Search

Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant genetic condition that carries increased risk for premature atherosclerotic cardiovascular disease, cardiovascular events, and death. Due to low uptake of evidence-based practices, up to 80% of FH patients remain undiagnosed and most are undertreated. This project aimed to understand patient and clinician perceptions across the care pathway of evidence-based diagnosis and treatment of FH, to inform implementation strategy design for two clinical trials seeking to increase evidence-based care. Methods With input from FH experts, we identified key points along the FH care pathway that might be targeted with broad-scale implementation efforts, including: (a) identification of the need for screening; (b) completion of screening test(s); (c) diagnosis; (d) connection to treatment; and (e) family cascade screening (a process used to identify and screen relatives of individuals diagnosed with FH). Then, we conducted qualitative interviews with patients who had participated in a prior FH quality improvement initiative and with clinicians who treat high cholesterol. We analyzed data using thematic analysis. Results We interviewed 21 patients and 17 clinicians. Patient themes offered insights related to the impact of family history, reactions to a diagnosis of high cholesterol and/or FH, experiences with FH treatment and clinical care, perceptions of tools to diagnose FH, motivations and preferences for FH screening efforts, and reactions to family screening. Clinician themes offered insights into the perceived value of FH screening and diagnosis, current FH-related practice and context, and attitudes toward tools to aid clinical practice. In both sets of interviews, confusion and misconceptions about what makes FH unique and its clinical implications were common, as were concerns about logistics and competing priorities. Conclusion Qualitative inquiry generated insights into several modifiable patient and clinician determinants of engagement with evidence-based implementation along the FH care pathway, many of which can be targeted with behavioral economics strategies that simplify complex decisions and by addressing informational and emotional needs. These findings offer actionable insights to inform future implementation research that seeks to close the evidence-to-practice gap in diagnosis and delivery of evidence-based care for FH.

Objective This study identifies preoperative risk factors associated with blood transfusion in women undergoing surgery for ectopic pregnancy. A retrospective chart review of 252 cases was performed at a single academic-affiliated community hospital system between January 2014 and October 2017. Univariate analysis was performed using non-parametric testing where appropriate, and significant variables were incorporated in multivariate modelling.Methods In this cohort of 252 women, the overall transfusion rate was 8.7% (n=22). Increasing age (OR 1.12, 95% CI 1.03 to 1.22), lower systolic blood pressure (SBP) on presentation (OR 0.96, 95% CI 0.93 to 1.00), lower minimum systolic and diastolic blood pressure (DBP) (OR 0.92, 95% CI 0.89 to 1.95 and OR 0.9, 95% CI 0.84 to 0.93) and lower preoperative haemoglobin (g/L) (OR 0.46, 95% CI 0.33 to 0.62) were associated with higher rates of blood transfusion. Women who had prior care in their current pregnancy and women treated in a women’s specific emergency room (compared with a general emergency room) were less likely to be transfused (OR 0.16, 95% CI 0.05 to 0.51 and OR 0.09, 95% CI 0.03 to 0.30, respectively). Our study used a model in which variance in transfusion can reliably be explained by location of presentation to care, pain alone as a presenting complaint and haemoglobin level (Area under the curve (AUC) =0.87).Conclusion History of caesarean section and a presenting complaint of pain alone are newly identified indicators for women at higher risk of transfusion at the time of surgical management of ectopic pregnancy. Additionally, care provided in women’s specific emergency rooms may decrease the risk of blood transfusion in this population.

Abstract Background Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science—including mixed-methods contextual inquiry with clinicians, patients, and health system constituents—to co-design two patient-facing implementation strategies to address this care gap: (a) an automated health system-mediated strategy and (b) a nonprofit foundation-mediated strategy with contact from a foundation-employed care navigator. This trial will test the comparative effectiveness of these strategies on completion of cascade screening for relatives of individuals with FH, centering equitable reach. Methods We will conduct a hybrid effectiveness-implementation type III randomized controlled trial testing the comparative effectiveness of two strategies for implementing cascade screening with 220 individuals with FH (i.e., probands) per arm identified from a large northeastern health system. The primary implementation outcome is reach, or the proportion of probands with at least one first-degree biological relative (parent, sibling, child) in the USA who is screened for FH through the study. Our secondary implementation outcomes include the number of relatives screened and the number of relatives meeting the American Heart Association criteria for FH. Our secondary clinical effectiveness outcome is post-trial proband cholesterol level. We will also use mixed methods to identify implementation strategy mechanisms for implementation strategy effectiveness while centering equity. Discussion We will test two patient-facing implementation strategies harnessing insights from behavioral economics that were developed collaboratively with constituents. This trial will improve our understanding of how to implement evidence-based cascade screening for FH, which implementation strategies work, for whom, and why. Learnings from this trial can be used to equitably scale cascade screening programs for FH nationally and inform cascade screening implementation efforts for other genetic disorders. Trial registration ClinicalTrials.gov, NCT05750667. Registered 15 February 2023—retrospectively registered, https://clinicaltrials.gov/study/NCT05750667 .

