involvement in outpatient psychotherapy and behavioral health clinicians with adolescent SUD treatment caseloads were recruited. Across 2 assessment phases, 40 participants (alpha: 10 youths and 10 clinicians; beta: 10 youths and 10 clinicians) viewed an app demonstration and completed semistructured interviews and questionnaires about app content and functionality. RESULTS: Participants expressed positive impressions of the app and its potential utility in augmenting outpatient therapy for youth with SUDs and mental health concerns. Noted strengths included valuable educational content, useful embedded resources, and a variety of activities. Adolescents and clinicians favored the app over conventional (paper-and-pencil) modalities, citing convenience and familiarity. The app was found to be user-friendly and likely to improve treatment engagement. Adolescents suggested the inclusion of privacy settings, and clinicians recommended more detailed instructions and simplified language. CONCLUSIONS: The novel app developed here appears to be a promising, acceptable, and highly scalable resource to support adolescents with SUDs and mental health concerns. Future studies should test the efficacy of such apps in enhancing adolescent behavioral health treatment engagement and outcomes.

Rapid prototyping of cell culture microdevices using parylene-coated 3D prints.

Fabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells. Furthermore, 3D prints are generally refractory to elastomer polymerization such that they cannot be used as master molds for fabricating devices from polymers (e.g. polydimethylsiloxane, or PDMS). Different post-print treatment strategies, such as heat curing, ultraviolet light exposure, and coating with silanes, have been explored to overcome these obstacles, but none have proven universally effective. Here, we show that deposition of a thin layer of parylene, a polymer commonly used for medical device applications, renders 3D prints biocompatible and allows them to be used as master molds for elastomeric device fabrication. When placed in culture dishes containing human neurons, regardless of resin type, uncoated 3D prints leached toxic material to yield complete cell death within 48 hours, whereas cells exhibited uniform viability and healthy morphology out to 21 days if the prints were coated with parylene. Diverse PDMS devices of different shapes and sizes were easily cast from parylene-coated 3D printed molds without any visible defects. As a proof-of-concept, we rapid prototyped and tested different types of PDMS devices, including triple chamber perfusion chips, droplet generators, and microwells. Overall, we suggest that the simplicity and reproducibility of this technique will make it attractive for fabricating traditional microdevices and rapid prototyping new designs. In particular, by minimizing user intervention on the fabrication and post-print treatment steps, our strategy could help make microfluidics more accessible to the biomedical research community.

A Community Partnered Approach to Promoting COVID-19 Vaccine Equity.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected communities of color. To dismantle these disparities, it is critical to promote COVID-19 vaccine equity, both through increasing vaccine access and addressing vaccine mistrust. This article describes a community-academic collaboration (the Community Vaccine Collaborative [CVC]), whose mission is to ensure COVID-19 vaccine equity among marginalized communities. Based in Pittsburgh, Pennsylvania, our group has focused on inclusion of marginalized groups into vaccine clinical trials, addressing vaccine mistrust, and building systems to ensuring equitable access to the COVID-19 vaccine. We review formation of the CVC, activities to-date, and recommendations for other communities interested in developing similar collaboratives.

Behavioral health policy for improving population health and wellbeing: opportunities for investment in evidence-based policymaking.

The high cost of behavioral health problems across the population continues to highlight the need to integrate high-quality behavioral interventions across a variety of service settings. To successfully achieve such a system-wide transformation will require supporting federal policies that invest in sustainable high-quality services. To support these efforts we provide a mixed-method study of all federal mental health legislation over the last three decades. Results indicate that mental and behavioral health policies have grown. Further, specific characteristics that comprise bills that are successfully enacted into law are identified. Finally, opportunities for the field to engage with policymakers to support widespread integration of behavioral health services are offered.

Vertical Transmission of Zika Virus in Aedes aegypti Produces Potentially Infectious Progeny.

Vertical transmission, or pathogen transfer from female to offspring, can facilitate the persistence of emerging arboviruses, such as Zika virus (ZIKV), through periods of low horizontal transmission or adverse environmental conditions. We aimed at determining the rate of vertical transmission for ZIKV in its principal vector, Aedes aegypti, and the vector competence of vertically infected progeny. Aedes aegypti females that consumed a blood meal provisioned with ZIKV were maintained under three temperature conditions (27°C, 30°C, and 33°C) following the infectious blood meal and allowed to complete three reproductive cycles. The overall vertical transmission rate was 6.5% (95% CI = 3.9-9.9). Vertical transmission of ZIKV was observed across all temperature conditions and virus detected in adult progeny up to 2 weeks postemergence. In total, 3.4% (95% CI = 1.6-6.2) of adult progeny produced saliva with ZIKV, indicating their vector competence. These results suggest the virus may be maintained in Ae. aegypti populations without a vertebrate host for short periods.

Patient Perspectives on the Usefulness of an Artificial Intelligence-Assisted Symptom Checker: Cross-Sectional Survey Study.

