Variation in Receipt of Cancer Screening and Immunizations by 10-year Life Expectancy among U.S. Adults aged 65 or Older in 2019.

IMPORTANCE: The likelihood of benefit from a preventive intervention in an older adult depends on its time-to-benefit and the adult's life expectancy. For example, the time-to-benefit from cancer screening is >10 years, so adults with <10-year life expectancy are unlikely to benefit. OBJECTIVE: To examine receipt of screening for breast, prostate, or colorectal cancer and receipt of immunizations by 10-year life expectancy. DESIGN: Analysis of 2019 National Health Interview Survey. PARTICIPANTS: 8,329 non-institutionalized adults >65 years seen by a healthcare professional in the past year, representing 46.9 million US adults. MAIN MEASURES: Proportions of breast, prostate, and colorectal cancer screenings, and immunizations, were stratified by 10-year life expectancy, estimated using a validated mortality index. We used logistic regression to examine receipt of cancer screening and immunizations by life expectancy and sociodemographic factors. KEY RESULTS: Overall, 54.7% of participants were female, 41.4% were >75 years, and 76.4% were non-Hispanic White. Overall, 71.5% reported being current with colorectal cancer screening, including 61.4% of those with <10-year life expectancy. Among women, 67.0% reported a screening mammogram in the past 2 years, including 42.8% with <10-year life expectancy. Among men, 56.8% reported prostate specific antigen screening in the past two years, including 48.3% with <10-year life expectancy. Reported receipt of immunizations varied from 72.0% for influenza, 68.8% for pneumococcus, 57.7% for tetanus, and 42.6% for shingles vaccination. Lower life expectancy was associated with decreased likelihood of cancer screening and shingles vaccination but with increased likelihood of pneumococcal vaccination. CONCLUSIONS: Despite the long time-to-benefit from cancer screening, in 2019 many US adults age >65 with <10-year life expectancy reported undergoing cancer screening while many did not receive immunizations with a shorter time-to-benefit. Interventions to improve individualization of preventive care based on older adults' life expectancy may improve care of older adults.

A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk.

Identification of the genes and processes mediating genetic association signals for complex diseases represents a major challenge. As many of the genetic signals for type 2 diabetes (T2D) exert their effects through pancreatic islet-cell dysfunction, we performed a genome-wide pooled CRISPR loss-of-function screen in a human pancreatic beta cell line. We assessed the regulation of insulin content as a disease-relevant readout of beta cell function and identified 580 genes influencing this phenotype. Integration with genetic and genomic data provided experimental support for 20 candidate T2D effector transcripts including the autophagy receptor CALCOCO2. Loss of CALCOCO2 was associated with distorted mitochondria, less proinsulin-containing immature granules and accumulation of autophagosomes upon inhibition of late-stage autophagy. Carriers of T2D-associated variants at the CALCOCO2 locus further displayed altered insulin secretion. Our study highlights how cellular screens can augment existing multi-omic efforts to support mechanistic understanding and provide evidence for causal effects at genome-wide association studies loci.