Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants.

We use the implementation science framework RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) to describe outcomes of In Our DNA SC, a population-wide genomic screening (PWGS) program. In Our DNA SC involves participation through clinical appointments, community events, or at home collection. Participants provide a saliva sample that is sequenced by Helix, and those with a pathogenic variant or likely pathogenic variant for CDC Tier 1 conditions are offered free genetic counseling. We assessed key outcomes among the first cohort of individuals recruited. Over 14 months, 20,478 participants enrolled, and 14,053 samples were collected. The majority selected at-home sample collection followed by clinical sample collection and collection at community events. Participants were predominately female, White (self-identified), non-Hispanic, and between the ages of 40-49. Participants enrolled through community events were the most racially diverse and the youngest. Half of those enrolled completed the program. We identified 137 individuals with pathogenic or likely pathogenic variants for CDC Tier 1 conditions. The majority (77.4%) agreed to genetic counseling, and of those that agreed, 80.2% completed counseling. Twelve clinics participated, and we conducted 108 collection events. Participants enrolled at home were most likely to return their sample for sequencing. Through this evaluation, we identified facilitators and barriers to implementation of our state-wide PWGS program. Standardized reporting using implementation science frameworks can help generalize strategies and improve the impact of PWGS.

The role of geography, ecology, and hybridization in the evolutionary history of Canary Island Descurainia.

PREMISE: Oceanic islands offer the opportunity to understand evolutionary processes underlying rapid diversification. Along with geographic isolation and ecological shifts, a growing body of genomic evidence has suggested that hybridization can play an important role in island evolution. Here we use genotyping-by-sequencing (GBS) to understand the roles of hybridization, ecology, and geographic isolation in the radiation of Canary Island Descurainia (Brassicaceae). METHODS: We carried out GBS for multiple individuals of all Canary Island species and two outgroups. Phylogenetic analyses of the GBS data were performed using both supermatrix and gene tree approaches and hybridization events were examined using D-statistics and Approximate Bayesian Computation. Climatic data were analyzed to examine the relationship between ecology and diversification. RESULTS: Analysis of the supermatrix data set resulted in a fully resolved phylogeny. Species networks suggest a hybridization event has occurred for D. gilva, with these results being supported by Approximate Bayesian Computation analysis. Strong phylogenetic signals for temperature and precipitation indicate one major ecological shift within Canary Island Descurainia. CONCLUSIONS: Inter-island dispersal played a significant role in the diversification of Descurainia, with evidence of only one major shift in climate preferences. Despite weak reproductive barriers and the occurrence of hybrids, hybridization appears to have played only a limited role in the diversification of the group with a single instance detected. The results highlight the need to use phylogenetic network approaches that can simultaneously accommodate incomplete lineage sorting and gene flow when studying groups prone to hybridization; patterns that might otherwise be obscured in species trees.

Applying the R = MC2 implementation science heuristic to assess the impact of readiness on reach and implementation of a population-wide genomic screening program.

Population-wide genomic screening for genes that have high penetrance and clinical actionability enhances the opportunity to identify individuals at risk for developing hereditary conditions. Organizational readiness has been shown to influence the likelihood of successful implementation of complex initiatives such as the integration of population-wide genomic screening in clinical settings. We use the organizational readiness heuristic R = MC2 to better understand three factors that influence readiness for implementation of In Our DNA SC, a population-wide genomic screening program: motivation to implement, general capacity of an organization, and innovation-specific capacities. We then assessed the influence of these readiness factors on implementation outcomes of reach (measured through enrollment rate) and implementation (measured through the number of DNA samples collected). Data were collected pre-implementation and captured during the three-month pilot phase of the In Our DNA SC program. We collected administrative data from the electronic health record and quantitatively captured elements of readiness through surveys distributed to provider champions and clinical administrative champions at the 10 sites implementing the population-wide genomic screening program. We facilitated innovation-specific capacity through training offered at each site, as well as technical assistance through weekly meetings with other implementing sites, and resources available to all staff. Forty percent of provider champions attended training and 80% of administrative champions attended training. An average of 3.7 additional staff were trained at each implementing site. Satisfaction with training positively influenced reach (ß = 0.0121, p = 0.0271) but did not impact implementation. Provider engagement (innovation capabilities) was associated with reach (ß = 0.0020, p = 0.0251) and clinical administrator engagement was associated with sample collection rate (ß = 0.2599, ß = 0.038). Readiness to change is considered one of the most important factors in understanding the potential opportunity for implementation. We found that motivation to adopt a population-wide genomic screening program positively impacted the program's reach. The type of champion influenced discrete outcomes, with provider champions positively impacting reach and administrative champions influencing implementation (assessed through sample collection rate). As genomics continues to be integrated into clinical practice, it will be important to understand the contextual factors that influence readiness for implementation and design support throughout the life-course of implementation to ensure the success of large-scale, complex initiatives.

