Chronic psychological stress has been implicated as a risk factor for Alzheimer’s disease (AD), potentially through cortisol-mediated acceleration of disease progression. However, the molecular pathways underlying this relationship remain poorly understood. Epigenetic regulation of the glucocorticoid and mineralocorticoid receptor genes (NR3C1 and NR3C2), which encode receptors for cortisol, may play an important role, but has not been examined in relation to AD progression. Therefore, this study investigated associations between DNA methylation of NR3C1/NR3C2 and AD-related phenotypes, including cognition, brain amyloid-β (Aβ) burden, and regional brain volumes. These associations were examined in two independent cohorts of cognitively unimpaired individuals with accumulating brain Aβ (n = 89–298 across outcomes) using linear regression and meta-analyses. The study also explored whether DNA methylation within NR3C1 and NR3C2 interacted with depression symptoms to influence relationships with AD-related phenotypes. While only nominal associations were observed in direct analyses, stronger associations emerged in interaction with depressive symptoms. Interaction analyses showed that relationships between DNA methylation and AD-related phenotypes (cognition, hippocampal volume and ventricular expansion) differed depending on the presence of depression symptoms. Consistent patterns across cohorts were observed, with associations primarily evident among individuals with clinically relevant depressive symptoms. One site (NR3C1 cg24052866) was associated with cognitive decline, one (NR3C1 cg08845721) with cross-sectional hippocampal volume, and eight (NR3C1 cg21979215, cg16594263; NR3C2 cg27460943, cg17253842, cg04867484, cg10993059, cg25672354, cg27234800) with ventricular expansion. These exploratory findings suggest epigenetic variation within cortisol receptor genes may influence AD-related neurodegeneration in a depression-dependent manner.

White matter microstructural changes play a crucial role in cognitive decline in aging and neurodegenerative disorders including Alzheimer’s disease (AD). However, the processes underlying white matter microstructural changes and the molecular pathways leading to these changes in AD remain largely unknown. AD involves cortical and juxtacortical microstructural changes, with free water fraction (FWF) as a potential imaging marker. We measured FWF using diffusion magnetic resonance imaging in 68 juxtacortical regions of 153 cognitively normal controls and 194 patients with AD as evidenced by elevated amyloid PET. We estimated the expression of 15,633 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. The biological processes and cell types associated with the linked genes were evaluated. Mediation analysis was used to examine whether FWF mediates the association between APOE ε4 status and cognitive performance. Gene ontological analyses revealed that these genes were enriched for biological processes relating to lipid metabolic process, ensheathment of neurons, and synaptic signaling and were predominantly expressed in oligodendrocytes, GABAergic neurons, and pyramidal neurons from the hippocampus CA region. These ontological enrichment results were replicated in two additional datasets. Furthermore, mediation analyses revealed a domain-specific role of FWF in the association between APOE ε4 status and cognitive performance. Our findings provide mechanistic insights into regional juxtacortical microstructural changes in AD, particularly the processes involving lipid metabolism, offering potential therapeutic targets.

