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Background: Sofosbuvir use in patients with decompensated cirrhosis may be associated with reduced liver transplant waitlist mortality and reduced need for transplant. Methods: Data from the Scientific Registry of Transplant Recipients were linked with a national database of pharmacy claims. All adult patients on the liver transplant waitlist on January 1, 2014, or added to the list during 2014, with hepatitis C virus as reason for listing were identified (2009 patients). A subgroup of 1093 unique patients had consistent pharmacy claim capture and observations. We compared patients who were and were not treated with all sofosbuvir‐based regimens. Results: During the study period, 154 patients received sofosbuvir‐based regimens. These patients had lower model for end‐stage liver disease scores and significantly longer waiting times. We found a trend toward significance for more sofosbuvir‐treated than untreated patients being removed from the waitlist due to improved condition (4.54% vs 3.19%, p=0.03). In a propensity score‐adjusted analysis, sofosbuvir‐treated patients were less likely to undergo transplant (hazard ratio 0.57, 95% confidence interval 0.37–0.89, p=0.01). Conclusion: During the study period reflecting early sofosbuvir use, few liver transplant candidates received sofosbuvir. Use was associated with lower incidence of transplant and a trend toward more waitlist removals due to improved condition. [ABSTRACT FROM AUTHOR]

This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2–3.8 %, and within-laboratory imprecision 1.7–5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies. [ABSTRACT FROM AUTHOR]

Background: Despite adverse prognoses of type 2 myocardial infarction and myocardial injury, an effective, practical risk stratification method remains an unmet clinical need. We sought to develop an efficient clinical bedside tool for estimating the risk of major adverse cardiovascular events at 180 days for this patient population.Methods: The derivation cohort included patients with type 2 myocardial infarction or myocardial injury admitted to a tertiary hospital between 2012 and 2013 (n = 611). The primary outcome was a major adverse cardiovascular event (death or readmission for heart failure or myocardial infarction). The score included clinical variables significantly associated with the outcome. External validation was conducted using the UTROPIA cohort (n = 401).Results: The TARRACO Score included cardiac troponin (cTn) concentrations and 5 independent clinical predictors of adverse cardiovascular events: age, hypertension, absence of chest pain, dyspnea, and anemia. The score exhibited good discriminative accuracy (area under the curve = 0.74; 95% CI, 0.70-0.79). Patients were classified into low-risk (score 0-6) and high-risk (score ≥7) categories. Major adverse cardiovascular events rates were 5 times more likely in high-risk patients compared with those at low risk (78.9 vs 15.4 events/100 patient-years, respectively; logrank P < .001). The external validation showed equivalent prognostic capacity (area under the curve=0.71, 0.65-0.78).Conclusion: A novel risk score based on bedside clinical variables and cTn concentrations allows risk stratification for death and cardiac-related rehospitalizations in patients with type 2 myocardial infarctions and myocardial injury. This score identifies patients at the highest risk of adverse events, a subset of patients who may benefit from close observation, medical intensification, or both. [ABSTRACT FROM AUTHOR]

Objectives Our purpose was to determine a) overall and sex-specific 99th percentile upper reference limits (URL) and b) influences of statistical methods and comorbidities on the URLs. Methods Heparin plasma from 838 normal subjects (423 men, 415 women) were obtained from the AACC (Universal Sample Bank). The cobas e602 measured cTnT (Roche Gen 5 assay); limit of detection (LoD), 3 ng/L. Hemoglobin A1c (URL 6.5%), NT-proBNP (URL 125 ng/L) and eGFR (60 mL/min/1.73m 2 ) were measured, along with identification of statin use, to better define normality. 99th percentile URLs were determined by the non-parametric (NP), Harrell-Davis Estimator (HDE) and Robust (R) methods. Results 355 men and 339 women remained after exclusions. Overall < 50% of subjects had measureable concentrations ≥ LoD: 45.6% no exclusion, 43.5% after exclusion; compared to men: 68.1% no exclusion, 65.1% post exclusion; women: 22.7% no exclusion, 20.9% post exclusion. The statistical method used influenced URLs as follows: pre/post exclusion overall, NP 16/16 ng/L, HDE 17/17 ng/L, R not available; men NP 18/16 ng/L, HDE 21/19 ng/L, R 16/11 ng/L; women NP 13/10 ng/L, HDE 14/14 ng/L, R not available. Conclusions We demonstrated that a) the Gen 5 cTnT assay does not meet the IFCC guideline for high-sensitivity assays, b) surrogate biomarkers significantly lowers the URLs and c) statistical methods used impact URLs. Our data suggest lower sex-specific cTnT 99th percentiles than reported in the FDA approved package insert. We emphasize the importance of detailing the criteria used to include and exclude subjects for defining a healthy population and the statistical method used to calculate 99th percentiles and identify outliers. [ABSTRACT FROM AUTHOR]

