Clinically Actionable Findings Derived From Predictive Genomic Testing Offered in a Medical Practice Setting.

OBJECTIVE: To assess the presence of clinically actionable results and other genetic findings in an otherwise healthy population of adults seen in a medical practice setting and offered "predictive" genomic testing. PATIENTS AND METHODS: In 2014, a predictive genomics clinic for generally healthy adults was launched through the Mayo Clinic Executive Health Program. Self-identified interested patients met with a genomic nurse and genetic counselor for pretest advice and education. Two genome sequencing platforms and one gene panel-based health screen were offered. Posttest genetic counseling was available for patients who elected testing. From March 1, 2014, through June 1, 2019, 1281 patients were seen and 301 (23.5%) chose testing. Uptake rates increased to 36.3% [70 of 193]) in 2019 from 11.8% [2 of 17] in 2014. Clinically actionable results and genetic findings were analyzed using descriptive statistics. RESULTS: Clinically actionable results were detected in 11.6% of patients (35 of 301), and of those, 51.7% (15 of 29) with a cancer or cardiovascular result = did not have a personal or family history concerning for a hereditary disorder. The most common actionable results were in the BCHE, BRCA2, CHEK2, LDLR, MUTYH, and MYH7 genes. A carrier of at least one recessive condition was found in 53.8% of patients (162 of 301). At least one variant associated with multifactorial disease was found in 44.5% (134 of 301) (eg, 25 patients were heterozygous for the F5 factor V Leiden variant associated with thrombophilia risk). CONCLUSION: Our predictive screening revealed that 11.6% of individuals will test positive for a clinically actionable, likely pathogenic/pathogenic variant. This finding suggests that wider knowledge and adoption of predictive genomic services could be beneficial in medical practice, although additional studies are needed.

Financial Toxicity: A Review of the Literature and Nursing Opportunities.

BACKGROUND: Studies have demonstrated the negative effects of the costs of cancer care on the health and well-being of patients with cancer. Nurses require knowledge of the risk factors, experiences, and outcomes associated with financial toxicity prior to designing evidence-based studies and protocols to address financial toxicity. OBJECTIVES: This article summarizes the state of the science in financial toxicity among patients with cancer, with the goal of guiding nurses in leading research and evidence-based practice efforts to decrease the impact of financial toxicity on patient outcomes. METHODS: The authors reviewed published research, theoretical models, and research grants that focus on financial toxicity among patients with cancer. The authors also synthesized study findings and project goals while emphasizing opportunities for nurses to meaningfully engage within this area as researchers and clinicians. FINDINGS: Substantial cross-sectional descriptive work documents the risk factors, experiences, and outcomes of financial toxicity. Future work should address methodologic concerns by using comprehensive, validated measures and applying conceptual models to design and test financial toxicity interventions using prospective, rigorous methodologies. The authors propose a conceptual model to assist researchers and clinicians.

Underestimation of mortality due to chronic obstructive pulmonary disease (COPD) in Kentucky.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) mortality may be underestimated because it is frequently listed as a contributory cause of death, rather then the underlying cause of death, on state death certificates. Contributory causes of death are not counted in mortality statistics. This may underestimate the true burden of disease. OBJECTIVE: Determine the frequency in which COPD is listed as a contributory cause of death, rather than the underlying cause of death, per state mortality records for a one-year period, year 2000. METHODS: 15,036 mortality records from Kentucky death certificates were examined for year 2000 for all deaths due to diseases most often associated with COPD; notably, heart disease, pneumonia/influenza, and asthma. RESULTS: Cases in which COPD was listed as a contributory cause of death for asthma, pneumonia and influenza was small (less than 1%). Cases in which COPD was listed as a contributory cause of death for heart disease was much higher at 6.8% (824 out of 12,084). Counting these cases increases the COPD age-adjusted mortality rate 39%, from 52.4 to 72.7/ 100,000 people. CONCLUSION: This study provided evidence to generate and support the hypothesis that COPD mortality is underestimated in Kentucky when the underlying cause of death is heart disease, thus underestimating the true burden of disease. COPD is a chronic, often severe disease commonly associated with comorbid conditions such as heart disease that ultimately lead to death, but which may not be accurately reflected in mortality statistics. Accurate reporting is essential for health planning, education, research, and treatment options.