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state functional magnetic resonance imaging data from both Chinese and Western populations were analyzed. We proposed a framework of dynamic proportional loss of functional connectivity (DPLFC). After its stability was validated, the optimal parameters were applied for the clinical diagnosis of SCD. DPLFC yielded a relatively high intraclass correlation coefficient. In particular, the DPLFC of the left superior frontal gyrus (SFG) progressively decreased along the Alzheimer’s disease (AD) continuum. Compared with the traditional index, the DPLFC had better classification performance between cognitively normal controls and patients with SCD. Furthermore, DPLFC was related to Aβ deposition and scale scores. Patients with lower DPLFC values had a greater risk of cognitive decline. Decreased DPLFC in the left SFG may be a potential AD-related neuroimaging biomarker at an early stage.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND:Following the expiration of brand name exclusivity of Plavix® in 2012, generic clopidogrel bisulfate was approved. As a widely prescribed medication with significant inter-patient pharmacokinetic and pharmacodynamic variability, data regarding the impact of switching to generic clopidogrel bisulfate on patients is needed.OBJECTIVE:The objective of this study was to determine whether generic clopidogrel bisulfate is as efficacious as Plavix® for the inhibition of platelet aggregation.METHODS:Patients treated with Plavix® monotherapy (n = 254) or generic clopidogrel bisulfate monotherapy (n = 185) were included in this retrospective review. Confounding factors previously found to affect clopidogrel responsiveness (diabetes, female sex, and smoking) were assessed, as well as medications classified as substrates, inducers, and inhibitors of enzymes involved in clopidogrel metabolism. Whole blood impedance aggregometry was used to measure platelet aggregation in response to adenosine diphosphate. Patients were tested after ≥2 weeks of treatment and designated as non-responders if aggregation response exceeded sensitivity thresholds of 6 ohms of impedance.RESULTS:The introduction of generic clopidogrel bisulfate was associated with a decrease in antiplatelet resistance (44% to 31%, p < 0.01) and decreased mean ohms of resistance (5.06 ± 4.55 to 3.32 ± 4.03, p < 0.01). Prior to analysis of secondary outcomes, 217 patients were eliminated due to antiplatelet usage for longer than 3 years (n = 123 for Plavix® and n = 118 for clopidogrel). There was no statistically significant finding in prevalence of secondary events.CONCLUSION:Resistance rates to the antiplatelet, clopidogrel are significantly lower since the switch to generic formulations. Further investigation into the impact of variability between clopidogrel bisulfate formulations is needed.

Introduction Aspirin and clopidogrel are mainstays in secondary stroke prevention; however, some patients do not demonstrate optimal antiplatelet effects from these therapies. Objectives The primary objective of this study was to determine if pharmacist medication intervention paired with anti-platelet medication monitoring with whole blood aggregometry improved responsiveness to antiplatelet treatment when compared with standard-of-care, alone in patients at risk of recurrent stroke or transient ischemic attack (TIA). Methods This retrospective chart review at an outpatient neurology practice examined patients treated post-stroke or post-TIA between 2005 and 2017. Patients were categorized as either having undergone platelet function testing (PFT) with pharmacist intervention and standard-of-care or standard-of-care alone. Patient populations for each group were matched based on age, sex, and ABCD(2) risk scores. Pharmacotherapeutic management and interventions were assessed in each group. Results A total of 342 patients were included as two matched groups (n = 171 for each group) with parallel baseline characteristics. Drug-drug interactions were identified (P < .0001), and counseling on adherence (P = .0008) occurred statistically significantly more often with a pharmacist involved in patient care. After pharmacist intervention and PFT, 83% of patients were considered responsive to their antiplatelet therapy compared with 27% at baseline in the pharmacist intervention group (P < .0001). Conclusion Pharmacist interventions optimized secondary stroke/TIA prophylaxis therapy, decreased drug-drug interactions, and increased adherence counseling. Patients who underwent PFT and pharmacist intervention transitioned from nonresponsive to responsive to their antiplatelet therapy regimen.

