Evaluation of methods for characterizing the fine particulate matter emissions from aircraft and other diffusion flame combustion aerosol sources.

The U. S. Environmental Protection Agency in collaboration with the U. S. Air Force Arnold Engineering Development Complex conducted the VAriable Response In Aircraft nvPM Testing (VARIAnT) 3 and 4 test campaigns to compare nonvolatile particulate matter (nvPM) emissions measurements from a variety of diffusion flame combustion aerosol sources (DFCASs), including a Cummins diesel engine, a diesel powered generator, two gas turbine start carts, a J85-GE-5 turbojet engine burning multiple fuels, and a Mini-CAST soot generator. The VARIAnT research program was devised to understand reported variability in the ARP6320A sampling system nvPM measurements. The VARIAnT research program has conducted four test campaigns to date with the VARIAnT 3 and 4 campaigns devoted to: (1) assessing the response of three different black carbon mass analyzers to particles of different size, morphology, and chemical composition; (2) characterizing the particles generated by 6 different combustion sources according to morphology, effective density, and chemical composition; and (3) assessing any significant difference between black carbon as determined by the 3 mass analyzers and the total PM determined via other techniques. Results from VARIAnT 3 and 4 campaigns revealed agreement of about 20% between the Micro-Soot Sensor, the Cavity Attenuated Phase Shift (CAPS PMSSA) monitor and the thermal-optical reference method for elemental carbon (EC) mass, independent of the calibration source used. For the LII-300, the measured mass concentrations in VARIAnT 3 fall within 18% and in VARIAnT 4 fall within 27% of the reference EC mass concentration when calibrated on a combustor rig in VARIAnT 3 and on an LGT-60 start cart in VARIAnT 4, respectively. It was also found that the three mass instrument types (MSS, CAPS PMSSA, and LII-300) can exhibit different BC to reference EC ratios depending on the emission source that appear to correlate to particle geometric mean mobility diameter, morphology, or some other parameter associated with particle geometric mean diameter (GMD) with the LII-300 showing a slightly stronger apparent trend with GMD. Systematic differences in LII-300 measured mass concentrations have been reduced by calibrating with a turbine combustion as a particle source (combustor or turbine engine). With respect to the particle size measurements, the sizing instruments (TSI SMPS, TSI EEPS, and Cambustion DMS 500) were found to be in general agreement in terms of size distributions and concentrations with some exceptions. Gravimetric measurements of the total aerosol mass produced by the various DFCAs differed from the reference EC, BC and integrated particle size distribution measured aerosol masses. The measurements of particle size distributions and single particle analysis performed using the miniSPLAT indicated the presence of larger particles (≳150 nm) having more compact morphologies, higher effective density, and a composition dominated by OC and containing ash. This increased large particle fraction is also associated with higher values of single scattering albedo measured by the CAPS PMSSA instrument and higher OC measurements. These measurements indicate gas turbine engine emissions can be a more heterogeneous mix of particle types beyond the original E-31 assumption that engine exit exhaust particles are mainly composed of black carbon.

The value of residency program characteristics changes throughout urology training.

INTRODUCTION: The purpose of this study was to determine which characteristics of urology residency programs are most highly valued by medical students and residents, and how these change during training. MATERIALS AND METHODS: We distributed a survey to urology residents and medical students interested in urology via program director email and social media. The survey collected demographic data, future career plans, and asked respondents to rank the relative importance of six categories of residency program characteristics and specific characteristics within each category. RESULTS: Among the six categories of residency characteristics, resident experience was ranked most important by both medical students and residents, followed by geography and clinical experience which were tied. Medical students ranked clinic experience and formal mentorship with greater importance while residents placed higher value on the active role of clinical faculty and help from advanced practice providers. Trainees planning for an academic career ranked research experiences and resident diversity as more important than those entering private practice. CONCLUSIONS: Residents and medical students mostly agreed on the relative importance of residency program characteristics. The differences observed suggest that as trainees gain experience they place greater importance on informal relationships with faculty and value characteristics that enhance surgical training such as support from advanced practice providers and less time in clinic. These findings may guide programs on what information to include on their websites and presentations.

