Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients ≥60 years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the United States (or 1.5 million people), the phenotypic penetrance is not known. Methods and Results The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) study is a currently accruing prospective multisite study designed to determine the prevalence of ATTR-CM using technetium-99m-pyrophosphate imaging in older (≥60 years of age) self-identified Black and Hispanic individuals with HF. Calculations of the penetrance and prevalence of the V122I allele, along with analyses of functional, biochemical, and echocardiographic parameters, were performed for the first 278 Black participants in SCAN-MP. The prevalence of ATTR-CM was 6.8% (95% CI, 4.2-10.5; n=19 cases), of whom 63% were ATTR wild-type. The prevalence of V122I was 6.5% (n=18 carriers), of whom 7 had ATTR-CM, yielding a phenotypic penetrance of 39% (95% CI, 17-64). V122I carriers with ATTR-CM evidenced more advanced HF than carriers without ATTR-CM. Prealbumin concentration was lowest among V122I carriers with ATTR-CM (12.9 mg/dL) versus carriers without ATTR-CM (21.0 mg/dL) and HF controls (25.0 mg/dL, P<0.0001). Conclusions Among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR-CM, 63% had wild-type, and of those with V122I, the phenotypic penetrance of ATTR-CM was 39% (95% CI, 17-64), suggesting that genotype alone is insufficient for diagnosis. Prealbumin concentration may be useful to identify V122I carriers with ATTR-CM. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.

Design and Rationale the SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an important cause of heart failure in older individuals. Misfolding and deposition of transthyretin or prealbumin protein causes ATTR-CM in the context of a normal (wild-type) or variant TTR sequence. Variant ATTR-CM is most commonly caused by the substitution of valine for isoleucine at position 122 in transthyretin (Val122Ile or pV142I, almost exclusively observed in individuals of West African ancestry), demonstrated in 3.4% of self-identified Black individuals in the United States with an estimated 1.5 million carriers. Despite the large number of known pV142I carriers, the proportion of older Black patients with heart failure attributable to ATTR-CM remains unknown. Methods To address this knowledge gap, the SCAN-MP (Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations) study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL139671) to enroll a targeted population of self-identified, community-dwelling Black or Caribbean Hispanic patients (many of whom are of West African ancestry) >60 years of age with heart failure and identify ATTR-CM by noninvasive nuclear imaging. The principal objective of SCAN-MP is to determine the prevalence of ATTR-CM in this population. Secondary objectives will explore TTR genotype, demographics, progression of variant versus wild-type ATTR-CM, and biochemical mechanisms of transthyretin amyloid fibril formation. Conclusions The SCAN-MP study is the largest, prospective study of cardiac amyloidosis in Black and Hispanic individuals. Both wild-type and variant ATTR-CM are now treatable with the US Food and Drug-approved drug tafamidis. The insights gained from SCAN-MP are likely to improve those at risk for or afflicted with ATTR-CM. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03812172.

Clinical and social determinants of health features of SARS-CoV-2 infection among Black and Caribbean Hispanic patients with heart failure: The SCAN-MP Study.

Patients with heart failure (HF) often have multiple chronic conditions and are at increased risk for severe disease and mortality when infected by SARS-CoV-2, the virus that causes COVID-19. Furthermore, disparities in outcomes with COVID-19 have been associated with both racial/ethnic identity but also social determinants of health. Among older, urban-dwelling, minority patients with HF, we sought to characterize medical and non-medical factors associated with SARS-CoV-2 infection. Patients with HF living in Boston and New York City over 60 years of age participating in the Screening for Cardiac Amyloidosis with Nuclear Imaging (SCAN-MP) study between 12/1/2019 and 10/15/2021 (n = 180) were tested for nucleocapsid antibodies to SARS-CoV-2 and queried for symptomatic infection with PCR verification. Baseline testing included the Kansas City Cardiomyopathy Questionnaire (KCCQ), assessment of health literacy, biochemical, functional capacity, echocardiography, and a novel survey tool that determined living conditions, perceived risk of infection, and attitudes towards COVID-19 mitigation. The association of infection with prevalent socio-economic conditions was assessed by the area deprivation index (ADI). There were 50 overall cases of SARS-CoV-2 infection (28%) including 40 demonstrating antibodies to SARS-CoV-2 (indicative of prior infection) and 10 positive PCR tests. There was no overlap between these groups. The first documented case from New York City indicated infection prior to January 17, 2020. Among active smokers, none tested positive for prior SARS-CoV-2 infection (0 (0%) vs. 20 (15%), p = 0.004) vs. non-smokers. Cases were more likely to be taking ACE-inhibitors/ARBs compared to non-cases (78% vs 62%, p = 0.04). Over a mean follow-up of 9.6 months, there were 6 total deaths (3.3%) all unrelated to COVID-19. Death and hospitalizations (n = 84) were not associated with incident (PCR tested) or prior (antibody) SARS-CoV-2 infection. There was no difference in age, co-morbidities, living conditions, attitudes toward mitigation, health literacy, or ADI between those with and without infection. SARS-CoV-2 infection was common among older, minority patients with HF living in New York City and Boston, with evidence of infection documented in early January 2020. Health literacy and ADI were not associated with infection, and there was no increased mortality or hospitalizations among those infected with SARS-CoV-2.

