Search

Objective: Estimated glomerular filtration rate (eGFR) calculated by cystatin C (cysC) has been recommended for broader adoption. This study assessed the discrepancy between eGFR calculated by cysC (eGFRcys) and creatinine (eGFRcr) in different patient care settings and explored potential contributing factors to such discrepancies., Methods: This retrospective study included 2072 patients with paired cysC and creatinine results in different patient care settings. Delta eGFRcr-cys (eGFRcr - eGFRcys) was analyzed in relationship to patient care settings and the Elixhauser Comorbidity index. The 90-day survival in patients with different delta eGFR was assessed by Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard models. In addition, discrepancy between eGFRcys and eGFRcr was analyzed in 50 ambulatory patients with systemic inflammation but normal kidney function., Results: Inpatients had higher cysC (median 1.91 mg/L), lower eGFRcys (median 31 mL/min/1.73 m 2 ), and larger delta eGFRcr-cys (median 18 mL/min/1.73 m 2 ) than outpatients (cysC median 1.53 mg/L, p < 0.0001, eGFRcys median 41 mL/min/1.73 m 2 , p < 0.0001, delta eGFRcr-cys median 4 mL/min/1.73 m 2 , p < 0.0001). Higher Elixhauser Comorbidity index correlated with lower eGFRcys and larger delta eGFRcr-cys, with median delta eGFRcr-cys 11 and 6 mL/min/1.73 m 2 in patients with a Comorbidity index > 15 and ≤ 15, respectively (p < 0.0001). Increased delta eGFRcr-cys was associated with worse 90-day survival. Patients with systemic inflammation but normal kidney function had lower eGFRcys (median 77.5 mL/min/1.73 m 2 ) than eGFRcr (median 97 mL/min/1.73 m 2 , p < 0.001), with red blood cell abnormalities as associated factors., Conclusion: Inflammation and comorbidities are associated with decreased eGFRcys and large discrepancies between eGFRcr and eGFRcys independent of kidney function and are most apparent in inpatients. Creatinine-cysC combined eGFR reduces this discrepancy and should be broadly adopted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: Complete blood count and differential (CBC diff) is a common laboratory test that may be overused or misordered, particularly in an inpatient setting. We assessed the ability of a clinical decision support (CDS) alert to decrease unnecessary orders for CBC diff and analyzed its impact in the laboratory., Methods: We designed 3 CDS alerts to provide guidance to providers ordering CBC diff on inpatients at frequencies of daily, greater than once daily, or as needed., Results: The 3 alerts were highly effective in reducing orders for CBC diff at the frequencies targeted by the alert. Overall, test volume for CBC diff decreased by 32% (mean of 5257 tests per month) after implementation of the alerts, with a corresponding decrease of 22% in manual differentials performed (mean of 898 per month). Turnaround time for manual differentials decreased by a mean of 41.5 minutes, with a mean decrease of up to 90 minutes during peak morning hours., Conclusions: The 3 CDS alerts successfully decreased inpatient orders for CBC diff and improved the quality of patient care by decreasing turnaround time for manual differentials., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening., Competing Interests: Declaration of interests M.G. Best, R.J.A.N., and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc., and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To select and standardize point-of-care (POC) glucose meters across a multi-hospital system., Methods: We formed a multidisciplinary POC glucose standardization working group including key stakeholders from each site. A set of selection criteria: usability, clinical and laboratory performance, indications for use, interface connectivity, ease of implementation and ongoing operational costs were used to develop a scoring schemato facilitate a consensus-driven selection process., Results: Method comparison and consensus error grid evaluation against the clinically validated reference methods demonstrated that the analytical performance for all candidate meters was comparable for both the laboratory and clinical evaluation. However, Meter 1 ranked highest in usability evaluations, implementation and streamlined interface connectivity. The meter selection process and implementation were staggered across sites due to complexity of transitioning to a new manufacturer's meter and limitations in vendor support for training and ongoing troubleshooting of interface connectivity., Conclusions: Standardization of POC glucose meters in a large multi-hospital system is a complex undertaking requiring robust, multidisciplinary organizational structure both system-wide and locally, development of consensus-driven selection tools, usability evaluation by end-users, laboratory and clinical evaluation of the analytical performance, and a strong vendor-laboratory partnership during the implementation process., (Copyright © 2022. Published by Elsevier B.V.)

