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Biomedical subjects

Alan H B Wu

Publications and source records attributed to Alan H B Wu.

At least 19 recordsLinked to original sources
PubMed2025

Multicenter Evaluation of a New Strip-Based Blood Glucose System for Point-of-Care Testing in Critical and Non-Critical Care Settings.

BACKGROUND: Evaluation of the performance of Cobas® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. METHODS: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. RESULTS: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO2, hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. CONCLUSIONS: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

Humans↗
PubMed2007

N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease.

CONTEXT: Identification of individuals at high risk for cardiovascular events is important for the optimal use of primary and secondary prevention measures. OBJECTIVE: To determine whether plasma levels of amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular events or death independent of other available prognostic tests. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (2000-2002) of 987 individuals in California with stable coronary heart disease in the Heart and Soul Study, who were followed up for a mean of 3.7 (range, 0.1-5.3) years. MAIN OUTCOME MEASURES: The association of baseline NT-proBNP levels with death or cardiovascular events (myocardial infarction, stroke, or heart failure). Traditional clinical risk factors, echocardiographic measures, ischemia, other biomarkers, and New York Heart Association classification were adjusted for to determine whether NT-proBNP levels were independent of other prognostic factors. Receiver operating characteristic (ROC) curves were used to assess the incremental prognostic value of adding NT-proBNP level to these other measures. RESULTS: A total of 256 participants (26.2%) had a cardiovascular event or died. Each increasing quartile of NT-proBNP level (range of quartile 1, 8.06-73.95 pg/mL; quartile 2, 74-174.5 pg/mL; quartile 3, 175.1-459 pg/mL; quartile 4, > or =460 pg/mL) was associated with a greater risk of cardiovascular events or death, ranging from 23 of 247 (annual event rate, 2.6%) in the lowest quartile to 134 of 246 (annual event rate, 19.6%) in the highest quartile (unadjusted hazard ratio [HR] for quartile 4 vs quartile 1, 7.8; 95% confidence interval [CI], 5.0-12.1; P<.001). Each SD increase in log NT-proBNP level (1.3 pg/mL) was associated with a 2.3-fold increased rate of adverse cardiovascular outcomes (unadjusted HR, 2.3; 95% CI, 2.0-2.6; P<.001), and this association persisted after adjustment for all of the other prognostic measures (adjusted HR, 1.7; 95% CI, 1.3-2.2; P<.001). The addition of NT-proBNP level to standard clinical assessment and complete echocardiographic parameters significantly improved the area under the ROC curves for predicting subsequent adverse cardiovascular outcomes (0.80 for clinical risk factors and echocardiographic parameters plus log NT-proBNP vs 0.76 for clinical risk factors and echocardiographic parameters only; P = .006). CONCLUSIONS: Elevated levels of NT-proBNP predict cardiovascular morbidity and mortality, independent of other prognostic markers, and identify at-risk individuals even in the absence of systolic or diastolic dysfunction by echocardiography. Level of NT-proBNP may help guide risk stratification of high-risk individuals, such as those with coronary heart disease.

Aged↗
PubMed2006

Toward standardization of cardiac troponin I measurements part II: assessing commutability of candidate reference materials and harmonization of cardiac troponin I assays.

