COVID-19 Screening in the Pediatric Emergency Department.

BACKGROUND: Screening for COVID-19 infection in pediatrics is challenging as its clinical presentation may be asymptomatic or mimic other common childhood infections. We examined the use of a COVID-19 screening protocol (CSP) in the pediatric emergency department (PED) to determine the incidence of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests in patients who are CSP+ and CSP-. METHODS: We conducted a retrospective cohort study of pediatric patients with SARS-CoV-2 testing completed in an urban tertiary care PED from November 1 to December 31, 2020. Demographics, CSP designation, test results, and disposition were compared. Statistical significance was determined using chi-square or a comparison of means. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% confidence intervals (CI) were calculated. RESULTS: A total of 1,613 patients had SARS-CoV-2 tests completed with 9.1% (N=147) having positive test results. Of 1,014 (62.9%) patients who were CSP+, 12.9% tested positive. Comparatively, 599 (37.1%) patients were CSP- with only 2.7% positive tests, p<0.0001. The sensitivity, specificity, NPV, and PPV of the CSP in all tested patients were 89.1%, 39.8%, 97.3%, and 12.9%, respectively. Of tested patients, 887 (55.0%) were admitted to the hospital and were more likely to be positive if CSP+, p≤0.001. Within the admitted group, 16.8% were admitted to the operating room, of whom 83.9% were CSP- with 4.0% testing positive for SARS-CoV-2. CONCLUSIONS: COVID-19 screening in the pediatric population is a useful modality to risk stratify most patients presenting to the PED for the purpose of selective testing and guiding personal protective equipment use. This may be particularly useful in low-resource settings.

Evaluating a Project Extension for Community Health Outcomes Pediatric Behavioral Health Series in a Rural and Frontier State: An Exploratory Investigation.

Background: Idaho, a predominately rural state, has a high prevalence of mental illness with minimal access to care. Barriers in diagnosis and treatment of pediatric behavioral health disorders could be mitigated with an accessible and effective specialty training program. Methods: A 10-session Project Extension for Community Health Outcomes (ECHO) series was designed to expand provider knowledge about pediatric behavioral health conditions and improve perceived clinical practice skills. Pre- and postseries evaluation surveys and individual session evaluations were used to assess the program. Results: A total of 148 individuals attended at least 1 of the 10 sessions. Participants reported high satisfaction with individual sessions and indicated that attendance positively impacted their knowledge and competency. Participants also reported that the knowledge and skills gained from the series would benefit more than half of their patients or clients. Conclusion: The short ECHO series appears to be a viable and valuable option to provide Idaho providers with effective specialty training that is well attended and well received.

Stakeholder perceptions of the use of a rapidly deployed modified ECHO to train and prepare healthcare providers for COVID-19.

Background: Innovative approaches to deliver timely information to rural healthcare providers are necessary with the COVID-19 pandemic. Project Extension for Community Healthcare Outcomes (ECHO) is a telementoring program designed to provide practitioners in rural communities with opportunities to engage in specialty training. We examined participant perceptions of a rapidly deployed, single continuing education session to improve healthcare provider preparedness for COVID-19 in Idaho. Methods: A modified Project ECHO session was developed to inform providers about emergency preparedness, treatment, testing, and resources for COVID-19. A post-session survey examined session impact and barriers on clinical practice. Results: Respondents believed the modified ECHO session increased COVID-19 knowledge and would improve their clinical practice and preparedness. Respondents were satisfied with the session and identified content, interdisciplinary collaboration, and format as beneficial; perceived barriers for utilizing session information included a lack of relevance of content and clinical applicability, and time constraints. Conclusions: A rapidly deployed modified Project ECHO session was perceived as an effective mechanism to foster collaboration and relay information to promote best practices at the start of the COVID-19 pandemic. An established Project ECHO network may be useful to rapidly exchange knowledge and information during a health emergency.

Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care: The Personalized Diabetes Medicine Program.

