Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry.Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing.Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1–40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16).Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation.

PurposeThe purpose of this paper is to determine the cost effectiveness of palliative care on patients in a home health and hospice setting. Secondary data set was utilized to test the hypotheses of this study. Home health care and hospice care services have the potential to avert hospital admissions in patients requiring palliative care, which significantly affects medicare spending. With the aging population, it has become evident that demand of palliative care will increase four-fold. It was determined that current spending on end-of-life care is radically emptying medicare funds and fiscally weakening numerous families who have patients under palliative care during life-threatening illnesses. The study found that a majority of people registering for palliative and hospice care settings are above the age group of 55 years old.Design/methodology/approachDifferent variables like length of stay, mode of payment and disease diagnosis were used to filter the available data set. Secondary data were utilized to test the hypothesis of this study. There are very few studies on hospice and palliative care services and no study focuses on the cost associated with this care. Since a very large number of the USA, population is turning 65 and over, it is very important to analyze the cost of care for palliative and hospice care. For the purpose of this analysis, data were utilized from the National Home and Hospice Care Survey (NHHCS), which has been conducted periodically by the Centers for Disease Control and Prevention’s National Center for Health Statistics. Descriptive statistics, χ2 tests and t-tests were used to test for statistical significance at the p<0.05 level.FindingsThe Statistical Package for Social Sciences (SPSS) was utilized for this result. H1 predicted that patients in the age group of 65 years and up have the highest utilization of home and hospice care. This study examined various demographic variables in hospice and home health care which may help to evaluate the cost of care and the modes of payments. This section of the result presents the descriptive analysis of dependent, independent and covariate variables that provide the overall national estimates on differences in use of home and hospice care in various age groups and sex.Research limitations/implicationsThe data set used was from the 2007 NHHCS survey, no data have been collected thereafter, and therefore, gap in data analysis may give inaccurate findings. To compensate for this gap in the data set, recent studies were reviewed which analyzed cost in palliative care in the USA. There has been a lack of evidence to prove the cost savings and improved quality of life in palliative/hospice care. There is a need for new research on the various cost factors affecting palliative care services as well as considering the quality of life. Although, it is evident that palliative care treatment is less expensive as compared to the regular care, since it eliminates the direct hospitalization cost, but there is inadequate research to prove that it improves the quality of life. A detailed research is required considering the additional cost incurred in palliative/hospice care services and a cost-benefit analysis of the same.Practical implicationsWhile various studies reporting information applicable to the expenses and effect of family caregiving toward the end-of-life were distinguished, none of the previous research discussed this issue as their central focus. Most studies addressed more extensive financial effect of palliative and end-of-life care, including expenses borne by the patients themselves, the medicinal services framework and safety net providers or beneficent/willful suppliers. This shows a significant hole in the current writing.Social implicationsWith the aging population, it has become evident that demand of palliative/hospice care will increase four-fold. The NHHCS have stopped keeping track of the palliative care requirements after 2007, which has a negative impact on the growing needs. Cost analysis can only be performed by analyzing existing data. This review has recognized a huge niche in the evidence base with respect to the cost cares of giving care and supporting a relative inside a palliative/hospice care setting.Originality/valueThe study exhibited that cost diminishments in aggressive medications can take care of the expenses of palliative/hospice care services. The issue of evaluating result in such a physically measurable way is complicated by the impalpable nature of large portions of the individual components of outcome. Although physical and mental well-being can be evaluated to a certain degree, it is significantly more difficult to gauge in a quantifiable way, the social and profound measurements of care that help fundamentally to general quality of care.

