Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.

PURPOSE: The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs. METHODS: An observational study in an area representing one-fifth of England. RESULTS: Data were collected from 89 adult AF recipients. At disclosure, among 57 recipients of a cancer-predisposition-associated AF and 32 recipients of an FH-associated AF, 35% and 88%, respectively, had personal and/or family history evidence of AF-related disease. During post-disclosure investigations, 4 cancer-AF recipients had evidence of disease, including 1 medullary thyroid cancer. Six women with an HBOC AF, 3 women with a Lynch syndrome AF, and 2 individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidemia diagnoses were made in 6 FH-AF recipients and treatment (re-)initiated for 7 with prior hyperlipidemia. Generating and disclosing AFs in this region cost £1.4m; £8680 per clinically significant AF. CONCLUSION: Generation and disclosure of AFs identifies individuals with and without personal or familial evidence of disease and prompts appropriate clinical interventions. Results can inform policy toward secondary findings.

The Missing COVID-19 Demographic Data: A Statewide Analysis of COVID-19-Related Demographic Data From Local Government Sources and a Comparison With Federal Public Surveillance Data.

Objectives. To collect and standardize COVID-19 demographic data published by local public-facing Web sites and analyze how this information differs from Centers for Disease Control and Prevention (CDC) public surveillance data. Methods. We aggregated and standardized COVID-19 data on cases and deaths by age, gender, race, and ethnicity from US state and territorial governmental sources between May 24 and June 4, 2021. We describe the standardization process and compare it with the CDC's process for public surveillance data. Results. As of June 2021, the CDC's public demographic data set included 80.9% of total cases and 46.7% of total deaths reported by states, with significant variation across jurisdictions. Relative to state and territorial data sources, the CDC consistently underreports cases and deaths among African American and Hispanic or Latino individuals and overreports deaths among people older than 65 years and White individuals. Conclusions. Differences exist in amounts of data included and demographic composition between the CDC's public surveillance data and state and territory reporting, with large heterogeneity across jurisdictions. A lack of standardization and reporting mechanisms limits the production of complete real-time demographic data.

Disparities in SARS-CoV-2 Testing for Hispanic/Latino Populations: An Analysis of State-Published Demographic Data.

Racial and ethnic minorities in the United States have been disproportionately affected by the COVID-19 pandemic, experiencing increased risk of infection, hospitalization, and death. In this study, we sought to examine race- and ethnicity-based differences in SARS-CoV-2 testing. We used publicly available US state dashboards to extract demographic data for COVID-19 cases and tests. Poisson regression models were used to model the effect of race and ethnicity on the number of SARS-CoV-2 tests performed per case. In total, just 8 states reported testing data by race and ethnicity. In regression models, race and ethnicity was a significant predictor of testing rate per case. In all states, Hispanic/Latino patients had a significantly lower testing rate than their non-Hispanic/Latino counterparts, with an incident rate ratio varying from 0.45 to 0.81, depending on the state and referent race category. These results suggest disparities in testing access among Hispanic/Latino individuals, who are already at a disproportionate risk for infection and severe outcomes.

Highly emotional vicarious memories.

Vicarious memories are memories that people have in reference to events that they have not directly experienced, rather heard second-hand. Little research has investigated vicarious memory; when it has, it has predominantly focused on vicarious trauma. The purpose of this study was to compare vicarious memories with personal memories. University students (N = 142) completed an in-person interview in which they recalled four memories: a highly positive personal memory, a highly negative personal memory, a highly positive vicarious memory and a highly negative vicarious memory. Personal and vicarious memory reports were compared and contrasted in terms of memory qualities, memory functions and event centrality. The results indicate that vicarious and personal memory reports share many phenomenological and functional properties. Although to a lesser degree than personal memories, vicarious memories do influence decision-making and problem-solving. Current models of episodic memory only include events that individuals have directly experienced. The current study adds to a growing body of literature which suggests that current models of episodic memory are too restrictive and should expand to include vicarious memory reports.

Effect of Low-dose and Standard-dose Aspirin on PGE2 Biosynthesis Among Individuals with Colorectal Adenomas: A Randomized Clinical Trial.

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

The Influence of Socioeconomic Status on Psychological Distress in Canadian Adults With ADD/ADHD.

OBJECTIVE: The primary purpose of this study was to examine the relationship between socioeconomic status (SES) and psychological distress in individuals self-reporting a diagnosis of attention deficit disorder (ADD)/ADHD. METHOD: This correlational study encompasses cross-sectional data from 488 male and female adults (20-64 years) who reported that they have been diagnosed with ADD/ADHD. Psychological distress was measured with the Kessler Psychological Distress Scale (K10). RESULTS: Adults with ADD/ADHD and high incomes have significantly lower K10 scores than Canadians with ADD/ADHD and low incomes. Income, but not education, was significant in predicting psychological distress among the sample. Canadian adults with ADD/ADHD have an increased risk for developing psychological distress and comorbid psychiatric disorders. CONCLUSION: The findings suggest that negative outcomes associated with ADD/ADHD are not necessarily pervasive. High income may serve as a protective factor for psychological distress among adults with ADD/ADHD.

Reproductive decision making: interviews with mothers of children with undiagnosed developmental delay.

Reproductive decision making is complex and personal. Having a child with undiagnosed developmental delay can further complicate these decisions, as recurrence risks are unknown. This qualitative study is an exploration of the experiences of parents who have a child with an undiagnosed developmental disorder, focusing on their reproductive decisions. The aims of the research were to explore the reproductive decision making process and examine the factors that influence these decisions. Data were collected from in-depth semi-structured interviews with five mothers of children without a diagnosis. Transcripts were analysed using an interpretative phenomenological analysis. Analysis identified five factors that were considered by participants when contemplating reproductive decisions: future uncertainty, perceptions of risk, the potential impact a child would have on their current children, expectations of a family and the desire for another child. Being aware of the factors that influence reproductive decisions for these mothers and being sensitive to them can enable genetic counsellors to carry out their role more effectively, as they are aware of the factors that need to be discussed and explored before a decision is made.

ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial.

BACKGROUND: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. METHODS/DESIGN: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function. DISCUSSION: Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers. TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769 . Registered on 16 March 2015.