A Ring Expansion Approach To N-oxy-2,5-diketopiperazines.

A ring expansion of tetramic acids (pyrrolidine-2,4-diones) to N-oxy-2,5-diketopiperazines (DKPs) is described. This method allows for the facile and late-stage construction of the hydroxamic acid moiety and can thereby serve as a general method for accessing N-oxy-2,5-DKP natural products.

Understanding public preferences for different dairy farming systems using a mixed-methods approach.

Global production of milk has doubled over the past 50 yr, yet dairy farming in high-income countries faces scrutiny over practices perceived to affect animal welfare. One such practice is housing dairy cows year-round without access to pasture, which is the norm across North America and increasing within Europe, despite evidence of significant public support for grazing. Diverging opinion between the farming community and the public about what animal welfare means could be a key factor; however, lack of insight into the understanding and motivations underpinning public preferences for grazing could also hamper resolution. On the basis that more information could increase engagement between parties, 60 members of the public across the United Kingdom were interviewed to understand their perspectives of 3 dairy farming scenarios incorporating different amounts of grazing or housing. Their responses were analyzed using a mixed-methods approach combining reflexive thematic analysis with linguistic analysis. The integrated results indicated participants had a dual vision of the cow, seeing her as both domestic and wild. A scenario with housing in winter and grazing in summer therefore suited her, providing both protection and naturalness, and was most associated with analytic thinking. Interviewees also confessed ignorance about the cow's needs, either deferring to others' judgment-including the cow herself-or using familiarity and anthropomorphism to assess the scenarios. This again resulted in most optimism, confidence, and positivity for housing in winter and grazing in summer, and most negativity for housing cows year-round. Grazing was aspirational, but keeping cows outside in winter was confusing and concerning. These findings offer opportunities for the dairy industry to adapt communication or systems to better meet societal views; for example, incorporating access to pasture or increasing cow choice.

Understanding Perceived Appreciation to Create a Culture of Wellness.

OBJECTIVE: To fully address physician burnout, academic medical centers need cultures that promote well-being. One observed driver of a culture of wellness is perceived appreciation. The authors identified several contributors to perceived appreciation among faculty at a large, metropolitan academic institution through use of a novel survey. METHODS: The authors surveyed clinical faculty in five departments: psychiatry, emergency medicine, internal medicine, thoracic surgery, and radiology. Two open-ended response questions assessed sources of perceived and lack of perceived appreciation in narrative form. The authors also collected data on gender and department identity. Grounded theory methodology was used to analyze the narrative responses and design thinking to brainstorm specific recommendations based on the main themes identified. RESULTS: A total of 179 faculty respondents filled out the survey for an overall response rate of 29%. Major drivers of perceived appreciation were patient and families (42%); physician, trainee and non-physician colleagues (32.7%); chairs (10%); and compensation (3.3%). Major drivers of perceived lack of appreciation were disrespect for time and skill level, including inadequate staffing (30%); devaluation by a physician colleague, chief of one's service or the chair (29%); poor communication and transparency (13%); and patient and family anger (6%). CONCLUSIONS: Opportunities to improve perceived appreciation include structured communication of patient gratitude, community building programs, top of licensure initiatives and accountability for physician wellness, and inclusivity efforts from organizational leaders.

Total Syntheses of (±)-Dracocephalone A and (±)-Dracocequinones A and B.

