Hongqiu Yang - Academia.edu (original) (raw)

Papers by Hongqiu Yang

Research paper thumbnail of LBA02-08 RISK Factors for Increased Stent-Associated Symptoms Following Ureteroscopy for Urinary Stones: Results from the Urinary Stone Disease Research Network (Usdrn) Stents Study

Journal of Urology

FTIR spectra (Fig 1D) shows the presence of calcium carbonate (CaCO3) in post-treatment stones, w... more FTIR spectra (Fig 1D) shows the presence of calcium carbonate (CaCO3) in post-treatment stones, which results from thermal degradation of the calcium oxalate phase. This suggests that the mode of failure includes a component of photothermal degradation. CONCLUSIONS: We have shown that photonic nanoparticles can fragment stones using a laser wavelength that is minimally absorbed by kidney tissue. Importantly, the FTIR results suggest that photothermal degradation is a component of the failure mechanism, as observed with the formation of CaCO3. Mechanistic studies will help in optimizing parameters for photonic lithotripsy.

Research paper thumbnail of Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: Results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial

American Heart Journal, 2013

Background Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a ... more Background Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Methods and results Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS 2). Fewer VKAnaive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P b .001). Conclusion The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/ systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.

Research paper thumbnail of Abstract 19509: Palliative Care and Hospital Readmissions in Patients With Advanced Heart Failure: Insights From the PAL-HF Trial

Circulation, Nov 11, 2016

Research paper thumbnail of Improving racial disparities in unmet palliative care needs among intensive care unit family members with a needs-targeted app intervention: The ICUconnect randomized clinical trial

Contemporary clinical trials, 2021

INTRODUCTION The technologies used to treat the millions who receive care in intensive care unit ... more INTRODUCTION The technologies used to treat the millions who receive care in intensive care unit (ICUs) each year have steadily advanced. However, the quality of ICU-based communication has remained suboptimal, particularly concerning for Black patients and their family members. Therefore we developed a mobile app intervention for ICU clinicians and family members called ICUconnect that assists with delivering need-based care. OBJECTIVE To describe the methods and early experiences of a clustered randomized clinical trial (RCT) being conducted to compare ICUconnect vs. usual care. METHODS AND ANALYSIS The goal of this two-arm, parallel group clustered RCT is to determine the clinical impact of the ICUconnect intervention in improving outcomes overall and for each racial subgroup on reducing racial disparities in core palliative care outcomes over a 3-month follow up period. ICU attending physicians are randomized to either ICUconnect or usual care, with outcomes obtained from family...

Research paper thumbnail of Abstract 14771: Apixaban versus warfarin in Patients with Atrial Fibrillation in relation to Prior Warfarin Use: Insights from the ARISTOTLE trial

Circulation, 2012

Background: Patients with atrial fibrillation (AF) who are new to anticoagulation (warfarin-naive... more Background: Patients with atrial fibrillation (AF) who are new to anticoagulation (warfarin-naive [WN]) may have a higher risk of thrombosis and/or bleeding than patients who are warfarin-experienced (WE). In the ARISTOTLE trial, centers were asked to include at least 40% WN patients. We assessed the treatment effect of apixaban versus warfarin in WN and WE cohorts. We also tested the hypothesis that, overall, the risk of adverse outcomes would be higher in the WN cohort. Methods: Patients were defined as WN if they had used warfarin for Results: Of all 18,201 pts enrolled, 7,800 (43%) were WN and 10,401 were WE. Compared to WE pts, WN pts were more often female (39% vs. 33%). WN and WE pts were similar with respect to age and CHADS 2 score. At baseline, fewer WN pts had a history of or prior stroke (18% vs. 21%) and prior bleeding (10% vs. 22%). During the 1.8 years of randomized treatment compared to warfarin, apixaban reduced the risk of stroke/SE and caused less bleeding, irresp...

Research paper thumbnail of Abstract 20846: The Impact of a Palliative Care Intervention on Polypharmacy in Advanced HF: Results From Pal-HF

Circulation, 2017

Introduction: Palliative care (PC) aims to improve symptoms and QOL in advanced HF, in part throu... more Introduction: Palliative care (PC) aims to improve symptoms and QOL in advanced HF, in part through medication management. However, the impact of PC on polypharmacy (≥5 medications) in advanced HF ...