Background: Anaplasmosis presents with fever, headache, and laboratory abnormalities including leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) is the preferred diagnostic but is overutilized. We determined if routine laboratory tests could exclude anaplasmosis, improving PCR utilization., Methods: Anaplasma PCR results from a 3-year period, with associated complete blood count (CBC) and liver function test results, were retrospectively reviewed. PCR rejection criteria, based on white blood cell (WBC) and platelet (PLT) counts, were developed and prospectively applied in a mock stewardship program. If rejection criteria were met, a committee mock-refused PCR unless the patient was clinically unstable or immunocompromised., Results: WBC and PLT counts were the most actionable routine tests for excluding anaplasmosis. Retrospective review demonstrated that rejection criteria of WBC ≥11 000 cells/µL or PLT ≥300 000 cells/µL would have led to PCR refusal in 428 of 1685 true-negative cases (25%) and 3 of 66 true-positive cases (5%) involving clinically unstable or immunocompromised patients. In the prospective phase, 155 of 663 PCR requests (23%) met rejection criteria and were reviewed by committee, which endorsed refusal in 110 of 155 cases (71%) and approval in 45 (29%), based on clinical criteria. PCR was negative in all 45 committee-approved cases. Only 1 of 110 mock-refused requests yielded a positive PCR result; this patient was already receiving doxycycline at the time of testing., Conclusions: A CBC-based stewardship algorithm would reduce unnecessary Anaplasma PCR testing, without missing active cases. Although the prospectively evaluated screening approach involved medical record review, this was unnecessary to prevent errors and could be replaced by a rejection comment specifying clinical situations that might warrant overriding the algorithm., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program., Methods: We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing., Results: We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features., Conclusions: This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

Objectives: Laboratory-based utilization management programs typically rely primarily on data derived from the laboratory information system to analyze testing volumes for trends and utilization concerns. We wished to examine the ability of an electronic health record (EHR) laboratory orders database to improve a laboratory utilization program., Methods: We obtained a daily file from our EHR containing data related to laboratory test ordering. We then used an automated process to import this file into a database to facilitate self-service queries and analysis., Results: The EHR laboratory orders database has proven to be an important addition to our utilization management program. We provide three representative examples of how the EHR laboratory orders database has been used to address common utilization issues. We demonstrate that analysis of EHR laboratory orders data has been able to provide unique insights that cannot be obtained by review of laboratory information system data alone. Further, we provide recommendations on key EHR data fields of importance to laboratory utilization efforts., Conclusion: We demonstrate that an EHR laboratory orders database may be a useful tool in the monitoring and optimization of laboratory testing. We recommend that health care systems develop and maintain a database of EHR laboratory orders data and integrate this data with their laboratory utilization programs., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

: Coagulation laboratories have largely stopped transporting whole blood specimens on ice, due to adverse effects on factor VIII, von Willebrand factor, and the prothrombin time. However, it is unknown whether ice should be required or avoided for other coagulation assays. Furthermore, the amount of time that specimens remain stable during transportation at room temperature (RT) is also largely unknown for many coagulation tests. Therefore, this study investigated specimen stability on ice and RT for a comprehensive panel of coagulation tests. One tube of whole blood from each volunteer (n = 22) was centrifuged immediately (time 0), one was stored for 4 h on ice, and one was stored for 4 h at RT before centrifugation. Among time 0, 4 h on ice, and 4 h at RT samples, no statistically significant differences were found for fibrinogen, activated protein C resistance, thrombin time, reptilase time, antithrombin activity, chromogenic protein C, factor XII, and antiplasmin activity. Prothrombin time, activated partial thromboplastin time, factors IX, XI, protein S activity, and plasminogen activity showed statistically, but not clinically, significant differences. On ice, the only analytes that showed clinically significant changes (≥6.0% from time 0) were factors VII, VIII, von Willebrand factor antigen, and ristocetin cofactor, which were 14.0% higher, and 19.2, 9.5, and 18.8% lower than time 0, respectively. At RT, all analytes were stable except factor VIII was 9.4% lower than time 0. Only factors II, V, X, and PTT-LA lupus anticoagulant showed a possible slight benefit from ice, but the statistically significant differences were not clinically significant. Ice did not substantially benefit any of the coagulation assays. All tests were stable at RT, except more study is needed regarding factor VIII.

