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Background: Despite therapies proven effective for heart failure with systolic dysfunction, the condition continues to cause substantial hospitalization, disability, and death, especially among African- American and other nonwhite populations.Objective: To compare the effects of a nurse-led intervention focused on specific management problems versus usual care among ethnically diverse patients with systolic dysfunction in ambulatory care practices.Design: Randomized effectiveness trial conducted from September 2000 to September 2002.Setting: The 4 hospitals in Harlem, New York.Patients: 406 adults (45.8% were non-Hispanic black adults, 32.5% were Hispanic adults, 46.3% were women, and 36.7% were > or =65 years of age) who met eligibility criteria: systolic dysfunction, English- or Spanish-language speakers, community-dwelling patients, and ambulatory care practice patients.Intervention: During a 12-month intervention, bilingual nurses counseled patients on diet, medication adherence, and self-management of symptoms through an initial visit and regularly scheduled follow-up telephone calls and facilitated evidence-based changes to medications in discussions with patients' clinicians.Measurements: Hospitalizations (in 406 of 406 patients during follow-up) and self-reported functioning (in 286 of 406 patients during follow-up) at 12 months.Results: At 12 months, nurse management patients had had fewer hospitalizations (143 hospitalizations vs. 180 hospitalizations; adjusted difference, -0.13 hospitalization/person-year [95% CI, -0.25 to -0.001 hospitalization/person-year]) than usual care patients. They also had better functioning: The Short Form-12 physical component score was 39.9 versus 36.3, respectively (difference, 3.6 [CI, 1.2 to 6.1]), and the Minnesota Living with Heart Failure Questionnaire score was 38.6 versus 47.3, respectively (difference, -8.8 [CI, -15.3 to -2.2]). Through 12 months, 22 deaths occurred in each group and percentages of patients who were hospitalized at least once were similar in each group (30.5% of nurse management patients vs. 36.5% of control patients; adjusted difference, -7.1 percentage points [CI, -16.9 to 2.6 percentage points]).Limitations: Three nurses at 4 hospitals delivered interventions in this modest-sized trial, and 75% of the participants were from 1 site. It is not clear which aspects of the complex intervention accounted for the results.Conclusions: Nurse management can improve functioning and modestly lower hospitalizations in ethnically diverse ambulatory care patients who have heart failure with systolic dysfunction. Sustaining improved functioning may require continuing nurse contact. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) is a common chronic disease with effective therapy, yet interventions to improve outcomes have met with limited success. Though problems in self-management are suspected causes for deterioration, few efforts have been made to understand how self-management could be improved to enhance the lives of affected patients. We conducted semi-structured interviews of 19 patients with CHF treated at an urban United States hospital to elucidate their knowledge and beliefs about CHF and to understand what underlies their self-care routines. A comparison of the themes generated from these interviews with the common-sense model for self-management of illness threats, clarifies how patients' perceptions and understanding of CHF affected their behaviors. Patients had an acute model of CHF. They did not connect chronic symptoms with a chronic disease, CHF, and did not recognize that these symptoms worsened over time from their baseline of moderate, chronic distress, to a severe state that required urgent care. As a consequence, they often did not manage symptoms on a routine basis and did not, therefore, prevent or minimize exacerbations. When they worsened, many patients reported barriers to reaching their physicians and most reported seeking care primarily in an emergency room. These in depth responses elucidate how the interplay between acute and chronic models of a chronic illness effect self-management behaviors. These factors play a previously not understood role in patient's efforts to understand and manage the ever-present but symptomatically variable chronic illness that is CHF. These new concepts illustrate the tools that may be needed to effectively manage this serious and disabling illness, and suggest possible ways to enhance the self-management process and ultimately improve patients' lives. [ABSTRACT FROM AUTHOR]

Objectives. Our community-academic partnership employed community-based participatory research to develop and pilot a simple, peer-led intervention to promote weight loss, which can prevent diabetes and eliminate racial/ethnic disparities in incident diabetes among overweight adults with prediabetes. Methods. We recruited overweight adults at community sites, performed oral glucose tolerance testing to identify persons with blood glucose levels in the prediabetes range, and randomized eligible people to a peer-led lifestyle intervention group or delayed intervention in 1 year. Outcomes, including weight, blood pressure, and health behaviors, were measured at baseline and 3, 6, and 12 months. Results. More than half of those tested (56%, or 99 of 178) had prediabetes and enrolled in the study. Participants were predominantly Spanish-speaking, low-income, undereducated women. The intervention group lost significantly more weight than the control group and maintained weight loss at 12 months (7.2 versus 2.4 pounds; P < .01). One fourth (24 of 99) of participants progressed to diabetes. Conclusions. In underserved minority communities, prediabetes prevalence may be higher than previously reported. Low-cost, community-based interventions can succeed in encouraging weight loss to prevent diabetes. [ABSTRACT FROM AUTHOR]

Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States. The trial aims for families who self-identify as Black/African American or Hispanic/Latino to make up more than 50% of final enrollment, and key aspects of the trial design were co-developed with a community advisory board. All enrolled families receive genetic counseling and a family history report. Half of enrolled infants are randomized to receive GS with comprehensive interpretation of pathogenic and likely pathogenic variants in more than 4,300 genes associated with childhood-onset and actionable adult-onset conditions, as well as larger-scale chromosomal copy number variants classified as pathogenic or likely pathogenic. GS result reports include variants associated with disease (Mendelian disease risks) and carrier status of autosomal-recessive and X-linked disorders. Investigators evaluate the utility and impacts of implementing a GS screening program in a diverse cohort of infants using medical record review and longitudinal parent surveys. In this perspective, we describe the rationale for the second iteration of the BabySeq Project, the outcomes being assessed, and the key decisions collaboratively made by the study team and community advisory board., Competing Interests: Declaration of interests H.S.S. has received consulting income from Illumina unrelated to this work. N.D.S. is a member of the Scientific Advisory Board for Neuberg Center for Genomic Medicine. A.L.M. is a paid advisor for Nurture Genomics. B.R.K. is a member of medical advisory boards for Alexion, SpringWorks, Healx, Infixion, and Recursion and has stock options in GenomeMedical. R.C.G. has received compensation for advising Allelica, Atria, Fabric, Genome Web, and Genomic Life and is a cofounder of Genome Medical and Nurture Genomics., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: The Bridging Income Generation with Group Integrated Care (BIGPIC) trial in rural Kenya showed that integrating usual care with group medical visits or microfinance interventions reduced systolic blood pressure and cardiovascular risk in participants. We aimed to estimate the incremental cost-effectiveness of three BIGPIC interventions for a modelled cohort and by sex, as well as the cost of implementing these interventions., Methods: For this analysis, we used data collected during the BIGPIC trial, a four-group, cluster-randomised trial conducted in the western Kenyan catchment area of the Academic Model Providing Access to Healthcare. BIGPIC enrolled participants from 24 rural health facilities in rural western Kenya aged 35 years or older with either increased blood pressure or diabetes. Participants were assigned to receive either usual care, group medical visits, microfinance, or a combination of group medical visits and microfinance (GMV-MF). Our model estimated the incremental cost-effectiveness of the three BIGPIC interventions via seven health states (ie, a hypertensive state, five chronic cardiovascular-disease states, and a death state) by simulating transitions between health states for a hypothetical cohort of individuals with hypertension on the basis of QRISK3 scores. In every cycle, participants accrued costs and disability-adjusted life-years (DALYs) associated with their health state. Incremental cost-effectiveness ratios (ICERs) were calculated for the entire modelled cohort and by sex by dividing the incremental cost by the incremental effectiveness of the next most expensive intervention. The main outcome of this analysis was ICERs for each intervention evaluated. This analysis is registered at ClinicalTrials.gov (NCT02501746)., Findings: Between Feb 6, 2017, and Dec 29, 2019, 2890 people were recruited to the BIGPIC trial. 2020 (69·9%) of 2890 participants were female and 870 (30·1%) were male. At baseline, mean QRISK3 score was 11·5 (95% CI 11·1-11·9) for the trial population, 11·9 (11·5-12·2) for male participants, and 11·3 (11·0-11·6) for female participants. For the population of Kenya, group medical visits were estimated to cost US$7 more per individual than usual care and result in 0·005 more DALYs averted (ICER $1455 per DALY averted). Microfinance was estimated to cost $19 more than group medical visits but was only estimated to avert 0·001 more DALYs. Relative to group medical visits, GMV-MF was estimated to cost $29 more and avert 0·009 more DALYs ($3235 per DALY averted). Relative to usual care, GMV-MF was estimated to cost $37 more and avert 0·014 more DALYs ($2601 per DALY averted). In the first year of the intervention, usual care was estimated to be the least expensive intervention to implement ($87 per participant; $10 238 per health-facility catchment area [HFCA]), then group medical visits ($99 per participant; $12 268 per HFCA), then microfinance ($120 per participant; $14 172 per HFCA), with GMV-MF estimated to be the most expensive intervention to implement ($139 per participant; $16 913 per HFCA)., Interpretation: Group medical visits and GMV-MF were estimated to be cost-effective strategies to improve blood-pressure control in rural Kenya. However, which intervention to pursue depends on resource availability. Policy makers should consider these factors, in addition to sex differences in programme effectiveness, when selecting optimal implementation strategies., Funding: US National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

There is increasing evidence of the clinical utility of genetic and genomic testing (GT); however, factors influencing personal utility of GT, especially in diverse, multilingual populations, remain unclear. We explored these factors in a diverse cohort of parents/guardians (participants) whose children received clinical GT through the NYCKidSeq program. A total of 847 participants completed surveys at baseline, post-results disclosure, and 6 months (6m) post-results. The largest population groups were Hispanic/Latino(a) (48%), White/European American (24%), and Black/African American (16%). Personal utility was assessed using the Personal Utility (PrU) scale, adapted for pediatric populations and included on the surveys. Three PrU subscales were identified using factor analysis: practical, educational, and parental psychological utility. Overall personal utility summary score and the three subscales significantly decreased after receiving results and over time. Hispanic/Latino(a) participants identified greater overall personal utility than European American and African American participants at all time points (p < 0.001) as did participants whose children received positive/likely positive results compared with those with negative and uncertain results (post-results: p < 0.001 and p < 0.001; 6m post-results: p = 0.002 and p < 0.001, respectively). Post-results, higher subscale scores were associated with lower education levels (practical, parental psychological: p ≤ 0.02) and higher levels of trust in the healthcare system (practical, parental psychological: p ≤ 0.04). These findings help to understand the perspectives of diverse parents/guardians, which is critical to tailoring pre- and post-test counseling across a variety of populations and clinical settings., Competing Interests: Declaration of interests N.S.A.-H. is currently employed by 23andMe, was previously employed by Regeneron Pharmaceuticals, received personal fees from Genentech, Allelica, and 23andMe, received research funding from Akcea, and serves as a scientific advisory board member for Allelica. E.E.K. received personal fees from Illumina, 23andMe, Allelica, and Regeneron Pharmaceuticals, received research funding from Allelica, and serves as a scientific advisory board member for Encompass, Bio, Overtone, and Galateo Bio., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine associations between Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and PedsQL Infant Scales with formal health care resource utilization (HCRU) and informal caregiver burden., Methods: We studied a pediatric cohort of 837 patients (median age: 8.4 years) with suspected genetic disorders enrolled January 2019 through July 2021 in the NYCKidSeq program for diagnostic sequencing. Using linked ~ nine-month longitudinal survey and physician claims data collected through May 2022, we modeled the association between baseline PedsQL scores and post-baseline HCRU (median follow-up: 21.1 months) and informal care. We also assessed the longitudinal change in PedsQL scores with physician services using linear mixed-effects models., Results: Lower PedsQL total and physical health scores were independently associated with increases in 18-month physician services, encounters, and weekly informal care. Comparing low vs. median total scores, increases were 10.6 services (95% CI: 1.0-24.6), 3.3 encounters (95% CI: 0.5-6.8), and $668 (95% CI: $350-965), respectively. For the psychosocial domain, higher scores were associated with decreased informal care. Based on adjusted linear mixed-effects modeling, every additional ten physician services was associated with diminished improvement in longitudinal PedsQL total score trajectories by 1.1 point (95% confidence interval: 0.6-1.6) on average. Similar trends were observed in the physical and psychosocial domains., Conclusion: PedsQL scores were independently associated with higher utilization of physician services and informal care. Moreover, longitudinal trajectories of PedsQL scores became less favorable with increased physician services. Adding PedsQL survey instruments to conventional measures for improved risk stratification should be evaluated in further research., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults., Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science., Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions., Clinical Trials.gov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brett Anderson reported receiving direct support for work not related to RECOVER work/publications from Genentech and the National Institute of Allergy and Immunology. Walter Dehority reported receiving grant support from Merck and participating in research for the Moderna COVID-19 pediatric vaccine trial and the Pfizer Paxlovid trial. Alex Fiks reported receiving support from NJM insurance and personal consulting fees not related to this paper from Rutgers University and the American Academy of Pediatrics. Ashraf Harahsheh reported serving as a scientific advisory board member unrelated to this paper for OP2 DRUGS. Lawrence Kleinman reported serving as an unpaid member of the Board of Directors for the DARTNet Institute, as a principle investigator at Quality Matters, Inc., and as the Vice Chair for the Borough of Metuchen Board of Health. Dr. Kleinman also reported grant support for work not related to RECOVER work/publications from NIH, HRSA, and the Robert Wood Johnson Foundation. Dr. Kleinman also reported minority individual stock ownership in Apple Computer, Sanofi SA, Experion, GlaxoSmithKline, Magyar Bank, Regeneron Pharmaceuticals, JP Morgan Chase, and Amgen Inc. Torri Metz reported participating as a Principle Investigator in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She is also a principle investigator for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Joshua Milner reported serving as a member of the Scientific Advisory Board for Blueprint Medicines, in a capacity unrelated to RECOVER work/publications. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Gross et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To examine patient and provider perspectives on privacy and security considerations in telemedicine during the COVID-19 pandemic., Study Design: Qualitative study with patients and providers from primary care practices in 3 National Patient-Centered Clinical Research Network sites in New York, New York; North Carolina; and Florida., Methods: Semistructured interviews were conducted, audio recorded, transcribed verbatim, and coded using an inductive process. Data related to privacy and information security were analyzed., Results: Sixty-five patients and 21 providers participated. Patients and providers faced technology-related security concerns as well as difficulties ensuring privacy in the transformed shared space of telemedicine. Patients expressed increased comfort doing telemedicine from home but often did not like their providers to offer virtual visits from outside an office setting. Providers initially struggled to find secure and Health Insurance Portability and Accountability Act-compliant platforms and devices to host the software. Whereas some patients preferred familiar platforms such as FaceTime, others recognized potential security concerns. Audio-only encounters sometimes raised patient concerns that they would not be able to confirm the identity of the provider., Conclusions: Telemedicine led to novel concerns about privacy because patients and providers were often at home or in public spaces, and they shared concerns about software and hardware security. In addition to technological safeguards, our study emphasizes the critical role of physical infrastructure in ensuring privacy and security. As telemedicine continues to evolve, it is important to address and mitigate concerns around privacy and security to ensure high-quality and safe delivery of care to patients in remote settings.

