Evaluation of the Panbio™ COVID-19 IgG rapid test device performance.

Background: The Panbio™ COVID-19 IgG Rapid Test Device ("Panbio™") detects IgG antibodies against the SARS-CoV-2 spike protein from viral infection or vaccination. Objectives: To determine the diagnostic sensitivity and specificity of the Panbio™ professional use test, using fingerstick whole blood and venous plasma. Study design: Fingerstick whole blood and venous plasma from each participant were tested with Panbio™ and compared against the SARS-CoV-2 IgG II assay on the Abbott Architect™ platform (Europe) or the equivalent AdviseDx SARS-CoV-2 IgG II Abbott Alinity i™ platform (US). 447 evaluable participants were enrolled across 6 US and 9 European clinical centers. Results: For unvaccinated participants with PCR-confirmed infection ≥21 days post-symptom onset, the Panbio™ sensitivity with fingerstick whole blood was 92.6 % (95 % CI: 85.9, 96.7), and the specificity was 97.0 % (95 % CI: 93.1, 99.0). For venous plasma, the sensitivity was 90.0 % (95 % CI: 79.5, 96.2) for participants with PCR-confirmed infection and symptom onset 22-180 days ago; the specificity was 96.3 % (92.2, 98.6). For vaccinated participants, the sensitivity was 98.4 % (95 % CI: 91.2, 100.0) for fingerstick whole blood and 96.7 % (95 % CI: 88.7, 99.6) for venous plasma. Conclusion: The Panbio™ test had high sensitivity and specificity for detecting IgG against the SARS-CoV-2 spike protein.

Methods and Lessons Learned from a Current State Workflow Assessment following Transition to a New Electronic Health Record System.

The transition to a new electronic health record (EHR) system requires an understanding of how the new system addresses the needs, business processes, and current activities of a healthcare system. To address such requirements, a multidisciplinary team conducted a current state workflow assessment (CSWFA) of clinical and administrative functions to elicit and document business processes (via process diagrams), requirements, workarounds, and process issues (i.e., user interface issues, training gaps) at one healthcare facility. We provided a novel method of evaluating the implementation process to ensure that a CSWFA was documented with key stakeholders. In this analysis, we describe the CSWFA approach and expected outcomes with a specific emphasis on how a qualitative approach can be integrated to explore underlying patterns and relationships in the data. Overall, this methodology enables practitioners to deliver data-driven support initiatives that optimize EHR implementation while considering user experience, productivity, and patient safety.

wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome.

Bone and muscle are coupled through developmental, mechanical, paracrine, and autocrine signals. Genetic variants at the CPED1-WNT16 locus are dually associated with bone- and muscle-related traits. While Wnt16 is necessary for bone mass and strength, this fails to explain pleiotropy at this locus. Here, we show wnt16 is required for spine and muscle morphogenesis in zebrafish. In embryos, wnt16 is expressed in dermomyotome and developing notochord, and contributes to larval myotome morphology and notochord elongation. Later, wnt16 is expressed at the ventral midline of the notochord sheath, and contributes to spine mineralization and osteoblast recruitment. Morphological changes in wnt16 mutant larvae are mirrored in adults, indicating that wnt16 impacts bone and muscle morphology throughout the lifespan. Finally, we show that wnt16 is a gene of major effect on lean mass at the CPED1-WNT16 locus. Our findings indicate that Wnt16 is secreted in structures adjacent to developing bone (notochord) and muscle (dermomyotome) where it affects the morphogenesis of each tissue, thereby rendering wnt16 expression into dual effects on bone and muscle morphology. This work expands our understanding of wnt16 in musculoskeletal development and supports the potential for variants to act through WNT16 to influence bone and muscle via parallel morphogenetic processes.

Single-cell resolution of MET- and EMT-like programs in osteoblasts during zebrafish fin regeneration.