Objective: This case series highlights the effect of abrupt discontinuation of long term aspirin in correlation with the risk of recurrent cerebrovascular events in twenty-one patient cases. Background: Aspirin is the mainstay of treatment for primary and secondary prevention of cardiovascular disease and secondary prophylaxis of cerebrovascular disease. Literature suggests that following chronic use, a “rebound” phenomenon can occur which causes a higher risk for recurrent ischemic events. Design/Methods: Patients from an outpatient neurology clinic were evaluated; baseline demographics and characteristics surrounding initial and recurrent events were assessed. Current medication regimen and dosing, symptoms and duration of event, compliance with antiplatelet medication, delay between antiplatelet interruption and onset of ischemic event, reason for discontinuation, and surgical history were examined. Likelihood of recurrent cerebral ischemia was based on age, blood pressure, cholesterol, diabetes, duration of symptoms, and smoking status. Results: Seven hundred and eighty-four patients with a history of stroke/TIA were screened. Twenty-one of these patients (57% male, 71±10 years) experienced stroke or TIA within one month following aspirin withdrawal; thirteen patients (62%) experienced a new stroke while eight experienced a new TIA (38%). On average, 11.2±8.7 days separated aspirin discontinuation and recurrent event; six patients were unable to assign a numeric value to this duration (i.e., “a few days prior”). Surgery (n=5, 24%), other medical procedure (n=4, 19%), travel (n=4, 19%), running out of medication (n=2, 10%), aspirin side effects (n=2, 10%), dosing lapse (n=2, 10%), drug-drug interaction (n=1, 4 %), or clinician advised decision (n=1, 4%) encompassed reasons for discontinuation. Conclusions: Twenty-one patients discontinued their antiplatelet medication and had a subsequent event in this case series; this appears high due to lack of prophylactic treatment. The risks associated with abrupt antiplatelet discontinuation need to be further studied to determine the interval of aspirin discontinuation that places patients at higher risk of recurrent ischemic event. Disclosure: Dr. Wojcik has received research support from Dent Family Foundation. Dr. Greger has received research support from ASHP, Acadia, Dent Family Foundation.Dr. Zelen has nothing to disclose. Dr. Aladeen has received research support from Alexa, Acadia, ASHP, and Dent Family Foundation. Dr. Rainka has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Postgraduate Healthcare Education, LLC, and Biogen. Dr. Rainka has received research support from Alexa, Acadia, ASHP, Dent Family Foundation. Dr. Westphal has received research support from ASHP%252C%2520Acadia%252C%2520Dent%2520Family%2520Foundation. Dr. Bates has nothing to disclose. Dr. Gengo has received research support from Dent Family Foundation.

Legalization of medical cannabis has occurred in 33 states and the District of Columbia, and recreational use has increased exponentially since 2013. As a result, it is important to understand how cannabis interacts with other drugs and has potential risks for patients on concomitant medications. Components of medical cannabis can inhibit or compete for several cytochrome P450 (CYP) hepatic isoenzymes, UDP-glucuronosyltransferases, and P-glycoprotein. These enzymes and transporters are involved in the metabolism and absorption of numerous medications, including anticoagulants (ACs) and antiplatelet agents (APs), potentially causing harmful drug-drug interactions. ACs and/or APs are often prescribed to high-risk patients with cardiac conditions, a history of myocardial infarction, or stroke. Cannabis may cause these medications to be less efficacious and put patients at risk for recurrent cardiovascular and cerebrovascular events. Several case reports show cannabis may inhibit the metabolism of warfarin because of CYP2C9 interactions, resulting in increased plasma concentrations, increased international normalized ratio , and risk of bleeding. Cannabidiol inhibits CYP2C19, an isoenzyme responsible for the transformation of clopidogrel to its active thiol metabolite. This interaction could lead to subtherapeutic levels of active metabolite and possibly increased stroke risk. Within this review, a total of 665 articles were screened from PubMed and EMBASE. Four case reports, 1 in vitro study, and 1 pharmacokinetic article were found to be of relevance. This review serves to examine reported and potential cannabis interactions with APs/ACs to help inform patients and health care providers of possible risks and knowledge gaps.

Legalization of medical cannabis has occurred in 33 states and the District of Columbia, and recreational use has increased exponentially since 2013. As a result, it is important to understand how cannabis interacts with other drugs and has potential risks for patients on concomitant medications. Components of medical cannabis can inhibit or compete for several cytochrome P450 (CYP) hepatic isoenzymes, UDP‐glucuronosyltransferases, and P‐glycoprotein. These enzymes and transporters are involved in the metabolism and absorption of numerous medications, including anticoagulants (ACs) and antiplatelet agents (APs), potentially causing harmful drug‐drug interactions. ACs and/or APs are often prescribed to high‐risk patients with cardiac conditions, a history of myocardial infarction, or stroke. Cannabis may cause these medications to be less efficacious and put patients at risk for recurrent cardiovascular and cerebrovascular events. Several case reports show cannabis may inhibit the metabolism of warfarin because of CYP2C9 interactions, resulting in increased plasma concentrations, increased international normalized ratio, and risk of bleeding. Cannabidiol inhibits CYP2C19, an isoenzyme responsible for the transformation of clopidogrel to its active thiol metabolite. This interaction could lead to subtherapeutic levels of active metabolite and possibly increased stroke risk. Within this review, a total of 665 articles were screened from PubMed and EMBASE. Four case reports, 1 in vitro study, and 1 pharmacokinetic article were found to be of relevance. This review serves to examine reported and potential cannabis interactions with APs/ACs to help inform patients and health care providers of possible risks and knowledge gaps.

