Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing.

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.

The genetic architecture of pediatric cardiomyopathy.

To understand the genetic contribution to primary pediatric cardiomyopathy, we performed exome sequencing in a large cohort of 528 children with cardiomyopathy. Using clinical interpretation guidelines and targeting genes implicated in cardiomyopathy, we identified a genetic cause in 32% of affected individuals. Cardiomyopathy sub-phenotypes differed by ancestry, age at diagnosis, and family history. Infants < 1 year were less likely to have a molecular diagnosis (p < 0.001). Using a discovery set of 1,703 candidate genes and informatic tools, we identified rare and damaging variants in 56% of affected individuals. We see an excess burden of damaging variants in affected individuals as compared to two independent control sets, 1000 Genomes Project (p < 0.001) and SPARK parental controls (p < 1 × 10-16). Cardiomyopathy variant burden remained enriched when stratified by ancestry, variant type, and sub-phenotype, emphasizing the importance of understanding the contribution of these factors to genetic architecture. Enrichment in this discovery candidate gene set suggests multigenic mechanisms underlie sub-phenotype-specific causes and presentations of cardiomyopathy. These results identify important information about the genetic architecture of pediatric cardiomyopathy and support recommendations for clinical genetic testing in children while illustrating differences in genetic architecture by age, ancestry, and sub-phenotype and providing rationale for larger studies to investigate multigenic contributions.

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.

A human importin-ß-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8.

Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-ß protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-ß signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes. Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay, connective tissue findings, and craniofacial dysmorphic features. A C57BL/6N Ipo8 knockout mouse model recapitulates TAA development from 8-12 weeks onward in both sexes but most prominently shows ascending aorta dilatation with a propensity for dissection in males. Compliance assays suggest augmented passive stiffness of the ascending aorta in male Ipo8-/- mice throughout life. Immunohistological investigation of mutant aortic walls reveals elastic fiber disorganization and fragmentation along with a signature of increased TGF-ß signaling, as evidenced by nuclear pSmad2 accumulation. RT-qPCR assays of the aortic wall in male Ipo8-/- mice demonstrate decreased Smad6/7 and increased Mmp2 and Ccn2 (Ctgf) expression, reinforcing a role for dysregulation of the TGF-ß signaling pathway in TAA development. Because importin 8 is the most downstream TGF-ß-related effector implicated in TAA pathogenesis so far, it offers opportunities for future mechanistic studies and represents a candidate drug target for TAA.

Correlations Between Relative Prevalence of Celiac Disease and Sociodemographic Variables in the United States.

INTRODUCTION: We evaluated the associations between celiac disease (CD) prevalence and regional sociodemographic variables in the United States. METHODS: The outcome was CD relative prevalence, defined as number of patients with CD among those in a Medicare registry per 3-digit ZIP code. Linear regression models assessed associations between relative prevalence of CD and sociodemographic variables. RESULTS: CD relative prevalence was positively correlated with median income, urban area, and proximity to a CD specialty center and negatively correlated with Black race, Latino/Hispanic ethnicity, and median social deprivation index score ( P < 0.01, all). DISCUSSION: CD relative prevalence is associated with indicators of economic advantage.

Identifying competencies in advanced healthcare practice: an umbrella review.

The four pillars of advanced healthcare practice (AHCP) are clinical practice, leadership and management, education, and research. It is unclear, however; how competencies of AHCP as defined by individual health professions relate to these pillars. Addressing this knowledge gap will help to facilitate the operationalization of AHCP as a concept and help inform educational curricula. To identify existing competencies across AHCP literature and examine how they relate to the four pillars of a multi-professional AHCP framework. An umbrella review was conducted in accordance with JBI methodology. The electronic search for published and grey literature was completed using CINAHL, Scopus, Medline (OVID), Embase (OVID), ERIC (OVID) and Google. Secondary reviews and research syntheses of master level AHCP programs published after 1990 in either English or French were considered for inclusion and results were analyzed using a directed content analysis. Seventeen publications detailing 620 individual competencies were included. AHCP competencies were described across four professions and 22 countries, with many publications related to nursing and AHCP in the United Kingdom, Canada, and Australia. Many retrieved competencies were found to map to the four pillars of AHCP, although clinical practice and leadership and management pillars were addressed more often. Competencies of AHCP are generally consistent with the four pillars. However, the distribution of competencies is unequal across pillars, professions, and geographical regions, which may provide direction for further research. Doi: 10.17605/OSF.IO/KV2FD Published on March 07, 2023.