Research paper thumbnail of Cuidados paliativos en insuficiencia cardiaca. El ensayo clínico controlado y aleatorizado PAL-HF

Research paper thumbnail of Communication Coaching in Cardiology (CCC): A study protocol and methodological challenges and solutions of a randomized controlled trial in outpatient cardiology clinics

Contemporary clinical trials, 2021

Given the role of effective communication in improving patient adherence and satisfaction, high q... more Given the role of effective communication in improving patient adherence and satisfaction, high quality patient-clinician communication is critical. Building on previous communication interventions in oncology and pediatrics, we developed a tailored communication coaching intervention to improve empathic communication quality and patient-centered care. In this randomized controlled trial, cardiologists record their patient encounters for review by a communication coach who provides tailored feedback. We are recruiting 40 cardiologists and 400 patients, or 4 patients per cardiologist in the Pre-intervention phase and 6 patients per cardiologists in the Post-intervention phase, from outpatient cardiology clinics within the Duke Health System. The primary goal of the trial is to determine the efficacy of the clinician communication coaching versus usual care in the post-intervention phase (240 patient encounters). In this paper, we describe the development of the communication coaching...

Research paper thumbnail of Effect of Natriuretic Peptide-Guided Therapy on Outcomes in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Research paper thumbnail of The cultural meaning of health : social ties and health among the elderly in China and Japan

Research paper thumbnail of The Patient's Point of View: Characterizing Patient-Level Factors Associated with Perceptions of Health Care

Health Equity

Purpose: We explored the association between perception of care, as measured by the Interpersonal... more Purpose: We explored the association between perception of care, as measured by the Interpersonal Processes of Care (IPC) survey, and patient-level factors, including (1) Trust in physicians; (2) Perceived empathy; (3) Stereotype threat; (4) Perceived everyday discrimination; and (5) Self-Reported Health. Methods: Fifty participants from diverse racial backgrounds and education levels were surveyed. We examined the associations between the five patient-level factors and each subdomain of the IPC using multiple linear regression. We added a race interaction term to assess whether associations between IPC subdomains and predictors differed by race. We tested for correlation among factors found to be significantly associated with the IPC. Results: In adjusted analyses, trust in the physician, perceived empathy from the provider, and perceived everyday discrimination were significantly associated with most subdomains of the IPC. There was no significant race interaction. Conclusion: This exploratory study suggests that empathy, trust, and perceived everyday discrimination are significantly linked to patient perception of quality care, which are linked to clinical outcomes. Results present modifiable factors that may potentially improve patient care. Practice Implications: Increased efforts to improve clinician communication of empathy and general communication skill may have a positive effect on quality of care.

Research paper thumbnail of Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)

Neuropsychopharmacology

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreate... more Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.

Research paper thumbnail of Correction to: Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)

Neuropsychopharmacology

In this article a conflict of interest was missing. The co-author Sanjay J. Mathew served as a co... more In this article a conflict of interest was missing. The co-author Sanjay J. Mathew served as a consultant to Alkermes. The original article has been corrected.

Research paper thumbnail of A randomized proof-of-mechanism trial applying the ‘fast-fail’ approach to evaluating κ-opioid antagonism as a treatment for anhedonia