Objectives: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years., Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination., Results: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months., Conclusions: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data., (Copyright © 2024 by the American Academy of Pediatrics.)

Mental and financial hardship during the COVID-19 pandemic in New York City was severe, but how vulnerable groups have been disproportionately impacted is incompletely understood. In partnership with community stakeholders, we administered a web-based survey to a convenience sample of New York City residents (18 + years) from May 2020 to April 2021 to evaluate their financial and emotional stressors. We analyzed outcomes by race, ethnicity, and education level. A total of 1854 adults completed the survey across three consecutive non-overlapping samples. Fifty-five percent identified other than non-Latinx White. Sixty-four percent reported emotional stress; 38%, 32%, and 32% reported symptoms of anxiety, depression, and post-traumatic stress disorder respectively; and 21% reported a large adverse financial impact. The leading unmet needs were mental health and food services (both 19%), and health services (18%). Need for both resources grew over time. Adverse financial impact directly correlated with presence of all four adverse mental health outcomes above. In multivariate analysis, non-White race and lack of college degree were associated with adverse financial impact, whereas LGBT identity and lack of college degree were associated with mental health impact. Throughout the COVID-19 pandemic, participants in this research demonstrated a large and growing mental and financial strain, disproportionately associated with lower education level, non-White race, and LGBT status. Our findings suggest an urgent need to differentially target COVID-19 mental health and resource support in New York City to persons in these vulnerable communities., (© 2024. W. Montague Cobb-NMA Health Institute.)

Background: Previous studies have demonstrated the association between food security and cardiometabolic diseases (CMDs), yet none have investigated trends in prevalence of CMDs by food security status in the United States (US)., Methods: Serial cross-sectional analysis of the US nationally representative data from National Health and Nutrition Examination Survey (1999-2018) was conducted among adults aged 20 years or older. Food security status was defined by the US Household Food Security Survey Module (full, marginal, low, and very low food security). We estimated the age-adjusted prevalence of CMDs including obesity, hypertension, diabetes, and coronary heart disease by food security status. Racial and ethnic disparities in age-adjusted prevalence of CMDs by food security status were also assessed., Results: A total of 49,738 participants were included in this analysis (weighted mean age 47.3 years; 51.3% women). From 1999 to 2018, the age-adjusted prevalence of CMDs was lower in full food secure group as compared with other groups. For example, trends in hypertension decreased from 49.7% (47.5-51.8%) to 45.9% (43.8-48.0%) (P-trend = 0.002) among the full and from 54.2% (49.9-58.5%) to 49.7% (46.8-52.6%) (P-trend = 0.02) among the marginal but remained stable among the low at 49.7% (47.9-51.6%) and among the very low at 51.1% (48.9-53.3%) (P-interaction = 0.02). Prevalence of diabetes increased from 8.85% (8.15-9.60%) to 12.2% (11.1-13.5%) among the full (P-trend < 0.001), from 16.5% (13.2-20.4%) to 20.9% (18.6-23.5%) (P-trend = 0.045) among the marginal and from 14.6% (11.1-19.0%) to 20.9% (18.8-23.3%) (P-trend = 0.001) among the low but remained stable at 18.8% (17.0-20.9) among the very low (P-trend = 0.35) (P-interaction = 0.03). Racial and ethnic differences in prevalence of CMD by food security status were observed. For example, among individuals with full food secure status, the prevalence of diabetes was 9.08% (95% CI, 8.60-9.59%) for non-Hispanic whites, 17.3% (95% CI, 16.4-18.2%) for non-Hispanic blacks, 16.1% (95% CI, 15.0-17.4%) for Hispanics and 14.9% (95% CI, 13.3-16.7%) for others., Conclusions and Relevance: Prevalence of CMDs was greatest among those experiencing food insecurity, and food insecurity disproportionately affected racial/ethnic minorities. Disparities in CMD prevalence by food security status persisted or worsened, especially among racial/ethnic minorities., (© 2023. The Author(s).)