Cardiac genetic counseling services: Exploring downstream revenue in a pediatric medical center.

Genetic counseling is an important component of pediatric cardiac care. The financial costs and benefits of this care have yet to be defined in the literature. Downstream revenue (DSR) analysis can be used to assess the economic impact of genetic counselors (GCs) at their institution beyond the initial patient contact. Previous literature has reported DSR generated by oncology GCs, but there is no published DSR data from a cardiac GC setting. This study measured the DSR generated at a private hospital following a cardiac GC appointment. A chart review identified patients seen by a cardiac GC between 2018 and 2022. The study population included patients and their pediatric relatives who had not previously seen a cardiologist. Patients were included if they were affected with or at-risk for long QT syndrome, hypertrophic cardiomyopathy, dilated cardiomyopathy, or familial thoracic aortic aneurysm at the time of the GC visit. We recorded the frequency of common cardiac services and calculated the reimbursement for all cardiology services for 1 year following the initial GC appointment. The cohort included 121 participants from 61 families. Most individuals were at-risk for (n = 114, 94.3%) rather than affected by an inherited cardiac condition and presented for screening. The total DSR was $247,592.27, with an annual median of $1819.50 per patient (IQR $0, $3761.33). Revenue was similar among individuals who had undergone genetic testing and those who had not. Among participants, 72 (59.5%) had subsequent cardiology services. Most frequently, a patient who presented for subsequent care had an EKG, an echocardiogram, and a cardiology appointment. While the economic contributions of GC services do not speak to the broader value of GC involvement in patient care, they are important metrics for sustainability. This study outlines an approach to evaluating DSR and establishes a baseline understanding of DSR related to cardiac GC services.

Genetic testing and counseling for hypertrophic cardiomyopathy: An evidence-based practice resource of the National Society of Genetic Counselors.

Hypertrophic cardiomyopathy (HCM) is a common hereditary condition affecting approximately 1 in 500 adults. It is characterized by marked clinical heterogeneity with individuals experiencing minimal to no symptoms, while others may have more severe outcomes including heart failure and sudden cardiac death. Genetic testing for HCM is increasingly available due to advances in DNA sequencing technologies and reduced costs. While a diagnosis of HCM is a well-supported indication for genetic testing and genetic counseling, incorporation of genetic services into the clinical setting is often limited outside of expert centers. As genetic counseling and testing have become more accessible and convenient, optimal integration of genomic data into the clinical care of individuals with HCM should be instituted, including delivery via genetic counseling. Drawing on recommendations from recent disease guidelines and systematic evidence reviews, we highlight key recommendations for HCM genetic testing and counseling. This practice resource provides a comprehensive framework to guide healthcare providers in the process of genetic test selection, variant classification, and cascade testing for genetic evaluation of HCM.

Preparedness and training of genetic counselors practicing in inpatient settings.

As rapid genomic testing technology increasingly allows for real-time answers that could alter management for acutely ill patients, opportunities for genetic counselors to work in inpatient settings will increase. However, genetic counselors' preparedness and the training provided by graduate programs to work in inpatient settings are unknown. We conducted semi-structured interviews with 13 genetic counselors who provided services in varied inpatient settings to assess genetic counselors' readiness for inpatient positions. We also surveyed members of the Association of Genetic Counseling Program Directors (AGCPD) about inpatient training practices of genetic counseling graduate programs. Genetic counselors were recruited through the National Society of Genetic Counselors (NSGC) Inpatient Special Interest Group listserv and graduate program faculty were recruited through the AGCPD listserv. Some challenges reported by genetic counselors in inpatient settings included working in a fast-paced hospital environment which necessitated focused interactions with patients; collaborating with diverse providers who may not understand the role of genetic counselors; and navigating grief experiences of families and of themselves as a provider. Although genetic counselors felt that many of their skills developed in graduate school were transferrable to the inpatient setting, those who had minimal or no inpatient exposure in graduate school often described feeling unprepared for working in the inpatient setting. The majority of AGCPD respondents (23/28) indicated their program provided some type of exposure to the inpatient setting for students, the most common (22/23) being an inpatient clinical rotation, which suggests many graduate programs are already recognizing the importance of providing inpatient training. Our findings indicate that while many skills are transferrable to inpatient positions, genetic counselors face unique challenges in inpatient settings. Our results suggest that graduate exposure to the inpatient setting and professional support of inpatient genetic counselors are beneficial to support genetic counselors' preparedness to take on inpatient positions.