An Overview of Cancer in the First 315,000 All of Us Participants.

INTRODUCTION: The NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered. MATERIALS AND METHODS: This work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed. RESULTS AND DISCUSSION: Data collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data. CONCLUSIONS: This study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.

The All of Us Research Program: Data quality, utility, and diversity.

The All of Us Research Program seeks to engage at least one million diverse participants to advance precision medicine and improve human health. We describe here the cloud-based Researcher Workbench that uses a data passport model to democratize access to analytical tools and participant information including survey, physical measurement, and electronic health record (EHR) data. We also present validation study findings for several common complex diseases to demonstrate use of this novel platform in 315,000 participants, 78% of whom are from groups historically underrepresented in biomedical research, including 49% self-reporting non-White races. Replication findings include medication usage pattern differences by race in depression and type 2 diabetes, validation of known cancer associations with smoking, and calculation of cardiovascular risk scores by reported race effects. The cloud-based Researcher Workbench represents an important advance in enabling secure access for a broad range of researchers to this large resource and analytical tools.

Predictive Analytics for Glaucoma Using Data From the All of Us Research Program.

PURPOSE: To (1) use All of Us (AoU) data to validate a previously published single-center model predicting the need for surgery among individuals with glaucoma, (2) train new models using AoU data, and (3) share insights regarding this novel data source for ophthalmic research. DESIGN: Development and evaluation of machine learning models. METHODS: Electronic health record data were extracted from AoU for 1,231 adults diagnosed with primary open-angle glaucoma. The single-center model was applied to AoU data for external validation. AoU data were then used to train new models for predicting the need for glaucoma surgery using multivariable logistic regression, artificial neural networks, and random forests. Five-fold cross-validation was performed. Model performance was evaluated based on area under the receiver operating characteristic curve (AUC), accuracy, precision, and recall. RESULTS: The mean (standard deviation) age of the AoU cohort was 69.1 (10.5) years, with 57.3% women and 33.5% black, significantly exceeding representation in the single-center cohort (P = .04 and P < .001, respectively). Of 1,231 participants, 286 (23.2%) needed glaucoma surgery. When applying the single-center model to AoU data, accuracy was 0.69 and AUC was only 0.49. Using AoU data to train new models resulted in superior performance: AUCs ranged from 0.80 (logistic regression) to 0.99 (random forests). CONCLUSIONS: Models trained with national AoU data achieved superior performance compared with using single-center data. Although AoU does not currently include ophthalmic imaging, it offers several strengths over similar big-data sources such as claims data. AoU is a promising new data source for ophthalmic research.

Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study.

PURPOSE: Recruitment of participants from diverse backgrounds is crucial to the generalizability of genetic research, but has proven challenging. We retrospectively evaluated recruitment methods used for a study on return of genetic results. METHODS: The costs of study design, development, and participant enrollment were calculated, and the characteristics of the participants enrolled through the seven recruitment methods were examined. RESULTS: A total of 1118 participants provided consent, a blood sample, and questionnaire data. The estimated cost across recruitment methods ranged from $579 to $1666 per participant and required a large recruitment team. Recruitment methods using flyers and staff networks were the most cost-efficient and resulted in the highest completion rate. Targeted sampling that emphasized the importance of Latino/a participation, utilization of translated materials, and in-person recruitments contributed to enrolling a demographically diverse sample. CONCLUSIONS: Although all methods were deployed in the same hospital or neighborhood and shared the same staff, each recruitment method was different in terms of cost and characteristics of the enrolled participants, suggesting the importance of carefully choosing the recruitment methods based on the desired composition of the final study sample. This analysis provides information about the effectiveness and cost of different methods to recruit adults for genetic research.

Understanding susceptibility to e-cigarettes: A comprehensive model of risk factors that influence the transition from non-susceptible to susceptible among e-cigarette naïve adolescents.

The primary objective of this study was to identify risk factors associated with becoming susceptible to e-cigarette use over the course of a year among e-cigarette-naive adolescents considering a comprehensive model of risk factors (risk perceptions, social influences and norms, affective risk factors, and other behavioral risk factors). Data came from the Texas Adolescent Tobacco and Marketing Surveillance system (TATAMS), a longitudinal cohort study of students who were in the 6th, 8th, and 10th grades (n = 3907) during the 2014-2015 academic year. Weighted generalized linear mixed models assessed multiple predictors' associated with the transition to susceptibility to e-cigarettes at 12 months. Among 6th graders, family influence, use of other substances, and positive affect were important. Adolescents transitioning from 8th grade to high school presented the greatest number of risk factors (e.g., social and normative influences). Only sensation seeking increased the risk of susceptibility to e-cigarettes among 10th graders. Overall, by grade level, incidence of susceptibility to e-cigarettes at 12 months did not vary, but risk factor profiles varied substantially.