Nature Medicine

The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-mi... more The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach. NATuRE MEDICINE | www.nature.com/naturemedicine Articles Nature MediciNe The first comprehensive application of this approach is presented here. Under the auspices of the NIMH New Experimental Medicine Studies: Fast-Fail Trials in Mood and Anxiety Spectrum Disorders (FAST-MAS) Program, we assessed the potential of KOR antagonism to have brain effects consistent with therapeutic benefit for anhedonia, a symptom of major depressive disorder (MDD) that cuts across traditional DSM as well as medical diagnoses 12. Anhedonia can be defined in various ways and is not considered a diagnosis. Anhedonia, as broadly construed, is represented in several reward-related RDoC constructs ('reward responsiveness' , 'reward learning' and 'reward valuation') 11,13. Preclinical data strongly suggest that KOR antagonism will affect reward-related brain circuitry (in particular, ventral striatum) in a manner that could improve reward-associated function and reverse anhedonic symptoms and behaviors 13-21. We selected and evaluated JNJ-67953964 (previously CERC-501 and LY2456302), a highaffinity, selective KOR antagonist with favorable pharmacologic and safety profiles, on the basis of (1) completed preclinical toxicology and human single-and multiple-ascending-dose studies 22,23 and (2) PET evidence that it robustly engages KOR at tolerated doses 24. We based our decision to use reward-related activation in the ventral striatum as our primary target on the compelling preclinical literature indicating that KOR antagonism would release inhibition on dopamine (DA) neurons, increase nucleus accumbens function and prevent the development of anhedonic-like states 13,25. Evidence suggests that KOR stimulation inhibits dopamine release in the striatum (nucleus accumbens) and induces a negative mood state 15. Further, KOR agonists decrease phasic dopamine release in the nucleus accumbens and increase intracranial self-stimulation thresholds (an anhedonia model), whereas KOR antagonists have the opposite effect 14,17-19. In light of evidence of positive correlations between reward-related dopamine release (as assessed by PET) and blood-oxygen-level-dependent (BOLD) activation (as assessed by fMRI) 26,27 , reward-related BOLD activation in the ventral striatum was selected as the primary outcome variable (Fig. 1). Results Participants. A total of 163 participants were screened, and 94 met eligibility criteria (Extended Data Fig. 1). Of these, three withdrew consent before the baseline visit and two were unable to complete baseline procedures. Thus, 89 individuals were randomized, 45 to JNJ-67953964 and 44 to placebo. These 89 participants constituted the intention-to-treat (ITT) population. There were no significant differences (P < 0.05) between the groups on any demographic or baseline variables in the ITT population (Table 1). For baseline characteristics of the ITT, as-treated, per-protocol and completer populations, see Supplementary Tables 1 and 2. As-treated and per-protocol populations. Two participants were randomized to the JNJ-67953964 group but did not receive treatment and one participant in the placebo group received the wrong treatment, resulting in 43 participants receiving the assigned treatment in both groups. These 86 individuals constituted the as-treated population and the per-protocol population, as there were no major deviations from protocol. 0.63 (0.9) (n = 44) 0.64 (0.8) (n = 44) 0.63 (0.8) (n = 88) Mean maximum baseline fMRI ventral striatal activation in MID task (s.d.) in anticipation of gain contrasted with no-incentive trials (s.d.) 2.66 (1.2) (n = 44) 2.73 (1.2) (n = 44) 2.70 (1.2) (n = 88) Mean baseline fMRI ventral striatal activation in MID task in anticipation of loss contrasted with no-incentive trials (s.d.) 0.29 (0.8) (n = 44) 0.36 (0.7) (n = 44) 0.33 (0.7) (n = 88) Mean maximum baseline fMRI ventral striatal activation in MID task (s.d.) in anticipation of loss contrasted with no-incentive trials (s.d.) 2.15 (1.2) (n = 44) 2.23 (0.9) (n = 44) 2.19 (1.0) (n = 88) Mean baseline PRT change in response bias from block 1 to block 2 (s.d.) b 0.02 (0.2) (n = 35) 0.05 (0.2) (n = 41) 0.04 (0.2) (n = 76) Mean baseline SHAPS (s.d.) b 36.4 (8.5) (n = 44) 33.4 (5.9) (n = 44) 34.9 (7.4) (n = 88) Mean baseline PRT response bias (averaged across blocks) (s.d.) 0.108 (0.027) (n = 35) 0.113 (0.025) (n = 41) 0.111 (0.026) (n = 76) Mean baseline EEfRT (s.d.) 0.35 (0.2) (n = 42) 0.38 (0.2) (n = 41) 0.36 (0.2) (n = 83) Mean baseline TEPS anticipatory subscore (s.d.) 29.3 (5.7) (n = 44) 29.5 (5.6) (n = 44) 29.4 (5.7) (n = 88) Mean baseline TEPS consummatory subscore (s.d.) 26.3 (4.4) (n = 44) 26.1 (4.4) (n = 44) 26.2 (4.4) (n = 88) Mean baseline VAS anhedonia (s.d.) 2.93 (2.1) (n = 44) 3.59 (2.2) (n = 44) 3.26 (2.2) (n = 88) Mean baseline resting-state EEG delta current density in rostral anterior cingulate (s.d.