BACKGROUND: Patients are increasingly seeking Web-based symptom checkers to obtain diagnoses. However, little is known about the characteristics of the patients who use these resources, their rationale for use, and whether they find them accurate and useful. OBJECTIVE: The study aimed to examine patients' experiences using an artificial intelligence (AI)-assisted online symptom checker. METHODS: An online survey was administered between March 2, 2018, through March 15, 2018, to US users of the Isabel Symptom Checker within 6 months of their use. User characteristics, experiences of symptom checker use, experiences discussing results with physicians, and prior personal history of experiencing a diagnostic error were collected. RESULTS: A total of 329 usable responses was obtained. The mean respondent age was 48.0 (SD 16.7) years; most were women (230/304, 75.7%) and white (271/304, 89.1%). Patients most commonly used the symptom checker to better understand the causes of their symptoms (232/304, 76.3%), followed by for deciding whether to seek care (101/304, 33.2%) or where (eg, primary or urgent care: 63/304, 20.7%), obtaining medical advice without going to a doctor (48/304, 15.8%), and understanding their diagnoses better (39/304, 12.8%). Most patients reported receiving useful information for their health problems (274/304, 90.1%), with half reporting positive health effects (154/302, 51.0%). Most patients perceived it to be useful as a diagnostic tool (253/301, 84.1%), as a tool providing insights leading them closer to correct diagnoses (231/303, 76.2%), and reported they would use it again (278/304, 91.4%). Patients who discussed findings with their physicians (103/213, 48.4%) more often felt physicians were interested (42/103, 40.8%) than not interested in learning about the tool's results (24/103, 23.3%) and more often felt physicians were open (62/103, 60.2%) than not open (21/103, 20.4%) to discussing the results. Compared with patients who had not previously experienced diagnostic errors (missed or delayed diagnoses: 123/304, 40.5%), patients who had previously experienced diagnostic errors (181/304, 59.5%) were more likely to use the symptom checker to determine where they should seek care (15/123, 12.2% vs 48/181, 26.5%; P=.002), but they less often felt that physicians were interested in discussing the tool's results (20/34, 59% vs 22/69, 32%; P=.04). CONCLUSIONS: Despite ongoing concerns about symptom checker accuracy, a large patient-user group perceived an AI-assisted symptom checker as useful for diagnosis. Formal validation studies evaluating symptom checker accuracy and effectiveness in real-world practice could provide additional useful information about their benefit.

Biological signal generators: integrating synthetic biology tools and in silico control.

Biological networks sense extracellular stimuli and generate appropriate outputs within the cell that determine cellular response. Biological signal generators are becoming an important tool for understanding how information is transmitted in these networks and controlling network behavior. Signal generators produce well-defined, dynamic, intracellular signals of important network components, such as kinase activity or the concentration of a specific transcription factor. Synthetic biology tools coupled with in silico control have enabled the construction of these sophisticated biological signal generators. Here we review recent advances in biological signal generator construction and their use in systems biology studies. Challenges for constructing signal generators for a wider range of biological networks and generalizing their use are discussed.

The role of psychology in evidence-based policymaking: Mapping opportunities for strategic investment in poverty reduction.

Increasing efforts are being undertaken to understand how to improve the use of research evidence in policy settings. In particular, growing efforts to understand the use of research in legislative contexts. Although high-profile examples of psychology's contributions to public policy exist-particularly around antipoverty legislation-little systematic review has quantified how the field has informed federal policy across time. Recognizing the importance of exploring psychology's use in policymaking, we provide an overview of psychology's presence in federal antipoverty legislation over the last 2 decades by reviewing the over 6,000 antipoverty bills introduced to the U.S. Congress since 1993 for mentions of psychology. Further, to explore how psychology's contributions are related to policymakers' attributions about the causes of poverty, their public statements and voting behavior is considered. Key gaps in our scientific knowledge for informing poverty-related policy are identified. Opportunities to enhance the relevance of psychology in poverty reduction efforts, including the evidence-based policy movement, are described. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Nonsense-mediated mRNA decay of the ferric and cupric reductase mRNAs FRE1 and FRE2 in Saccharomyces cerevisiae.

The nonsense-mediated mRNA decay (NMD) pathway regulates mRNAs that aberrantly terminate translation. This includes aberrant mRNAs and functional natural mRNAs. Natural mRNA degradation by NMD is triggered by mRNA features and environmental cues. Saccharomyces cerevisiae encodes multiple proteins with ferric and cupric reductase activity. Here, we examined the regulation by NMD of two mRNAs, FRE1 and FRE2, encoding ferric and cupric reductases in S. cerevisiae. We found that FRE2 mRNAs are regulated by NMD under noninducing conditions and that the FRE2 3'-UTR contributes to the degradation of the mRNAs by NMD. Conversely, FRE1 mRNAs are not regulated by NMD under comparable conditions. These findings suggest that regulation of functionally related mRNAs by NMD can be differential and conditional.