Promoting harm reduction in rural South Dakota using an interdisciplinary consortium.

BACKGROUND: Deaths from drug-related overdoses are increasing. Rural areas continue to have fewer accessible resources than urban areas. The START-SD (Stigma, Treatment, Avoidance, and Recover in Time - South Dakota) project is funded by the Health Resources and Services Administration and aims to address needs surrounding substance use disorder (SUD) in South Dakota. Pharmacists can play a key role in these efforts. OBJECTIVE: Describe harm reduction and prevention activities implemented through START-SD to reduce the impact of SUD in South Dakota. PRACTICE DESCRIPTION: The interdisciplinary team at South Dakota State University, including pharmacists and student pharmacist researchers, partnered with collaborating organizations to provide improved access to prevention, treatment, and recovery services for those impacted by SUD. PRACTICE INNOVATION: Given the rural and conservative nature of the state, the START-SD team used an innovative framework to implement harm reduction and prevention programs that other states could adopt. EVALUATION METHODS: Because the START-SD project uses evidence-based programs, evaluation focuses on the number of programs implemented and the number of people subsequently served. Data are collected and reported biannually by the team. RESULTS: The core team established and expanded an interdisciplinary consortium and advisory board. A variety of harm reduction and prevention strategies were implemented: establishing and developing partnerships with key organizations, working to increase access to harm reduction programs, facilitating educational activities and trainings, and working to reduce stigma related to SUD and harm reduction. DISCUSSION: Reducing the impact of SUD requires a broad, multifaceted approach, as well as overcoming many environmental barriers. Pharmacists and pharmacy staff are uniquely positioned to positively affect harm reduction for patients. CONCLUSION: More work to decrease the impact of SUD is needed, particularly in rural areas. Pharmacists can play a key role in projects to increase the reach and impact of prevention, treatment, and recovery efforts.

Principles of microvascular surgery in the upper extremity.

Upper extremity replantation and microsurgery can be challenging even for the experienced hand and upper extremity surgeon and requires thoughtful consideration and evaluation. This review aims to discuss the general considerations in upper extremity replantation management from the preoperative through the postoperative period.

Smooth muscle differentiation shapes domain branches during mouse lung development.

During branching morphogenesis, a simple cluster of cells proliferates and branches to generate an arborized network that facilitates fluid flow. The overall architecture of the mouse lung is established by domain branching, wherein new branches form laterally off the side of an existing branch. The airway epithelium develops concomitantly with a layer of smooth muscle that is derived from the embryonic mesenchyme. Here, we examined the role of smooth muscle differentiation in shaping emerging domain branches. We found that the position and morphology of domain branches are highly stereotyped, as is the pattern of smooth muscle that differentiates around the base of each branch. Perturbing the pattern of smooth muscle differentiation genetically or pharmacologically causes abnormal domain branching. Loss of smooth muscle results in ectopic branching and decreases branch stereotypy. Increased smooth muscle suppresses branch initiation and extension. Computational modeling revealed that epithelial proliferation is insufficient to generate domain branches and that smooth muscle wrapping is required to shape the epithelium into a branch. Our work sheds light on the physical mechanisms of branching morphogenesis in the mouse lung.

A clinical scoring system for early onset (neonatal) Marfan syndrome.

PURPOSE: This study aimed to develop objective diagnostic criteria for early onset Marfan syndrome (eoMFS) to facilitate early diagnosis and timely interventions. METHODS: On the basis of an extensive literature review and the responses from a survey distributed among providers with expertise in the diagnosis and management of eoMFS, we developed an age-based, diagnostic scoring system encompassing 10 features common to eoMFS (9 clinical + 1 laboratory) and divided them into cardiac, systemic, and FBN1 (on the basis of the location of the pathogenic FBN1 variant) scores. RESULTS: In total, 77 individuals with eoMFS (13 newly reported) and 49 individuals diagnosed with classical Marfan syndrome during early childhood were used to validate the criteria. Median cardiac (8 vs 0, P < .001), systemic (11 vs 3, P < .001), FBN1 (5 vs 0, P < .001), and total (23 vs 4, P < .001) scores were significantly higher in individuals with eoMFS than in those without. A proposed clinical score (cardiac + systemic) cutoff of ≥14 points showed excellent sensitivity (100%), specificity (92%), and reliability (correctly classified = 94%). CONCLUSION: Distinct from classical Marfan syndrome in phenotype and morbidity, eoMFS can be diagnosed clinically using an objective scoring system encompassing the typical physical features and cardiac disease manifestations. Although genetic testing can be suggestive of eoMFS, genetic testing alone is insufficient for diagnosis.