In real-world networks, information from source to destination does not only flow along the shortest path connecting them, but can flow along any alternative route. Communicability is a network metric that accounts for this issue and, especially in diffusion-like processes, provides a reliable measure of the ease of communication between node pairs. Accordingly, communicability appears to be promising for highlighting the disruption of connectivity among brain regions, caused by the white matter degeneration due to Alzheimer's disease (AD). Such a degeneration can be captured by digital imaging techniques, in particular diffusion tensor imaging (DTI), which allow to build the brain connectivity network through tractography algorithms and studying its complexity through graph theory. In this study, a cohort of 122 DTI scans, composed by 52 healthy control (HC) subjects, 40 AD patients and 30 mild cognitive impairment (MCI) converter subjects, from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, has been employed to study the suitability of communicability to serve as discriminant factor for AD. We developed a two-fold investigation. On one hand, a statistical analysis has been carried out to ascertain the information content provided by communicability to detect the brain regions mostly affected by the disease: node pairs with statistical significant different communicability have been found, corresponding to some well-known AD-related brain regions. On the other hand, heterogeneous groups of network features (which include/not include communicability) were input to a support vector machine, to assess the impact of communicability on the classification performances in the HC/AD and the HC/AD/MCI discrimination. The best performances, i.e., AUC = 0.82 in the HC/AD case and multiclass AUC = 0.77 in the HC/AD/MCI task, were obtained by using the values of communicability, outperforming the performance obtained with the other network metrics. In summary, this article suggests that communicability can be promising for an automatized AD diagnosis.

With the rapid growth of modern technology, many biomedical studies are being conducted to collect massive datasets with volumes of multi-modality imaging, genetic, neurocognitive and clinical information from increasingly large cohorts. Simultaneously extracting and integrating rich and diverse heterogeneous information in neuroimaging and/or genomics from these big datasets could transform our understanding of how genetic variants impact brain structure and function, cognitive function and brain-related disease risk across the lifespan. Such understanding is critical for diagnosis, prevention and treatment of numerous complex brain-related disorders (e.g., schizophrenia and Alzheimer's disease). However, the development of analytical methods for the joint analysis of both high-dimensional imaging phenotypes and high-dimensional genetic data, a big data squared (BD2) problem, presents major computational and theoretical challenges for existing analytical methods. Besides the high-dimensional nature of BD2, various neuroimaging measures often exhibit strong spatial smoothness and dependence and genetic markers may have a natural dependence structure arising from linkage disequilibrium. We review some recent developments of various statistical techniques for imaging genetics, including massive univariate and voxel-wise approaches, reduced rank regression, mixture models and group sparse multi-task regression. By doing so, we hope that this review may encourage others in the statistical community to enter into this new and exciting field of research. The Canadian Journal of Statistics 47: 108-131; 2019 (c) 2019 Statistical Society of Canada