Compared with patients with baseline undetectable (

We sought to determine the prevalence and correlates of conventional and expanded adverse childhood experiences (ACEs), including exposure to violence and racism, in perinatal women with mental illness. 133 perinatal women with mental illness completed the original ACEs (conventional ACEs) survey and the 6-question adverse environmental experiences (expanded ACEs) survey from the Philadelphia ACEs study. Associations between racial groups and ACE scores, mental health and psychosocial variables were evaluated. Subjects were predominantly white (68%) and married/partnered (66%), and 57% had at least 4 conventional ACEs. Compared to White women, Black women were significantly more likely to report conventional and expanded ACEs including experiencing racism and witnessing violence. Early life adversity was exceedingly common among pregnant and postpartum women with moderate to severe mental illness. Childhood exposure to racism and environmental trauma are important risk categories for perinatal mental illness. [ABSTRACT FROM AUTHOR]

Background: Limited data exist on rapid risk-stratification strategies using the U.S. Food and Drug Administration-cleared high-sensitivity cardiac troponin I (hs-cTnI) assays.Objectives: This study sought to examine single measurement hs-cTnI to identify patients at low and high risk for acute myocardial infarction (MI).Methods: This was a prospective, multicenter, observational study of patients with suspected acute MI enrolled across 29 U.S. sites with hs-cTnI measured using the Atellica IM TnIH and ADVIA Centaur TNIH (Siemens Healthineers) assays. To identify low-risk patients, sensitivities and negative predictive values (NPVs) for acute MI and MI or death at 30 days were examined across baseline hs-cTnI concentrations. To identify high-risk patients, positive predictive values and specificities for acute MI were evaluated.Results: Among 2,212 patients, acute MI occurred in 12%. The limits of detection or quantitation resulted in excellent sensitivities (range 98.6% to 99.6%) and NPVs (range 99.5% to 99.8%) for acute MI or death at 30 days across both assays. An optimized threshold of <5 ng/l identified almost one-half of all patients as low risk, with sensitivities of 98.6% (95% confidence interval: 97.2% to 100%) and NPVs of 99.6% (95% confidence interval: 99.2% to 99.9%) for acute MI or death at 30 days across both assays. For high-risk patients, hs-cTnI ≥120 ng/l resulted in positive predictive values for acute MI of ≥70%.Conclusions: Recognizing the continuous relationship between baseline hs-cTnI and risk for adverse events, using 2 Food and Drug Administration-cleared hs-cTnI assays, an optimized threshold of <5 ng/l safely identified almost one-half of all patients as low risk at presentation, with hs-cTnI ≥120 ng/l identifying high-risk patients. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to examine the appropriateness of cardiac troponin (cTn) testing among patients with cTn increases.Methods: This is a planned secondary analysis of the Use of TROPonin In Acute coronary syndromes (UTROPIA, NCT02060760) observational cohort study. Appropriateness of cTn testing was adjudicated for emergency department patients with cTn increases >99th percentile and analyzed using both contemporary and high-sensitivity (hs) cTnI assays according to sub-specialty, diagnoses, and symptoms.Results: Appropriateness was determined from 1272 and 1078 adjudication forms completed for 497 and 422 patients with contemporary and hs-cTnI increases, respectively. Appropriateness of cTnI testing across adjudication forms was 71.5% and 72.0% for cTnI and hs-cTnI, respectively. Compared with emergency physicians, cardiologists were less likely to classify cTnI orders as appropriate (cTnI: 79% vs 56%, P < .0001; hs-cTnI: 82% vs 51%, P < .0001). For contemporary cTnI, appropriateness of 95%, 70%, and 39% was observed among adjudication forms completed by cardiologists for type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively; compared with 90%, 86%, and 71%, respectively, among emergency physicians. Similar findings were observed using hs-cTnI. Discordance in appropriateness adjudication forms occurred most frequently in cases of myocardial injury (62% both assays) or type 2 myocardial infarction (cTnI 31%; hs-cTnI 23%).Conclusions: Marked differences exist in the perception of what constitutes appropriate clinical use of cTn testing between cardiologists and emergency physicians, with emergency physicians more likely to see testing as appropriate across a range of clinical scenarios. Discordance derives most often from cases classified as myocardial injury or type 2 myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Studies addressing patients with type 2 myocardial infarction and myocardial injury, including the impact of using high-sensitivity (hs) cardiac troponin (cTn) assays on their incidence are needed.Methods: Ours is a prospective, observational US cohort study. Consecutive emergency department patients with serial cTnI measurements were studied. Outcomes included 180-day mortality and major adverse cardiac events, including 2-year follow-up for those with myonecrosis.Results: Among 1640 patients, using a contemporary cTnI assay, 30% (n = 497) had ≥1 cTnI >99th percentile, with 4.7% (n = 77), 8.5% (n = 140), and 17% (n = 280) classified as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Compared with patients without myonecrosis, 180-day mortality was higher for type 2 myocardial infarction (4% vs 13%, P < .0001) (adjusted hazard ratio 2.7; 95% confidence interval, 1.6-4.8; P = .0005) and myocardial injury (4% vs 11%, P < .0001) (adjusted hazard ratio 1.8; 95% confidence interval, 1.1-3.0; P = .02), both with mortality >20% at 2 years. Predictors of 2-year mortality for type 2 myocardial infarction included age, congestive heart failure, and beta-blockers. Relative to the contemporary cTnI assay, hs-cTnI had less myonecrosis (30% vs 26%, P = .003) and acute myocardial infarction (13.2% vs 10.8%, P = .032), including fewer type 2 myocardial infarctions (8.5% vs 6.3, P = .01), with no difference in myocardial injury (17% vs 15%, P = .1).Conclusions: cTnI increases are encountered in approximately a third of patients, the majority due to nonatherothrombotic conditions. Compared with patients without myonecrosis, type 2 myocardial infarction and myocardial injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs-cTnI assay does not lead to more myocardial injury or infarction. [ABSTRACT FROM AUTHOR]