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to address concerns regarding recurring inpatient laboratory test order practices (daily laboratory tests) through a multifaceted approach to changing ordering patterns., Methods: We engaged in an interdepartmental collaboration to foster mindful test ordering through clinical policy creation, electronic clinical decision support, and continuous auditing and feedback., Results: Annualized daily order volumes decreased from approximately 25,000 to 10,000 during a 33-month postintervention review. This represented a significant change from preintervention order volumes (95% confidence interval, 0.61-0.64; P < 10-16). Total inpatient test volumes were not affected., Conclusions: Durable changes to inpatient order practices can be achieved through a collaborative approach to utilization management that includes shared responsibility for establishing clinical guidelines and electronic decision support. Our experience suggests auditing and continued feedback are additional crucial components to changing ordering behavior. Curtailing daily orders alone may not be a sufficient strategy to reduce in-laboratory costs., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

To advance the development of point-of-care technology (POCT), the National Institute of Biomedical Imaging and Bioengineering established the POCT Research Network (POCTRN), comprised of Centers that emphasize multidisciplinary partnerships and close facilitation to move technologies from an early stage of development into clinical testing and patient use. This paper describes the POCTRN and the three currently funded Centers as examples of academic-based organizations that support collaborations across disciplines, institutions, and geographic regions to successfully drive innovative solutions from concept to patient care.

Objectives: The biomarker suppression of tumorigenicity 2 (ST2) is a well-established clinical biomarker of cardiac strain and is frequently elevated in a variety of cardiac conditions. Here, we sought to evaluate the prognostic value of ST2 in critically ill medical intensive care unit (MICU) patients without primary cardiac illness., Methods: We measured ST2 and high-sensitivity troponin T (hsTnT) on plasma specimens collected on 441 patients following admission to a noncardiac MICU and evaluated the prognostic power of ST2 both alone and in multivariate models., Results: Of these critically ill patients, 96% exhibited ST2 concentrations above the reference interval. ST2 concentrations were highly predictive of intensive care unit and hospital length of stay, as well as in-hospital mortality, with high concentrations predicting a poor prognosis. Rates of in-hospital mortality were more than four times higher in patients with ST2 concentrations in the highest compared with the lowest quartile. In multivariate analysis, ST2 remained an important predictor of death after adjustment for age, hsTnT, and common diagnoses., Conclusions: ST2 is increased and predictive of prognosis in critically ill patients without primary cardiac disease, suggesting that critically ill patients may often have unrecognized cardiac injury. Clinical decision support algorithms incorporating ST2 and hsTnT results may be useful in patient risk stratification., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: While acute kidney injury (AKI) can be diagnosed based on specified increases in a patient's plasma creatinine level, standard creatinine reporting methods typically only flag creatinine results as abnormal when outside the reference range and often fail to identify rising creatinine values indicative of AKI. Here, we evaluate the impact of this limitation in standard creatinine reporting and develop and implement an enhanced creatinine reporting algorithm., Methods: We evaluated 59,712 plasma creatinine results collected over approximately 3 months, using computational simulations and statistical analyses., Results: Our analyses demonstrated that 29% of creatinine results substantially increased over the patient's baseline and concerning for AKI remained within the normal reference range. These concerning results would not be flagged as abnormal using standard reporting. Likewise, we found that simple delta checks are also insensitive at AKI detection. To improve creatinine reporting, we developed and implemented an algorithm within our laboratory information system to alert clinicians to rising creatinine results, which we describe in this report., Conclusion: While both creatinine reference limits and simple delta checks are insensitive for AKI identification, a simple algorithm can be implemented within a common laboratory information system to enhance AKI identification., (Copyright© by the American Society for Clinical Pathology.)