Transforming entomology to adapt to global concerns: 2021 student debates.

The 2021 Student Debates of the Entomological Society of America (ESA) were held at the Annual Meeting in Denver, CO. The event was organized by the Student Debates Subcommittee (SDS) of the Student Affairs Committee (SAC). The theme of the 2021 Student Debates was "Transforming Entomology to Adapt to Global Concerns", with 3 topics. Each topic had an unbiased introduction and 2 teams. The debate topics were (i) Nonnative insect introduction is an ethical approach for counteracting proliferation and overpopulation of consumers, (ii) What is the best technology to control undesirable insect pests in urban and agricultural settings? and (iii) Compared to other solutions, like plant-based diets, insect farming is the best method to address rising human global food and nutrient supply demands. Unbiased introduction speakers and teams had approximately 6 months to prepare for their presentations.

Whole genome sequencing identifies a cryptic SOX9 regulatory element duplication underlying a case of 46,XX ovotesticular difference of sexual development.

Ovotesticular differences of sexual development (OT-DSD) are rare genetic variances defined by the coexistence of both testicular and ovarian tissues. Various molecular etiologies including SRY translocation or SOX9 pathogenic variants with different modes of inheritance have been associated with 46,XX OT-DSD. Here we describe a child diagnosed with SRY-negative 46,XX OT-DSD after completing a series of complex clinical genetic analyses, including chromosomal microarray, DSD gene panel (sequencing and deletion/duplication analysis), whole exome sequencing, and whole genome sequencing. Of these, only whole genome sequencing reported a pathogenic duplication in a non-coding region that contains the RevSex regulatory element, which modifies SOX9 expression and is associated with 46,XX OT-DSD and complete sex reversal. This is the first clinical RevSex duplication detected by clinical whole genome sequencing. We highlight the utility of whole genome sequencing in shortening the diagnostic odyssey and the importance of optimal counseling through a team-based multi-specialty approach for patients with DSDs.

Stony coral populations are more sensitive to changes in vital rates in disturbed environments.

Reef-building corals, like many long-lived organisms, experience environmental change as a combination of separate but concurrent processes, some of which are gradual yet long-lasting, while others are more acute but short-lived. For corals, some chronic environmental stressors, such as rising temperature and ocean acidification, are thought to induce gradual changes in colonies' vital rates. Meanwhile, other environmental changes, such as the intensification of tropical cyclones, change the disturbance regime that corals experience. Here, we use a physiologically structured population model to explore how chronic environmental stressors that impact the vital rates of individual coral colonies interact with the intensity and magnitude of disturbance to affect coral population dynamics and cover. We find that, when disturbances are relatively benign, intraspecific density dependence driven by space competition partially buffers coral populations against gradual changes in vital rates. However, the impact of chronic stressors is amplified in more highly disturbed environments, because disturbance weakens the buffering effect of space competition. We also show that coral cover is more sensitive to changes in colony growth and mortality than to external recruitment, at least in open populations, and that space competition and size structure mediate the extent and pace of coral population recovery following a large-scale mortality event. Understanding the complex interplay among chronic environmental stressors, mass-mortality events, and population size structure sharpens our ability to manage and to restore coral-reef ecosystems in an increasingly disturbed future.

Pharmacoepidemiology: A time for a new multidisciplinary approach to precision medicine.

The advent of the genomic age has created a rapid increase in complexity for the development and selection of drug treatments. A key component of precision medicine is the use of genetic information to improve therapeutic effectiveness of drugs and prevent potential adverse drug reactions. Pharmacoepidemiology, as a field, uses observational methods to evaluate the safety and effectiveness of drug treatments in populations. Pharmacoepidemiology by virtue of its focus, tradition, and research orientation can provide appropriate study designs and analysis methods for precision medicine. The objective of this manuscript is to demonstrate how pharmacoepidemiology can impact and shape precision medicine and serve as a reference for pharmacoepidemiologists interested in contributing to the science of precision medicine. This paper depicts the state of the science with respect to the need for pharmacoepidemiology and pharmacoepidemiological methods, tools and approaches for precision medicine; the need for and how pharmacoepidemiologists use their skills to engage with the precision medicine community; and recommendations for moving the science of precision medicine pharmacoepidemiology forward. We propose a new integrated multidisciplinary approach dedicated to the emerging science of precision medicine pharmacoepidemiology.