Exposure to e-cigarette marketing and product use among Mexican American young adults on the US-Mexico border: A pilot study.

Historically, the tobacco industry has marketed directly to minority groups, which is associated with increased product use; the advent of e-cigarettes poses a new risk. The purpose of this study is to examine associations between exposure to tobacco marketing via traditional and digital marketing channels and ever use of e-cigarettes among Mexican-American young adults. Ninety-two Mexican-American young adults between 18 and 29 years of age (61% female) were recruited from the Cameron County Hispanic Cohort, a well-characterized population-based cohort on the U.S.- Mexico border. Participants reported their use of e-cigarettes and exposure to pro- and anti-media messages about these products in traditional and digital venues. Nearly one third reported ever using e-cigarettes and exposure to media overall was low. However, exposure to pro e-cigarette messages via digital sources was associated with increased odds of ever using e-cigarettes (OR: 2.86; 95% CI: 1.11-7.38). Results suggest that regulations on e-cigarette digital media may help to reduce e-cigarette use.

Overcoming challenges to meaningful informed consent for whole genome sequencing in pediatric cancer research.

BACKGROUND: Introducing whole genome sequencing (WGS) into pediatric cancer research at diagnosis poses unique challenges related to informed consent. WGS requires tissue obtained prior to initiating treatment, when families may be overwhelmed with uncertainty and fear. Motivation to participate may be high without fully understanding the range of possible results, including secondary findings. Little is known about parental knowledge, attitudes, and beliefs about this type of research. PROCEDURE: A qualitative study was conducted to investigate parental knowledge about genetic concepts and WGS, thoughts about the informed consent process, and preferences for secondary findings. Focus groups were conducted with parents/guardians of children with cancer and semi-structured interviews were conducted in a control group without cancer. All transcripts were analyzed using content analysis. RESULTS: Four focus groups included 15 participants; eight semi-structured interviews included 10 participants. Basic knowledge about genetics was limited to heredity. Some knowledge of genomic analysis was present in 3/15 focus group participants. Major factors related to participation in WGS research were: (i) hope for their child and future children; (ii) no additional procedures; (iii) and protection of privacy. All favored a two-step consent process, first to store extra tissue from a diagnostic biopsy/resection, followed by consenting to WGS research, one-to-two months later. The desire to receive secondary findings was high among both groups, but there were individuals who did not want these results, fearing increased anxiety. CONCLUSIONS: Parents/guardians of children with cancer have limited knowledge about WGS. A two-step consent process may improve their ability to provide meaningful informed consent.

Measuring the process and quality of informed consent for clinical research: development and testing.

PURPOSE/OBJECTIVES: To develop and assess the reliability and validity of an observational instrument, the Process and Quality of Informed Consent (P-QIC). DESIGN: A pilot study of the psychometrics of a tool designed to measure the quality and process of the informed consent encounter in clinical research. The study used professionally filmed, simulated consent encounters designed to vary in process and quality. SETTING: A major urban teaching hospital in the northeastern region of the United States. SAMPLE: 63 students enrolled in health-related programs participated in psychometric testing, 16 students participated in test-retest reliability, and 5 investigator-participant dyads were observed for the actual consent encounters. METHODS: For reliability and validity testing, students watched and rated videotaped simulations of four consent encounters intentionally varied in process and content and rated them with the proposed instrument. Test-retest reliability was established by raters watching the videotaped simulations twice. Inter-rater reliability was demonstrated by two simultaneous but independent raters observing an actual consent encounter. MAIN RESEARCH VARIABLES: The essential elements of information and communication for informed consent. FINDINGS: The initial testing of the P-QIC demonstrated reliable and valid psychometric properties in both the simulated standardized consent encounters and actual consent encounters in the hospital setting. CONCLUSIONS: The P-QIC is an easy-to-use observational tool that provides a quick assessment of the areas of strength and areas that need improvement in a consent encounter. It can be used in the initial trainings of new investigators or consent administrators and in ongoing programs of improvement for informed consent. IMPLICATIONS FOR NURSING: The development of a validated observational instrument will allow investigators to assess the consent process more accurately and evaluate strategies designed to improve it.

Use of dimensional analysis to reduce medication errors.

The purpose of this pilot study was to determine whether using dimensional analysis as the method of mathematical computation could reduce nursing medication calculation errors. The sample for this study consisted of second-year baccalaureate nursing students in a required clinical skills course. Students in the control group were taught medication calculations using the traditional math method during one semester, whereas students in the experimental group were taught the same material using dimensional analysis during the next semester. Analysis of the collected data from a medication dosage calculation examination revealed the dimensional analysis group scored with greater accuracy than the traditional math group.