Using artificial intelligence to support rapid, mixed-methods analysis: Developing an automated qualitative assistant (AQUA).

Context: Qualitative research - crucial for understanding human behavior - remains underutilized, in part due to the time and cost of annotating qualitative data (coding). Artificial intelligence (AI) has been suggested as a means to reduce those burdens. Older AI techniques (Latent Semantic Indexing / Latent Dirichlet Allocation (LSI/LDA)) have fallen short, in part because qualitative data is rife with idiom, non-standard expressions, and jargon. Objective: To develop an AI platform using updated techniques to augment qualitative data coding. Study Design and Analysis: We previously completed traditional qualitative analysis of a large dataset, with 11 qualitative categories and 72 subcategories (categories), and a final Cohen's kappa ≥ 0.65 as a measure of human inter-coder reliability (ICR) after coding. We built our Automated Qualitative Assistant (AQUA) using a semi-classical approach, replacing LSI/LDA with a graph-theoretic topic extraction and clustering method. AQUA was given the previously-identified qualitative categories and tasked with coding free-text data into those categories. Item coding was scored using cosine-similarity. Population Studied: Pennsylvanian adults. Instrument: Free-text responses to five open ended questions related to the COVID-19 pandemic (e.g. "What worries you most about the COVID-19 pandemic?"). Outcome Measures: AQUA's coding was compared to human coding using Cohen's kappa. This was done on all categories in aggregate, and also on category clusters to identify category groups amenable to AQUA support. AQUA's time to complete coding was compared to the time taken by the human coding team. Dataset: Five unlimited free-text survey answers from 538 responders. Results: AQUA's kappa for all categories was low (kappa~0.45), reflecting the challenge of automated analysis of diverse language. However, for several 3-category combinations (with less linguistic diversity), AQUA performed comparably to human coders, with an ICR kappa range of 0.62 to 0.72 based on test-train split. AQUA's analysis (including human interpretation) took approximately 5 hours, compared to approximately 30 person hours for traditional coding. Conclusions: AQUA enables qualitative researchers to identify categories amenable to automated coding, and to rapidly conduct that coding on the entirety of very large datasets. This saves time and money, and avoids limitations inherent in limiting qualitative analysis to limited samples of a given dataset.

Perceptions and knowledge regarding the COVID-19 pandemic between U.S. and China: a mixed methods study.

BACKGROUND: SARS-CoV-2, a new coronavirus first reported by China on December 31st, 2019, has led to a global health crisis that continues to challenge governments and public health organizations. Understanding COVID-19 knowledge, attitudes, and practices (KAP) is key for informing messaging strategies to contain the pandemic. Cross-national studies (e.g.: comparing China to the U.S.) are needed to better understand how trans-cultural differences may drive differences in pandemic response and behaviors. The goal of the study is to compare knowledge and perceptions of COVID-19 between adults in China and the U.S. These data will provide insight into challenges these nations may face in coordinating pandemic response. METHODS: This is a convergent mixed methods study comparing responses from China and the U.S. to a multinational COVID-19 KAP online survey. The survey included five quantitative constructs and five open-ended questions. Chinese respondents (n = 56) were matched for gender, age, education, perceived social standing, and time of survey completion with a U.S. cohort (n = 57) drawn from 10,620 U.S. RESPONDENTS: Quantitative responses were compared using T-test & Fisher-Exact tests. Inductive thematic analysis was applied to open-ended questions. RESULTS: Both U.S. and Chinese samples had relatively high intention to follow preventive behaviors overall. Differences in intended compliance with a specific recommendation appear to be driven by the different cultural norms in U.S. and China. Both groups expressed trepidation about the speed of COVID-19 vaccine development, driven by concern for safety among Chinese respondents, and concern for efficacy among U.S. RESPONDENTS: The Chinese cohort expressed worries about other countries' passive handling of the pandemic while the U.S. cohort focused on domestic responses from individuals and government. U.S. participants appeared more knowledgeable on some aspects of COVID-19. Different perspectives regarding COVID-19 origins were identified among the two groups. Participants from both samples reported high trust in health professionals and international health organizations. CONCLUSIONS: Mixed methods data from this cross-national analysis suggests sociocultural differences likely influence perceptions and knowledge of COVID-19 and its related public health policies. Discovering and addressing these culturally-based differences and perceptions are essential to coordinate a global pandemic response.