Assessment of a regulatory measurement system for the determination of the non-volatile particulate matter emissions from commercial aircraft engines.

The SAE International has published Aerospace Information Report (AIR) 6241 which outlined the design and operation of a standardized measurement system for measuring non-volatile particulate matter (nvPM) mass and number emissions from commercial aircraft engines. Prior to this research, evaluation of this system by various investigators revealed differences in nvPM mass emissions measurement on the order of 15-30% both within a single sampling system and between two systems operating in parallel and measuring nvPM mass emissions from the same source. To investigate this issue, the U. S. Environmental Protection Agency in collaboration with the U. S. Air Force's Arnold Engineering Development Complex initiated the VAriable Response In Aircraft nvPM Testing (VARIAnT) research program to compare nvPM measurements within and between AIR-compliant sampling systems used for measuring combustion aerosols generated both by a 5201 Mini-CAST soot generator and a J85-GE-5 turbojet engine burning multiple fuels. The VARIAnT research program has conducted four test campaigns to date. The first campaign (VARIAnT 1) compared two essentially identical commercial versions of the sampling system while the second campaign (VARIAnT 2) compared a commercial system to the custom-designed Missouri University of Science and Technology's North American Reference System (NARS) built to the same specifications. Comparisons of nvPM particle mass (i.e., black carbon), number, and size were conducted in both campaigns. Additionally, the sensitivity to variation in system operational parameters was evaluated in VARIAnT 1. Results from both campaigns revealed agreement of about 12% between the two sampling systems, irrespective of manufacturer, in all aspects except for black carbon determination. The major source of measurement differences (20-70%) was due to low BC mass measurements made by the Artium Technologies LII-300 as compared to the AVL 483 Micro-Soot Sensor, the Aerodyne Cavity Attenuated Phase Shift (CAPS PMSSA) monitor, and the thermal-optical reference method for elemental carbon (EC) determination, which was used as the BC reference.

Information Sources Used by Oncologists to Understand Multi-marker Tumor Panel Tests for Cancer Patients.

Precision medicine using multi-marker tumor panel (MMTP) testing can help inform cancer treatment decisions. Oncologists' knowledge of these tests and their ability to find up-to-date information about their application in clinical care is essential. This study aimed to (1) describe information sources used by oncologists to learn about new genomic tests and (2) examine characteristics associated with the use of each information source. The National Cancer Institute's National Survey of Precision Medicine in Cancer Treatment surveyed a nationally representative sample of oncologists about MMTP testing. We examined the use of 11 information sources among oncologists that reported using MMTP tests (n = 1222). Bivariate analyses were used to examine whether information sources differed by oncologist- and practice-level characteristics and type of MMTP test. Most oncologists reported using peer-reviewed medical literature (88.8%), scientific conferences (87.9%), and medical professional societies (83.8%) to learn about MMTPs. In contrast, government websites, FDA inserts, and foundation resources were each used by < 36% of oncologists. The use of information sources differed by oncologist and practice characteristics. For example, a greater percentage of oncologists with an academic affiliation used peer-reviewed medical literature and scientific conferences, as compared to those without an academic affiliation (p = 0.006). As the number and type of MMTP tests increase, providing oncologists with current information about their appropriate application is essential. Further understanding of how oncologists use specific information sources may improve the dissemination and effective implementation of new MMTPs and help tailor educational interventions based on provider characteristics.