OBJECTIVE: To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes. RESEARCH DESIGN AND METHODS: Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions. RESULTS: Three hundred thirteen probands with suspected monogenic diabetes (but most diagnosed with type 2 diabetes) were enrolled from October 2014 to January 2019. Sequencing identified 38 individuals with monogenic diabetes, with most variants found in GCK or HNF1A. Positivity rates for ascertainment methods were 3.1% for clinic screening, 5.3% for electronic health record portal screening, 16.5% for physician recognition, and 32.4% for self-referral. The algorithmic criterion of non-type 1 diabetes before age 30 years had an overall positivity rate of 15.0%. CONCLUSIONS: We successfully modeled the efficient incorporation of monogenic diabetes diagnosis into the diabetes care setting, using multiple strategies to screen and identify a subpopulation with a 12.1% prevalence of monogenic diabetes by molecular testing. Self-referral was particularly efficient (32% prevalence), suggesting that educating the lay public in addition to clinicians may be the most effective way to increase the diagnosis rate in monogenic diabetes. Scaling up this model will assure access to diagnosis and customized treatment among those with monogenic diabetes and, more broadly, access to personalized medicine across disease areas.

Ethical and Safety Concerns Regarding the Use of Mental Health-Related Apps in Counseling: Considerations for Counselors.

Mental health-related smartphone apps (MHapps) have the potential to greatly enhance and enrich the counseling relationship, and dramatically improve the lives of clients. However, a large portion of MHapps have not been empirically researched and found to be effective. An average of 2 million apps are available in the Apple and Android stores, and users average more than 80 apps on their phones. Many of the apps lack disclaimers about the collection of user information, and there is no governing body to oversee and regulate app development and availability. This is particularly problematic with mental health-related smartphone apps, because many developers are not affiliated with mental health professionals, and many apps do not provide emergency information should a mental health emergency occur while using the app. Moreover, users are left to haphazardly make decisions about health-related apps usage without assistance. Counselors who supplement counseling with mental health-related smartphone apps could unknowingly violate their Code of Ethics by integrating apps that may jeopardize their clients' safety. The authors review literature related to mental health-related app efficacy, safety, and ethics and provide a compilation of items to consider that can be used before supplementing counseling with mental health-related apps.

KCNQ1 and Long QT Syndrome in 1/45 Amish: The Road From Identification to Implementation of Culturally Appropriate Precision Medicine.

BACKGROUND: In population-based research exome sequencing, the path from variant discovery to return of results is not well established. Variants discovered by research exome sequencing have the potential to improve population health. METHODS: Population-based exome sequencing and agnostic ExWAS were performed 5521 Amish individuals. Additional phenotyping and in vitro studies enabled reclassification of a KCNQ1 variant from variant of unknown significance to pathogenic. Results were returned to participants in a community setting. RESULTS: A missense variant was identified in KCNQ1 (c.671C>T, p.T224M), a gene associated with long QT syndrome type 1, which can cause syncope and sudden cardiac death. The p.T224M variant, present in 1/45 Amish individuals is rare in the general population (1/248 566 in gnomAD) and was highly associated with QTc on electro-cardiogram (P=5.53E-24, ß=20.2 ms/allele). Because of the potential importance of this variant to the health of the population, additional phenotyping was performed in 88 p.T224M carriers and 54 noncarriers. There was stronger clinical evidence of long QT syndrome in carriers (38.6% versus 5.5%, P=0.0006), greater history of syncope (32% versus 17%, P=0.020), and higher rate of sudden cardiac death in first degree relatives

Delineation of Novel Compound Heterozygous Variants in LTBP2 Associated with Juvenile Open Angle Glaucoma.

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C>G, p.(Pro989Arg); c.5235T>G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 (LTBP2) segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles.

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Prioritizing Approaches to Engage Community Members and Build Trust in Biobanks: A Survey of Attitudes and Opinions of Adults within Outpatient Practices at the University of Maryland.