Background: An age, sex, and blood gene expression score (ASGES) has been previously validated to detect obstructive coronary artery disease (CAD) in non-diabetic patients presenting with stable chest pain in the outpatient setting. However, the diagnostic performance of this test in ruling out obstructive CAD in patients presenting with acute chest pain (ACP) to the emergency department (ED) is unknown. Methods: In an ongoing study, 371 low-intermediate risk patients with ACP and no prior history of CAD (TIMI risk score ≤ 2, negative troponins and normal/non-diagnostic ECG) underwent coronary CT angiography (CCTA) using institutional protocols. Patients were classified based on severity of stenosis (obstructive CAD, &gt;50%; high grade stenosis, &gt;70%) and ASGES. The ASGES blood test sample was drawn before ED discharge and analyzed in a commercial reference laboratory (Redwood City, CA). We excluded 23 (6%) patients with unreportable ASGES and 47 (13%) diabetics from this primary analysis. Results: 301 (53±10 years, 45% males, 78% Hispanics) non-diabetic ACP patients undergoing CCTA in an ED setting were included in this analysis. No plaque was detected in 183 (60%) patients, and 22 (7%) patients had obstructive CAD. In this population, 51% of patients had scores below the previously defined threshold of ASGES≤ 15. This threshold yielded sensitivity, specificity, NPV, and PPV of 71% (52-86%), 53% (47-59%), 97% (93-98%), and 12% (9-14%) for obstructive CAD. Furthermore, ASGES≤15 yielded a 100% sensitivity and NPV for patients with high grade stenosis (n=7, 2%). In a multivariable analysis including patient demographics and clinical covariates, ASGES ≤15 was significantly associated with obstructive CAD (OR: 0.15, 95% CI: 0.04-0.62). As a continuous variable, increasing ASGES was positively correlated with the presence of obstructive CAD and CCTA-defined plaque burden (p&lt;0.0001). Conclusions: This is the first study validating the use of this blood-based precision medicine test to rule out obstructive CAD among low-intermediate risk non-diabetic patients presenting with ACP in ED setting. 30-day follow-up is underway to evaluate the prognostic implications of these findings.

BackgroundCardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events. Gene expression analysis can inform on the molecular underpinnings of risk factors for cardiovascular events. Smoking and aspirin have known opposing effects on platelet reactivity and MACE, however their effects on each other and on MACE are not well described.MethodsWe measured peripheral blood gene expression levels of ITGA2B, which is upregulated by aspirin and correlates with platelet reactivity on aspirin, and a 5 gene validated smoking gene expression score (sGES) where higher expression correlates with smoking status, in participants from the previously reported PREDICT trial (NCT 00500617). The primary outcome was a composite of death, myocardial infarction, and stroke/TIA (MACE). We tested whether selected genes were associated with MACE risk using logistic regression.ResultsGene expression levels were determined in 1581 subjects (50.5% female, mean age 60.66 +/−11.46, 18% self-reported smokers); 3.5% of subjects experienced MACE over 12 months follow-up. Elevated sGES and ITGA2B expression were each associated with MACE (odds ratios [OR] =1.16 [95% CI 1.10–1.31] and 1.42 [95% CI 1.00–1.97], respectively; p < 0.05). ITGA2B expression was inversely associated with self-reported smoking status and the sGES (p < 0.001). A logistic regression model combining sGES and ITGA2B showed better performance (AIC = 474.9) in classifying MACE subjects than either alone (AIC = 479.1, 478.2 respectively).ConclusionGene expression levels associated with smoking and aspirin are independently predictive of an increased risk of cardiovascular events.

Diagnosing obstructive coronary artery disease (CAD) is challenging in elderly adults, and current diagnostic approaches for CAD expose these individuals to risks from contrast dye and invasive procedures. A Registry to Evaluate Patterns of Care Associated with the Use of Corus CAD in Real World Clinical Care Settings (PRESET; NCT01677156), pragmatic clinical trial. Community, 21 primary care practices. Of 566 stable, nonacute outpatients presenting with symptoms suggestive of obstructive CAD, the 176 who were aged 65 and older (median age 70, 61% female) were the current study participants. Blood-based precision medicine test, incorporating age, sex, and gene expression score (ASGES) to improve clinical decision-making and quality of care. Information on demographic characteristics, clinical factors, ASGES results (range 1-40; low (≤15), high (>15)), referral patterns to cardiology and advanced cardiac testing, and major adverse cardiac events (MACEs) was collected in a subgroup analysis of elderly adults in the PRESET Registry. Follow-up was for 1 year after ASGES testing. Median ASGES was 25, and 40 (23%) participants had a low score. Clinicians referred 12.5% of participants with a low ASGES and 49.3% with a high ASGES to cardiology or advanced cardiac testing (odds ratio for referral = 0.12, P < .001, adjusted for participants demographics and clinical covariates). Higher scores were associated with greater likelihood of posttest cardiac referral. At 1-year follow-up, the incidence of a MACE or revascularization was 10% (13/136) in the high ASGES group and 0% (0/40) in the low ASGES group (P = .04). The ASGES test showed potential clinical utility in the evaluation of elderly outpatients with symptoms suggestive of obstructive CAD. Test use may reduce unnecessary referrals and the risk of procedure-related complications in individuals with low ASGES, who are unlikely to benefit from further testing, while also identifying individuals who may benefit from further cardiac evaluation and management.