Organ Dysfunction in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Real-world data enables evaluation of immune checkpoint inhibitor (ICI) use in advanced melanoma management. We examined characteristics and outcomes of ICI-treated patients with advanced melanoma and organ dysfunction (baseline and emergent). MATERIALS AND METHODS: This retrospective observational study used electronic health records derived from a nationwide data set to examine advanced melanoma patients treated with first-line ICIs (2011-2018). Clinical characteristics, real-world time to treatment discontinuation (rwTTD), and overall survival (OS) were analyzed for patients with normal organ function and those with organ dysfunction prior to ICI initiation. Patients with emergent dysfunction in the 90 days following ICI initiation were identified, and potentially associated characteristics were explored. RESULTS: Of 2,407 patients included, 1,884 and 1,717 had evaluable renal and hepatic laboratory values, respectively. Patients with baseline renal dysfunction (2.4%) were older and more frequently male, and less frequently treated with ICI combinations, than patients with normal renal function. Patients with baseline hepatic dysfunction (2.8%) were similar to patients with normal hepatic function regarding demographics and treatments received. Patients with baseline organ dysfunction displayed shorter rwTTD and OS. Among patients with normal baseline organ function, 4.6% and 7.4% developed renal and hepatic dysfunction within 90 days of ICI initiation, respectively; this was associated with combination ICI treatment. CONCLUSION: Patients with advanced melanoma and baseline organ dysfunction frequently receive ICI treatment but have poorer clinical outcomes than patients with normal organ function. Among patients with normal renal and hepatic function at ICI initiation, emergent organ dysfunction rates in this real-world cohort are similar to those reported in clinical trials. IMPLICATIONS FOR PRACTICE: Real-world data provide an opportunity to understand treatment patterns, toxicity, and clinical outcomes among patients treated outside of clinical trials. This study confirms that patients with advanced melanoma and baseline renal or hepatic dysfunction are being treated with ICI therapy more frequently as monotherapy than in combination therapy. For those real-world patients with normal baseline organ function, emergent renal and hepatic dysfunction are both more common in patients treated with combination versus ICI monotherapy.

Gaze behavior during navigation with reduced acuity.

Navigating unfamiliar indoor spaces while visually searching for objects of interest is a challenge faced by people with visual impairment. We asked how restricting visual acuity of normally sighted subjects would affect visual search and navigation in a real world environment, and how their performance would compare to subjects with naturally occurring low vision. Two experiments were conducted. In the first, 8 normally sighted subjects walked along an indoor path, looking for objects placed at unpredictable intervals to the left and right of the path, and identified single letters posted on the objects. A head-mounted eye tracker was used to assess their gaze direction in the environment. For half the trials, blur foils were used to restrict visual acuity to approximately logMAR 1.65. Gaze behavior, travel time, and letter recognition accuracy were compared between blurred and unrestricted conditions. In the second experiment, the same procedure was conducted, but performance was compared between acuity-restricted normally-sighted subjects and subjects with naturally occurring low vision (mean acuity 1.09 logMAR, range 0.48-1.85 logMAR). In Experiment 1, neither Blur nor the Letter Recognition Task individually had a statistically significant effect on travel time. However, when combined, there was an interaction between the two that increased travel time by approximately 63%, relative to baseline trials. Blur modified gaze behavior such that subjects spent more time looking down toward the floor while walking, at the expense of time spent looking in other directions. During Letter Recognition Task trials with Blur, subjects spent extra time examining objects, though more objects were missed altogether. In Experiment 2, low-vision subjects spent more time looking toward the boundary between the floor and the wall, but gaze patterns were otherwise similar to acuity-restricted subjects with normal vision. Low-vision subjects were also more likely to miss objects compared to acuity-restricted subjects. We conclude that under conditions of artificially restricted acuity, normally sighted subjects look downward toward the floor more frequently while navigating and take extra time to examine objects of interest, but are less likely to detect them. Low-vision subjects tend to direct their gaze toward the boundary between the wall and the floor, which may serve as a high contrast cue for navigation.

Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer.

PURPOSE: Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients. METHODS: A retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis. RESULTS: ADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03-1.23) as well as an increased risk of each individual complication compared to non-use. CONCLUSION: ADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.

Risks and rewards of using prepaid vs. postpaid incentive checks on a survey of physicians.