Objectives: The prevalences of hypertension and depression in sub-Saharan Africa are substantial and rising, despite limited data on their sociodemographic and behavioral risk factors and their interactions. We undertook a cross-sectional study in 4 communities in the Upper East Region of Ghana to identify persons with hypertension and depression in the setting of a pilot intervention training local nurses and health volunteers to manage these conditions., Methods: We quantified hypertension and depression prevalence across key sociodemographic factors (age, sex, occupation, education, religion, ethnicity, and community) and behavioral factors (tobacco use, alcohol use, and physical activity) and tested for association by multivariable logistic regression., Results: Hypertension prevalence was higher in older persons (7.6% among 35- to 50-year-olds vs 16.4% among 51- to 70-year-olds) and among those reporting alcohol use (18.9% vs 8.5% between users and nonusers). In multivariable models, only older age (AOR 2.39 [1.02, 5.85]) and residence in the community of Wuru (AOR 7.60 [1.81, 32.96]) were independently associated with hypertension, and residence in Wuru (AOR 23.58 [7.75-78.25]) or Navio (AOR 7.41 [2.30-24.74]) was the only factor independently associated with depression., Conclusions: We report a high prevalence of both diseases overall and in select communities, a trend that requires further research to inform targeted chronic disease interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DJH reports support from Hess Corporation, who was not involved in any way in the creation of this manuscript or the conduct of this research, as a potential competing interest. DJH and RAA report funding from Teva Pharmaceutical Industries, who funded this research but were not involved in any way in the creation of this manuscript or the conduct of this research. No other author has any potential conflict to state or disclose.

Purpose: To better understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders., Methods: Longitudinal physician claims data after diagnostic sequencing were obtained for patients aged 0 to 21 years with neurologic, cardiac, and immunologic disorders with suspected genetic etiology. We assessed specialist consultation rates prompted by primary diagnostic results, as well as marginal effects on overall 18-month physician services and costs., Results: We included data on 857 patients (median age: 9.6 years) with a median follow-up of 17.3 months after disclosure of diagnostic sequencing results. The likelihood of having ≥1 recommendation for specialist consultation in 155 patients with positive findings was high (72%) vs 23% in 443 patients with uncertain findings and 21% in 259 patients with negative findings (P < .001). Follow-through consultation occurred in 30%. Increases in 18-month physician services and costs following a positive finding diminished after multivariable adjustment. Also, no significant differences between those with uncertain and negative findings were demonstrated., Conclusion: Our study did not provide evidence for significant increases in downstream physician services and costs after returning positive or uncertain diagnostic sequencing findings. More large-scale longitudinal studies are needed to confirm these findings., Competing Interests: Conflict of Interest Dr Kenny has received speaker honoraria from Illumina, 23andMe, Allelica, and Regeneron Pharmaceuticals, received research funding from Allelica, and serves as a scientific advisory board member for Encompass Biosciences, Overtone, and Galateo Bio. Dr Abul-Husn is an employee and equity holder of 23andMe; serves as a scientific advisory board member for Allelica; received personal fees from Genentech, Allelica, and 23andMe; received research funding from Akcea; and was previously employed by Regeneron Pharmaceuticals. All other authors declare they have no conflicts of interest to report. Ethics Declaration The NYCKidSeq and TeleKidseq studies were approved by the Icahn School of Medicine at Mount Sinai and the Albert Einstein College of Medicine Institutional Review Boards. Written informed consent was obtained from pediatric participants who were capable of providing (≥18 years of age and cognitively able) and all parent or legal guardian participants., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics., Competing Interests: Declaration of interests E.E.K. has received speaker honoraria from Illumina, 23&Me, Allelica, and Regeneron Pharmaceuticals; received research funding from Allelica; and serves as a scientific advisory board member for Encompass Biosciences, Foresite Labs, and Galateo Bio. N.S.A.-H. is an equity holder of 23andMe; serves as a scientific advisory board member for Allelica; received personal fees from Genentech, Allelica, and 23andMe; received research funding from Akcea; and was previously employed by Regeneron Pharmaceuticals., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Community-based organizations (CBOs) are on the frontlines offering resources and support to residents during times of distress. Through a community-academic partnership, an interdisciplinary team developed, collected, and analyzed 91 surveys from social services providers across New York City assessing the impact of the COVID-19 pandemic on their organizations' operations. The majority (93%) of these organizations stayed open during the pandemic but had to shift the services they offered to meet new needs. Although most (89%) shared they were not offering on-site testing for COVID-19, 53% expressed interest in becoming a test site, citing needs such as funding, test kits, and skills-building for staff. More than half of the respondents were eager to get involved in public health efforts in other ways, such as joining local research advisory boards. Despite increasing the services they provided, CBOs saw decreases in staffing and volunteers. Furthermore, although nearly half (48%) received governmental aid, many faced financial pressures and several had to close offices during the pandemic. As trusted resources, CBOs can help meet public health needs if provided with proper support and resources. It is critical that those working in prevention and relief are considerate about how and when they leverage effective partnerships between public health organizations and CBOs, offering organizations the resources they need to be effective in this charge, given the role they can have in promoting health equity.

Purpose: To examine the impact of telemedicine use on precepting and teaching among preceptors and patients during the COVID-19 pandemic., Method: The authors conducted a secondary analysis of a qualitative study focusing on providers' and patients' experiences with and attitudes toward telemedicine at 4 academic health centers. Teaching and precepting were emergent codes from the data and organized into themes. Themes were mapped to domains from the 2009 Consolidated Framework for Implementation Research (CFIR), a framework that assists with effective implementation and consists of 5 domains: intervention characteristics, outer settings, inner settings, characteristics of individuals, and process., Results: In total, 86 interviews were conducted with 65 patients and 21 providers. Nine providers and 3 patients recounted descriptions related to teaching and precepting with telemedicine. Eight themes were identified, mapping across all 5 CFIR domains, with the majority of themes (n = 6) within the domains of characteristics of individuals, processes, and intervention characteristics. Providers and patients described how a lack of prepandemic telemedicine experience and inadequate processes in place to precept and teach with telemedicine affected the learning environment and perceived quality of care. They also discussed how telemedicine exacerbated existing difficulties in maintaining resident continuity. Providers described ways communication changed with telemedicine use during the pandemic, including having to wear masks while in the same room as the trainee and sitting closely to remain within range of the camera, as well as the benefit of observing trainees with the attending's camera off. Providers expressed a lack of protected structure and time for teaching and supervising with telemedicine, and a general view that telemedicine is here to stay., Conclusions: Efforts should focus on increasing knowledge of telemedicine skills and improving processes to implement telemedicine in the teaching setting in order to best integrate it into undergraduate and graduate medical education., (Copyright © 2023 by the Association of American Medical Colleges.)