BACKGROUND:Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.METHOD:To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.RESULTS:There were 219 normal subjects with mean age 75.9 (range from 59.9 to 89.6) and 52.5% male participants, and 372 MCI subjects with mean age 74.8 (range from 55.1 to 89.3) and 63.7% male participants included in the analysis. For normal subjects, six trajectories were identified. Trajectories were classified into three types, determined by the shape, each of which may comprise more than one trajectory: stable (~30% of subjects), curvilinear decline (~ 28%), and linear decline (~ 42%). Notably, none of the normal subjects assigned to the stable stratum progressed to dementia during the study period. In contrast, all trajectories identified for the MCI group tended to decline, although some participants were later re-diagnosed with normal cognition. Age, sex, and education were significantly associated with trajectory membership for both diagnostic groups, while APOE ɛ4 was only significantly associated with trajectories among MCI participants.CONCLUSION:Memory trajectory is a strong indicator of dementia risk. If likely trajectory of memory performance can be identified early, such work may allow clinicians to monitor or predict progression of individual patient cognition. This work also shows the importance of longitudinal cognitive testing and monitoring.

Aspirin remains the standard for stroke prophylaxis. However, as many as 20%‐25% of patients may fail to show a full response to aspirin. Ideally, patients who are resistant to aspirin could be identified, then receive an increased dose of aspirin or be changed to an alternative therapy more efficiently. We have developed an in vitro assay that may make this possible. Healthy volunteers (n = 13) between 18 and 50 years of age were tested for both ex vivo and in vivo responses to aspirin. Dimethyl sulfoxide (DMSO) was selected as the solvent for aspirin in the assay. DMSO can exhibit antiplatelet effects, necessitating the use of a concentration low enough to avoid such antiplatelet effects. Blood samples were tested against DMSO 0%, 0.05%, 0.5%, and 1% w/v with and without aspirin 0, 50, and 100 μM. The effects of both agents were measured via whole‐blood aggregometry. A 3‐dimensional response model described the data well, quantifying the combinatorial effect of DMSO and aspirin on platelet aggregation. Across all participants, baseline aggregation stimulated with collagen 1 μM or arachidonate 0.5 mM was approximately 18 and 13 Ω, respectively. The response model showed that 0.05% DMSO with 100 μM aspirin would provide platelet aggregation of 3.4 Ω. A DMSO concentration of 0.05% in the absence of aspirin would result in no discernable effects on platelet aggregation (17.7 Ω). Overall, the use of 100 μM of aspirin in 0.05% DMSO provides a robust method to test for ex vivo inhibition of platelet aggregation.

We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago.

Background and Goal: Cytochrome P450 (CYP) enzymes are responsible for the conversion of clopidogrel into its active metabolite and the metabolism of proton pump inhibitors (PPIs), which may also inhibit CYP enzymes. A current Food and Drug Administration advisory suggests avoiding esomeprazole and omeprazole while taking clopidogrel because of concerns that PPIs may compromise clopidogrel's antiplatelet effects. The objective of the present study was to examine the robustness of this interaction using a well-controlled study design in a population of participants free of confounders. Materials and Methods: Twenty-eight healthy male participants, with a mean age 24.2 +/- 3.2, were randomized to an incomplete crossover design schedule. Participants underwent platelet aggregation testing after clopidogrel alone, while on clopidogrel in combination with 1 of 3 PPIs (40 mg of pantoprazole, 20 mg of omeprazole, 20 mg of rabeprazole, 40 mg of esomeprazole, 30 mg of lansoprazole, or 30 mg of dexlansoprazole), and during 1 week of clopidogrel-only washout periods. Findings: The median platelet aggregation to adenosine diphosphate during a drug-free baseline was 10 Omega (2.5 interquartile range) of impedance and decreased to 0 Omega on clopidogrel alone. Aggregation did not significantly change with concomitant use of PPIs and clopidogrel. Conclusion: These data do not demonstrate a significant interaction between common individual PPIs and clopidogrel in healthy volunteers who respond to clopidogrel alone. This adds data to a growing body of evidence indicating that the addition of a PPI may have a weak effect on clopidogrel's antiplatelet properties, and may only be relevant in specific clinical circumstances.

