Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning One Year after a Negative Fecal Occult Blood Test, among Screen-Eligible 76- to 85-Year-Olds.

BACKGROUND: Colorectal cancer screening is universally recommended for adults ages 45 to 75 years. Noninvasive fecal occult blood tests are effective screening tests recommended by guidelines. However, empirical evidence to inform older adults' decisions about whether to continue screening is sparse, especially for individuals with prior screening. METHODS: This study used a retrospective cohort of older adults at three Kaiser Permanente integrated healthcare systems (Northern California, Southern California, Washington) and Parkland Health. Beginning 1 year following a negative stool-based screening test, cumulative risks of colorectal cancer incidence, colorectal cancer mortality (accounting for deaths from other causes), and non-colorectal cancer mortality were estimated. RESULTS: Cumulative incidence of colorectal cancer in screen-eligible adults ages 76 to 85 with a negative fecal occult blood test 1 year ago (N = 118,269) was 0.23% [95% confidence interval (CI), 0.20%-0.26%] after 2 years and 1.21% (95% CI, 1.13%-1.30%) after 8 years. Cumulative colorectal cancer mortality was 0.03% (95% CI, 0.02%-0.04%) after 2 years and 0.33% (95% CI, 0.28%-0.39%) after 8 years. Cumulative risk of death from non-colorectal cancer causes was 4.81% (95% CI, 4.68%-4.96%) after 2 years and 28.40% (95% CI, 27.95%-28.85%) after 8 years. CONCLUSIONS: Among 76- to 85-year-olds with a recent negative stool-based test, cumulative colorectal cancer incidence and mortality estimates were low, especially within 2 years; death from other causes was over 100 times more likely than death from colorectal cancer. IMPACT: These findings of low absolute colorectal cancer risk, and comparatively higher risk of death from other causes, can inform decision-making regarding whether and when to continue colorectal cancer screening beyond age 75 among screen-eligible adults.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning Ten Years after a Negative Colonoscopy, among Screen-Eligible Adults 76 to 85 Years Old.

BACKGROUND: Few empirical data are available to inform older adults' decisions about whether to screen or continue screening for colorectal cancer based on their prior history of screening, particularly among individuals with a prior negative exam. METHODS: Using a retrospective cohort of older adults receiving healthcare at three Kaiser Permanente integrated healthcare systems in Northern California (KPNC), Southern California (KPSC), and Washington (KPWA), we estimated the cumulative risk of colorectal cancer incidence and mortality among older adults who had a negative colonoscopy 10 years earlier, accounting for death from other causes. RESULTS: Screen-eligible adults ages 76 to 85 years who had a negative colonoscopy 10 years earlier were found to be at a low risk of colorectal cancer diagnosis, with a cumulative incidence of 0.39% [95% CI, 0.31%-0.48%) at 2 years that increased to 1.29% (95% CI, 1.02%-1.61%) at 8 years. Cumulative mortality from colorectal cancer was 0.04% (95% CI, 0.02%-0.08%) at 2 years and 0.46% (95% CI, 0.30%-0.70%) at 8 years. CONCLUSIONS: These low estimates of cumulative colorectal cancer incidence and mortality occurred in the context of much higher risk of death from other causes. IMPACT: Knowledge of these results could bear on older adults' decision to undergo or not undergo further colorectal cancer screening, including choice of modality, should they decide to continue screening. See related commentary by Lieberman, p. 6.

Limited Marginal Utility of Deep Sequencing for HIV Drug Resistance Testing in the Age of Integrase Inhibitors.

HIV drug resistance genotyping is a critical tool in the clinical management of HIV infections. Although resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect low-frequency alleles. However, the clinical value added from NGS approaches to antiviral resistance testing remains to be demonstrated. We compared the variant detection capacity of NGS versus Sanger sequencing methods for resistance genotyping in 144 drug resistance tests (105 protease-reverse transcriptase tests and 39 integrase tests) submitted to our clinical virology laboratory over a four-month period in 2016 for Sanger-based HIV drug resistance testing. NGS detected all true high-frequency drug resistance mutations (>20% frequency) found by Sanger sequencing, with greater accuracy in one instance of a Sanger-detected false positive. Freely available online NGS variant callers HyDRA and PASeq were superior to Sanger methods for interpretations of allele linkage and automated variant calling. NGS additionally detected low-frequency mutations (1 to 20% frequency) associated with higher levels of drug resistance in 30/105 (29%) protease-reverse transcriptase tests and 4/39 (10%) integrase tests. In clinical follow-up of 69 individuals for a median of 674 days, we did not find a difference in rates of virological failure between individuals with and without low-frequency mutations, although rates of virological failure were higher for individuals with drug-relevant low-frequency mutations. However, all 27 individuals who experienced virological failure reported poor adherence to their drug regimen during the preceding follow-up time, and all 19 who subsequently improved their adherence achieved viral suppression at later time points, consistent with a lack of clinical resistance. In conclusion, in a population with low antiviral resistance emergence, NGS methods detected numerous instances of minor alleles that did not result in subsequent bona fide virological failure due to antiviral resistance.