Zebrafish regenerate fin rays following amputation through epimorphic regeneration, a process that has been proposed to involve the epithelial-to-mesenchymal transition (EMT). We performed single-cell RNA sequencing (scRNA-seq) to elucidate osteoblastic transcriptional programs during zebrafish caudal fin regeneration. We show that osteoprogenitors are enriched with components associated with EMT and its reverse, mesenchymal-to-epithelial transition (MET), and provide evidence that the EMT markers cdh11 and twist2 are co-expressed in dedifferentiating cells at the amputation stump at 1 dpa, and in differentiating osteoblastic cells in the regenerate, the latter of which are enriched in EMT signatures. We also show that esrp1, a regulator of alternative splicing in epithelial cells that is associated with MET, is expressed in a subset of osteoprogenitors during outgrowth. This study provides a single cell resource for the study of osteoblastic cells during zebrafish fin regeneration, and supports the contribution of MET- and EMT-associated components to this process.

Evaluation of serum cardiac troponin-I concentrations for diagnosis of infective endocarditis in dogs.

BACKGROUND: Infective endocarditis (IE) in dogs is associated with severe disease and a high case fatality rate but often presents with nonspecific clinical signs. HYPOTHESIS/OBJECTIVES: Serum concentration of cardiac troponin-I (cTnI) is elevated in dogs with IE and can differentiate dogs with IE from dogs with other diseases with similar clinical features. Concentration of serum cTnI is negatively correlated with survival time in dogs with IE. ANIMALS: Seventy-two client-owned dogs; 29 with IE, 27 with stage-B myxomatous mitral valve disease (MMVD), and 16 with immune-mediated disease (IMD). METHODS: Retrospective clinical cohort study. Concentration of serum cTnI was measured in all dogs at time of diagnosis. Clinical findings and echocardiographic interpretation were also recorded. Statistical analyses included Kruskal-Wallis test, pairwise Mann-Whitney U tests, receiver operator characteristic, and Cox proportional hazards. RESULTS: Serum concentration of cTnI was significantly higher in the IE group (0.69 ng/mL [0.03-80.8]) than in the MMVD (0.05 ng/mL [0.02-0.11], P < .001) and IMD groups (0.05 ng/mL [0.03-0.57], P < .001). Increased cTnI was a moderately accurate predictor of IE (area under the curve 0.857 (95% confidence interval [CI] 0.745-0.968, P < .001). A cTnI cutoff of 0.625 ng/mL had 100% specificity (95% CI 90%-100%) and 52% sensitivity (95% CI 33%-70%) in this study sample. There was no association between cTnI concentration and survival time in dogs with IE (hazard ratio 1.013, 95% CI 0.993-1.034, P = .2). CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac troponin-I concentrations are higher in dogs with IE compared to dogs with preclinical MMVD or IMD. In dogs with a compatible clinical presentation, serum cTnI concentrations >0.625 ng/mL are supportive of IE.

A Community-Based Participatory Research Approach to Hurricane Katrina: When Disasters, Environmental Health Threats, and Disparities Collide.

In 2005, Hurricane Katrina resulted in long-term flooding of 80% of New Orleans, Louisiana. Mold-infested homes gave rise to concerns about increased childhood asthma. To address these concerns, a diverse community-academic partnership used a community-based participatory research (CBPR) approach to implement the Head-off Environmental Asthma in Louisiana (HEAL) study in 2007.The study examined the relationship between post-Katrina mold and other environmental exposures and asthma morbidity, while testing an asthma counselor (AC) intervention. Both the AC intervention and the CBPR approach were effectively implemented in the postdisaster setting. However, homes had lower levels of mold and other allergens than expected, possibly because of the timing of environmental sampling. Also, HEAL illustrated the vulnerability of the study community, especially to the interconnected threats of health disparities, environmental health stressors, and disasters.We examine the implications of these threats for public health science, policy, and practice, not only through the lens of Hurricane Katrina but also for future disasters faced by communities in the Gulf Coast and nationally.

Phenomics-Based Quantification of CRISPR-Induced Mosaicism in Zebrafish.

Genetic mosaicism can manifest as spatially variable phenotypes that vary from site to site within an organism. Here, we use imaging-based phenomics to quantitate phenotypes at many sites within the axial skeleton of CRISPR-edited G0 zebrafish. Through characterization of loss-of-function cell clusters in the developing skeleton, we identify a distinctive size distribution shown to arise from clonal fragmentation and merger events. We quantitate the phenotypic mosaicism produced by somatic mutations of two genes, plod2 and bmp1a, implicated in human osteogenesis imperfecta. Comparison of somatic, CRISPR-generated G0 mutants to homozygous germline mutants reveals phenotypic convergence, suggesting that CRISPR screens of G0 animals can faithfully recapitulate the biology of inbred disease models. We describe statistical frameworks for phenomic analysis of spatial phenotypic variation present in somatic G0 mutants. In sum, this study defines an approach for decoding spatially variable phenotypes generated during CRISPR-based screens.