Objectives: The scope of activities performed by clinical laboratory directors is sometimes unfamiliar to other physicians or hospital administrators. Consequently, hospital leadership may undervalue the role and assume that many director level activities could be delegated to a professional manager. In this study, we sought to define the activities of academic laboratory directors, and to determine which activities require doctorate level medical or scientific expertise., Methods: We performed an audit of laboratory director activities at a large academic medical center by reviewing electronic calendars and other available records from the preceding 12 consecutive months. For episodic activities, the directors estimated the average number of hours devoted over the 1-year period., Results: On average, directors worked 54.9 hours per week and performed at least some service work 47.7 weeks per year. Administrative duties accounted for the greatest proportion of effort (47.1%), followed by clinical activities (33.1%) and academic activities (19.8%). Among administrative duties, those that required doctorate level medical or scientific expertise comprised 60.3% of the total administrative effort, whereas the remaining 39.7% (18.7% of total activity) could be performed by a professional manager.., Conclusions: Although the activities of clinical laboratory directors have been described elsewhere, this is the first study detailing the effort allocated to these various activities in quantitative terms. The study demonstrated that less than 20% of an academic laboratory director's effort involves administrative activities that could potentially be performed by a professional manager lacking doctorate level medical or scientific expertise., (Copyright© by the American Society for Clinical Pathology.)

Background: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from Western populations. No data are available regarding expected values in Asian populations., Methods: A total of 1157 age- and sex-matched healthy individuals (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n = 565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT-proBNP. Median values were determined for each country and compared in unadjusted analyses and in analyses adjusted for age, sex, body mass index, study site, race, and vital signs., Results: Median hs-cTnT concentrations were slightly higher for individuals from the US than for those from Vietnam, but both were below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US participants had an hs-cTnT concentration above the limit of detection (57.2% vs 47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P = 0.54). Median NT-proBNP concentrations were slightly higher for US participants compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001). Following adjustment, differences in concentrations of NT-proBNP between healthy US and Vietnamese populations remained significant, whereas for hs-cTnT the differences were no longer significant. Inclusion of hs-cTnT values down to the limit of blank did not change the result., Conclusions: The differences in hs-cTnT and NT-proBNP between healthy individuals from the US and Vietnam are small. Previously derived reference intervals for both analytes may be applied in Asian populations.

Objectives: To assess the frequency, magnitude, and prognostic significance of elevations in cardiac troponin T in noncardiac critically ill patients, including elevations at levels below the limit of detection of traditional assays., Methods: Using a high-sensitivity assay, we measured troponin T (high-sensitivity troponin T [hsTnT]) in 451 unique patients within 12 hours of their admission to a noncardiac medical intensive care unit. Outcomes of patients, grouped by hsTnT level, were compared., Results: Overall, 98% of the study patients had detectable levels of hsTnT (>3 ng/L), and 33% had levels above the diagnostic cutoff of a traditional fourth-generation cardiac troponin T assay. Patient groups with higher hsTnT levels had markedly higher rates of in-hospital mortality (P < .001) and longer stays in the hospital and intensive care unit (P < .01)., Conclusions: In noncardiac critically ill patients, cardiac troponin T elevations are common but often at levels undetectable by traditional assays. hsTnT elevations predict a more complex clinical course and an increased risk of death.