Abstract Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration’s GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs.

Background: In 2012, Philadelphia's Department of Behavioral Health and Intellectual disAbility Services (DBHIDS) developed an initiative to implement an evidence-based treatment for posttraumatic stress disorder (PTSD), trauma-focused cognitive behavioral therapy (TF-CBT), across the city's behavioral health system. This report evaluates the initiative's 10-year implementation and effectiveness outcomes. Method: The Exploration, Preparation, Implementation, and Sustainment framework guided our implementation evaluation. The implementation outcomes include adoption, reach, and sustainment; these were obtained during regular evaluation data collection from publicly funded behavioral health agencies participating in the TF-CBT initiative. We analyze effectiveness outcomes (i.e., changes in PTSD symptoms) from a subset of patients receiving TF-CBT, which were collected in 6-month intervals by our research team between 2013 and 2021. Results: From 2012 to 2021, DBHIDS trained 478 clinicians in TF-CBT across 20 behavioral health agencies. During this time, 23,401 youths were screened for potentially traumatic events and PTSD symptoms, and 7,550 youths received TF-CBT. Through the TF-CBT initiative, the city expanded the network of TF-CBT providers from 3 to 20 agencies. DBHIDS sustained this network by maintaining the participation of 16 behavioral health agencies over the course of a decade. The subset of 202 youths who were evaluated to assess TF-CBT effectiveness was drawn from 94 therapists and 20 agencies across Philadelphia. All participating youths completed a baseline assessment, and 151 (75%) completed at least one follow-up assessment. Linear mixed-effects models accounting for observations nested within participants and nested within clinicians found that treatment significantly reduced PTSD symptoms. Conclusion: Between 2012 and 2021, DBHIDS successfully implemented and sustained TF-CBT across the city's behavioral health system. Adoption, reach, and sustainment of TF-CBT were high. Despite the considerable adverse experiences faced by youths seeking treatment in Philadelphia's behavioral health system, TF-CBT was effective. Future directions to improve TF-CBT implementation in the next iteration of the initiative are described.

Abstract Background People with dementia have unique palliative and end-of-life needs. However, access to quality palliative and end-of-life care for people with dementia living in nursing homes is often suboptimal. There is a recognised need for nursing home staff training in dementia-specific palliative care to equip them with knowledge and skills to deliver high quality care. Objective The primary aim was to evaluate the effectiveness of a simulation training intervention (IMPETUS-D) aimed at nursing home staff on reducing unplanned transfers to hospital and/or deaths in hospital among residents living with dementia. Design Cluster randomised controlled trial of nursing homes with process evaluation conducted alongside. Subjects & setting One thousand three hundred four people with dementia living in 24 nursing homes (12 intervention/12 control) in three Australian cities, their families and direct care staff. Methods Randomisation was conducted at the level of the nursing home (cluster). The allocation sequence was generated by an independent statistician using a computer-generated allocation sequence. Staff from intervention nursing homes had access to the IMPETUS-D training intervention, and staff from control nursing homes had access to usual training opportunities. The predicted primary outcome measure was a 20% reduction in the proportion of people with dementia who had an unplanned transfer to hospital and/or death in hospital at 6-months follow-up in the intervention nursing homes compared to the control nursing homes. Results At 6-months follow-up, 128 (21.1%) people with dementia from the intervention group had an unplanned transfer or death in hospital compared to 132 (19.0%) residents from the control group; odds ratio 1.14 (95% CI, 0.82-1.59). There were suboptimal levels of staff participation in the training intervention and several barriers to participation identified. Conclusion This study of a dementia-specific palliative care staff training intervention found no difference in the proportion of residents with dementia who had an unplanned hospital transfer. Implementation of the intervention was challenging and likely did not achieve adequate staff coverage to improve staff practice or resident outcomes. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618002012257 . Registered 14 December 2018.