Using zebrafish to study skeletal genomics.

While genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of skeletal diseases, animal models are required to identify causal mechanisms and to translate underlying biology into new therapies. Despite large-scale knockout mouse phenotyping efforts, the skeletal functions of most genes residing at GWAS-identified loci remain unknown, highlighting a need for complementary model systems to accelerate gene discovery. Over the past several decades, zebrafish (Danio rerio) has emerged as a powerful system for modeling the genetics of human diseases. In this review, our goal is to outline evidence supporting the utility of zebrafish for accelerating our understanding of human skeletal genomics, as well as gaps in knowledge that need to be filled for this purpose. We do this by providing a basic foundation of the zebrafish skeletal morphophysiology and phenotypes, and surveying evidence of skeletal gene homology and the use of zebrafish for post-GWAS analysis in other tissues and organs. We also outline challenges in translating zebrafish mutant phenotypes. Finally, we conclude with recommendations of future directions and how to leverage the large body of tools and knowledge of skeletal genetics in zebrafish for the needs of human skeletal genomic exploration. Due to their amenability to rapid genetic approaches, as well as the large number of conserved genetic and phenotypic features, there is a strong rationale supporting the use of zebrafish for human skeletal genomic studies.

Factors associated with adolescent and caregiver reported problems in using asthma medications.

OBJECTIVES: The purpose of this study was to: (a) describe the types of medication problems/concerns youth with asthma and their caregivers reported and (b) examine the association between sociodemographic characteristics and youth and caregiver reported medication problems/concerns. METHODS: English- and Spanish-speaking youth ages 11-17 with persistent asthma were recruited at four pediatric clinics. Youth were interviewed and caregivers completed questionnaires about reported asthma medication concerns/problems. Multiple logistic regression was used to analyze the data. RESULTS: Three hundred and fifty-nine youth were recruited. Eighty percent of youth and 70% of caregivers reported one or more problems in using asthma medications. The most commonly reported problems by youth were: (a) hard to remember when to take the asthma medication (54%) and (b) hard to use asthma medication at school (34%). Younger children were significantly more likely to report difficulty in understanding their asthma medication's directions and difficulty reading the print on the medication's package. Caregivers' top-reported problem was that it is hard for their child to remember to take their asthma medications (49%). Caregivers without Medicaid were significantly more likely to express difficulty paying for their child's asthma medications. CONCLUSIONS: Difficulty remembering to take asthma medication was a significant problem for youth and their caregivers. Providers should work with youth and their caregivers to identify asthma medication problems and discuss strategies to address those problems.

Health beliefs associated with poor disease self-management in smokers with asthma and/or COPD: a pilot study.

Background: Compared to nonsmokers, smokers with chronic disease are less likely to adhere to self-management recommendations for the management of their chronic conditions. Although the literature notes poor adherence trends in smokers, actual influences of adherence in these patients require further study. This study examines the health beliefs that influence self-management behaviors in smokers with chronic lung disease. Methods: This prospective, cross-sectional study surveyed patients (n = 83) seen in the pulmonary outpatient clinics of the University Medical Center of New Orleans between November 2015 and February 2016. Eligible patients included those between 40-64 years old diagnosed with asthma and/or chronic obstructive pulmonary disease (COPD). Primary measures included perceived beliefs related to the susceptibility to asthma and/or COPD becoming worse, perceived barriers to adherence, and perceived benefits to adherence. Patient characteristics under-study included smoking status, race, gender, and diagnosis. Descriptive and chi-square analyses were performed to characterize the sample. Student's t and and regression analyses were conducted to examine the relationships between perceptions, smoking status, race, gender, and diagnosis. Results: Compared to nonsmokers, smokers perceived their asthma and/or COPD becoming worse (p = 0.0023). Smokers also perceived more barriers (p < 0.0001), and fewer benefits to adherence than nonsmokers (p = 0.0021). Conclusion: The health beliefs of smokers may influence their self-management behaviors. Results of this study can inform the development of services that target smokers in order to improve adherence to self-management behaviors and health outcomes.