Described herein are the first total syntheses of (±)-dracocephalone A (1) and (±)-dracocequinones A (4) and B (5). The synthesis was initially envisioned as proceeding through an intramolecular isobenzofuran Diels-Alder reaction, a strategy that eventually evolved into a Lewis acid-promoted spirocyclization. This highly diastereoselective transformation set the stage for trans-decalin formation and a late-stage Suárez oxidation that produced a [3.2.1] oxabicycle suited for conversion to 1. Brønsted acid-mediated aromatization, followed by a series of carefully choreographed oxidations, allowed for rearrangement to a [2.2.2] oxabicycle poised for conversion to 4 and 5.

Building a nursing legacy.

ABSTRACT: A nurse's legacy can be defined in multiple ways. This article describes a project based on a qualitative research study that focused on legacy building in nursing.

Is it just about grazing? UK citizens have diverse preferences for how dairy cows should be managed.

Conflicting views between the dairy industry and the public about how dairy cows should be managed, together with an increase in the availability of alternatives to dairy foods, challenge future markets for milk producers. Members of the public value animal welfare as well as naturalness and grazing, but neither the relative importance of specific aspects of management nor the diversity of views underlying these preferences have been established. To better understand these issues, 2,054 UK citizens recruited through a research panel took part in an online survey. They were asked to rank 17 attributes relating to dairy cow management and milk production through the novel application of best-worst scaling, a discrete choice methodology that allows a trade-off between items. Hierarchical Bayesian analysis of the results revealed 3 attributes of equal top importance: (1) access to grazing, (2) cow health and welfare, and (3) cow comfort. Alongside this overarching ranking, underlying differences in preferences were identified in 6 approximately equally sized citizen groups within the sample, which were identified through latent class analysis. Each latent class expressed significantly different priorities from the other, and each had different indicative sociodemographic, attitudinal, experiential, and value-oriented characteristics, as established through a multinomial logistic model. If the diversity of preference between the citizen groups found in the sample is reflected within wider populations, there may be opportunities for the dairy industry to improve communication about positive practices, develop new dairy product markets, and consider changes to dairy farming systems to better meet different citizens' needs. Furthermore, the defining characteristics and priorities of each group raise the question of whether grazing in particular, but also other attributes presented within the study, is understood in different ways by different subgroups of citizens.

Total Synthesis of (±)-Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen-Oxygen Bonds.

The development of a concise total synthesis of (±)-phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen-oxygen (N-O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early-stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N-O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide.

Evaluation of community pharmacist-provided telephone interventions to improve adherence to hypertension and diabetes medications.

OBJECTIVES: To 1) identify specific patient barriers and pharmacist interventions to medication adherence by means of the Drug Adherence Work-Up (DRAW) tool; and 2) measure patient adherence to antihypertensive and antidiabetic medications by calculating proportion of days covered (PDC) before and after pharmacist telephone adherence interview. DESIGN: This prospective quality-improvement study consisted of telephonic interviews and targeted interventions to increase medication adherence based on patient-specific barriers. The baseline PDC was electronically calculated for each patient, and postintervention PDCs were manually calculated at 90 days and 180 days after baseline. The measurement period in each PDC calculation was 180 days. SETTING AND PATIENTS: This study was conducted in a small-chain independent pharmacy in rural Midwest United States. Patients taking an antihypertensive or oral antidiabetic medication were identified through an online platform and contacted if they had a PDC of less than 80% during the previous 180 days. OUTCOME MEASURES: Baseline and postinterview PDC were calculated for each patient who received an adherence interview. Frequency of specific barriers and pharmacist interventions were identified and analyzed. RESULTS: Ninety-seven eligible patients were identified. Fifty-six patients participated in an interview. Of these, a total of 66 barriers to adherence were identified. Pharmacists implemented 76 interventions for these patients, and 43 patients were included in final PDC calculations. From baseline, 69.0% of patients with hypertension and 64.3% of patients with diabetes reached a PDC of greater than 80% within 3 months. The most frequently identified barrier was forgetfulness on routine days, and the most common interventions were patient education, deactivated drug, and recommend or start medication synchronization program. CONCLUSION: Using pharmacists to identify and address patient barriers to adherence resulted in a significant increase in PDC among patients with hypertension and diabetes. The DRAW tool can be used in a community pharmacist-delivered telephonic intervention to improve medication adherence.

