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.
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.
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
Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acu... more Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS). Apixaban's effect on D-dimer and prothrombin fragment 1.2 (F1.2) (coagulation activity biomarkers ) was determined in a randomised, double-blinded, placebo-controlled, phase 2 study. Patients (n=1,715) with either ST- segment elevation or non-ST-segment elevation ACS received either placebo or apixaban 2.5 mg twice daily, 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months. Samples were obtained at baseline (before study drug administration), week 3 and week 26. Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry, and anti-Xa activity was determined using apixaban as a reference standard. D-dimer and F 1.2 were measured using ELISA-based methods. Most patients had elevated D-dimer and F1.2 levels at baseline. Both coagulation activity biomarkers decreased by week 3 in all treatment groups, but ...
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...
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 ...
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...
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.
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.
The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of... more 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. 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). 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 ≤40%), 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. 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. 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. 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. In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. clinicaltrials.gov Identifier: NCT01685840.
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 < 0.001) and enoxaparin (194% higher, p < 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 < 0.001) and 198% higher (p…
An ability to readily determine an anticoagulant effect with an emerging class of direct, active ... more An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. Anti-Xa activity, determined by either anti-Xa-LMWH (r = 0.9671; P < 0.0001) or anti-Xa-apixaban (r = 0.9669; P < 0.0001) correlated strongly and in a linear fashion with apixaban plasma concentrations. The correlations for each method were equally strong at low (<100 ng/ml) (r = 0.86,…
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.
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.
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
Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acu... more Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS). Apixaban's effect on D-dimer and prothrombin fragment 1.2 (F1.2) (coagulation activity biomarkers ) was determined in a randomised, double-blinded, placebo-controlled, phase 2 study. Patients (n=1,715) with either ST- segment elevation or non-ST-segment elevation ACS received either placebo or apixaban 2.5 mg twice daily, 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months. Samples were obtained at baseline (before study drug administration), week 3 and week 26. Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry, and anti-Xa activity was determined using apixaban as a reference standard. D-dimer and F 1.2 were measured using ELISA-based methods. Most patients had elevated D-dimer and F1.2 levels at baseline. Both coagulation activity biomarkers decreased by week 3 in all treatment groups, but ...
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...
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 ...
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...
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.
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.
The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of... more 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. 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). 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 ≤40%), 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. 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. 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. 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. In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. clinicaltrials.gov Identifier: NCT01685840.
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 < 0.001) and enoxaparin (194% higher, p < 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 < 0.001) and 198% higher (p…
An ability to readily determine an anticoagulant effect with an emerging class of direct, active ... more An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. Anti-Xa activity, determined by either anti-Xa-LMWH (r = 0.9671; P < 0.0001) or anti-Xa-apixaban (r = 0.9669; P < 0.0001) correlated strongly and in a linear fashion with apixaban plasma concentrations. The correlations for each method were equally strong at low (<100 ng/ml) (r = 0.86,…
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