In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD ...has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education.
Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers.
Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results.
Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.
Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly ...understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.
While the electronic health record (EHR) has become a standard of care, pediatric patients pose a unique set of risks in adult-oriented systems. We describe medication safety and implementation ...challenges and solutions in the pediatric population of a large academic center transitioning its EHR to Epic.
Examination of the roll-out of a new EHR in a mixed neonatal, pediatric and adult tertiary care center with staggered implementation. We followed the voluntarily reported medication error rate for the neonatal and pediatric subsets and specifically monitored the first 3 months after the roll-out of the new EHR. Data was reviewed and compiled by theme.
After implementation, there was a 5-fold increase in the overall number of medication safety reports; by the third month the rate of reported medication errors had returned to baseline. The majority of reports were near misses. Three major safety themes arose: (1) enterprise logic in rounding of doses and dosing volumes; (2) ordering clinician seeing a concentration and product when ordering medications; and (3) the need for standardized dosing units through age contexts created issues with continuous infusions and pump library safeguards.
Future research and work need to be focused on standards and guidelines on implementing an EHR that encompasses all age contexts.
Environmental DNA (eDNA) sampling provides sensitive early detection capabilities for recently introduced taxa. However, natural resource managers struggle with how to integrate eDNA results into an ...early detection rapid response program because positive eDNA detections are not always indicative of an eventual infestation. We used a structured decision making (SDM) framework to evaluate appropriate response actions to hypothetical eDNA early detections of an introduced aquatic plant in Sebago Lake (Maine, USA). The results were juxtaposed to a recent study that used a similar SDM approach to evaluate response actions to hypothetical eDNA early detections of introduced mussels in Jordanelle Reservoir (Utah, USA). We found that eDNA early detections were not actionable in Sebago Lake because the plant's invasion potential was spatially constrained and the current management activities provided acceptable levels of mitigation. In Jordanelle Reservoir, eDNA detections were actionable due to high invasion potential and analyses supported management actions to contain the invasion. The divergent outcomes of the two case studies are related to the unique attributes of the habitats and species, highlighting the utility of the SDM approach when considering an eDNA monitoring program. We use these two case studies to present a general SDM framework and a set of heuristics that can be efficiently applied to eDNA early detection rapid response scenarios and other instances associated with indeterminant eDNA detections, especially when there is an imperative to make decisions as quickly as possible.
•Decision support tools are needed to link eDNA detections to manager responses.•Structured decision making was examined as an eDNA decision support tool.•eDNA results are especially actionable when potential invader impacts are high.•Containing the invasion can be a more optimal response than control actions.•Structured decision making is useful for communicating why a decision was made.
Background. Systemic immune activation is a strong predictor of progression of human immunodeficiency virus type 1 (HIV-1) disease and a prominent feature of infection with Mycobacterium ...tuberculosis. Objective. To understand the role of systemic immune activation and microbial translocation in HIV/tuberculosis dually infected patients over the full spectrum of HIV-1 immunodeficiency, we studied circulating sCD14 and lipopolysaccharide (LPS) and their relationship to HIV-1 activity. Methods. Two cohorts of HIV/tuberculosis subjects defined by CD4 T-cell count at time of diagnosis of tuberculosis were studied: those with low (<350/μL) and those with high (≥350/μL) CD4 T-cell count. Circulating soluble CD14 (sCD14) and LPS were assessed. Results. Levels of sCD14 were higher in HIV/tuberculosis with high (≥350/μL) as compared to low CD4 T-cell count (P < .001). Whereas sCD14 levels remained elevated in HIV/tuberculosis subjects with lower CD4 T-cell counts despite treatment of tuberculosis, in HIV/tuberculosis patients with higher CD4 T-cell count (≥350/μL), levels declined regardless of whether highly active antiretroviral therapy (HAART) was included with the antituberculosis regimen. Circulating LPS levels in HIV/tuberculosis patients with CD4 T-cell count ≥350/μL were unaffected by treatment of tuberculosis with or without HAART. Conclusion. During HIV/tuberculosis, systemic immune activation is dissociated from microbial translocation. Changes in circulating sCD14 and LPS are dependent on CD4 T-cell count.
Interprofessional teams positively affect the quadruple aim of improving patient experience, improving the health of populations, enhancing provider satisfaction, and reducing cost. This report ...details a nurse-led care model developed for a complex patient population in Archer, Florida. The practice, Archer Family Health Care, is a Rural Health Clinic providing integrated primary care and mental health services. The team model included nursing, medicine, and pharmacy professionals and expanded care for case management and mental health. Evaluation included team functionality and clinical outcome data for selected populations. This report describes lessons learned during the implementation process and provides recommendations for the future.
•Implementing an interprofessional nurse-led team can affect patient care outcomes.•Care team impact relies on dissemination of best practices for implementing teams.•Care teams can positively impact patient care outcomes in health care settings.
Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no ...decline in markers of cellular activation in response to TB therapy alone.
This prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm3) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.
Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.
TB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts>350 cells/mm3.
Abstract Background Interprofessional team care is a model that demonstrates positive effects on the triple aim of improving quality of care, improving health and reducing costs. Nurse-led practices ...are well suited for these models. Archer Family Health Care (AFHC) is a nurse-led practice that utilizes interprofessional team care. Purpose To describe interprofessional team training at AFHC and evaluate effects of training on perceived team functioning. Methods The AFHC team participated in TeamSTEPPS® guided trainings throughout the three year grant period. All staff and providers were included in the team trainings. Training consisted of participation in team retreats, training modules and focus group discussions on team functionality, goal setting and workflow analysis and revision. Standardized assessment of the team competencies was completed five times over three years using the TeamSTEPPS® Team Perceptions Questionnaire (T-TPQ), the Collaborative Practice Assessment Tool (CPAT), and the Team Competencies (TC) questionnaire. Results identified perceived strengths and weaknesses of interprofessional team and served to guide team training activities. Discussion Improvements occurred over time for several measures, including teamwork, team performance, communication, and decision-making. Conclusion Standardized evaluation of team competencies is a useful tool to enhance perceived functioning of a nurse-led interprofessional team. Results support the need for ongoing interprofessional team evaluation and training.
Objectives. To determine the academic pharmacy community’s perceptions of and recommendations for tenure and tenure reform.
Methods. A survey instrument was administered via either a live interview ...or an online survey instrument to selected members of the US academic pharmacy community.
Results. The majority of respondents felt that tenure in academic pharmacy was doing what it was intended to do, which is to provide academic freedom and allow for innovation (59.6%). Respondents raised concern over the need for faculty mentoring before and after achieving tenure, whether tenure adequately recognized service, and that tenure was not the best standard for recognition and achievement. The majority (63%) agreed that tenure reform was needed in academic pharmacy, with the most prevalent recommendation being to implement post-tenure reviews. Some disparities in opinions of tenure reform were seen in the subgroup analyses of clinical science vs basic science faculty members, public vs private institutions, and administrators vs nonadministrators.
Conclusions. The majority of respondents want to see tenure reformed in academic pharmacy.
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