Introduction Names are a reflection of identity and often have personal meaning. The chronic mispronunciation of names can undermine one's identity and be experienced as a microaggression. This workshop aims to provide historical context for names as well as resources for correct name pronunciation. Methods We developed a 60-minute interactive virtual workshop with didactics, small-group sharing of personal experiences, and case discussions. We used an anonymous postworkshop survey to evaluate workshop effectiveness. Results We presented the workshop at one local academic conference and two local educational conferences to learners of all levels from medical students to faculty. We collected postworkshop survey results from 78 participants of diverse racial and ethnic backgrounds. Participants reported learning historical context, ways to ask about correct name pronunciation, correcting name mispronunciation, documenting pronunciation, and sources for applications to practice. The main barriers to implementing workshop lessons included personal and structural factors. Discussion This workshop effectively fills an educational gap by addressing the importance of correct name pronunciation in order to provide a more inclusive environment for clinicians and patients alike.

Abstract Background Insights from behavioral economics, or how individuals’ decisions and behaviors are shaped by finite cognitive resources (e.g., time, attention) and mental heuristics, have been underutilized in efforts to increase the use of evidence-based practices in implementation science. Using the example of firearm safety promotion in pediatric primary care, which addresses an evidence-to-practice gap in universal suicide prevention, we aim to determine: is a less costly and more scalable behavioral economic-informed implementation strategy (i.e., “Nudge”) powerful enough to change clinician behavior or is a more intensive and expensive facilitation strategy needed to overcome implementation barriers? Methods The Adolescent and child Suicide Prevention in Routine clinical Encounters (ASPIRE) hybrid type III effectiveness-implementation trial uses a longitudinal cluster randomized design. We will test the comparative effectiveness of two implementation strategies to support clinicians’ use of an evidence-based firearm safety practice, S.A.F.E. Firearm, in 32 pediatric practices across two health systems. All pediatric practices in the two health systems will receive S.A.F.E. Firearm materials, including training and cable locks. Half of the practices (k = 16) will be randomized to receive Nudge; the other half (k = 16) will be randomized to receive Nudge plus 1 year of facilitation to target additional practice and clinician implementation barriers (Nudge+). The primary implementation outcome is parent-reported clinician fidelity to the S.A.F.E Firearm program. Secondary implementation outcomes include reach and cost. To understand how the implementation strategies work, the primary mechanism to be tested is practice adaptive reserve, a self-report practice-level measure that includes relationship infrastructure, facilitative leadership, sense-making, teamwork, work environment, and culture of learning. Discussion The ASPIRE trial will integrate implementation science and behavioral economic approaches to advance our understanding of methods for implementing evidence-based firearm safety promotion practices in pediatric primary care. The study answers a question at the heart of many practice change efforts: which strategies are sufficient to support change, and why? Results of the trial will offer valuable insights into how best to implement evidence-based practices that address sensitive health matters in pediatric primary care. Trial registration ClinicalTrials.gov, NCT04844021 . Registered 14 April 2021.

Abstract Background Complement activation is a central mechanism in systemic inflammation and remote organ dysfunction following major trauma. Data on temporal changes of complement activation early after injury is largely missing. We aimed to describe in detail the kinetics of complement activation in individual trauma patients from admission to 10 days after injury, and the association with trauma characteristics and outcome. Methods In a prospective cohort of 136 trauma patients, plasma samples obtained with high time resolution (admission, 2, 4, 6, 8 h, and thereafter daily) were assessed for terminal complement complex (TCC). We studied individual TCC concentration curves and calculated a summary measure to obtain the accumulated TCC response 3 to 6 h after injury (TCC-AUC3–6). Correlation analyses and multivariable linear regression analyses were used to explore associations between individual patients’ admission TCC, TCC-AUC3–6, daily TCC during the intensive care unit stay, trauma characteristics, and predefined outcome measures. Results TCC concentration curves showed great variability in temporal shapes between individuals. However, the highest values were generally seen within the first 6 h after injury, before they subsided and remained elevated throughout the intensive care unit stay. Both admission TCC and TCC-AUC3–6 correlated positively with New Injury Severity Score (Spearman’s rho, p-value 0.31, 0.0003 and 0.21, 0.02) and negatively with admission Base Excess (− 0.21, 0.02 and − 0.30, 0.001). Multivariable analyses confirmed that deranged physiology was an important predictor of complement activation. For patients without major head injury, admission TCC and TCC-AUC3–6 were negatively associated with ventilator-free days. TCC-AUC3–6 outperformed admission TCC as a predictor of Sequential Organ Failure Assessment score at day 0 and 4. Conclusions Complement activation 3 to 6 h after injury was a better predictor of prolonged mechanical ventilation and multiple organ dysfunction syndrome than admission TCC. Our data suggest that the greatest surge of complement activation is found within the first 6 h after injury, and we argue that this time period should be in focus in the design of future experimental studies and clinical trials using complement inhibitors.