Occupational exposure to trichloroethylene and cancer risk for workers at the Paducah Gaseous Diffusion Plant.

OBJECTIVE: The Paducah Gaseous Diffusion Plant (PGDP) became operational in 1952; it is located in the western part of Kentucky. We conducted a mortality study for adverse health effects that workers may have suffered while working at the plant, including exposures to chemicals. MATERIALS AND METHODS: We studied a cohort of 6820 workers at the PGDP for the period 1953 to 2003; there were a total of 1672 deaths to cohort members. Trichloroethylene (TCE) is a specific concern for this workforce; exposure to TCE occurred primarily in departments that clean the process equipment. The Life Table Analysis System (LTAS) program developed by NIOSH was used to calculate the standardized mortality ratios for the worker cohort and standardized rate ratio relative to exposure to TCE (the U.S. population is the referent for ageadjustment). LTAS calculated a significantly low overall SMR for these workers of 0.76 (95% CI: 0.72-0.79). A further review of three major cancers of interest to Kentucky produced significantly low SMR for trachea, bronchus, lung cancer (0.75, 95% CI: 0.72-0.79) and high SMR for Non-Hodgkin's lymphoma (NHL) (1.49, 95% CI: 1.02-2.10). RESULTS: No significant SMR was observed for leukemia and no significant SRRs were observed for any disease. Both the leukemia and lung cancer results were examined and determined to reflect regional mortality patterns. However, the Non-Hodgkin's Lymphoma finding suggests a curious amplification when living cases are included with the mortality experience. CONCLUSIONS: Further examination is recommended of this recurrent finding from all three U.S. Gaseous Diffusion plants.

Mortality patterns among Paducah Gaseous Diffusion Plant workers.

OBJECTIVE: To determine whether Paducah Gaseous Diffusion Plant workers had mortality patterns that differed from the general US population and to investigate whether mortality patterns were associated with job title or workplace exposures. METHODS: A retrospective occupational cohort mortality study was conducted on 6759 workers. Standardized mortality ratio analyses compared the cohort with the referent US population. Internal comparisons producing standardized rate ratios were conducted by job title, metal exposure, and cumulative internal and external radiation exposures. RESULTS: Overall mortality and cancer rates were lower than the referent population, reflecting a strong healthy worker effect. Individual not significant standardized mortality ratios and standardized rate ratios were noted for cancers of the lymphatic and hematopoietic tissue. CONCLUSIONS: Although relatively low exposures to radiation and metals did not produce statistically significant health effects, no significant elevations for lymphatic and hematopoietic cancers were consistent with previous studies of nuclear workers.

Cohort follow-up: the 21st century procedures.

The basic logic of designing an occupational cohort study has changed little since William R. Gaffey outlined the issues of follow-up, measurement of exposure, and analysis of data. However, many new avenues of tracking workers for epidemiological studies have been developed since Gaffey wrote his paper in 1973. Many disease registries also perform follow-up of subjects for vital status determination, so the procedures used with this process are common to the two applications. This article speaks to cohort construction for this occupational research as well as describes the 2007 methods for vital status follow-up. Rises in concern about work-related disease risks and the scientific resources for performing these studies coincided with the computer revolution. Government and private sources of data on vital status have changed in several ways over the 35 years since Gaffey's seminal paper. Some systems make the process of follow-up more rapid and productive, and some barriers have been imposed as societal concerns for privacy have risen. We describe the process of linking 5 sources of data to compile a roster of 6,820 workers employed at the Paducah Gaseous Diffusion Plant from 1953 to 2003. The record linkage processes achieved a final death cohort of 1672 deaths--the ascertainment of these deaths (by time period) was 1379 (1979-2003) and 293 (1953-1978); follow-up then was 100% for this cohort.