BACKGROUND: Cardiac tropoin I (cTnI) measurements show an approximately 20- to 40-fold difference between assays, and better standardization and harmonization are needed. Toward this goal, the AACC cTnI Standardization Committee collaborated with the National Institute of Standards and Technology (NIST) in an earlier study to select 2 candidate reference materials (cRMs). METHODS: Two troponin cRMs, a troponin C-troponin I-troponin T (CIT) complex from human heart tissue and a CIT complex from recombinant technology, were supplied to NIST for assessment of composition and purity, and cTnI value assignment. These cRMs and 6 cTnI-positive human serum pools were shipped to manufacturers of 15 cTnI assays. Commutability of the materials was examined by determining the numerical relationship for the cRM preparations between each manufacturer-specified field method and each of the other 14 field methods. These relationships were then compared with the corresponding numerical relationships for the human serum pools. Harmonization of methods was accomplished by determining regression parameters relative to the analytical system yielding values closest to the median for each serum pool. These regression parameters were used to recalculate pool values to harmonize the assays. Interassay CVs before and after harmonization were determined. RESULTS: Characterization of the CIT and CI cRMs showed that these materials were of specified composition. The proportion of cTnI methods that demonstrated commutability for the CIT cRM was 45%; for the CI cRM, 39% of methods demonstrated commutability. Interassay cTnI variability for the field methods ranged from 82% to 97%, median 88%. After harmonization, variability of the serum pools for the cTnI methods was decreased to between 9.0% and 23%, median 15.5%. CONCLUSIONS: The proportion of methods demonstrating commutability was too low for use as a common calibrator for the cTnI field methods. However a simple strategy using serum pools can improve harmonization of field cTnI methods by more than 5-fold. The CIT cRM was selected by the AACC cTnI standardization committee, and a new lot has been classified as the cTnI certified reference material Standard Reference Material 2921 by NIST.

Calibration↗
PubMed2006

A selected history and future of immunoassay development and applications in clinical chemistry.

BACKGROUND: The first immunoassay was described by Berson and Yalow in 1959. Their work resulted in their receipt of the Nobel Prize in Medicine in 1977. Since this introduction, immunoassays have evolved considerably. METHODS: There have been several milestones that have led to the proliferation of modern immunoassays. The development of monoclonal antibodies from mouse hydridoma cells by Millstein and Kohler (Nobel Prize in 1984) enabled the production of high quantities of antibodies with well characterized epitope specificity. The first homogenous immunoassay (no separation step required) was the Enzyme Multiplied Immunoassay Technique (EMIT), which enabled adaptation of this assay onto automated chemistry platforms. EMIT was also one of the first immunoassay that made use of non-isotopic labels. Other non-isotopic labels became available such as chemiluminescence to improve the analytical sensitivity of immunoassays. The advantages of high-sensitivity immunoassays have created expanded diagnostic roles for some existing assays such as thyroid stimulating hormone for hyperthyroidism, C-reactive protein for cardiovascular risk assessment, and other applications. The development of instrumentation capable of automated heterogeneous immunoassays (separation step to improve sensitivity) has enabled movement of this technology from the "special chemistry" sections of a clinical laboratory into the "core" laboratory with other high-volume testing. CONCLUSION: Today, immunoassays play a prominent role in the analysis of many clinical laboratory analytes such as proteins, hormones, drugs, and nucleic acids. The future involves development of assays with higher sensitivities which will enable the discovery of new biomarkers for disease diagnosis, and technology that will enable simultaneous multimarker analysis of tests whose needs are naturally grouped together (e.g., cytokines and allergens).

Animals↗
PubMed2006

Influence of imprecision on ROC curve analysis for cardiac markers.

BACKGROUND: There has been considerable debate regarding the impact of assay imprecision on the performance of cardiac biomarkers for diagnosis of acute coronary syndromes (ACS) and risk stratification for future adverse cardiac events. METHODS: Using existing data from 2 published clinical trials, we used a resampling method to statistically introduce 5%, 10%, and 20% imprecision to results for B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) and examined its impact on ROC curve analysis. RESULTS: Superimposition of artificial imprecision produced no significant difference in the area under the ROC curve observed for BNP for diagnosis of heart failure or for cTnI for 30-day risk stratification of patients with ACS. CONCLUSION: Assay imprecision does not appear to be a critical determinant in the interpretation of cardiac marker results for patients with heart disease.

Acute Disease↗
PubMed2006

How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study.

BACKGROUND: B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. METHODS: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. RESULTS: Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients. CONCLUSIONS: Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP > or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to increase specificity.

Acute Disease↗
PubMed2006

Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results.