Beyond Self-Report: Performance Measures of Emotional Competencies Predict Symptoms of Depression and Anxiety, Physical Symptoms, Self-Rated Health, and Immunoregulatory Molecules.

BACKGROUND: Most work testing links between emotional competencies and health has focused on self-reported and/or trait assessments. However, more objective assessments of skills and knowledge may also predict health relevant outcomes. PURPOSE: The current study investigated whether performance-based tests of emotional knowledge and expressive skill predicted symptoms of depression and anxiety, self-reported physical symptoms, perceived health, and a range of immunoregulatory molecules. METHODS: Eighty females aged 18-35 completed self-report assessments before attending a testing session in which they provided blood samples and completed performance-based assessments of expressive skill and emotional knowledge. RESULTS: Greater expressive skill predicted better self-reported outcomes, but links to immunoregulatory molecules were mixed. Expressive skill for contempt and anger predicted higher, whereas skill for happiness predicted lower, concentrations of immunoregulatory molecules. CONCLUSIONS: These data highlight the need to extend research beyond self-reported emotional competencies and suggest that performance-based skill and knowledge metrics may be associated with health relevant outcomes.

Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis.

Telehealth Palliative Care in Nursing Homes: A Scoping Review.

OBJECTIVES: Many adults older than 65 spend time in a nursing home (NH) at the end of life where specialist palliative care is limited. However, telehealth may improve access to palliative care services. A review of the literature was conducted to synthesize the evidence for telehealth palliative care in NHs to provide recommendations for practice, research, and policy. DESIGN: Joanna Briggs Institute guidance for scoping reviews, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews frameworks were used to guide this literature review. SETTINGS AND PARTICIPANTS: Reviewed articles focused on residents in NHs with telehealth palliative care interventionists operating remotely. Participants included NH residents, care partner(s), and NH staff/clinicians. METHODS: We searched Medline (Ovid), Embase (Elsevier), Cochrane Library (WileyOnline), Scopus (Elsevier), CINHAL (EBSCOhost), Trip PRO, and Dissertations & Theses Global (ProQuest) in June 2021, with an update in January 2022. We included observational and qualitative studies, clinical trials, quality improvement projects, and case and clinical reports that self-identified as telehealth palliative care for NH residents. RESULTS: The review yielded 11 eligible articles published in the United States and internationally from 2008 to 2020. Articles described live video as the preferred telehealth delivery modality with goals of care and physical aspects of care being most commonly addressed. Findings in the articles focused on 5 patient and family-centered outcomes: symptom management, quality of life, advance care planning, health care use, and evaluation of care. Consistent benefits of telehealth palliative care included increased documentation of goals of care and decrease in acute care use. Disadvantages included technological difficulties and increased NH financial burden. CONCLUSIONS AND IMPLICATIONS: Although limited in scope and quality, the current evidence for telehealth palliative care interventions shows promise for improving quality and outcomes of serious illness care in NHs. Future empirical studies should focus on intervention effectiveness, implementation outcomes (eg, managing technology), stakeholders' experience, and costs.

Use of a multi-phased approach to identify and address facilitators and barriers to the implementation of a population-wide genomic screening program.

INTRODUCTION: Population-wide genomic screening for CDC Tier-1 conditions offers the ability to identify the 1-2% of the US population at increased risk for Hereditary Breast and Ovarian Cancer, Lynch Syndrome, and Familial Hypercholesterolemia. Implementation of population-wide screening programs is highly complex, requiring engagement of diverse collaborators and implementation teams. Implementation science offers tools to promote integration of these programs through the identification of determinants of success and strategies to address potential barriers. METHODS: Prior to launching the program, we conducted a pre-implementation survey to assess anticipated barriers and facilitators to reach, effectiveness, adoption, implementation, and maintenance (RE-AIM), among 51 work group members (phase 1). During the first year of program implementation, we completed coding of 40 work group meetings guided by the Consolidated Framework for Implementation Research (CFIR) (phase 2). We matched the top barriers to implementation strategies identified during phase 2 using the CFIR-ERIC (Expert Recommendation for Implementing Change) matching tool. RESULTS: Staffing and workload concerns were listed as the top barrier in the pre-implementation phase of the program. Top barriers during implementation included adaptability (n = 8, 20%), complexity (n = 14, 35%), patient needs and resources (n = 9, 22.5%), compatibility (n = 11, 27.5%), and self-efficacy (n = 9, 22.5%). We identified 16 potential implementation strategies across six ERIC clusters to address these barriers and operationalized these strategies for our specific setting and program needs. CONCLUSION: Our findings provide an example of successful use of the CFIR-ERIC tool to guide implementation of a population-wide genomic screening program.