Introduction: High sensitivity cardiac troponin (hs-cTn) assays are able to quantitate low concentrations of cTn and provide an opportunity to rule out acute myocardial infarction (MI) at an early stage following a patient's presentation to an emergency department. Hypothesis: The objectives of the current study were to examine the performance of single hs-cTnI measurement strategy to rule out acute MI and predict 30-day safety outcomes at presentation in these patients. Methods: This was a prospective, observational study of patients (n = 2342) presenting to US emergency departments with suspected acute coronary syndrome in whom cTnI measurements were obtained using the Siemens Atellica IM High Sensitivity Troponin I Assay (Siemens Healthcare Diagnostics). Clinical data and hs-cTnI results were analyzed to determine: 1) clinical sensitivity and negative predictive value (NPV) for ruling out acute MI and 2) safety outcomes of acute MI and death at 30 days, using the hs-cTnI limit of detection (LoD) 1.6 ng/L concentration. Results: Acute MI occurred in 306 patients (13.1%). In patients with a hs-cTnI

Renal dysfunction is known to increase the risk of cardiovascular events such as acute myocardial infarction (MI). The goals of the current study were to evaluate, according to varying renal function, the diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay both for MI and for outcomes in patients presenting to the emergency department with symptoms suggestive of ischemia. Enrolled were 1555 consecutive patients who presented to the emergency department with clinical indications suggestive of MI, with at least two hs-cTnI measurements (UTROPIA; NCT02060760). hs-cTnI was measured on the Abbott ARCHITECT using sex-specific 99th percentile upper reference limits (URL: female 16 ng/L; male 34 ng/L). MI was adjudicated along universal MI guidelines. One-hundred-eighty-day mortality outcomes were determined. Renal function was defined by eGFR (mL/min/1.73m2; MDRD). Categorical variables were compared using Pearson χ-square test and continuous variables were compared using the F-test. Cox model assessed mortality with respect to both renal insufficiency and cTn together. Sensitivities (0h 68%, 3h 92%, 6h 94%) and negative predictive values (NPVs; 0h 97%, 3 and 6h >99%) were not significantly affected by renal function. However, specificities decreased with impaired renal function; ranging 90%-92% with normal renal function (eGFR ≥60; n = 1168); 68%-79% with impaired renal function (eGFR ≥30–59; n = 227); 56–60% with severely impaired renal function (eGFR <30; n = 83); 40%-42% in the dialysis group (n = 77). Positive predictive values (PPVs) also decreased with decreasing renal function; ranging 45%-57% with normal renal function, 35%-50% with impaired renal function; 29%-44% with severely impaired renal function; 15%-32% on dialysis. One-hundred-eighty-day all-cause mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, 10.4%) and was significantly higher in patients with hs-cTnI greater than sex-specific URLs (11.7%) compared to patients with concentrations between their sex-specific URL and the LOD (6.2%) vs concentrations less than LOD (1.1%). In conclusion, our results suggest that renal dysfunction and dialysis treatment reduced the rule-in performance of hs-cTnI for AMI, and that mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction. [ABSTRACT FROM AUTHOR]

Background: This study examined the performance of single high-sensitivity cardiac troponin I (hs-cTnI) measurement strategies to rule out acute myocardial infarction.Methods: This was a prospective, observational study of consecutive patients presenting to the emergency department (n = 1631) in whom cTnI measurements were obtained using an investigational hs-cTnI assay. The goals of the study were to determine 1) negative predictive value (NPV) and sensitivity for the diagnosis of acute myocardial infarction, type 1 myocardial infarction, and type 2 myocardial infarction; and 2) safety outcome of acute myocardial infarction or cardiac death at 30 days using hs-cTnI less than the limit of detection (LoD) (<1.9 ng/L) or the High-STEACS threshold (<5 ng/L) alone and in combination with normal electrocardiogram (ECG).Results: Acute myocardial infarction occurred in 170 patients (10.4%), including 68 (4.2%) type 1 myocardial infarction and 102 (6.3%) type 2 myocardial infarction. For hs-cTnIConclusion: Strategies using a single hs-cTnI alone or in combination with a normal ECG allow the immediate identification of patients unlikely to have acute myocardial infarction and who are at very low risk for adverse events at 30 days. [ABSTRACT FROM AUTHOR]