The increasing prevalence of carbon nanotubes (CNTs) in manufacturing and research environments, together with the potential exposure risks, necessitates development of reliable and accurate monitoring methods for these materials. We examined quantification of CNTs by two distinct methods based on Raman spectroscopy. First, as measured by the Raman peak intensity of aqueous CNT suspensions, and second, by Raman mapping of air filter surfaces onto which CNTs were collected as aerosols or applied as small-area (0.05 cm2) deposits. Correlation (R2 = 0.97) between CNT concentration and Raman scattering intensity for suspensions in cuvettes was found over a concentration range from about 2 to 10 microg/ml, but measurement variance precludes practical determination of a calibration curve. Raman mapping of aerosol sample filter surfaces shows correlation with CNT mass when the surface density is relatively high (R2 = 0.83 and 0.95 above about 5 microg total mass on filter), while heterogeneity of CNT deposition makes obtaining representative maps of lower density samples difficult. This difficulty can be mitigated by increasing the area mapped relative to the total sample area, improving both precision and the limit of detection (LOD). For small-area deposits, detection of low masses relevant to occupational monitoring can be achieved, with an estimated LOD of about 50 ng.

The article by Petrilli et al.1 points to the important but complicated issue of ordering laboratory testing for thrombophilia despite multiple guidelines that dispute the clinical utility of such testing for many indications. We question the basis of these authors’ assertion that Medicare spends $300–$672 million for thrombophilia testing annually. They arrived at this figure by multiplying the price of a thrombophilia test panel (between $1,100 and $2,400) by the number of annual Medicare claims for thrombophilia analysis which they estimated at 280,000. The price of the panel is derived from two papers: (1) a 2001 review2 that lists prices of various thrombophilia-related tests adding up to $1,782, and (2) a 2006 evaluation by Somma et al.3 of thrombophilia screening at one hospital in New York in 2005. The latter paper refers to various thrombophilia panels from Quest Diagnostics with list prices ranging from $1,311 to $2,429. However, the repertoire of available test panels and their prices have changed over the last decade. The cost evaluation of thrombophilia testing should be based on actual current payments for tests, and not on list prices for laboratory offerings from over a decade ago. Several laboratories offer mutational analysis of three genes—F5, F2 and MTHFR—as a thrombophilia risk panel. Based on the Current Procedural Terminology (CPT) codes listed by the test suppliers (81240, 81241, and 81291), the average Medicare payment for the combination of these three markers in 2013 was $172.4 A broader panel of several biochemical, immunological and genetic assays had a maximum Medicare payment in 2015 of $405 (Table 1).5

Purpose We examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors. Methods We estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18-64 years using private claims data and publicly reported revenues from the primary BRCA testing provider. Results The percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013-2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013-2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity. Conclusion The observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity. GENETICS in MEDICINE advance online publication, 21 September 2017; doi:10.1038/gim.2017.118.

PROBLEM/CONDITION: Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined. PERIOD COVERED: 2009-2014. DESCRIPTION OF SYSTEM: Medical claims data from Truven Health Analytics MarketScan Commercial Claims and Encounters databases were used to estimate rates of BRCA testing and receipt of preventive interventions after BRCA testing among women aged 18-64 years with employer-sponsored health insurance in metropolitan and nonmetropolitan areas of the United States, both nationally and regionally. RESULTS: From 2009 to 2014, BRCA testing rates per 100,000 women aged 18-64 years with employer-sponsored health insurance increased 2.3 times (102.7 to 237.8) in metropolitan areas and 3.0 times (64.8 to 191.3) in nonmetropolitan areas. The relative difference in BRCA testing rates between metropolitan and nonmetropolitan areas decreased from 37% in 2009 (102.7 versus 64.8) to 20% in 2014 (237.8 versus 191.3). The relative difference in BRCA testing rates between metropolitan and nonmetropolitan areas decreased more over time in younger women than in older women and decreased in all regions except the West. Receipt of preventive services 90 days after BRCA testing in metropolitan versus nonmetropolitan areas throughout the period varied by service: the percentage of women who received a mastectomy was similar, the percentage of women who received magnetic resonance imaging of the breast was lower in nonmetropolitan areas (as low as 5.8% in 2014 to as high as 8.2% in 2011) than metropolitan areas (as low as 7.3% in 2014 to as high as 10.3% in 2011), and the percentage of women who received mammography was lower in nonmetropolitan areas in earlier years but was similar in later years. INTERPRETATION: Possible explanations for the 47% decrease in the relative difference in BRCA testing rates over the study period include increased access to genetic services in nonmetropolitan areas and increased demand nationally as a result of publicity. The relative differences in metropolitan and nonmetropolitan BRCA testing rates were smaller among women at younger ages compared with older ages. PUBLIC HEALTH ACTION: Improved data sources and surveillance tools are needed to gather comprehensive data on BRCA testing in the United States, monitor adherence to evidence-based guidelines for BRCA testing, and assess receipt of preventive interventions for women with BRCA mutations. Programs can build on the recent decrease in geographic disparities in receipt of BRCA testing while simultaneously educating the public and health care providers about U.S. Preventive Services Task Force recommendations and other clinical guidelines for BRCA testing and counseling.