BACKGROUND: Achieving high participation of communities representative of all sub-populations is needed in order to ensure broad applicability of biobank study findings. This study aimed to understand potentially mutable attitudes and opinions commonly correlated with biobank participation in order to inform approaches to promote participation in biobanks. METHODS: Adults from two University of Maryland (UMD) Faculty Physicians, Inc. outpatient practices were invited to watch a video and complete a survey about a new biobank initiative. We used: Chi-square to assess the relationship between willingness to join the biobank and participant characteristics, other potentially mutable attitudes and opinions, and trust in the UMD. We also used t-test to assess the relationship with trust in medical research. We also prioritize proposed actions to improve attitudes and opinions about joining biobanks according to perceived responsiveness. RESULTS: 169 participants completed the study, 51% of whom indicated a willingness to join the biobank. Willingness to join the biobank was not associated with age, gender, race, or education but was associated with respondent comfort sharing samples and clinical information, concerns related to confidentiality, potential for misuse of information, trust in UMD, and perceived health benefit. In ranked order, potential actions we surveyed that might alleviate some of these concerns include: increase chances to learn more about the biobank, increase opportunities to be updated, striving to put community concerns first, including involving community members as leaders of biobank research, and involving community members in decision making. CONCLUSIONS: This study identified several attitudes and opinions that influence decisions to join a biobank, including many concerns that could potentially be addressed by engaging community members. We also demonstrate our method of prioritizing ways to improve attitudes and opinions about joining a biobank according to perceived responsiveness.

Implementation of pharmacogenetics: the University of Maryland Personalized Anti-platelet Pharmacogenetics Program.

Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients' are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within 5 hr along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine.

Safety and immunogenicity of a recombinant multivalent group a streptococcal vaccine in healthy adults: phase 1 trial.

CONTEXT: Group A streptococcal infections and their sequelae represent a global health problem. Recent advances have allowed previous obstacles associated with group A streptococcal vaccine development to be overcome. OBJECTIVE: To preliminarily evaluate the safety and immunogenicity of ascending doses of a recombinant fusion peptide group A streptococcal vaccine containing N-terminal M protein fragments from serotypes 1, 3, 5, 6, 19, and 24 in healthy volunteers. DESIGN, SETTING, AND PARTICIPANTS: An open-label, uncontrolled, dose-ascending phase 1 vaccine trial of 28 healthy adult volunteers aged 18 to 50 years recruited from the metropolitan area of Baltimore, Md, between October 5, 1999, and February 26, 2003, using newspaper advertisements and posted fliers, and evaluated in the outpatient facility of the Center for Vaccine Development. INTERVENTIONS: Each volunteer received 3 spaced intramuscular injections of 50 microg (n = 8), 100 micro g (n = 10), or 200 microg (n = 10) of hexavalent group A streptococcal vaccine formulated with aluminum hydroxide into the deltoid muscle of alternating arms. MAIN OUTCOME MEASURES: Assessments of clinical safety, including elicitation of antibodies that cross-react with host tissues, and immunogenicity as measured by enzyme-linked immunosorbent assay (ELISA) and assays of opsonophagocytic- and bactericidal-antibody responses. RESULTS: One year of intensive follow-up revealed the vaccine to be well tolerated. There was no evidence of tissue cross-reactive antibodies or immunological complications. At the highest (200 microg) dose, vaccination elicited significant increases in geometric mean antibody levels to all 6 component M antigens by ELISA (all P<.01) and to 5 of 6 M types in the opsonophagocytosis assay (all P<.05). In addition, postvaccination increases in serum bactericidal activity of at least 30% were observed in 31 (55%) of 56 assays. CONCLUSION: These results provide the first evidence in humans that a hybrid fusion protein is a feasible strategy for evoking type-specific opsonic antibodies against multiple serotypes of group A streptococcus without eliciting antibodies that cross-react with host tissues, which represents a critical step in the development of a vaccine.