Behaviour of nonhuman primate mothers toward their dead infants: uncovering mechanisms.

In comparative thanatology, most reports for nonhuman mammals concern mothers' behavioural responses to their dead offspring: most prominently, dead-infant carrying (sometimes of extended duration); but also inspection, proximity, maternal care such as grooming, protective behaviours and filial cannibalism. Documented across many primate species, these behaviours remain poorly understood in all. The literature is dominated by relatively brief qualitative descriptions of isolated anecdotal cases in apes and monkeys. We argue for quantitative coding in case reports, alongside analyses of longitudinal records of such events to allow objective evaluation of competing theories, and systematic comparisons within and across species and populations. Obtaining necessary datasets depends on raised awareness in researchers of the importance of recording occurrences and knowledge of pertinent data to collect. We review proposed explanatory hypotheses and outline data needed to test each empirically. To determine factors influencing infant-corpse carriage, we suggest analyses of deaths resulting in 'carry' versus 'no carry'. For individual cases, we highlight behavioural variables to code and the need for hormonal samples. We discuss mothers' stress and welfare in relation to infant death, continued transportation and premature removal of the corpse. Elucidating underlying proximate and ultimate causes is important for understanding phylogeny of maternal responses to infant death.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.

Provider use of a participatory decision-making style with youth and caregivers and satisfaction with pediatric asthma visits.

BACKGROUND: We conducted a randomized controlled trial to test the effectiveness of an asthma question prompt list with video intervention to engage the youth during clinic visits. We examined whether the intervention was associated with 1) providers including youth and caregiver inputs more into asthma treatment regimens, 2) youth and caregivers rating providers as using more of a participatory decision-making style, and 3) youth and caregivers being more satisfied with visits. METHODS: English- or Spanish-speaking youth aged 11-17 years with persistent asthma and their caregivers were recruited from four pediatric clinics and randomized to the intervention or usual care groups. The youth in the intervention group watched the video with their caregivers on an iPad and completed a one-page asthma question prompt list before their clinic visits. All visits were audiotaped. Generalized estimating equations were used to analyze the data. RESULTS: Forty providers and their patients (n=359) participated in this study. Providers included youth input into the asthma management treatment regimens during 2.5% of visits and caregiver input during 3.3% of visits. The youth in the intervention group were significantly more likely to rate their providers as using more of a participatory decision-making style (odds ratio=1.7, 95% confidence interval=1.1, 2.5). White caregivers were significantly more likely to rate the providers as more participatory (odds ratio=2.3, 95% confidence interval=1.2, 4.4). Youth (beta=4.9, 95% confidence interval=3.3, 6.5) and caregivers (beta=7.5, 95% confidence interval=3.1, 12.0) who rated their providers as being more participatory were significantly more satisfied with their visits. Youth (beta=-1.9, 95% confidence interval=-3.4, -0.4) and caregivers (beta=-8.8, 95% confidence interval=-16.2, -1.3) who spoke Spanish at home were less satisfied with visits. CONCLUSION: The intervention did not increase the inclusion of youth and caregiver inputs into asthma treatment regimens. However, it did increase the youth's perception of participatory decision-making style of the providers, and this in turn was associated with greater satisfaction.

Improving youth question-asking and provider education during pediatric asthma visits.

OBJECTIVE: We conducted a pragmatic randomized controlled trial to test the effectiveness of an asthma question prompt list with video intervention to increase youth question-asking and provider education during visits. METHODS: English or Spanish-speaking youth ages 11-17 with persistent asthma and their parents were enrolled from four rural and suburban pediatric clinics. Youth were randomized to the intervention or usual care groups. Intervention group adolescents watched the video on an iPad and then completed an asthma question prompt list before their visits. Generalized estimating equations were used to analyze the data. RESULTS: Forty providers and 359 patients participated. Intervention group youth were significantly more likely to ask one or more questions about medications, triggers, and environmental control than usual care youth. Providers were significantly more likely to educate intervention group youth about rescue medications, triggers, and environmental control. Intervention group caregivers were not significantly more likely to ask questions. CONCLUSION: The intervention increased youth question-asking and provider education about medications, triggers, and environmental control. The intervention did not impact caregiver question-asking. PRACTICE IMPLICATIONS: Providers/practices should consider having youth complete question prompt lists and watch the video with their parents before visits to increase youth question-asking during visits.

ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system.

Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of phenotypic measures comprised of morphological and densitometric traits at a large number of sites within the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ system. Analyzing phenotypic patterns may increase productivity in genetic screens, and facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

Acceptance of a pre-visit intervention to engage teens in pediatric asthma visits.

OBJECTIVE: The objectives of this study were to: (a) describe teen feedback on an asthma question prompt list/video intervention designed to motivate teens to be more engaged during visits and (b) examine teen demographics associated with teen acceptance of the intervention. METHODS: Two hundred and fifty-nine teens ages 11 to 17 with persistent asthma were enrolled into a randomized, controlled trial and assigned to either a standard care or an intervention group where they watched an educational video with their parents and received a prompt list to complete before visits. Teens were interviewed after visits. RESULTS: Of the 185 teens randomized to the intervention group: 93% said teens should complete the prompt lists before visits; 95% recommended teens should watch the video before visits; teens with moderate/severe persistent asthma were significantly more likely to find the prompt list useful; non-White teens were significantly more likely to find the prompt list and video more useful. CONCLUSIONS: Teens exposed to the question prompt list/video had very positive feedback about the intervention. PRACTICE IMPLICATIONS: Providers/practices should consider having teens complete question prompt lists during pre-visit wait time for use during visits and watch the video with their parents before visits.

A Dynamic Anesthesia System for Long-Term Imaging in Adult Zebrafish.

Long-term in vivo imaging in adult zebrafish (i.e., 1-24 h) has been limited by the fact that regimens for long-term anesthesia in embryos and larvae are ineffective in adults. Here, we examined the potential for dynamic administration of benzocaine to enable long-term anesthesia in adult zebrafish. We developed a computer-controlled perfusion system comprised of programmable peristaltic pumps that enabled automatic exchange between anesthetic and system water. Continuous administration of benzocaine in adult zebrafish resulted in a mean time to respiratory arrest of 5.0 h and 8-h survival of 14.3%. We measured characteristic sedation and recovery times in response to benzocaine, and used them to devise an intermittent dosing regimen consisting of 14.5 min of benzocaine followed by 5.5 min of system water. Intermittent benzocaine administration in adult zebrafish resulted in a mean time to respiratory arrest of 7.6 h and 8-h survival of 71.4%. Finally, we performed a single 24-h trial and found that intermittent dosing maintained anesthesia in an adult zebrafish over the entire 24-h period. In summary, our studies demonstrate the potential for dynamic administration of benzocaine to enable prolonged anesthesia in adult zebrafish, expanding the potential for imaging in adult physiologies that unfold over 1-24 h.

Adapting and implementing an evidence-based asthma counseling intervention for resource-poor populations.

OBJECTIVE: To report implementation strategies and outcomes of an evidence-based asthma counseling intervention. The Head-off Environmental Asthma in Louisiana (HEAL) intervention integrated asthma counseling (AC) capacity and addressed challenges facing children with asthma in post-disaster New Orleans. METHODS: The HEAL intervention enrolled 182 children (4-12 years) with moderate-to-severe persistent asthma. Recruitment occurred from schools in the Greater New Orleans area for one year. Participants received home environmental assessments and tailored asthma counseling sessions during the study period based on the National Cooperative Inner City Asthma Study and the Inner City Asthma Study. Primary (i.e., asthma symptoms) and secondary outcomes (i.e., healthcare utilization) were captured. During the study, changes were made to meet the demands of a post-hurricane and resource-poor environment which included changes to staffing, training, AC tools, and AC sessions. RESULTS: After study changes were made, the AC visit rate increased by 92.3%. Significant improvements were observed across several adherence measures (e.g., running out of medications (p = 0.009), financial/insurance problems for appointments (p = 0.006), worried about medication side-effects (p = 0.01), felt medications did not work (p < 0.001)). Additionally, an increasing number of AC visits was modestly associated with a greater reduction in symptoms (test-for-trend p = 0.059). CONCLUSION: By adapting to the needs of the study population and setting, investigators successfully implemented a counseling intervention that improved participant behaviors and clinical outcomes. The strategies for implementing the AC intervention may serve as a guide for managing asthma and other chronic conditions in resource-poor settings.