PURPOSE: We examined the utilization of precision medicine tests among Medicare beneficiaries through analysis of gene-specific tier 1 and 2 billing codes developed by the American Medical Association in 2012. METHODS: We conducted a retrospective cross-sectional study. The primary source of data was 2013 Medicare 100% fee-for-service claims. We identified claims billed for each laboratory test, the number of patients tested, expenditures, and the diagnostic codes indicated for testing. We analyzed variations in testing by patient demographics and region of the country. RESULTS: Pharmacogenetic tests were billed most frequently, accounting for 48% of the expenditures for new codes. The most common indications for testing were breast cancer, long-term use of medications, and disorders of lipid metabolism. There was underutilization of guideline-recommended tumor mutation tests (e.g., epidermal growth factor receptor) and substantial overutilization of a test discouraged by guidelines (methylenetetrahydrofolate reductase). Methodology-based tier 2 codes represented 15% of all claims billed with the new codes. The highest rate of testing per beneficiary was in Mississippi and the lowest rate was in Alaska. CONCLUSIONS: Gene-specific billing codes significantly improved our ability to conduct population-level research of precision medicine. Analysis of these data in conjunction with clinical records should be conducted to validate findings.

PURPOSE: We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of guideline-recommended genomic testing. METHODS: Genomic Health provided test orders for calendar year 2011.We summarized utilization at the hospital and state levels. Using logistic regression, we analyzed the association between the likelihood to order the test and the hospital's institutional and regional characteristics. RESULTS: In 2011, 45% of 4,712 acute-care hospitals ordered the test, which suggests that 25% of newly diagnosed invasive female breast cancer cases were tested. Significant predictors of testing included participation in National Cancer Institute (NCI) clinical research cooperative groups (odds ratio (OR) 3.73; 95% confidence interval, 2.96-4.70), advanced imaging (OR, 2.19; CI, 1.78-2.68), high-complexity laboratory (OR, 2.15; CI, 1.24-3.70), affiliation with a medical school (OR, 1.57; CI, 1.31-1.88), and reconstructive surgery (OR, 1.23; CI, 1.01-1.50). Significant regional predictors included metropolitan county (OR, 3.77; CI, 2.83-5.03), above-mean income (OR, 1.37; CI, 1.11-1.69), and education (OR, 1.26; CI, 1.03-1.54). Negative predictors included designation as a critical-access hospital (OR, 0.10; CI, 0.07-0.14) and distance from an NCI cancer center (OR, 0.998; CI, 0.997-0.999), with a 15% decrease in likelihood for every 100 miles. CONCLUSION: Despite considerable market penetration of the test, there are significant regional and site-of-care differences in implementation, particularly in rural states.Genet Med advance online publication 18 February 2016Genetics in Medicine (2016); doi:10.1038/gim.2015.218.

PURPOSE: We examined hospital use of the epidermal growth factor receptor assay in patients with lung cancer in the United States. Our goal was to inform the development of a model to predict phase 3 translation of guideline-directed molecular diagnostic tests. METHODS: This was a retrospective observational study. Using logistic regression, we analyzed the association between hospitals' institutional and regional characteristics and the likelihood that an epidermal growth factor receptor assay would be ordered. RESULTS: Significant institutional predictors included affiliation with an academic medical center (odds ratio, 1.48; 95% confidence interval, 1.20-1.83), participation in a National Cancer Institute clinical research cooperative group (odds ratio, 2.06, 1.66-2.55), and -availability of positron emission tomography scan (odds ratio, 1.44, 1.07-1.94) and cardiothoracic surgery (odds ratio, 1.90, 1.52-2.37) services. Significant regional predictors included metropolitan county (odds ratio, 2.08, 1.48-2.91), population with above-average education (odds ratio, 1.46, 1.09-1.96), and population with above-average income (odds ratio, 1.46, 1.04-2.05). Distance from a National Cancer Institute cancer center was a negative predictor (odds ratio, 0.996, 0.995-0.998), with a 34% decrease in likelihood for every 100 miles. CONCLUSION: In 2010, only 12% of US acute-care hospitals ordered the epidermal growth factor receptor assay, suggesting that most patients with lung cancer did not have access to this test. This case study illustrated the need for: (i) increased dissemination and implementation research, and (ii) interventions to improve adoption of guideline-directed molecular diagnostic tests by community hospitals.Genet Med 2013:15(8):630-638.