Purpose: Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions., Methods: Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design., Results: A total of 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs TGPs in Hispanic/Latino(a) (17.2% vs 9.5%, P < .001) and White/European American (19.8% vs 7.9%, P < .001) but not in Black/African American (11.5% vs 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS., Conclusion: GS may yield up to twice as many diagnoses in pediatric patients compared with TGP testing but not yet across all population groups., Competing Interests: Conflict of Interest Noura S. Abul-Husn is an employee and equity holder of 23andMe; serves as a scientic advisory board member for Allelica; received personal fees from Genentech, Allelica, and 23andMe; received research funding from Akcea; and was previously employed by Regeneron Pharmaceuticals. Eimear E. Kenny received personal fees from Illumina, 23andMe, Allelica, and Regeneron Pharmaceuticals; received research funding from Allelica; and serves as a scientific advisory board member for Encompass Bio, Foresite Labs, and Galateo Bio. All other authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: Racial and ethnic disparities in outcomes for children with congenital heart disease (CHD) coexist with disparities in educational, environmental, and economic opportunity., Objectives: We sought to determine the associations between childhood opportunity, race/ethnicity, and pediatric CHD surgery outcomes., Methods: Pediatric Health Information System encounters aged <18 years from 2016 to 2022 with International Classification of Diseases-10th edition codes for CHD and cardiac surgery were linked to ZIP code-level Childhood Opportunity Index (COI), a score of neighborhood educational, environmental, and socioeconomic conditions. The associations of race/ethnicity and COI with in-hospital surgical death were modeled with generalized estimating equations and formal mediation analysis. Neonatal survival after discharge was modeled by Cox proportional hazards., Results: Of 54,666 encounters at 47 centers, non-Hispanic Black (Black) (OR: 1.20; P = 0.01), Asian (OR: 1.75; P < 0.001), and Other (OR: 1.50; P < 0.001) groups had increased adjusted mortality vs non-Hispanic Whites. The lowest COI quintile had increased in-hospital mortality in unadjusted and partially adjusted models (OR: 1.29; P = 0.004), but not fully adjusted models (OR: 1.14; P = 0.13). COI partially mediated the effect of race/ethnicity on in-hospital mortality between 2.6% (P = 0.64) and 16.8% (P = 0.029), depending on model specification. In neonatal multivariable survival analysis (n = 13,987; median follow-up: 0.70 years), the lowest COI quintile had poorer survival (HR: 1.21; P = 0.04)., Conclusions: Children in the lowest COI quintile are at risk for poor outcomes after CHD surgery. Disproportionally increased mortality in Black, Asian, and Other populations may be partially mediated by COI. Targeted investment in low COI neighborhoods may improve outcomes after hospital discharge. Identification of unmeasured factors to explain persistent risk attributed to race/ethnicity is an important area of future exploration., Competing Interests: Funding Support and Author Disclosures This work was supported by American Academy of Pediatrics CHANGE grant reference number 18-15592265. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis., Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms., Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options., Registration: NCT05172024., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Helen Chu reported consulting for Merck, GSK, Pfizer, Ellume, Janssen, Vindico CME, and the Bill and Melinda Gates Foundation, and receiving research support from Gates Ventures, Ellume, and Sanofi Pasteur. She also serves as a co-investigator on studies funded by Pfizer, Novavax, and GSK. Maged Costantine reported receiving grant support for work not related to RECOVER work/publications from Baxter International and Siemens Healthcare and personal consulting fees not related to this paper from Progenity, Quidel Ortho, and Siemens Healthcare. Kristine Erlandson reported research funding from Gilead Sciences and consulting payments from Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to the University of Colorado. Emily Gallagher reported consulting for Novartis, Flare Therapeutics and Seagen. Edward Gardner reported research support (clinical trials) from Gilead Sciences, ViiV Healthcare, and Cepheid. Jason Goldman reported research support from Gilead, Eli Lilly and Regeneron; grants from Gilead, Merck (BARDA); personal fees for consulting from Gilead, Eli Lilly; and non-financial support from Adaptive Biotechnologies and Labcorp/Monogram Biosciences outside the submitted work. Timothy Heinrich reported grant support from Merck Inc. and consulting fees from Roche. Rachel Hess reported serving as Data Safety Monitoring Board member for Astellas Pharmaceuticals unrelated to the current work. Leora Horwitz reported being a member of the National Academy of Medicine Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. Priscilla Hsue reported receiving honoraria from Gilead and Merck unrelated to study topic, receiving study drug from Regeneron unrelated to study topic, and receiving a research grant from Novartis. Judith James reported OMRF has licensed her IP to Progentec Biosciences, has received grant support from Progentec Biosciences, and serves on Advisory Committees to Glaxo Smith Klein, Merck and Novartis. Arthur Kim reports providing educational materials to Clinical Care Options and UpToDate and serving on a Data Safety Monitoring board for Kintor Pharmaceuticals, Ltd. Bruce Levy reported serving as a consultant for AstraZeneca, Entrinsic Biosciences, Gossamer Bio and Nocion Therapeutics and receiving research support from Amgen, Genentech, GlaxoSmithKline, Pieris Pharmaceuticals, SRA and Sanofi unrelated to the current work. Vincent Marconi reported receiving grants from NIH during the conduct of the study and grants from NIH, Veteran Affairs, and Centers for Disease Control and Prevention; grants, personal fees, nonfinancial support, and other from Lilly and Gilead; grants and personal fees from ViiV; and nonfinancial support from Bayer outside the submitted work. Grace McComsey reported serving as consultant for Merck, Gilead, ViiV, Janssen and have received research support from Pfizer, Vanda, Genentech, Roche, Redhill and Cognivue. Torri Metz reported being a site PI and a participant in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She also reported being a site PI for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Janet Mullington reported support for investigator-initiated research by "Open Medicine Foundation and the Patient-Led Research Collaborative" Princess Ogbogu reported research support from Astrazeneca, GSK, Blueprint medical; advisory board for Astrazeneca, GSK, Sanofi, Kalvista; and consulting for Astrazeneca, GSK Sairam Parthasarathy reported research funding to Institution from Sergey Brin foundation of COVID and Long-COVID research. Michael Peluso reported consulting fees from Gilead Sciences and AstraZeneca, and service on data safety monitoring board for American Gene Technologies. Sean Quigley reported service on speaker Board for Servier, Alnylam, Agios; service on advisory board for Recordati, Alexion. Franz Rischard reported research support from NIH/NHLBI, United Therapeutics, Acceleron/Merck, Janssen, Insmed, Aerovate, and Bayer; and consulting/advisory compensation from Acceleron and Bayer. Nadine Rouphael reported being a consultant for ICON and EMMES as a safety consultant for clinical trials; service on the advisory boards for Moderna; funds to institution from Sanofi, Lilly, Merck, Quidel and Pfizer. PJ Utz reported stock ownership of Gilead and PI of biomarker studies for Pfizer STOP-PASC paxlovid trial Juan Wisnivesky received receiving consulting honorarium from Sanofi, Banook, Prospero, PPD and Atea and research grants from Sanofi, Regeneron, Axella, and Arnold Consultants., (Copyright: © 2023 Horwitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The necessary suspension of nonacute services by healthcare systems early in the COVID-19 pandemic was predicted to cause delays in routine care in the United States, with potentially serious consequences for chronic disease management. However, limited work has examined provider or patient perspectives about care delays and their implications for care quality in future healthcare emergencies., Objective: This study explores primary care provider (PCP) and patient experiences with healthcare delays during the COVID-19 pandemic., Methods: PCPs and patients were recruited from four large healthcare systems in three states. Participants underwent semistructured interviews asking about their experiences with primary care and telemedicine. Data were analyzed using interpretive description., Results: Twenty-one PCPs and 65 patients participated in interviews. Four main topics were identified: (1) types of care delayed, (2) causes for delays, (3) miscommunication contributing to delays, and (4) patient solutions to unmet care needs., Conclusions: Both patients and providers reported delays in preventive and routine care early in the pandemic, driven by healthcare system changes and patient concerns about infection risk. Primary care practices should develop plans for care continuity and consider new strategies for assessing care quality for effective chronic disease management in future healthcare system disruptions., Competing Interests: No conflicts of interest exist for the following authors: K. A. Muellers, K. Andreadis, J. S. Ancker, C. R. Horowitz, and J. J. Lin. Dr. R. Kaushal serves on Curai's Board of Advisors and has an equity stake in the company., (Copyright © 2023 National Association for Healthcare Quality.)