BACKGROUND: B-Type natriuretic peptide (BNP) and NTpro-BNP are widely used for diagnosis and risk stratification of patients with heart failure (HF). Although not currently cleared by the Food and Drug Administration as a test indication, there is interest in using these biomarkers for monitoring the success of HF medications. An assessment of the analytical and biologic variations is necessary to interpret the results of serial testing. METHODS AND RESULTS: The intra-individual biologic variances and analytical assay variances of BNP and NT-proBNP from healthy subjects and those with stable HF were reviewed. The analytical variability of BNP and NT-proBNP assays was reported, as some have suggested that only the analytical variance is important in interpreting the results of tightly regulated hormones. The reference change values (RCV) for serial measurements were derived and used to interpret results of therapeutic studies whereby serial changes in BNP and NT-proBNP concentrations were obtained to evaluate the therapeutic success of short-term (inpatient) and long-term (outpatient) management. The use of RCV may also be important in studies comparing BNP-guided versus physician-guided HF drug therapy. CONCLUSIONS: Relative to the RCV, short-term therapeutic studies of inpatients have largely resulted in a statistically significant decline in BNP and NT-proBNP with clinical evidence of patient improvements. In contrast, many therapeutic studies involving long-term outpatient monitoring have produced changes in BNP/NT-proBNP that do not exceed the biologic variances. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels.

Adult↗
PubMed2006

Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study.

PURPOSE: B-type natriuretic peptide is known to correlate with hemodynamic state, presence and severity of congestive heart failure, and prognosis. Although low-range B-type natriuretic peptide less than 100 pg/mL has a high negative predictive value (90%), and high-range B-type natriuretic peptide greater than 500 pg/mL has a high positive predictive value (87%), there remains some ambiguity in the interpretation of results in the medium range (100-500 pg/mL). We hypothesized that taking into account the history of congestive heart failure along with other clinical variables would be helpful in this range of B-type natriuretic peptide levels. METHOD: The Breathing Not Properly Multicenter Study was an international, 7-center, prospective study including 1475 patients with a mean age of 63 years (57% were male, and 54% were female); 35% of patients with a history of congestive heart failure were enrolled, and a final diagnosis of congestive heart failure was made in 46%. The index criteria was defined as positive if any 2 index findings (ie, history of coronary artery disease, lower extremity edema, pulmonary edema, cephalization of the pulmonary arteries, and cardiomegaly) were present. RESULTS: The interval likelihood ratios (LR) for low, medium, and high B-type natriuretic peptide ranges are 0.13, 1.85, and 8.1, respectively. For medium B-type natriuretic peptide levels a positive history of congestive heart failure makes the diagnosis of congestive heart failure more probable with a cumulative LR of 4.3. Also in this range a positive index criterion was strongly indicative of congestive heart failure even in the absence of a history of congestive heart failure (LR 3.3). Where there are both a positive history of congestive heart failure and a positive index criteria for the medium B-type natriuretic peptide group, the cumulative LR (10.2) is similar to that of a high B-type natriuretic peptide level (8.1). CONCLUSION: Even in the medium range (100-500 pg/mL), when using the history of congestive heart failure and index criteria, B-type natriuretic peptide can be a powerful diagnostic tool in the hands of clinicians in the emergency department.

Aged↗
PubMed2006

Incomplete recovery of prescription opioids in urine using enzymatic hydrolysis of glucuronide metabolites.