Research paper thumbnail of African Americans With Advanced Heart Failure Are More Likely to Die in a Health Care Facility Than at Home or in Hospice: An Analysis From the PAL-HF Trial

Journal of Cardiac Failure

Research paper thumbnail of Palliative care and hospital readmissions in patients with advanced heart failure: Insights from the PAL-HF trial

American heart journal, Jan 20, 2018

Background: The PAL-HF trial intervention improved quality of life (QOL) compared to usual care i... more Background: The PAL-HF trial intervention improved quality of life (QOL) compared to usual care in advanced heart failure (HF) patients. Patients with end-stage HF have a significant symptom burden...

Research paper thumbnail of Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction

JAMA

IMPORTANCE The natriuretic peptides are biochemical markers of heart failure (HF) severity and pr... more IMPORTANCE The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. OBJECTIVE To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). DESIGN, SETTINGS, AND PARTICIPANTS The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction Յ40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. INTERVENTIONS Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. MAIN OUTCOMES AND MEASURES The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. RESULTS The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; (95% CI, 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. CONCLUSIONS AND RELEVANCE In high-risk patients with HFrEF, a strategy of NT-proBNPguided therapy was not more effective than a usual care strategy in improving outcomes.

Research paper thumbnail of 861-1 Direct, selective, factor Xa inhibition in patients with non-ST elevation acute coronary syndromes from the United States, Canada, and Japan: Results of the XaNADU-ACS trial

Journal of the American College of Cardiology, 2004

Research paper thumbnail of Effect of Apixaban an Oral Direct and Selective Factor Xa Inhibitor on Inflammatory Biomarkers Following Acute Coronary …

Journal of the …, 2011

... 366 Authors: Richard C. Becker, Annie Lin, Hongqiu Yang, Yuchen Barrett, Puneet Mohan, Jessie... more ... 366 Authors: Richard C. Becker, Annie Lin, Hongqiu Yang, Yuchen Barrett, Puneet Mohan, Jessie Wang, John Alexander, Duke Clinical Research Institute, Durham,NC, Bristol-Myers Squibb, Princeton, NJ Background: Apixaban ...

Research paper thumbnail of Vascular Endothelial Tissue Factor Pathway Inhibitor Kinetics in Culture Following Exposure to DX-9065a—A Selective and Direct Factor Xa Inhibitor

Journal of thrombosis …, 2004

Tissue factor (TF), a membrane-bound glycoprotein that initiates blood coagulation by allosteric ... more Tissue factor (TF), a membrane-bound glycoprotein that initiates blood coagulation by allosteric activation of factor (f) VII, is regulated predominantly by tissue factor pathway inhibitor (TFPI). Because vascular endothelial cells synthesize and constitutively secrete TFPI and fXa may directly influence its cellular clearance, we sought to determine the effects of DX-9065a, a direct and selective fXa inhibitor, on TFPI kinetics in culture. Human umbilical vein endothelial cells were grown to confluence and incubated with unfractionated heparin (1.0 U/mL), enoxaparin (1.5 U/mL), or DX-9065a at low (10 ng/ml), moderate (30 ng/ml), or high (90 ng/ml) concentrations. Compared to control, increases in TFPI were seen with both unfractionated heparin (182% higher, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and enoxaparin (194% higher, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Low concentration DX-9065a did not increase TFPI levels above control (0.8% higher, p = 0.91). In contrast, moderate and high concentrations produced 124% higher (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 198% higher (p…

Research paper thumbnail of LBA02-08 RISK Factors for Increased Stent-Associated Symptoms Following Ureteroscopy for Urinary Stones: Results from the Urinary Stone Disease Research Network (Usdrn) Stents Study

Journal of Urology

FTIR spectra (Fig 1D) shows the presence of calcium carbonate (CaCO3) in post-treatment stones, w... more FTIR spectra (Fig 1D) shows the presence of calcium carbonate (CaCO3) in post-treatment stones, which results from thermal degradation of the calcium oxalate phase. This suggests that the mode of failure includes a component of photothermal degradation. CONCLUSIONS: We have shown that photonic nanoparticles can fragment stones using a laser wavelength that is minimally absorbed by kidney tissue. Importantly, the FTIR results suggest that photothermal degradation is a component of the failure mechanism, as observed with the formation of CaCO3. Mechanistic studies will help in optimizing parameters for photonic lithotripsy.