There is a significant unmet need in the diagnosis and prediction of coronary artery disease (CAD) and subsequent major adverse cardiovascular events including myocardial infarction. Recently, a number of genomic approaches have been taken to address these problems, including genetic, transcriptomic, and proteomic methodologies. Most of these efforts focused on the discovery of putative markers and initial construction of multimarker classifiers for these clinical endpoints and were limited by incomplete clinical validation and comparison to clinical factor models. However, one such classifier for obstructive CAD has been validated in independent multicenter validation cohorts. Initial forays into combining different types of classifiers (genetic, proteomic, etc.) using so-called systems biology approaches is in its infancy but holds considerable promise to further improve the outlook for patients at risk for these serious and prevalent conditions.

Our objective was to evaluate an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive coronary artery disease (CAD) in patients with rheumatoid arthritis (RA). We evaluated 20 pairs of nondiabetic coronary patients with and without RA, selected by matching on age, sex, race, body mass index, tobacco use, and number of diseased coronary vessels. Peripheral blood gene expression levels of 23 CAD-associated genes were measured, and a previously validated CAD risk score including age, sex, and gene expression levels (Corus CAD) was computed. Linear regression was used to determine effects of both CAD and RA on the ASGES. Among patients with RA, the ASGES was not associated with CAD. The ASGES was elevated in patients with RA (P<.04) when compared with matched controls. The presence of RA was associated with significantly altered expression for 6 of the 23 genes (P<.05 for all, not adjusted for multiple comparisons): S100 calcium binding protein A12, interleukin-18 receptor accessory protein, caspase 5, S100 calcium binding protein A8, aquaporin 9, and cluster of differentiation 79b. Across a range of coronary artery disease severity, RA was associated with altered expression of CAD-associated genes. Notably, 2 of these genes, S100 calcium binding protein A8 and A12, are associated with neutrophil activation and are under investigation as therapeutic targets for both RA and CAD. These findings highlight common pathogenic mechanisms for RA and CAD and validate the prior exclusion of RA patients from ASGES-based evaluation of CAD likelihood.

Background: Myocardial perfusion imaging (MPI) is the predominant diagnostic tool for evaluating outpatients with typical and atypical symptoms suggestive of obstructive coronary artery disease (CAD) and is commonly followed by invasive coronary angiography in patients with abnormal findings. Despite this paradigm, a significant proportion of patients do not need intervention, suggesting better diagnostic methods are needed to identify appropriate patients who would benefit from the risks, resource utilization, and healthcare costs incurred after a positive MPI. A previously validated, blood-based test incorporating age, sex and genomic expression score (ASGES) utilizing peripheral blood cell expression has demonstrated clinical validity in assessing the likelihood of obstructive CAD (≥50% luminal diameter stenosis by quantitative coronary angiography) early in the cardiac workup. Objective: The objective of this study is to evaluate if the utilization of the ASGES in conjunction with a positive MPI would assist in the determination of a patient’s risk of obstructive coronary artery disease. Methods: A total of 249 patients (mean age 58, 45% female) from 59 sites in the PREDICT (NCT00500617) and COMPASS (NCT01117506) studies were identified with a positive MPI study, defined as at least one reversible of fixed defect consistent with obstructive CAD and a subsequent invasive coronary angiography. ASGES scores were performed in all patients and were categorized into 3 groups based on score: low (1-15, 25%), mid-range (16-27, 43%) and high (28-40, 32%). Obstructive CAD rates defined by invasive coronary angiography were measured. The association between obstructive CAD and ASGES was evaluated using Cochran-Armitage trend test and area under the receiver-operating characteristics curve (AUC) analyses. Results: The rate of obstructive CAD among patients with a positive MPI was 35% (88/249). There was a net redistribution of risk based on ASGES testing in 52% (49/88) of these patients. The rate of obstructive CAD was 11% (7/63), 37% (39/106), and 53% (42/80) in the low, mid-range, and high score groups respectively (p&lt;0.001). AUC for the ASGES use with a positive MPI was 0.704. Conclusion: The ASGES test, when used in patients after positive MPI, improved the diagnostic accuracy in the assessment of obstructive CAD. The use of this precision medicine test may help minimize unnecessary referral of low-intermediate risk patients as well as improve diagnostic yield among patients with abnormal MPI findings scheduled to undergo invasive coronary angiography.