BACKGROUND: Survey researchers use monetary incentives as a strategy to motivate physicians' survey participation. Experiments from general population surveys demonstrate that prepaid incentives increase response rates and lower survey administration costs relative to postpaid incentives. Experiments comparing these two incentive strategies have rarely been attempted with physician samples. METHODS: A nationally representative sample of oncologists was recruited to participate in the National Survey of Precision Medicine in Cancer Treatment. To determine the optimal strategy for survey incentives, sample members were randomly assigned to receive a $50 prepaid incentive check or a $50 promised (postpaid) incentive check. Outcome measures for this incentives experiment include cooperation rates, speed of response, check-cashing behavior, and comparison of hypothetical costs for different incentive strategies. RESULTS: Cooperation rates were considerably higher for sample members in the prepaid condition (41%) than in the postpaid condition (29%). Similar differences in cooperation rates were seen for physicians when stratified by region, size of the physician's metropolitan statistical area, specialty, and gender by age. Survey responders in the prepaid condition responded earlier in the field period than those in the postpaid condition, thus requiring fewer contacts. In the prepaid group, 84% of sample members who responded with a completed survey cashed the incentive check and only 6% of nonresponders cashed the check. In the postpaid condition, 72% of survey responders cashed the check; nonresponders were not given a check. The relatively higher cooperation rates and earlier response of the responders in the prepaid condition was associated with a 30% cost savings for the prepaid condition compared to the postpaid incentive condition. CONCLUSIONS: The results of this study suggest that the rewards of offering physicians a prepaid incentive check outweigh the possible risks of nonresponders cashing the check. The relative cost benefit of this strategy is likely to vary depending on the amount of the incentive relative to the costs of additional contact attempts to nonresponders.

A Symptom-Triggered Benzodiazepine Protocol Utilizing SAS and CIWA-Ar Scoring for the Treatment of Alcohol Withdrawal Syndrome in the Critically Ill.

BACKGROUND: There are limited data on the efficacy of symptom-triggered therapy for alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU). OBJECTIVE: To evaluate the safety and efficacy of a symptom-triggered benzodiazepine protocol utilizing Riker Sedation Agitation Scale (SAS) scoring for the treatment of AWS in the ICU. METHODS: We performed a before-and-after study in a medical ICU. A protocol incorporating SAS scoring and symptom-triggered benzodiazepine dosing was implemented in place of a protocol that utilized the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale and fixed benzodiazepine dosing. RESULTS: We enrolled 167 patients (135 in the preintervention and 32 in the postintervention group). The median duration of AWS was shorter in the postintervention (5, interquartile range [IQR] = 4-8 days) than in the preintervention group (8, IQR = 5-12 days; P < 0.01). Need for mechanical ventilation (31% vs 57%, P = 0.01), median ICU length of stay (LOS; 4, IQR = 2-7, vs 7, IQR = 4-11 days, P = 0.02), and hospital LOS (9, IQR = 6-13, vs 13, IQR = 9-18 days; P = 0.01) were less in the postintervention group. There was a reduction in mean total benzodiazepine exposure (74 ± 159 vs 450 ± 701 mg lorazepam; P < 0.01) in the postintervention group. CONCLUSION: A symptom-triggered benzodiazepine protocol utilizing SAS in critically ill patients is associated with a reduction in the duration of AWS treatment, benzodiazepine exposure, need for mechanical ventilation, and ICU and hospital LOS compared with a CIWA-Ar-based protocol using fixed benzodiazepine dosing.