Anticipating adaptation: tracking the impact of planned and unplanned adaptations during the implementation of a complex population-based genomic screening program.

In 2021, the Medical University of South Carolina (MUSC) launched In Our DNA SC. This large-scale initiative will screen 100,000 individuals in South Carolina for three preventable hereditary conditions that impact approximately two million people in the USA but often go undetected. In anticipation of inevitable changes to the delivery of this complex initiative, we developed an approach to track and assess the impact of evaluate adaptations made during the pilot phase of program implementation. We used a modified version of the Framework for Reporting Adaptations and Modification-Enhanced (FRAME) and Adaptations to code adaptations made during the 3-month pilot phase of In Our DNA SC. Adaptations were documented in real-time using a REDCap database. We used segmented linear regression models to independently test three hypotheses about the impact of adaptations on program reach (rate of enrollment in the program, rate of messages viewed) and implementation (rate of samples collected) 7 days pre- and post-adaptation. Effectiveness was assessed using qualitative observations. Ten adaptations occurred during the pilot phase of program implementation. Most adaptations (60%) were designed to increase the number and type of patient contacted (reach). Adaptations were primarily made based on knowledge and experience (40%) or from quality improvement data (30%). Of the three adaptations designed to increase reach, shortening the recruitment message potential patients received significantly increased the average rate of invitations viewed by 7.3% (p = 0.0106). There was no effect of adaptations on implementation (number of DNA samples collected). Qualitative findings support improvement in effectiveness of the intervention after shortening the consent form and short-term positive impact on uptake of the intervention as measured by team member's participation. Our approach to tracking adaptations of In Our DNA SC allowed our team to quantify the utility of modifications, make decisions about pursuing the adaptation, and understand consequences of the change. Streamlining tools for tracking and responding to adaptations can help monitor the incremental impact of interventions to support continued learning and problem solving for complex interventions being delivered in health systems based on real-time data.

We tracked adaptations to a large-scale population genetic screening program at the Medical University of South Carolina (MUSC) using the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME). We found adaptations during program roll-out that impacted implementation outcomes. Our approach to tracking adaptations for the program allowed us to quantify the utility of modifications, make decision about pursuing changes, and understand consequences of adaptations.

Innate immune activation during Salmonella infection initiates extramedullary erythropoiesis and splenomegaly.

Systemic Salmonella infection commonly induces prolonged splenomegaly in murine or human hosts. Although this increase in splenic cellularity is often assumed to be due to the recruitment and expansion of leukocytes, the actual cause of splenomegaly remains unclear. We monitored spleen cell populations during Salmonella infection and found that the most prominent increase is found in the erythroid compartment. At the peak of infection, the majority of spleen cells are immature CD71(-)Ter119(+) reticulocytes, indicating that massive erythropoiesis occurs in response to Salmonella infection. Indeed, this increase in RBC precursors corresponded with marked elevation of serum erythropoietin (EPO). Furthermore, the increase in RBC precursors and EPO production required innate immune signaling mediated by Myd88/TRIF. Neutralization of EPO substantially reduced the immature RBC population in the spleen and allowed a modest increase in host control of infection. These data indicate that early innate immunity to Salmonella initiates marked splenic erythropoiesis and may hinder bacterial clearance.

Disaster Preparedness: Keeping Nursing Staff and Students at the Ready.

Humanity is facing an increasing threat to life and property due to an increase in disasters. Disasters occur with little warning and can last for hours or months. Current literature reveals that most nurses are not prepared for a disaster in their community. Continual readiness requires the engagement of staff and nursing students in disaster plan development, review, and implementation. Development of educational training programs that are ongoing, easily accessible, engaging, and realistic is best for skills and competency acquisition. Technology, such as virtual simulation, shows great potential to prepare health care professionals and should be incorporated into disaster preparedness plans.