Background: The COVID-19 pandemic forced healthcare institutions and many clinical research programs to adopt telehealth modalities in order to mitigate viral spread. With the expanded use of telehealth, there is the potential to increase access to genomic medicine to medically underserved populations, yet little is known about how best to communicate genomic results via telehealth while also ensuring equitable access. NYCKidSeq, a multi-institutional clinical genomics research program in New York City, launched the TeleKidSeq pilot study to assess alternative forms of genomic communication and telehealth service delivery models with families from medically underserved populations., Methods: We aim to enroll 496 participants between 0 and 21 years old to receive clinical genome sequencing. These individuals have a neurologic, cardiovascular, and/or immunologic disease. Participants will be English- or Spanish-speaking and predominantly from underrepresented groups who receive care in the New York metropolitan area. Prior to enrollment, participants will be randomized to either genetic counseling via videoconferencing with screen-sharing or genetic counseling via videoconferencing without screen-sharing. Using surveys administered at baseline, results disclosure, and 6-months post-results disclosure, we will evaluate the impact of the use of screen-sharing on participant understanding, satisfaction, and uptake of medical recommendations, as well as the psychological and socioeconomic implications of obtaining genome sequencing. Clinical utility, cost, and diagnostic yield of genome sequencing will also be assessed., Discussion: The TeleKidSeq pilot study will contribute to innovations in communicating genomic test results to diverse populations through telehealth technology. In conjunction with NYCKidSeq, this work will inform best practices for the implementation of genomic medicine in diverse, English- and Spanish-speaking populations., (© 2023. The Author(s).)

The increased use of next-generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total of eleven cases: nine in which mosaic variants detected by genome sequencing (GS) and/or targeted gene panels (TGPs) were considered to be causative for the proband's phenotype, and two of apparent parental mosaicism. Variants were identified in the following genes: PHACTR1, SCN8A, KCNT1, CDKL5, NEXMIF, CUX1, TSC2, GABRB2, and SMARCB1. In addition, we identified one large duplication including three genes, UBE3A, GABRB3, and MAGEL2, and one large deletion including deletion of ARFGAP1, EEF1A2, CHRNA4, and KCNQ2. All patients were enrolled in the NYCKidSeq study, a research program studying the communication of genomic information in clinical care, as well as the clinical utility and diagnostic yield of GS for children with suspected genetic disorders in diverse populations in New York City. We observed variability in the correlation between reported variant allele fraction and the severity of the patient's phenotype, although we were not able to determine the mosaicism percentage in clinically relevant tissue(s). Although our study was not sufficiently powered to assess differences in mosaicism detection between the two testing modalities, we saw a trend toward better detection by GS as compared with TGP testing. This case series supports the importance of mosaicism in childhood-onset genetic conditions and informs guidelines for laboratory and clinical interpretation of mosaic variants detected by GS., (© 2022 Wiley Periodicals LLC.)

Clinical research studies have navigated many changes throughout the COVID-19 pandemic. We sought to describe the pandemic's impact on research operations in the context of a clinical genomics research consortium that aimed to enroll a majority of participants from underrepresented populations. We interviewed (July to November 2020) and surveyed (May to August 2021) representatives of six projects in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, which studies the implementation of genome sequencing in the clinical care of patients from populations that are underrepresented in genomics research or are medically underserved. Questions focused on COVID's impact on participant recruitment, enrollment, and engagement, and the transition to teleresearch. Responses were combined and thematically analyzed. Projects described factors at the project, institutional, and community levels that affected their experiences. Project factors included the project's progress at the pandemic's onset, the urgency of in-person clinical care for the disease being studied, and the degree to which teleresearch procedures were already incorporated. Institutional and community factors included institutional guidance for research and clinical care and the burden of COVID on the local community. Overall, being responsive to community experiences and values was essential to how CSER navigated evolving challenges during the COVID-19 pandemic., (© 2022 Wiley Periodicals LLC.)