The utility of blood biomarkers of cardiac myocyte damage such as troponin T and I in the evaluation of acute coronary syndromes and heart failure is well established. However, some of these markers may also be elevated in other conditions, such as myocarditis, cardiac transplant rejection, and several other conditions. Recognizing this phenomenon is essential to avoid misdiagnosis of acute coronary syndromes. Furthermore, identifying an elevated troponin level in patients without acute coronary syndrome or heart failure may often have diagnostic or prognostic significance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Laboratory testing for blood-based biomarkers of myocardial injury has steadily evolved over the past 60 years. Initial assays were cumbersome and were neither sensitive nor specific for myocardial necrosis. Major improvements have included the development of more cardiospecific markers, the introduction of random access immunoassays that facilitated near-real-time reporting of results, the development of rapid whole-blood point-of-care testing, and progressive improvements in assay design leading to modern high-sensitivity troponin assays that are now being introduced to the market. These new high-sensitivity assays will dramatically change the approach to patients presenting with acute coronary syndromes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Coronary heart disease is a common and costly epidemic in the Western world. Intensive study has led to a deeper understanding of the pathogenesis of coronary disease and risk stratification. Traditional risk factor assessment has focused on parameters derived from the Framingham Heart Study (age, hypertension, cholesterol, family history, and cigarette smoking). New emerging risk factors, both biological and genetic, are reshaping the understanding of heart disease and the approach to risk stratification. As these emerging assays become more standardized, automated, and inexpensive to perform, they are becoming increasingly important tools in the assessment and treatment of coronary heart disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Preanalytic laboratory testing errors are often difficult to identify. We demonstrate how laboratories can integrate statistical models with clinical judgment to develop protocols for preanalytic error detection. Specifically, we developed a protocol to identify spuriously elevated glucose values resulting from improper "line draws" or related phlebotomy errors. Using a decision tree-generating algorithm and an annotated set of training data, we generated decision trees to classify critically elevated glucose results as "real" or "spurious" based on available laboratory parameters. Decision trees revealed that a 30-day patient-specific average glucose concentration lower than 186.3 mg/dL (10.3 mmol/L), a current glucose concentration higher than 663 mg/dL (37 mmol/L), and an anion gap lower than 16.5 mEq/L (16.5 mmol/L) suggested a spurious result. We then used the results from the decision tree analysis to inform the implementation of a clinical protocol that significantly improved the laboratory's identification of spurious results. Similar approaches may be useful in developing protocols to identify other errors or to assist in clinical interpretation of results.

Background: Point-of-care devices for performing a prothrombin time/international normalized ratio (PT/INR) using capillary blood samples are being increasingly used to monitor patients receiving anticoagulation therapy. However, the performance of some devices has been shown to be suboptimal and there are only limited published data comparing specific devices to various central laboratory coagulation analyzers. We report an evaluation of the iSTAT PT/INR with a comparison to the Tcoag MDA II analyzer., Methods: We obtained simultaneous capillary/venous samples on 20 healthy volunteers for a normal range study and on 50 anticoagulated patients for a clinical evaluation. Testing was performed by phlebotomists. We also obtained 68 near simultaneous capillary/venous test results for assessment of performance by non-laboratory personnel. The criteria for determining clinical equivalence of the iSTAT to the MDA II were (1) same clinical category (subtherapeutic INR<2, therapeutic INR 2-3, and supratherapeutic INR>3) or (2) paired values within ≤ 0.4 INR., Results: Forty nine of 50 patient sample pairs collected by phlebotomists showed acceptable clinical agreement. Sixty one (61) of 68 patient sample pairs collected by nurses showed acceptable agreement. In all discordant cases the differences were minor and would have resulted in either no or minimal change in therapy., Conclusions: The iSTAT PT/INR compares well to the MDA II when performed by phlebotomists or nurses., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Laboratory ordering functions within computerized provider order entry (CPOE) systems typically support the display of electronic alert messages to improve test utilization or implement new ordering policies. However, alert strategies have been shown to vary considerably in their success and the characteristics contributing to an alert's success are poorly understood. Improved methodologies are needed to evaluate alerts and their mechanisms of action., Materials and Methods: Clinicians order inpatient and emergency department laboratory tests using our institutional CPOE system. We analyzed user interaction data captured by our CPOE system to evaluate how clinicians responded to an alert. We evaluated an alert designed to implement an institutional policy restricting the indications for ordering creatine kinase-MB (CKMB)., Results: Within 2 months of alert implementation, CKMB-associated searches declined by 79% with a corresponding decline in CKMB orders. Furthermore, while prior to alert implementation, clinicians searching for CKMB ultimately ordered this test 99% of the time, following implementation, only 60% of CKMB searches ultimately led to CKMB test orders. This difference presumably represents clinicians who reconsidered the need for CKMB in response to the alert, demonstrating the alert's just-in-time advisory capability. In addition, as clinicians repeatedly viewed the alert, there was a "dose-dependant" decrease in the fraction of searches without orders. This presumably reflects the alerting strategy's long-term educational component, as clinicians aware of the new policy will not search for CKMB when not indicated., Conclusions: Our analytic approach provides insight into the mechanism of a CPOE alert and demonstrates that alerts may act through a combination of just-in-time advice and longer term education. Use of this approach when implementing alerts may prove useful to improve the success of a given alerting strategy.