Prediagnostic aspirin use and mortality in women with stage I to III breast cancer: A cohort study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: There is a body of evidence indicating that aspirin may reduce the risk of cancer mortality. However, to the authors' knowledge, the optimal exposure timing and mechanism of action remain unclear. In the current study, the authors investigated associations between prediagnostic aspirin use and breast cancer-specific mortality in a US population. METHODS: Postmenopausal women diagnosed with stage I to III breast cancer (1993-2009) were identified (2925 women with a total of 18,073 person-years) from the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Prediagnostic aspirin use (1274 women) was identified from study questionnaires. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) for associations between aspirin use and breast cancer-specific mortality. Effect modification by lymph node status was evaluated. RESULTS: Prediagnostic aspirin use was not found to be associated with lower breast cancer-specific mortality (HR, 0.95; 95% CI, 0.68-1.31 [P = .74]). In analyses stratified by lymph node status, aspirin use was found to be associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.54; 95% CI, 0.32-0.93 [P = 0.02]), but not those with lymph node-positive tumors (HR, 1.41; 95% CI, 0.92-2.16 [P = 0.11]). Tests for interaction were found to be statistically significant (P for interaction =.006). No association was noted between aspirin use and lymph node status. CONCLUSIONS: Prediagnostic aspirin use was not found to be associated with a reduction in breast cancer-specific mortality overall. However, effect modification by lymph node status was observed and mortality was found to be reduced by approximately one-half among aspirin users with lymph node-negative disease. This represents a clinically significant reduction in breast cancer mortality. These findings contribute to the understanding of aspirin's mechanism of action in breast cancer. However, further etiologic research to understand this association is warranted. Cancer 2016;122:2067-75. © 2016 American Cancer Society.

Cardiovascular toxicity after antiangiogenic therapy in persons older than 65 years with advanced renal cell carcinoma.

BACKGROUND: Sorafenib and sunitinib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006, respectively, for the treatment of patients with renal cell carcinoma (RCC). A population-based, observational cohort study of the cardiovascular risk of VEGFR TKI therapy in elderly RCC patients was conducted. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, this study analyzed patients who were 66 years old or older and were diagnosed with RCC from 2000 to 2009. The incidence of cardiovascular adverse events, including congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction (AMI), stroke, and cardiovascular deaths, was examined through December 2010. A Cox proportional hazards model was created to calculate the hazard ratio (HR), and adjustments were made for age, sex, comorbidity, and the use of other systemic therapy. RESULTS: A total of 171 of 670 patients who received sunitinib or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, and stroke were 0.87, 0.14, and 0.14 per 1000 person-days, respectively. Sunitinib or sorafenib use was associated with an increased risk of cardiovascular events (HR, 1.38; 95% confidence interval [CI], 1.02-1.87) and especially stroke (HR, 2.84; 95% CI, 1.52-5.31) in comparison with 788 patients diagnosed with advanced RCC from 2007 to 2009 who were eligible for Part D but did not receive either agent. In subgroup analyses, patients who were 66 to 74 years old at diagnosis had the highest increased risk of stroke associated with the use of either or both drugs. CONCLUSIONS: Sunitinib and sorafenib might be associated with an increased risk of cardiovascular events and particularly stroke.

Dosing recommendations for pharmacogenetic interactions related to drug metabolism.

OBJECTIVE: Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations. METHODS: Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers. RESULTS: Eighty four gene-drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations. CONCLUSION: For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers.

Implementation of the 21-gene recurrence score test in the United States in 2011.

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 18 10, 982-990.

Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population.

PURPOSE: The objective of this study was to describe trends in the prevalence of regular aspirin and nonsteroidal anti-inflammatory drug (NSAID) use among adults in the United States during 2005 and 2010, and to identify characteristics of regular users. METHODS: Data from the 2005 and 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of regular use of aspirin and NSAIDs among U.S. adults aged 18 years and older. Results were stratified by demographics and self-reported medical conditions and extrapolated to provide U.S. population estimates. RESULTS: In 2010, around 43 million adults (19.0%) took aspirin at least three times per week for more than 3 months (i.e. regular users), and more than 29 million adults (12.1%) were regular users of NSAIDs. Compared with 2005, this was an overall increase of 57% in aspirin use and 41% in NSAID use. These increases were consistent across the strata of age, sex, race, and selected medical conditions, including cardiovascular disease (CVD), arthritis, peptic ulcers, cancer, and severe headache, except for Asian Americans. CONCLUSION: Large increases in the use of both aspirin and NSAIDs were observed over a 5 year period. The increase may be the result of increasing media attention reporting that regular aspirin use lowers the risk of CVD and related deaths, and may also prevent cancer. Moreover, safety concerns related to alternative medications such as acetaminophen and selective COX-2 inhibitors may influence users of these drugs to switch to aspirin and NSAIDs.