Research paper thumbnail of Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: Results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial

American Heart Journal, 2013

Background Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a ... more Background Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Methods and results Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS 2). Fewer VKAnaive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P b .001). Conclusion The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/ systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.

Research paper thumbnail of Abstract 19509: Palliative Care and Hospital Readmissions in Patients With Advanced Heart Failure: Insights From the PAL-HF Trial

Circulation, Nov 11, 2016

Research paper thumbnail of Improving racial disparities in unmet palliative care needs among intensive care unit family members with a needs-targeted app intervention: The ICUconnect randomized clinical trial

Contemporary clinical trials, 2021

INTRODUCTION The technologies used to treat the millions who receive care in intensive care unit ... more INTRODUCTION The technologies used to treat the millions who receive care in intensive care unit (ICUs) each year have steadily advanced. However, the quality of ICU-based communication has remained suboptimal, particularly concerning for Black patients and their family members. Therefore we developed a mobile app intervention for ICU clinicians and family members called ICUconnect that assists with delivering need-based care. OBJECTIVE To describe the methods and early experiences of a clustered randomized clinical trial (RCT) being conducted to compare ICUconnect vs. usual care. METHODS AND ANALYSIS The goal of this two-arm, parallel group clustered RCT is to determine the clinical impact of the ICUconnect intervention in improving outcomes overall and for each racial subgroup on reducing racial disparities in core palliative care outcomes over a 3-month follow up period. ICU attending physicians are randomized to either ICUconnect or usual care, with outcomes obtained from family...

Research paper thumbnail of Abstract 14771: Apixaban versus warfarin in Patients with Atrial Fibrillation in relation to Prior Warfarin Use: Insights from the ARISTOTLE trial

Circulation, 2012

Background: Patients with atrial fibrillation (AF) who are new to anticoagulation (warfarin-naive... more Background: Patients with atrial fibrillation (AF) who are new to anticoagulation (warfarin-naive [WN]) may have a higher risk of thrombosis and/or bleeding than patients who are warfarin-experienced (WE). In the ARISTOTLE trial, centers were asked to include at least 40% WN patients. We assessed the treatment effect of apixaban versus warfarin in WN and WE cohorts. We also tested the hypothesis that, overall, the risk of adverse outcomes would be higher in the WN cohort. Methods: Patients were defined as WN if they had used warfarin for Results: Of all 18,201 pts enrolled, 7,800 (43%) were WN and 10,401 were WE. Compared to WE pts, WN pts were more often female (39% vs. 33%). WN and WE pts were similar with respect to age and CHADS 2 score. At baseline, fewer WN pts had a history of or prior stroke (18% vs. 21%) and prior bleeding (10% vs. 22%). During the 1.8 years of randomized treatment compared to warfarin, apixaban reduced the risk of stroke/SE and caused less bleeding, irresp...

Research paper thumbnail of Abstract 20846: The Impact of a Palliative Care Intervention on Polypharmacy in Advanced HF: Results From Pal-HF

Circulation, 2017

Introduction: Palliative care (PC) aims to improve symptoms and QOL in advanced HF, in part throu... more Introduction: Palliative care (PC) aims to improve symptoms and QOL in advanced HF, in part through medication management. However, the impact of PC on polypharmacy (≥5 medications) in advanced HF ...

Research paper thumbnail of Cuidados paliativos en insuficiencia cardiaca. El ensayo clínico controlado y aleatorizado PAL-HF

Research paper thumbnail of Communication Coaching in Cardiology (CCC): A study protocol and methodological challenges and solutions of a randomized controlled trial in outpatient cardiology clinics

Contemporary clinical trials, 2021

Given the role of effective communication in improving patient adherence and satisfaction, high q... more Given the role of effective communication in improving patient adherence and satisfaction, high quality patient-clinician communication is critical. Building on previous communication interventions in oncology and pediatrics, we developed a tailored communication coaching intervention to improve empathic communication quality and patient-centered care. In this randomized controlled trial, cardiologists record their patient encounters for review by a communication coach who provides tailored feedback. We are recruiting 40 cardiologists and 400 patients, or 4 patients per cardiologist in the Pre-intervention phase and 6 patients per cardiologists in the Post-intervention phase, from outpatient cardiology clinics within the Duke Health System. The primary goal of the trial is to determine the efficacy of the clinician communication coaching versus usual care in the post-intervention phase (240 patient encounters). In this paper, we describe the development of the communication coaching...