Background: Cardiovascular disease (CVD) prevalence is high in Ghana-but awareness, prevention, and treatment is sparse, particularly in rural regions. The nurse-led Community-based Health Planning and Services program offers general preventive and primary care in these areas, but overlooks CVD and its risk factors., Methods: We conducted in-depth interviews with 30 community members (CM) in rural Navrongo, Ghana to understand their knowledge and beliefs regarding the causes and treatment of CVD and the potential role of community nurses in rendering CVD care. We transcribed audio records, coded these data for content, and qualitatively analyzed these codes for key themes., Results: CMs described CVD as an acute, aggressive disease rather than a chronic asymptomatic condition, believing that CVD patients often die suddenly. Yet CMs identified causal risk factors for CVD: not only tobacco smoking and poor diet, but also emotional burdens and stressors, which cause and exacerbate CVD symptoms. Many CMs expressed interest in counseling on these risk factors, particularly diet. However, they felt that nurses could provide comprehensive CVD care only if key barriers (such as medication access and training) are addressed. In the interim, many saw nurses' main CVD care role as referring to the hospital., Conclusions: CMs would like CVD behavioral education from community nurses at local clinics, but feel the local health system is now too fragile to offer other CVD interventions. CMs believe that a more comprehensive CVD care model would require accessible medication, along with training for nurses to screen for hypertension and other cardiovascular risk factors-in addition to counseling on CVD prevention. Such counseling should build upon existing community beliefs and concerns regarding CVD-including its behavioral and mental health causes-in addition to usual measures to prevent CVD mortality such as diet changes and physical exercise., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DJH, RA, and KJ report research funding from Teva Pharmaceutical Industries. DJH and KJ report consulting funding from the Hess Corporation. Neither of these funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright: © 2023 Patil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Rationale and Objective: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease., Study Design: Multicenter, pragmatic, randomized controlled clinical trial., Setting and Participants: 6650 individuals with African ancestry and hypertension from 13 health systems., Intervention: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use., Outcomes: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months., Results: To date, the trial has enrolled 3423 participants., Conclusions: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record., Trial Registration: ClinicalTrials.govNCT04191824., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objectives: Successful clinical integration of genomic sequencing (GS) requires evidence of its utility. While GS potentially has benefits (utilities) or harms (disutilities) across multiple domains of life for both patients and their families, there is as yet no empirically informed conceptual model of these effects. Our objective was to develop an empirically informed conceptual model of perceived utility of GS that captures utilities and disutilities for patients and their families across diverse backgrounds., Methods: We took a patient-centered approach, in which we began with a review of existing literature followed by collection of primary interview data. We conducted semi-structured interviews to explore types of utility in a clinically and sociopolitically diverse sample of 60 adults from seven Clinical Sequencing Evidence-Generating Research (CSER) consortium projects. Interviewees had either personally received, or were parents of a child who had received, GS results. Qualitative data were analyzed using thematic analysis. Findings from interviews were integrated with existing literature on clinical and personal utility to form the basis of an initial conceptual model that was refined based on expert review and feedback., Results: Five key utility types that have been previously identified in qualitative literature held up as primary domains of utility and disutility in our diverse sample. Interview data were used to specify and organize subdomains of an initial conceptual model. After expert refinement, the five primary domains included in the final model are clinical, emotional, behavioral, cognitive, and social, and several subdomains are specified within each., Conclusion: We present an empirically informed conceptual model of perceived utility of GS. This model can be used to guide development of instruments for patient-centered outcome measurement that capture the range of relevant utilities and disutilities and inform clinical implementation of GS., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into the design and implementation of genomics research has yet to be realized., Methods: The National Institutes of Health-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination., Results: Projects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle., Conclusion: Each CSER project used more than 1 approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Risk variants in the apolipoprotein L1 (APOL1 [OMIM 603743]) gene on chromosome 22 are common in individuals of West African ancestry and confer increased risk of kidney failure for people with African ancestry and hypertension. Whether disclosing APOL1 genetic testing results to patients of African ancestry and their clinicians affects blood pressure, kidney disease screening, or patient behaviors is unknown., Objective: To determine the effects of testing and disclosing APOL1 genetic results to patients of African ancestry with hypertension and their clinicians., Design, Setting, and Participants: This pragmatic randomized clinical trial randomly assigned 2050 adults of African ancestry with hypertension and without existing chronic kidney disease in 2 US health care systems from November 1, 2014, through November 28, 2016; the final date of follow-up was January 16, 2018. Patients were randomly assigned to undergo immediate (intervention) or delayed (waiting list control group) APOL1 testing in a 7:1 ratio. Statistical analysis was performed from May 1, 2018, to July 31, 2020., Interventions: Patients randomly assigned to the intervention group received APOL1 genetic testing results from trained staff; their clinicians received results through clinical decision support in electronic health records. Waiting list control patients received the results after their 12-month follow-up visit., Main Outcomes and Measures: Coprimary outcomes were the change in 3-month systolic blood pressure and 12-month urine kidney disease screening comparing intervention patients with high-risk APOL1 genotypes and those with low-risk APOL1 genotypes. Secondary outcomes compared these outcomes between intervention group patients with high-risk APOL1 genotypes and controls. Exploratory analyses included psychobehavioral factors., Results: Among 2050 randomly assigned patients (1360 women [66%]; mean [SD] age, 53 [10] years), the baseline mean (SD) systolic blood pressure was significantly higher in patients with high-risk APOL1 genotypes vs those with low-risk APOL1 genotypes and controls (137 [21] vs 134 [19] vs 133 [19] mm Hg; P = .003 for high-risk vs low-risk APOL1 genotypes; P = .001 for high-risk APOL1 genotypes vs controls). At 3 months, the mean (SD) change in systolic blood pressure was significantly greater in patients with high-risk APOL1 genotypes vs those with low-risk APOL1 genotypes (6 [18] vs 3 [18] mm Hg; P = .004) and controls (6 [18] vs 3 [19] mm Hg; P = .01). At 12 months, there was a 12% increase in urine kidney disease testing among patients with high-risk APOL1 genotypes (from 39 of 234 [17%] to 68 of 234 [29%]) vs a 6% increase among those with low-risk APOL1 genotypes (from 278 of 1561 [18%] to 377 of 1561 [24%]; P = .10) and a 7% increase among controls (from 33 of 255 [13%] to 50 of 255 [20%]; P = .01). In response to testing, patients with high-risk APOL1 genotypes reported more changes in lifestyle (a subjective measure that included better dietary and exercise habits; 129 of 218 [59%] vs 547 of 1468 [37%]; P < .001) and increased blood pressure medication use (21 of 218 [10%] vs 68 of 1468 [5%]; P = .005) vs those with low-risk APOL1 genotypes; 1631 of 1686 (97%) declared they would get tested again., Conclusions and Relevance: In this randomized clinical trial, disclosing APOL1 genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure, increased kidney disease screening, and positive self-reported behavior changes in those with high-risk genotypes., Trial Registration: ClinicalTrials.gov Identifier: NCT02234063.