Historically, it has been difficult for hospitals to change methods for activated clotting time (ACT) testing because of differences in ACT values obtained with different instruments, wide differences in target ranges used in different procedures, and the difficulty of performing crossover studies at the bedside in critical care situations. There are limited published data comparing the i-STAT (Abbott Point of Care, Princeton, NJ) kaolin ACT with the Medtronic ACT Plus (Medtronic, Minneapolis, MN). The i-STAT system can perform ACT testing in addition to testing of a number of critical care analytes and may offer potential advantages over other ACT analyzers. Comparison of ACT values on 121 simultaneous split-sample tests yielded an R(2) of 0.88 with i-STAT = 0.79 Medtronic + 72.0. The Pearson correlation was R = 0.94, indicating statistically significant correlation between the 2 methods. Based on this comparison, we were able to implement the i-STAT ACT throughout our institution without changing target ranges for any individual procedure.

Management of laboratory test utilization presents an ongoing challenge. Most studies reported in the literature have described efforts to control one or a few tests, but the results cannot be generalized to a broader utilization management strategy. Herein we report our experiences with an organizational utilization management program during a 10-year period. Cumulatively, our program has achieved significant success, saving millions of dollars in blood components and reducing inpatient tests per discharge by 26%. Highlights from our experiences include the importance of implementing an institutional organizational structure to support utilization management, the central role fulfilled by clinical pathologists as leaders of the program, the ability to obtain timely utilization data, and careful selection of the most appropriate implementation tools tailored to the unique circumstances of each utilization management initiative.

Dysnatremia may cause life-threatening encephalopathy in marathon runners. Hypernatremia and exercise-associated hyponatremia (EAH) may manifest with mental status changes and, if untreated, progress to coma and death. We reviewed the on-site blood sodium testing and treatment in collapsed runners at the finish-line medical tent at the Boston marathons from 2001 through 2008. Dysnatremia was diagnosed in 429 (32.5%) of 1,319 collapsed runners. Hypernatremia was present in 366 (27.7%) and hyponatremia in 63 (4.8%). Hypernatremic runners unable to drink fluids were treated with intravenous normal (0.9%) saline. Hyponatremic runners with seizures or coma received intravenous hypertonic (3%) saline. Sixteen runners with EAH able to drink a concentrated oral hypertonic solution recovered within 30 minutes. Based on on-site sodium testing, dysnatremic runners were treated with appropriate intravenous fluids according to validated standards of care. Hyponatremic runners able to drink an oral hypertonic solution recovered promptly.

A total of 1,429 serum samples from 389 consecutive patients with acute chest pain were analyzed with the goal to aid the rapid diagnosis of acute myocardial infarction. To the best of our knowledge this is the largest and most comprehensive study on mid-infrared spectroscopy in cardiology. We were able to identify those signatures in the mid-infrared spectra of the samples, which were specific to either acute myocardial infarction or chest pain of other origin (angina pectoris, oesophagitis, etc). These characteristic spectral differences were used to distinguish between the cause of the donor's acute chest pain using robust linear discriminant analysis. A sensitivity of 88.5% and a specificity of 85.1% were achieved in a blind validation. The area under the receiver operating characteristics curve amounts to 0.921, which is comparable to the performance of routine cardiac laboratory markers within the same study population. The biochemical interpretation of the spectral signatures points towards an important role of carbohydrates and potentially glycation. Our studies indicate that the "Diagnostic Pattern Recognition (DPR)" method presented here has the potential to aid the diagnostic procedure as early as within the first 6 hours after the onset of chest pain.