This study tested the capability of an assay to predict aspirin response and reduce ischemic events, and healthcare costs, and delays to optimal treatment. Patients who needed aspirin in the course of normal medical care were included. Patients were excluded if they had disorders affecting platelet function, alcohol use within 24 hours of a test, or NSAID use. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to 325 mg daily occurred based on the results of whole blood impedance aggregation testing to the agonists, collagen (1ug/mL, 5 ug/mL) and arachidonate (0.5 mM) after 10-14 days of treatment. The experimental in vitro test was conducted in triplicate by performing aggregometry on samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Of the 36 patients who were compliant 16 were found to be resistant to the antiplatelet effects of 81 mg daily aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose while six actually did. Predicted response to increased doses of aspirin was in good agreement with actual response. Sensitivity of the assay was 83% and specificity was 80%. Results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin necessitating an alternative antiplatelet regimen. Larger, multisite studies are inevitably needed.

Traditional neuroimaging analysis, such as clustering the data collected for the Alzheimer's disease (AD), usually relies on the data from one single imaging modality. However, recent technology and equipment advancements provide with us opportunities to better analyze diseases, where we could collect and employ the data from different image and genetic modalities that may potentially enhance the predictive performance. To perform better clustering in AD analysis, in this paper we conduct a new study to make use of the data from different modalities/views. To achieve this goal, we propose a simple yet efficient method based on Non-negative Matrix Factorization (NMF) which can not only achieve better prediction performance but also deal with some data missing in some views. Experimental results on the ADNI dataset demonstrate the effectiveness of our proposed method.

Many existing studies on complex brain disorders, such as Alzheimer's Disease, usually employed regression analysis to associate the neuroimaging measures to cognitive status. However, whether these measures in multiple modalities have the predictive power to infer the trajectory of cognitive performance over time still remain under-explored. In this paper, we propose a high-order multi-modal multi-mask feature learning model to uncover temporal relationship between the longitudinal neuroimaging measures and progressive cognitive output scores. The regularizations through sparsity-induced norms implemented in the proposed learning model enable the selection of only a small number of imaging features over time and capture modality structures for multi-modal imaging markers. The promising experimental results in extensive empirical studies performed on the ADNI cohort have validated the effectiveness of the proposed method.

Objective: This study tested the capability of an assay that was previously developed in healthy volunteers, to differentiate between pharmacokinetic and pharmacodynamic resistance to aspirin in patients. Background: Early identification of patients as pharmacokinetically or pharmacodynamically resistant to aspirin has the potential to become an invaluable clinical tool, reducing delays to optimal treatment, cardiovascular events, and healthcare costs. Design/Methods: Patients who needed aspirin treatment in the course of normal medical care were included. Patients were excluded if they had any disorders affecting platelet function, an abnormal CBC, alcohol use within 24 hours of a test, NSAID use. Dose escalation of chewable aspirin from 81mg, to 162mg, to 325mg daily occurred every 10–14 days based on the results of whole blood impedance aggregation testing to the agonists, collagen (1ug/mL, 5ug/mL) and arachidonate (0.5mM). The in vitro test was conducted in triplicate by performing the same aggregometry test on blood samples spiked to a concentration of 10uM of aspirin in 0.05% dimethyl sulfoxide. Results: Of the 36 patients included who were compliant with their 81 mg aspirin regimen based on pill count, 16 were found to be resistant to 81 mg of aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten actually remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose of aspirin while six actually did. No statistical difference was found between predicted aspirin response and actual aspirin response (p=0.61). Sensitivity was 83% and specificity was 80%. Conclusions: Results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin therapy necessitating an alternative antiplatelet regimen. Larger, multi-site studies are inevitably needed. Study Supported by: This study was funded by the Dent Family Foundation. Disclosure: Dr. Westphal has nothing to disclose. Dr. Rainka has nothing to disclose. Dr. Amsler has nothing to disclose. Dr. Aladeen has nothing to disclose. Dr. Bates has nothing to disclose. Dr. Gengo has nothing to disclose.

The objectives of this study were to compare indirect urine testing to a direct measure of platelet activity, determine the impact on clinical decision making if only urinary thromboxane B2 (TXB2) were measured, and compare time to obtain results from both procedures.