Abstract: While increased obesity prevalence among persons of African ancestry (AAs) compared to persons of European ancestry (EAs) is linked to social, environmental and behavioral factors, there are no gene variants that are common and significantly associated with obesity in AA populations. We sought to explore the association between ancestry specific renal risk variants in the apolipoprotein L1 (APOL1) gene with obesity related traits in AAs.We conducted a genotype-phenotype association study from 3 electronic medical record linked cohorts (BioMe Biobank, BioVU, nuGENE); randomized controlled trials (genetic testing to understand and address renal disease disparities) and prospective cohort study (Jackson Heart Study). We analyzed association of APOL1 renal risk variants with cross-sectional measures of obesity (average body mass index (BMI), and proportion of overweight and obesity) and with measures of body composition (in Jackson Heart Study).We had data on 11,930 self-reported AA adults. Across cohorts, mean age was from 42 to 49 years and percentage female from 58% to 75.3%. Individuals who have 2 APOL1 risk alleles (14% of AAs) have 30% higher obesity odds compared to others (recessive model adjusted odds ratio 1.30; 95% confidence interval 1.16-1.41; P = 2.75 × 10-6). An additive model better fit the association, in which each allele (47% of AAs) increases obesity odds by 1.13-fold (adjusted odds ratio 1.13; 95% confidence interval 1.07-1.19; P = 3.07 × 10-6) and increases BMI by 0.36 kg/m2 (∼1 kg, for 1.7 m height; P = 2 × 10-4). APOL1 alleles are not associated with refined body composition traits overall but are significantly associated with fat free mass index in women [0.30 kg/m2 increment per allele; P = .03].Thus, renal risk variants in the APOL1 gene, found in nearly half of AAs, are associated with BMI and obesity in an additive manner. These variants could, either on their own or interacting with environmental factors, explain a proportion of ethnic disparities in obesity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Making a diagnosis from clinical genomic sequencing requires well-structured phenotypic data to guide genotype interpretation. A patient's phenotypic features can be documented using the Human Phenotype Ontology (HPO), generating terms used to prioritize genes potentially causing the patient's disease. We have developed GenomeDiver to provide a user interface for clinicians that allows more effective collaboration with the clinical diagnostic laboratory, with the goal of improving the success of the diagnostic process., Methods: GenomeDiver uses genomic data to prompt reverse phenotyping of patients undergoing genetic testing, enriching the amount and quality of structured phenotype data for the diagnostic laboratory, and helping clinicians to explore and flag diseases potentially causing their patient's presentation., Results: We show how GenomeDiver communicates the clinician's informed insights to the diagnostic lab in the form of HPO terms for interpretation of genomic sequencing data. We describe our user-driven design process, the engineering of the software for efficiency, security and portability, and examples of the performance of GenomeDiver using genomic testing data., Conclusion: GenomeDiver is a first step in a new approach to genomic diagnostics that enhances laboratory-clinician interactions, with the goal of directly engaging clinicians to improve the outcome of genomic diagnostic testing., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Objectives: Management of cardiovascular disease (CVD) is an urgent challenge in low-income and middle-income countries, and interventions may require appraisal of patients' social networks to guide implementation. The purpose of this study is to determine whether egocentric social network characteristics (SNCs) of patients with chronic disease in western Kenya are associated with overall CVD risk and individual CVD risk factors., Design: Cross-sectional analysis of enrollment data (2017-2018) from the Bridging Income Generation with GrouP Integrated Care trial. Non-overlapping trust-only, health advice-only and multiplex (trust and health advice) egocentric social networks were elicited for each participant, and SNCs representing social cohesion were calculated., Setting: 24 communities across four counties in western Kenya., Participants: Participants (n=2890) were ≥35 years old with diabetes (fasting glucose ≥7 mmol/L) or hypertension., Primary and Secondary Outcomes: We hypothesised that SNCs would be associated with CVD risk status (QRISK3 score). Secondary outcomes were individual CVD risk factors., Results: Among the 2890 participants, 2020 (70%) were women, and mean (SD) age was 60.7 (12.1) years. Forty-four per cent of participants had elevated QRISK3 score (≥10%). No relationship was observed between QRISK3 level and SNCs. In unadjusted comparisons, participants with any individuals in their trust network were more likely to report a good than a poor diet (41% vs 21%). SNCs for the trust and multiplex networks accounted for a substantial fraction of variation in measures of dietary quality and physical activity (statistically significant via likelihood ratio test, adjusted for false discovery rate)., Conclusion: SNCs indicative of social cohesion appear to be associated with individual behavioural CVD risk factors, although not with overall CVD risk score. Understanding how SNCs of patients with chronic diseases relate to modifiable CVD risk factors could help inform network-based interventions., Trial Registration Number: ClinicalTrials.gov identifier: NCT02501746; https://clinicaltrials.gov/ct2/show/NCT02501746., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Genomics is increasingly used for diagnostic testing in children. This study describes the expectations of parents whose child received genomic testing and whether or not they were met., Methods: A diverse stratified, purposive sample of parents of 22 children in New York City was interviewed using a semi-structured guide. Genomic test results were positive, negative, or uncertain., Results: Parents expressed their expectations in narrative and numeric fashion. Parents expected that their child's test would have a direct effect on their child's diagnosis. Some believed that results would be definitive, while others recognized testing limitations. Expectations reflected parents' hope to find a diagnosis and led to disappointment when results were uninformative or did not impact clinical management., Conclusion: Results suggest pre-test genetic counseling emphasize the low likelihood of actionable results; however, parents' expectations of genomics' diagnostic capabilities are strongly rooted in their need to end the diagnostic odyssey and may be difficult to manage., Practice Implications: Parents' hope for a resolution and effective treatment for their child is a powerful context in which genetic counseling is heard. Clinicians who provide genomic testing should continue to acknowledge parents' preconceptions. Additional research in other settings will help understand how to best address and manage parent expectations of genomic medicine., Competing Interests: Declaration of Competing Interest Katherine E. Donohue, Siobhan M. Dolan, Dana Watnick, Katie M. Gallagher, Jacqueline A. Odgis, Sabrina A. Suckiel, Nehama Teitelman, Bruce D. Gelb, Melissa P. Wasserstein, Carol R. Horowitz, and Laurie J. Bauman declare no conflicts of interest. Eimear E. Kenny has received compensation as a speaker honorarium at Regeneron Pharmaceuticals and Illumnia, Inc., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The complexity of genomic medicine can be streamlined by implementing some form of clinical decision support (CDS) to guide clinicians in how to use and interpret personalized data; however, it is not yet clear which strategies are best suited for this purpose. In this study, we used implementation science to identify common strategies for applying provider-based CDS interventions across six genomic medicine clinical research projects funded by an NIH consortium. Each project's strategies were elicited via a structured survey derived from a typology of implementation strategies, the Expert Recommendations for Implementing Change (ERIC), and follow-up interviews guided by both implementation strategy reporting criteria and a planning framework, RE-AIM, to obtain more detail about implementation strategies and desired outcomes. We found that, on average, the three pharmacogenomics implementation projects used more strategies than the disease-focused projects. Overall, projects had four implementation strategies in common; however, operationalization of each differed in accordance with each study's implementation outcomes. These four common strategies may be important for precision medicine program implementation, and pharmacogenomics may require more integration into clinical care. Understanding how and why these strategies were successfully employed could be useful for others implementing genomic or precision medicine programs in different contexts.

Purpose: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions., Methods: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation., Results: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression., Conclusion: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.