Confirmation of opioids in urine samples of clinical patients requires liberation of opioids from their glucuronide conjugates. Both acid hydrolysis and enzyme hydrolysis using beta-glucuronidase from various sources have been reported, with the latter approach prevailing in most clinical toxicology laboratories. The goal of this study was to compare the efficiency of acid versus different enzyme hydrolysis methods in recovering morphine and common semisynthetic opioids from glucuronide standards and 78 patient urine samples that were screened positive for opioids as a class. Specimens were analyzed with a validated gas chromatography-mass spectrometry (GC-MS) procedure. With the exception of oxycodone, the results indicated that the majority of opioids tested were extensively glucuronide-conjugated in urine. Significantly, acid hydrolysis liberated > 90% of morphine and hydromorphone from their glucuronide standards but enzyme hydrolysis had lower and variable efficiency, depending on the opiate type and the enzyme source. In patient specimens, much higher concentrations of free codeine, morphine, hydromorphone, and oxymorphone were obtained with acid hydrolysis than with various enzyme methods. Incomplete hydrolysis using beta-glucuronidase could lead to false-negative results for many opioids when urine is tested for drugs of abuse. We conclude that acid hydrolysis is the method of choice for GC-MS confirmation of urine opioids.

Analgesics, Opioid↗
PubMed2006

Cardiovascular predictors of in-patient mortality after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Whether cardiac dysfunction contributes to morbidity and mortality after subarachnoid hemorrhage (SAH) remains controversial. The objective of this study was to test the hypothesis that cardiovascular abnormalities are independently related to in-patient mortality after SAH. METHODS: This was a prospective cohort study of patients with aneurysmal SAH. Heart rate and blood pressure were measured, a blood sample was obtained, and echocardiography was performed on three study days, starting as soon after admission as possible. The cardiovascular predictor variables were heart rate, systolic blood pressure (SBP), cardiac troponin I (cTi) level, B-type natriuretic peptide (BNP) level, and left ventricular ejection fraction. The primary outcome measure was in-patient mortality. The association between each predictor variable and mortality was quantified by multivariate logistic regression, including relevant covariates and reporting odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The study included 300 patients. An initial BNP level greater than 600 pg/mL was markedly associated with death (OR 37.7, p < 0.001). On the third study day (9.1 +/- 4.1 days after SAH symptom onset), a cTi level greater than 0.3 mg/L (OR 7.6, p = 0.002), a heart rate of 100 bpm or greater (OR 4.9, p = 0.009), and a SBP less than 130 mmHg (OR 6.7, p = 0.007) were significantly associated with death. CONCLUSIONS: Cardiovascular abnormalities are independent predictors of in-patient mortality after SAH. Though these effects may be explained by a reduction in cerebral perfusion pressure or other mechanisms, further research is required to determine whether or not they are causal in nature.

Adult↗
PubMed2005

B-type natriuretic peptide levels in patients in the emergency department with possible heart failure and previous stable angina pectoris and/or healed myocardial infarction.

We examined the relation between B-type natriuretic peptide (BNP) levels and a history of stable angina pectoris and/or healed myocardial infarction in 1,240 patients who were evaluated in the emergency department for possible heart failure. In patients who had heart failure, there was no relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction. However, in patients who did not have heart failure, there was a relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction but no significant independent relation in multiple regression analysis.

Adult↗
PubMed2005

Impact of atrial fibrillation on the diagnostic performance of B-type natriuretic peptide concentration in dyspneic patients: an analysis from the breathing not properly multinational study.

OBJECTIVES: This study was designed to assess the diagnostic performance of B-type natriuretic peptide (BNP) in the diagnosis of acute congestive heart failure (CHF) in patients with permanent/paroxysmal atrial fibrillation (AF) presenting with acute dyspnea. BACKGROUND: It is unknown to what extent AF affects the diagnostic performance of BNP in patients presenting with acute dyspnea. METHODS: We studied 1,431 patients drawn from a cohort of patients (n = 1,586) with acute dyspnea who had BNP levels measured on arrival. Patients were prospectively classified according to the presence or absence of permanent/paroxysmal AF. RESULTS: In total, 292 patients had permanent/paroxysmal AF. In patients without HF, permanent/paroxysmal AF was associated with significantly higher BNP levels (p = 0.001). Conversely, in patients with HF, BNP levels did not differ significantly between patients with and without AF (p = 0.533). A BNP cutoff value of 100 pg/ml had a specificity of 40% and 79% for the diagnosis of acute HF in patients with and without AF, respectively. The areas under the receiver-operating characteristic curves were 0.84 (95% confidence interval 0.78 to 0.89) and 0.91 (95% confidence interval 0.89 to 0.93) for patients with and without AF, respectively. CONCLUSIONS: In patients without, but not in those with HF, the presence of AF is associated with higher circulating BNP levels, suggesting that a higher diagnostic threshold should be used in patients with AF.