Retrospective comparison of parent-reported genetics knowledge, empowerment, and familial uptake of cardiac screening between parents who received genetic counseling by a certified genetic counselor and those who did not: A single US academic medical center study.

Bicuspid aortic valve (BAV) is the most common congenital heart defect, which can cause severe cardiac complications. BAVs cluster in families and demonstrate high heritability. Cardiac screening for first-degree relatives of individuals with a BAV is recommended. This retrospective two-group study evaluated the impact of cardiovascular genetic counseling provided by a board-certified genetic counselor on parent-reported outcomes by comparing parental responses of those who received genetic counseling by a genetic counselor (GC group) for family history of BAV to those who did not (non-GC group). A retrospective chart review from May 2016 to June 2019 identified 133 pediatric patients with an isolated BAV. Parents of eligible probands were invited to complete an online survey assessing genetics knowledge, empowerment (Genomics Outcome Scale), and familial uptake of cardiac screening. Surveys were completed by 38/97 (39%) parents in the non-GC group and 20/36 (56%) parents in the GC group. The median genetics knowledge score was not significantly different between the two groups (GC group: 8, range 3-11 out of a maximum possible of 12; non-GC group: 7, range 2-11; p = .08). The mean empowerment score was not significantly different between the two groups (GC group: mean 24.6, SD 2.2; non-GC group: mean 23.2, SD 3.5; p = .06). The uptake of cardiac screening was significantly higher in the GC group with 39/59 (66%) total first-degree relatives reported as having been screened compared with 36/91 (40%) in the non-GC group (p = .002). Parent-reported outcomes in our study suggest that receiving genetic counseling by a board-certified genetic counselor significantly increased familial uptake of cardiac screening for first-degree relatives of pediatric patients with a BAV. Studies with larger sample sizes are needed to confirm the findings of this study; however, a referral to a genetic counselor should be considered for patients with a BAV.

The Effect of Blood Flow Restriction Training on Muscle Atrophy Following Meniscal Repair or Chondral Restoration Surgery in Active Duty Military: A Randomized Controlled Trial.

CONTEXT: Recently, blood flow restriction (BFR) training has gained popularity as an alternative to high-load resistance training for improving muscle strength and hypertrophy. Previous BFR studies have reported positive treatment effects; however, clinical benefits to using BFR following meniscal repair or chondral surgery are unknown. The purpose of this study was to determine the effect of resistance exercises with BFR training versus exercises alone on self-reported knee function, thigh circumference, and knee flexor/extensor strength postmeniscal or cartilage surgery. DESIGN: Single-blinded randomized controlled trial in an outpatient military hospital setting. Twenty participants were randomized into 2 groups: BFR group (n = 11) and control group (n = 9). METHODS: Participants completed 12 weeks of postoperative thigh strengthening. The BFR group performed each exercise with the addition of BFR. Both groups continued with the prescribed exercises without BFR from 12 weeks until discharged from therapy. Thigh circumference and self-reported knee function were measured at 1, 6, 12, and 24 weeks postoperatively along with knee extensor and flexor strength at 12 and 24 weeks. Change scores between time points were calculated for knee function. Limb symmetry indices (LSI) were computed for thigh circumference and knee strength variables. RESULTS: Seventeen participants were included in the final analyses (BFR = 8 and control = 9) due to COVID-19 restrictions. There were no interactions or main effects for group. Time main effects were established for change in knee function scores, thigh circumference LSI, and knee extensor strength LSI. However, knee flexor strength LSI had no main effect for time. CONCLUSION: The outcomes of this trial suggest that resistance exercises with and without BFR training may result in similar changes to function, thigh atrophy, and knee extensor strength postmeniscus repair/chondral restoration, though further study with larger sample sizes is needed.

Uptake of Screening and Recurrence of Bicuspid Aortic Valve and Thoracic Aortic Aneurysm Among At-Risk Siblings of Pediatric Probands.