Research paper thumbnail of Effect of Natriuretic Peptide-Guided Therapy on Outcomes in High-Risk Patients with Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Research paper thumbnail of The cultural meaning of health : social ties and health among the elderly in China and Japan

Research paper thumbnail of The Patient's Point of View: Characterizing Patient-Level Factors Associated with Perceptions of Health Care

Health Equity

Purpose: We explored the association between perception of care, as measured by the Interpersonal... more Purpose: We explored the association between perception of care, as measured by the Interpersonal Processes of Care (IPC) survey, and patient-level factors, including (1) Trust in physicians; (2) Perceived empathy; (3) Stereotype threat; (4) Perceived everyday discrimination; and (5) Self-Reported Health. Methods: Fifty participants from diverse racial backgrounds and education levels were surveyed. We examined the associations between the five patient-level factors and each subdomain of the IPC using multiple linear regression. We added a race interaction term to assess whether associations between IPC subdomains and predictors differed by race. We tested for correlation among factors found to be significantly associated with the IPC. Results: In adjusted analyses, trust in the physician, perceived empathy from the provider, and perceived everyday discrimination were significantly associated with most subdomains of the IPC. There was no significant race interaction. Conclusion: This exploratory study suggests that empathy, trust, and perceived everyday discrimination are significantly linked to patient perception of quality care, which are linked to clinical outcomes. Results present modifiable factors that may potentially improve patient care. Practice Implications: Increased efforts to improve clinician communication of empathy and general communication skill may have a positive effect on quality of care.

Research paper thumbnail of Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)

Neuropsychopharmacology

Anhedonia remains a major clinical issue for which there is few effective interventions. Untreate... more Anhedonia remains a major clinical issue for which there is few effective interventions. Untreated or poorly controlled anhedonia has been linked to worse disease course and increased suicidal behavior across disorders. Taking a proof-of-mechanism approach under the auspices of the National Institute of Mental Health FAST-FAIL initiative, we were the first to show that, in a transdiagnostic sample screened for elevated self-reported anhedonia, 8 weeks of treatment with a kappa-opioid receptor (KOR) antagonist resulted in significantly higher reward-related activation in one of the core hubs of the brain reward system (the ventral striatum), better reward learning in the Probabilistic Reward Task (PRT), and lower anhedonic symptoms, relative to 8 weeks of placebo. Here, we performed secondary analyses of the PRT data to investigate the putative effects of KOR antagonism on anhedonic behavior with more precision by using trial-level model-based Bayesian computational modeling and probability analyses. We found that, relative to placebo, KOR antagonism resulted in significantly higher learning rate (i.e., ability to learn from reward feedback) and a more sustained preference toward the more frequently rewarded stimulus, but unaltered reward sensitivity (i.e., the hedonic response to reward feedback). Collectively, these findings provide novel evidence that in a transdiagnostic sample characterized by elevated anhedonia, KOR antagonism improved the ability to modulate behavior as a function of prior rewards. Together with confirmation of target engagement in the primary report (Krystal et al., Nat Med, 2020), the current findings suggest that further transdiagnostic investigation of KOR antagonism for anhedonia is warranted.

Research paper thumbnail of Correction to: Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)

Neuropsychopharmacology

In this article a conflict of interest was missing. The co-author Sanjay J. Mathew served as a co... more In this article a conflict of interest was missing. The co-author Sanjay J. Mathew served as a consultant to Alkermes. The original article has been corrected.