Background: Because of diagnostic uncertainty, patients with symptoms suggestive of obstructive coronary artery disease (CAD) are referred at high rates to cardiologists and advanced cardiac testing. This evaluation process may also expose patients to appreciable costs and health risks. A previously validated, blood-based test incorporating age, sex and genomic expression into an algorithmic score (1-40) has shown clinical validity in assessing the likelihood of obstructive CAD (≥50% luminal diameter stenosis by quantitative coronary angiography) early in the cardiac workup. This test has also shown clinical utility in association with decision making around cardiac referrals and helping clinicians determine the current likelihood of obstructive CAD in symptomatic patients. Hypothesis: We hypothesized that use of the age/sex/gene expression score (ASGES) test would influence cost of care in the diagnosis and management of symptomatic patients with suspected obstructive CAD. Methods: The prospective PRESET Registry (NCT01677156) enrolled stable, non-acute adult patients presenting with symptoms suggestive of obstructive CAD to 21 US primary care practices from September 2012 to August 2014. Primary care clinicians provided pre- and post-ASGES diagnosis and evaluation plans for each patient. Demographics, clinical factors, and ASGES results (predefined as low [ASGES ≤ 15] or elevated [ASGES &gt; 15]) were collected, as were management plans post-ASGES testing, including referrals to cardiology or further functional/anatomic testing. The economic analysis for cost of care after ASGES testing was based on the cost of cardiovascular-related tests, invasive procedures, office visits, emergency room visits, and hospital admissions during 1-year follow-up. Results: This sub-analysis cohort included 560 patients, with 50% females and median age 56 years. Patients had a median ASGES score of 18, with 246 (44%) patients with ASGES &lt; 15. The mean cost of care for patients in the year following ASGES testing was $234 (SD ±$707) in the low ASGES versus $1,296 (SD ±$5230) in the elevated ASGES group (p=0.03 by Wilcoxon rank test). Multivariate analysis incorporating patient demographics and clinical covariates showed that low ASGES was associated with a 51% reduction in cost of follow-up care compared to elevated ASGES group (p&lt;0.001 by log-linear regression). Conclusion: In this community-based cardiovascular registry, the ASGES influenced costs in the evaluation of patients with suspected obstructive CAD. Low score patients had approximately half the cardiovascular costs of elevated score patients in one year follow-up. Our work provides evidence supporting the economic value of using precision medicine in the delivery of cardiovascular care.

BackgroundIdentifying patients with obstructive coronary artery disease can be challenging for primary care physicians. Advances in precision medicine may help augment clinical tools and redefine the paradigm for evaluating coronary artery disease in the outpatient setting. A blood-based age/sex/gene expression score (ASGES) incorporating key features of precision medicine has shown clinical validity with a 96% negative predictive value and 89% sensitivity in estimating a symptomatic patient's current likelihood of obstructive coronary artery disease. To better characterize the clinical utility of the ASGES and measure its impact on clinician decision-making, a community-based registry was established. MethodsThe prospective PRESET Registry (NCT01677156) enrolled stable, nonacute adult patients presenting with typical or atypical symptoms suggestive of obstructive coronary artery disease from 21 US primary care practices from August 2012 to August 2014. Demographics, clinical characteristics, and ASGES results (predefined as low [ASGES ≤15] or elevated [ASGES >15]) were collected, as were referrals to Cardiology or further functional/anatomic cardiac testing after ASGES testing. Patients were followed for 1 year post ASGES testing. ResultsAmong the 566-patient cohort (median age 56 years), clinicians referred 26/252 (10%) of patients with low scores vs 137/314 (44%) of patients with elevated scores to Cardiology or advanced cardiac testing for further evaluation (unadjusted odds ratio 0.15, P <.0001; adjusted odds ratio after accounting for clinical covariates = 0.18, P <.0001). Data on 84 patients referred for advanced cardiac testing showed abnormal findings in 0 of 13 (0%) low ASGES and 10 of 71 (14%) elevated ASGES patients. Major adverse cardiovascular events and revascularization were noted in 3/252 (1.2%) patients with low ASGES and 14/314 (4.5%) patients with elevated ASGES score (P <.03). ConclusionsIn this community-based cardiovascular registry, the ASGES demonstrated clinical utility in the evaluation of patients with suspected obstructive coronary artery disease. Low-score patients were less likely to undergo cardiac referral, were unlikely to have positive findings on further cardiac work-up, and had a low rate of adverse cardiovascular events in 1-year follow-up. Our work provides evidence supporting the value of using precision medicine in the delivery of cardiovascular care.