COVID-19, caused by SARS-CoV-2, is a systemic illness due to its multiorgan effects in patients. The disease has a detrimental impact on respiratory and cardiovascular systems. One early symptom of infection is anosmia or lack of smell; this implicates the involvement of the olfactory bulb in COVID-19 disease and provides a route into the central nervous system. However, little is known about how SARS-CoV-2 affects neurological or psychological symptoms. SARS-CoV-2 exploits host receptors that converge on pathways that impact psychological symptoms. This systemic review discusses the ways involved by coronavirus infection and their impact on mental health disorders. We begin by briefly introducing the history of coronaviruses, followed by an overview of the essential proteins to viral entry. Then, we discuss the downstream effects of viral entry on host proteins. Finally, we review the literature on host factors that are known to play critical roles in neuropsychiatric symptoms and mental diseases and discuss how COVID-19 could impact mental health globally. Our review details the host factors and pathways involved in the cellular mechanisms, such as systemic inflammation, that play a significant role in the development of neuropsychological symptoms stemming from COVID-19 infection.

ObjectiveIn a recent study, we found an elevated level of interleukin 8 (IL-8) in response to bacterial incubation in thrombin-sufficient human whole blood anticoagulated by the fibrin polymerization blocking peptide GPRP. Whether thrombin directly activated leukocytes or mediated the release via thrombin-dependent activation of platelets remains unresolved. Herein, we addressed the role of thrombin and platelets in IL-8 release.MethodsWe separated platelets from whole blood using a combination of 0.7% (w/v) citrate and GPRP for attenuating the hemostatic response during the separation of platelets. Cytokine responses were compared in whole blood and platelet-depleted blood upon Escherichia coli incubation. Cytokine responses were also profiled with and without reconstitution of either platelets or the supernatant from activated platelets.ResultsPlatelets were not activated during the separation process but responded to stimuli upon re-calcification. Plasma levels of IL-1β, IL-1Ra, IL-6, IL-8, IP-10, MIP-1α, and MIP-1β were significantly reduced in platelet-depleted blood compared to whole blood, but recovered in the presence of platelets, or with the supernatant of activated platelets. The leukocyte fraction and platelets were each found to contribute to the elevation of IL-8 at around 5 ng/ml; however, if combined, the release of IL-8 increased to 26 ng/ml. This process was dependent on thrombin since the levels of IL-8 remained at 5 ng/ml in whole blood if thrombin was blocked. Intracellular staining revealed that monocytes were the main source for IL-8 expression.ConclusionOur findings suggest that the release of IL-8 is mediated by the leukocytes, mainly monocytes, but potentiated via thrombin-dependent activation of platelets.

Abstract Background Caller satisfaction with telephone advice nursing (TAN) is generally high, and the interaction is essential. However, a valid questionnaire exploring caller satisfaction in TAN with focus on perceived interaction is lacking. Objective To develop and assess content validity and test‐retest reliability of a theoretically anchored questionnaire, the Telenursing Interaction and Satisfaction Questionnaire (TISQ), that explores caller satisfaction in TAN by focusing on perceived interaction between the caller and the telenurse. Methods The study was performed in three stages. First, variables relevant for patient satisfaction in health care were identified through a literature search. Variables were then structured according to the Interaction Model of Client Health Behavior (IMCHB), which provided theoretical guidance. Items relevant for a TAN context were developed through consensus discussions. Then, evaluation and refinement were performed through cognitive interviews with callers and expert ratings of the Content Validity Index (CVI). Finally, test‐retest reliability of items was evaluated in a sample of 109 individuals using intraclass correlation coefficients (ICC). Results The TISQ consists of 60 items. Twenty items cover perceived interaction in terms of health information, affective support, decisional control and professional/technical competence. Five items cover satisfaction with interaction and five items overall satisfaction. Remaining items reflect singularity of the caller and descriptive items of the call. The TISQ was found to exhibit good content validity, and test‐retest reliability was moderate to good (ICC = 0.39‐0.84). Conclusions The items in the TISQ form a comprehensive and theoretically anchored questionnaire with satisfactory content validity and test‐retest reliability.