Research paper thumbnail of A randomized proof-of-mechanism trial applying the ‘fast-fail’ approach to evaluating κ-opioid antagonism as a treatment for anhedonia

Nature Medicine

The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-mi... more The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach. NATuRE MEDICINE | www.nature.com/naturemedicine Articles Nature MediciNe The first comprehensive application of this approach is presented here. Under the auspices of the NIMH New Experimental Medicine Studies: Fast-Fail Trials in Mood and Anxiety Spectrum Disorders (FAST-MAS) Program, we assessed the potential of KOR antagonism to have brain effects consistent with therapeutic benefit for anhedonia, a symptom of major depressive disorder (MDD) that cuts across traditional DSM as well as medical diagnoses 12. Anhedonia can be defined in various ways and is not considered a diagnosis. Anhedonia, as broadly construed, is represented in several reward-related RDoC constructs ('reward responsiveness' , 'reward learning' and 'reward valuation') 11,13. Preclinical data strongly suggest that KOR antagonism will affect reward-related brain circuitry (in particular, ventral striatum) in a manner that could improve reward-associated function and reverse anhedonic symptoms and behaviors 13-21. We selected and evaluated JNJ-67953964 (previously CERC-501 and LY2456302), a highaffinity, selective KOR antagonist with favorable pharmacologic and safety profiles, on the basis of (1) completed preclinical toxicology and human single-and multiple-ascending-dose studies 22,23 and (2) PET evidence that it robustly engages KOR at tolerated doses 24. We based our decision to use reward-related activation in the ventral striatum as our primary target on the compelling preclinical literature indicating that KOR antagonism would release inhibition on dopamine (DA) neurons, increase nucleus accumbens function and prevent the development of anhedonic-like states 13,25. Evidence suggests that KOR stimulation inhibits dopamine release in the striatum (nucleus accumbens) and induces a negative mood state 15. Further, KOR agonists decrease phasic dopamine release in the nucleus accumbens and increase intracranial self-stimulation thresholds (an anhedonia model), whereas KOR antagonists have the opposite effect 14,17-19. In light of evidence of positive correlations between reward-related dopamine release (as assessed by PET) and blood-oxygen-level-dependent (BOLD) activation (as assessed by fMRI) 26,27 , reward-related BOLD activation in the ventral striatum was selected as the primary outcome variable (Fig. 1). Results Participants. A total of 163 participants were screened, and 94 met eligibility criteria (Extended Data Fig. 1). Of these, three withdrew consent before the baseline visit and two were unable to complete baseline procedures. Thus, 89 individuals were randomized, 45 to JNJ-67953964 and 44 to placebo. These 89 participants constituted the intention-to-treat (ITT) population. There were no significant differences (P < 0.05) between the groups on any demographic or baseline variables in the ITT population (Table 1). For baseline characteristics of the ITT, as-treated, per-protocol and completer populations, see Supplementary Tables 1 and 2. As-treated and per-protocol populations. Two participants were randomized to the JNJ-67953964 group but did not receive treatment and one participant in the placebo group received the wrong treatment, resulting in 43 participants receiving the assigned treatment in both groups. These 86 individuals constituted the as-treated population and the per-protocol population, as there were no major deviations from protocol. 0.63 (0.9) (n = 44) 0.64 (0.8) (n = 44) 0.63 (0.8) (n = 88) Mean maximum baseline fMRI ventral striatal activation in MID task (s.d.) in anticipation of gain contrasted with no-incentive trials (s.d.) 2.66 (1.2) (n = 44) 2.73 (1.2) (n = 44) 2.70 (1.2) (n = 88) Mean baseline fMRI ventral striatal activation in MID task in anticipation of loss contrasted with no-incentive trials (s.d.) 0.29 (0.8) (n = 44) 0.36 (0.7) (n = 44) 0.33 (0.7) (n = 88) Mean maximum baseline fMRI ventral striatal activation in MID task (s.d.) in anticipation of loss contrasted with no-incentive trials (s.d.) 2.15 (1.2) (n = 44) 2.23 (0.9) (n = 44) 2.19 (1.0) (n = 88) Mean baseline PRT change in response bias from block 1 to block 2 (s.d.) b 0.02 (0.2) (n = 35) 0.05 (0.2) (n = 41) 0.04 (0.2) (n = 76) Mean baseline SHAPS (s.d.) b 36.4 (8.5) (n = 44) 33.4 (5.9) (n = 44) 34.9 (7.4) (n = 88) Mean baseline PRT response bias (averaged across blocks) (s.d.) 0.108 (0.027) (n = 35) 0.113 (0.025) (n = 41) 0.111 (0.026) (n = 76) Mean baseline EEfRT (s.d.) 0.35 (0.2) (n = 42) 0.38 (0.2) (n = 41) 0.36 (0.2) (n = 83) Mean baseline TEPS anticipatory subscore (s.d.) 29.3 (5.7) (n = 44) 29.5 (5.6) (n = 44) 29.4 (5.7) (n = 88) Mean baseline TEPS consummatory subscore (s.d.) 26.3 (4.4) (n = 44) 26.1 (4.4) (n = 44) 26.2 (4.4) (n = 88) Mean baseline VAS anhedonia (s.d.) 2.93 (2.1) (n = 44) 3.59 (2.2) (n = 44) 3.26 (2.2) (n = 88) Mean baseline resting-state EEG delta current density in rostral anterior cingulate (s.d.