Acute Disease↗
PubMed2005

Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.

Acute Disease↗
PubMed2005

Relationship of B-type natriuretic peptide and anemia in patients with and without heart failure: a substudy from the Breathing Not Properly (BNP) Multinational Study.

While anemia is a significant risk factor for poor outcomes in patients with heart failure (HF), it is not in defined guidelines for HF assessment. B-type natriuretic peptide (BNP) is a marker for diagnosis and management of patients with HF. We determined the incidence of anemia in patients with HF and the relationship between BNP and hemoglobin (Hgb) levels in patients with and without HF. Results from the Breathing Not Properly Multinational Trial consisted of 1,586 patients presenting to the emergency department (ED) with dyspnea. Because renal insufficiency is a confounding variable for BNP, patients with a creatinine of >or=2.0 mg/dL were excluded. The remaining data were evaluated from 620 non-HF patients (337 M, 283 F) and 547 HF patients (299 M, 248 F). The New York Heart Association (NYHA) HF classification and ejection fraction by echocardiography were assessed for HF patients. Blood was tested for Hgb, BNP, and creatinine. Using World Health Organization criteria for anemia, we observed that HF patients in NYHA class III or IV had lower mean Hgb levels (12.5 g/dL, P < 0.05) and a higher incidence of anemia (48.2%, P < 0.05) than did HF patients in class I or II (13.4 g/dL and 33.9%, respectively). There was no correlation between Hgb and log BNP for females without HF or the aggregate of all HF patients. In contrast, a significant inverse correlation was observed for males without HF (P < 0.001). Although there were differences in the BMI, age, and estimated glomerular filtration rate (eGFR) versus Hgb observed in this group, the log BNP correlation remained significant after multivariate analysis. A significant inverse correlation for log BNP and Hgb were also observed for diastolic (EF >or= 50) HF (P < 0.05) that was also not accounted for by the BMI, age, or eGFR. The presence of anemia is associated with worsening HF at ED presentation. For males without HF and diastolic HF patients of both genders, a low Hgb may be a confounding variable toward increasing BNP. Among systolic HF patients, the presence of a low hemoglobin concentration is not a factor in the interpretation of BNP results.

Anemia↗
PubMed2005

Predictors of elevated B-type natriuretic peptide concentrations in dyspneic patients without heart failure: an analysis from the breathing not properly multinational study.

STUDY OBJECTIVE: B-type natriuretic peptide (BNP) is an established tool for the diagnosis of acute congestive heart failure in patients presenting with dyspnea. Some patients have moderately elevated BNP levels (ie, 100 to 500 pg/mL) in the absence of acute congestive heart failure. The objective of the current study was to identify independent predictors of elevated BNP concentrations in the absence of congestive heart failure. METHODS: We studied 781 patients without acute congestive heart failure and BNP levels 0 to 500 pg/mL drawn from a cohort of 1,586 patients with acute dyspnea who had BNP levels measured on emergency department arrival. Two cardiologists blinded to BNP results reviewed all clinical data and categorized patients according to whether they had acute congestive heart failure or not. RESULTS: Independent predictors of elevated BNP levels (ie, >100 pg/mL) were a medical history of atrial fibrillation, radiographic cardiomegaly, decreased blood hemoglobin concentration, decreased body mass index, and increased age. CONCLUSION: Knowledge of these commonly obtained variables should aid clinicians in the interpretation of moderately elevated BNP results in patients presenting with acute dyspnea in the emergency department.

Aged↗