OBJECTIVE: To determine uptake of cardiac screening and recurrence of bicuspid aortic valve (BAV) and thoracic aortic aneurysm (TAA) in a population of at-risk siblings of pediatric probands. STUDY DESIGN: A retrospective chart review of pediatric patients with known BAV and/or TAA was performed. Echocardiogram data from identified siblings were collected to determine screening uptake and recurrence of BAV and TAA. Statistical analyses were performed using Wilcoxon signed-rank test and chi-square. RESULTS: The cohort included 251 probands and 388 at-risk siblings. Among the siblings, 150 had at least 1 echocardiogram, giving an overall screening uptake of 38.7%. The only factor found to be associated with increased uptake was documented recommendation for screening of first-degree relatives in the proband's initial cardiology note (P = .03). A total of 11 screened siblings (7.3%) had BAV and 19 had TAA (12.7%), with an overall combined recurrence of 15.3%. Siblings of probands who had both BAV and TAA had increased recurrence of TAA compared with siblings of probands with isolated BAV (16.1% vs 3.9%, respectively). CONCLUSIONS: Given low uptake in at-risk siblings, the opportunity exists to assess barriers for families in pursuing the recommended screening. Furthermore, the relatively high recurrence of BAV and TAA in at-risk siblings highlights the potential for improved health outcomes through increased screening and early detection. Developing standardized guidelines and promoting early cardiac screening in at-risk siblings while counseling families about hereditary risk for BAV and TAA may help improve uptake and optimize clinical management in at-risk pediatric patients.

Leptospira in river and soil in a highly endemic area of Ecuador.

BACKGROUND: Leptospira are shed into the environment via urine of infected animals. Rivers are thought to be an important risk factor for transmission to humans, though much is unknown about the types of environment or characteristics that favor survival. To address this, we screened for Leptospira DNA in two rivers in rural Ecuador where Leptospirosis is endemic. RESULTS: We collected 112 longitudinal samples and recorded pH, temperature, river depth, precipitation, and dissolved oxygen. We also performed a series of three experiments designed to provide insight into Leptospira presence in the soil. In the first soil experiment, we characterized prevalence and co-occurrence of Leptospira with other bacterial taxa in the soil at dispersed sites along the rivers (n = 64). In the second soil experiment, we collected 24 river samples and 48 soil samples at three points along eight transects to compare the likelihood of finding Leptospira in the river and on the shore at different distances from the river. In a third experiment, we tested whether Leptospira presence is associated with soil moisture by collecting 25 soil samples from two different sites. In our river experiment, we found pathogenic Leptospira in only 4 (3.7%) of samples. In contrast, pathogenic Leptospira species were found in 22% of shore soil at dispersed sites, 16.7% of soil samples (compared to 4.2% of river samples) in the transects, and 40% of soil samples to test for associations with soil moisture. CONCLUSIONS: Our data are limited to two sites in a highly endemic area, but the scarcity of Leptospira DNA in the river is not consistent with the widespread contention of the importance of river water for leptospirosis transmission. While Leptospira may be shed directly into the river, onto the shores, or washed into the river from more remote sites, massive dilution and limited persistence in rivers may reduce the environmental load and therefore, the epidemiological significance of such sources. It is also possible that transmission may occur more frequently on shores where people are liable to be barefoot. Molecular studies that further explore the role of rivers and water bodies in the epidemiology of leptospirosis are needed.

Knowledge, Perceptions, and Preferred Information Sources Related to COVID-19 Among Central Pennsylvania Adults Early in the Pandemic: A Mixed Methods Cross-Sectional Survey.

PURPOSE: To explore public knowledge, understanding of public health recommendations, perceptions, and trust in information sources related to COVID-19. METHODS: A cross-sectional survey of central Pennsylvanian adults evaluated self-reported knowledge, and a convergent, mixed methods design was used to assess beliefs about recommendations, intended behaviors, perceptions, and concerns related to infectious disease risk, and trust of information sources. RESULTS: The survey was completed by 5,948 adults. The estimated probability of correct response for the basic knowledge score, weighted with confidence, was 0.79 (95% CI, 0.79-0.80). Knowledge was significantly higher in patients with higher education and nonminority race. While the majority of respondents reported that they believed following CDC recommendations would decrease the spread of COVID-19 in their community and intended to adhere to them, only 65.2% rated social isolation with the highest level of belief and adherence. The most trusted information source was federal public health websites (42.8%). Qualitative responses aligned with quantitative data and described concerns about illness, epidemiologic issues, economic and societal disruptions, and distrust of the executive branch's messaging. The survey was limited by a lack of minority representation, potential selection bias, and evolving COVID-19 information that may impact generalizability and interpretability. CONCLUSIONS: Knowledge about COVID-19 and intended adherence to behavioral recommendations were high. There was substantial distrust of the executive branch of the federal government, however, and concern about mixed messaging and information overload. These findings highlight the importance of consistent messaging from trusted sources that reaches diverse groups.