Research paper thumbnail of African Americans With Advanced Heart Failure Are More Likely to Die in a Health Care Facility Than at Home or in Hospice: An Analysis From the PAL-HF Trial

Journal of Cardiac Failure

Research paper thumbnail of Palliative care and hospital readmissions in patients with advanced heart failure: Insights from the PAL-HF trial

American heart journal, Jan 20, 2018

Background: The PAL-HF trial intervention improved quality of life (QOL) compared to usual care i... more Background: The PAL-HF trial intervention improved quality of life (QOL) compared to usual care in advanced heart failure (HF) patients. Patients with end-stage HF have a significant symptom burden...

Research paper thumbnail of Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction

JAMA

IMPORTANCE The natriuretic peptides are biochemical markers of heart failure (HF) severity and pr... more IMPORTANCE The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. OBJECTIVE To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). DESIGN, SETTINGS, AND PARTICIPANTS The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction Յ40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. INTERVENTIONS Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. MAIN OUTCOMES AND MEASURES The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. RESULTS The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; (95% CI, 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. CONCLUSIONS AND RELEVANCE In high-risk patients with HFrEF, a strategy of NT-proBNPguided therapy was not more effective than a usual care strategy in improving outcomes.

Research paper thumbnail of 861-1 Direct, selective, factor Xa inhibition in patients with non-ST elevation acute coronary syndromes from the United States, Canada, and Japan: Results of the XaNADU-ACS trial

Journal of the American College of Cardiology, 2004

Research paper thumbnail of Effect of Apixaban an Oral Direct and Selective Factor Xa Inhibitor on Inflammatory Biomarkers Following Acute Coronary …

Journal of the …, 2011

... 366 Authors: Richard C. Becker, Annie Lin, Hongqiu Yang, Yuchen Barrett, Puneet Mohan, Jessie... more ... 366 Authors: Richard C. Becker, Annie Lin, Hongqiu Yang, Yuchen Barrett, Puneet Mohan, Jessie Wang, John Alexander, Duke Clinical Research Institute, Durham,NC, Bristol-Myers Squibb, Princeton, NJ Background: Apixaban ...

Research paper thumbnail of Vascular Endothelial Tissue Factor Pathway Inhibitor Kinetics in Culture Following Exposure to DX-9065a—A Selective and Direct Factor Xa Inhibitor

Journal of thrombosis …, 2004

Tissue factor (TF), a membrane-bound glycoprotein that initiates blood coagulation by allosteric ... more Tissue factor (TF), a membrane-bound glycoprotein that initiates blood coagulation by allosteric activation of factor (f) VII, is regulated predominantly by tissue factor pathway inhibitor (TFPI). Because vascular endothelial cells synthesize and constitutively secrete TFPI and fXa may directly influence its cellular clearance, we sought to determine the effects of DX-9065a, a direct and selective fXa inhibitor, on TFPI kinetics in culture. Human umbilical vein endothelial cells were grown to confluence and incubated with unfractionated heparin (1.0 U/mL), enoxaparin (1.5 U/mL), or DX-9065a at low (10 ng/ml), moderate (30 ng/ml), or high (90 ng/ml) concentrations. Compared to control, increases in TFPI were seen with both unfractionated heparin (182% higher, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and enoxaparin (194% higher, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Low concentration DX-9065a did not increase TFPI levels above control (0.8% higher, p = 0.91). In contrast, moderate and high concentrations produced 124% higher (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 198% higher (p…