With the recent rise of alternative instructional methodologies such as flipped classrooms and active learning, many core concepts are being introduced outside of the classroom prior to scheduled class meeting times. One popular means for external concept introduction in many undergraduate biology courses is the use of stand-alone online learning modules. Using a group of four large introductory biology course sections, we investigate the use of a stand-alone online learning module developed using animations from Virtual Cell Animation Collection as a resource for the introduction of cellular respiration concepts outside of the classroom. Results from four sections of introductory biology (n = 629) randomized to treatments show that students who interacted with the stand-alone online learning module had significantly higher normalized gain scores on a cellular respiration assessment than students who only attended a traditional lecture as a means of concept introduction (p < 0.001, d = 0.59). These findings suggest a superior ability to convey certain introductory cellular respiration topics in a stand-alone manner outside of the classroom than in a more traditional lecture-based classroom setting.

Many undergraduate biology courses have begun to implement instructional strategies aimed at increasing student interaction with course material outside of the classroom. Two examples of such practices are introducing students to concepts as preparation prior to instruction, and as conceptual reinforcement after the instructional period. Using a three-group design, we investigate the impact of an animation developed as part of the Virtual Cell Animation Collection on the topic of concentration gradients and their role in the actions of ATP synthase as a means of pre-class preparation or post-class reinforcement compared with a no-intervention control group. Results from seven sections of introductory biology (n = 732) randomized to treatments over two semesters show that students who viewed animation as preparation (d = 0.44, p < 0.001) or as reinforcement (d = 0.53, p < 0.001) both outperformed students in the control group on a follow-up assessment. Direct comparison of the preparation and reinforcement treatments shows no significant difference in student outcomes between the two treatment groups (p = 0.87). Results suggest that while student interaction with animations on the topic of concentration gradients outside of the classroom may lead to greater learning outcomes than the control group, in the traditional lecture-based course the timing of such interactions may not be as important.

A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom.

Statement of Purpose: Pediatric firearm access is a significant risk factor for unintentional injury and suicide. This study investigated parents' perspectives on an adapted firearm safety program, "S.A.F.E. Firearm," to ensure acceptability and optimize effectiveness prior to the launch of an upcoming hybrid effectiveness-implementation trial. Methods/Approach: We administered a cross-sectional survey with a convenience sample of U.S. parents to measure the acceptability of "S.A.F.E. Firearm" and other key variables (e.g., relationship with pediatrician) that may impact our implementation approach. The sample included 97 participants (52 firearm-owning and 45 non-owning) from across the country. We also conducted semi-structured interviews using a Think Aloud exercise with 11 survey participants that were analyzed with directed content analysis. Results: The mean acceptability score was 4.35 [SD 0.52] on a 1-5 Likert scale, indicating that participants viewed S.A.F.E. Firearm as highly acceptable. Most participants (84%) either agreed or completely agreed with recommending that a friend receive "S.A.F.E. Firearm." No significant differences in acceptability scores were found by firearm ownership status, gender, race and ethnicity, or region of residence. Parent-pediatrician depth of relationship was associated with acceptability (r= 0.21, p=0.038). Interviews indicated that a collaborative approach to decision-making, neutral messaging, and provision of tangible resources were key factors that contributed to the program's overall high acceptability scores. Conclusion & Significance: The present study served as the final check in our process of adapting an evidence-based safe firearm storage program to increase reach and effectiveness as a universal suicide prevention strategy in pediatric primary care. Convergent parent feedback confirms that "S.A.F.E. Firearm" is highly acceptable and ready for implementation. Moreover, our findings suggest that family-centeredness may be enhanced through explicit integration of parents' needs and preferences into program refinements. Use of qualitative Think Aloud exercises with end user groups can add value when actual implementation of firearm safety programs can only be approximated.