To assess current pediatric cholesterol screening practices, and attitudes, among pediatric primary care providers (PCPs) via qualitative semistructured interviews designed to identify barriers and ...facilitators to universal cholesterol screening practices recommended by the National Heart Blood and Lung Institute and the American Academy of Pediatrics.
An online survey and subsequent 30-minute semistructured phone interview were completed with PCPs from regions in Northern California and Minnesota (survey n = 25, interview n = 12). Interviews were qualitatively analyzed using the consolidated framework for implementation research to categorize barriers, facilitators, and strategies to increase pediatric cholesterol screening among PCPs.
PCPs from California (n = 8) and Minnesota (n = 4) consistently identified cost of cholesterol screening, particularly the cost of time due to competing visit priorities, as a barrier. A supportive learning environment, feelings of self-efficacy, access to resources, and well-established clinical networks with specialists (eg, cardiologists) were facilitators to screening. The perceived level of endorsement behind cholesterol screening within the clinic, perceived validity of national guidelines, and ability to adapt guidelines to existing clinical workflow were notable differentiators between high vs low self-reported screen rates.
Findings of this study suggest that efforts to increase universal pediatric cholesterol screening will likely require the development of strategies to increase provider education about the long-term benefits of cholesterol screening (knowledge and beliefs), and ensuring providers feel supported and empowered when assessing/acting on the results of this screening (self-efficacy, engaging leaders, networks, and communication).
APOE codes for apolipoprotein E (ApoE), which plays an important role in lipid and lipoprotein metabolism and homeostasis of tissue lipid content. Several variants in APOE have been associated with ...inherited dyslipidemias, and a subsequent increased risk of developing premature coronary artery disease (CAD). However, these variants and their impact on risk can be thought of on a spectrum, with some being more monogenic in nature, and others contributing in a polygenic/multifactorial manner. Despite these known associations, there is often hesitancy around ordering APOE genetic testing due to the association with Alzheimer's disease. This paper aims to catalyze discussion around APOE testing and counseling strategies, highlight the nuances around this topic, and advocate for inclusion of APOE testing on dyslipidemia panels when an inherited dyslipidemia is suspected.
Cardiovascular genetic counseling (CVGC) is recommended for a variety of inherited heart conditions; however, its impact on patient empowerment has not been assessed. The Genetic Counseling Outcome ...Scale (GCOS) is a validated patient reported outcome tool which measures empowerment to capture the impact of clinical genetics services. As a routine clinical practice at our center, adult patients attending a CVGC appointment complete the 24‐item GCOS survey and a 5‐item survey on knowledge of cardiac surveillance recommendations for relatives prior to the clinic visit. To investigate the effect of CVGC, we contacted participants after the appointment to repeat these surveys prior to genetic test result disclosure. Forty‐two participants completed pre‐ and post‐GC surveys. The mean difference between pre‐ and post‐GC empowerment scores was 17.5 points (mean pre‐GC score = 118.5, mean post‐GC score = 136, p < 0.0001; effect size, d = 0.94). Forty percent of individuals (17/42) were aware of surveillance recommendations for at‐risk family members prior to GC; this increased to 76% of individuals (32/42) post‐GC (p < 0.01). This is the first study to explore patient empowerment before and after GC in a cardiology setting. The results demonstrate a significant increase in empowerment and awareness of recommendations for at‐risk relatives as a result of CVGC. This study demonstrates the utility of CVGC in patient care.
Abstract
Genetic counseling and genetic testing are essential for individuals with congenital heart disease/defects (CHD/CHDs). However, the clinical practices of genetic counselors (GCs) and their ...preferences for different CHD genetic testing strategies are previously unexplored. To address these gaps, GCs (
n
= 112) representing diverse specialties completed an online survey regarding their counseling and testing practices for syndromic CHD and apparently isolated/non‐syndromic CHDs (iCHD). We found practice variability around family screening recommendations, with prenatal respondents reporting lower prevalence of this practice for iCHDs (
p
= 0.0004). We found that all specialties considered chromosomal microarray (CMA) the most common prioritized genetic test for syndromic and iCHD, while more prenatal respondents considered FISH and karyotype useful for iCHDs compared to postnatal respondents (
p
= 0.0002 and
p
= 0.002, respectively). Among postnatal respondents, a higher proportion considered exome/genome sequencing as useful compared to prenatal respondents (
p
= 0.0159); specifically, postnatal respondents' preference for exome/genome sequencing for iCHDs was ~2.6‐fold higher than prenatal respondents. We estimated participants' assessment of utility for different genetic testing modalities for iCHDs and found that prenatal respondents assigned higher mean utility to FISH (
p
= 0.0002), karyotype (
p
= 0.0006), and CMA (
p
< 0.0001). There were relatively moderate to decreased utility scores for gene panels and exome/genome sequencing for iCHDs compared to cytogenetic testing, across all specialties. Overall, these results provide insight into GC practices and use of various genetic testing strategies for syndromic CHDs and iCHDs. Findings may help inform and/or standardize clinical practices for CHD genetic testing, though additional studies are warranted.
Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations ...when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre‐ and postnatally.
Genetic counselors are one of the many providers involved in caring for patients with congenital heart defects (CHDs); however, little is known about the cardiovascular genetics training they receive ...by their graduate programs. To explore the recalled education experiences regarding CHDs by practicing genetic counselors, we surveyed graduates of programs primarily accredited by the American Council on Genetic Counseling (ACGC) about their graduate training in this area, the depth of CHD‐specific education they received, and whether CHDs are a substantial referral indication in their current practice. Genetic counselors were recruited from the National Society of Genetic Counselors and Twitter (n = 112), and participants reflecting multiple specialties and 35 graduate programs completed an online survey which included questions about fieldwork placements and lectures in cardiovascular genetics, exposure to classification schemes regarding cardiac embryology, and education in counseling strategies for CHDs and CHD‐related topics during their graduate training. When asked whether CHDs are a substantial referral indication seen in their current practice, 55% (62/112) responded yes. Most participants (79%, 88/112) recalled receiving some education about CHDs, but 91% (80/88) reported receiving little to no education regarding embryologic classification of CHDs and how to apply classification schemes to their counseling. Both participating prenatal and pediatric GCs reported that CHDs can be a common referral indication, yet they reported receiving limited education on teratogens associated with CHDs, family screening recommendations, and recurrence risk counseling for CHDs. Based on participant responses, the majority of respondents reported receiving sufficient education on syndromes with CHDs which can be beneficial in specialties such as pediatrics. This exploratory study provides insight into opportunities to further support genetic counseling educational opportunities for CHDs. These findings suggest genetic counseling graduate programs could consider implementing education on CHD counseling strategies as a standardized component of the curriculum and that practicing genetic counselors could benefit from educational opportunities and resources with updated information on this topic.
APOE codes for apolipoprotein E (ApoE), which plays an important role in lipid and lipoprotein metabolism and homeostasis of tissue lipid content. Several variants in APOE have been associated with ...inherited dyslipidemias, and a subsequent increased risk of developing premature coronary artery disease (CAD). However, these variants and their impact on risk can be thought of on a spectrum, with some being more monogenic in nature, and others contributing in a polygenic/multifactorial manner. Despite these known associations, there is often hesitancy around ordering APOE genetic testing due to the association with Alzheimer's disease. This paper aims to catalyze discussion around APOE testing and counseling strategies, highlight the nuances around this topic, and advocate for inclusion of APOE testing on dyslipidemia panels when an inherited dyslipidemia is suspected.
Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is ...critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including convalescent COVID-19 and sero-negative controls. Flow cytometry analyses revealed reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells within the patients who have recovered from severe COVID-19. sc-RNA seq analysis identifies seven heterogeneous clusters of monocytes and nine Treg clusters featuring distinct molecular signatures in association with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocytes and Tregs expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters featuring S100 family genes: one monocyte cluster of S100A8 & A9 coupled with high HLA-I and another cluster of S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, as well as a unique TGF-β high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-lived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (≥ 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.
•Single-cell RNA sequencing identifies 7 monocyte clusters and 10 Treg clusters in convalescent COVID-19 patients.•Monocytes and Treg clusters share signature genes in association with COVID-19 severity of convalescent patients.•Monocytes show dynamic changes in distinct clusters with S100A and interferon-responsive genes months after recovery.•TGFB+ KLF2+ Treg cluster is enriched in the hospitalized patients recovered from COVID-19.
The resting membrane potential enables neurons to rapidly initiate and conduct electrical signals. K2p channels are key in maintaining this membrane potential and electrical excitability. They direct ...the resting membrane potential toward the K+ equilibrium potential. Doxapram is a known blocker for a subset of K2p channels that are pH sensitive. We assessed the effects of 0.1 and 5 mM doxapram on the neural activity within the propodite-dactylopodite (PD) proprioceptive sensory organ in the walking legs of blue crabs (Callinectes sapidus). Results indicate that 0.1 mM doxapram enhances excitation, while the higher concentration 5 mM may over-excite the neurons and promote a sustained absolute refractory period until the compound is removed. The effect of 5 mM doxapram mimics the effect of 40 mM K+ exposure. Verapamil, another known K2p channel blocker as well as an L-type Ca2+ channel blocker, reduces neural activity at both 0.1 and 5 mM. Verapamil may block stretch activated channels in sensory endings, in addition to reducing the amplitude of the compound action potential with whole nerve preparations. These findings are notable as they demonstrate that doxapram has acute effects on neurons of crustaceans, suggesting a targeted K2p channel. The actions of verapamil are complex due to the potential of affecting multiple ion channels in this preparation. Crustacean neurons can aid in understanding the mechanisms of action of various pharmacological agents as more information is gained.
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