Context: Reporting of laboratory critical values has become an issue of national attention because of important regulatory, medicolegal, and clinical concerns., Objective: To survey aspects of the laboratory critical-value reporting process at a broad range of institutions., Design: A survey was developed regarding the operational and information-technology aspects of critical value reporting., Results: More than 730 responses were obtained from a broad distribution of hospitals. In addition, we analyzed more than 700 written responses from survey participants., Conclusions: The survey results provide insight into the standard of practice and level of compliance with current Joint Commission and College of American Pathologists requirements for critical values, demonstrate considerable heterogeneity, and suggest areas for improvement. A common issue raised during the survey and follow-up teleconference was the incidence of outpatient false-positive critical values. In this report, we also demonstrate that attention to preanalytic transport and processing issues can assist in minimizing this issue.

We measured analytes in collapsed Boston Marathon runners to compare with changes in asymptomatic runners. Of collapsed runners at the 2007 marathon, 18.2% had a measurable cardiac troponin T (cTnT) value with a mean postrace level of 0.017 ng/mL (0.017 microg/L; SD, 0.02 ng/mL [0.02 microg/L]). Three subjects had cTnT values above the cutoff (0.10 ng/mL [0.10 microg/L]) typically used for the diagnosis of acute myocardial infarction. The mean and median N-terminal pro-B-type natriuretic peptide levels were 73 ng/L (SD, 77.3 ng/L) and 54.3 ng/L (interquartile range, 22.8-87.3 ng/L), respectively, in collapsed runners. Only 4.9% had values more than the age-specific normal value (<125 ng/L for subjects younger than 75 years). In collapsed subjects at the 2006 marathon, 18.0% had an abnormal sodium value, including 18 cases of hypernatremia and 7 cases of hyponatremia. The ionized calcium level was low in 49% of subjects, and the ionized magnesium level was low in 19.5% and elevated in 1 subject. The blood lactate level was elevated in 95% of subjects. The frequency of elevated postrace cTnT levels in collapsed athletes after endurance exercise is similar to that in asymptomatic runners. Other metabolic abnormalities, including hypernatremia, hyponatremia, low ionized calcium and magnesium levels, and lactic acidosis may contribute to muscle fatigue and collapse.

Background: Dyspnea is a common complaint in the emergency department (ED) and may be a diagnostic challenge. We hypothesized that diagnostic uncertainty in this setting is associated with adverse outcomes, and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing would improve diagnostic accuracy and reduce diagnostic uncertainty., Methods: A total of 592 dyspneic patients were evaluated from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Managing physicians were asked to provide estimates from 0% to 100%of the likelihood of acutely destabilized heart failure (ADHF). A certainty estimate of either 20% or lower or 80% or higher was classified as clinical certainty, while estimates between 21% and 79% were defined as clinical uncertainty. Associations between clinical uncertainty,hospital length of stay, morbidity, and mortality were examined. The diagnostic value of clinical judgment vs NT-proBNP measurement was compared across categories of clinical certainty., Results: Clinical uncertainty was present in 185 patients (31%), 103 (56%) of whom had ADHF. Patients judged with clinical uncertainty had longer hospital length of stay and increased morbidity and mortality,especially those with ADHF. Receiver operating characteristic analysis of clinical judgment yielded an area under the curve (AUC) of 0.88 in the clinical certainty group and 0.76 in the uncertainty group (P<.001); NT-proBNP testing alone in these same groups had AUCs of 0.96 and 0.91, respectively. The combination of clinical judgment with NT-proBNP testing yielded improvements in AUC., Conclusions: Among dyspneic patients in the ED, clinical uncertainty is associated with increased morbidity and mortality, especially in those with ADHF.The addition of NT-proBNP testing to clinical judgment may reduce diagnostic uncertainty in this setting.

Background: Measurement of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is useful for evaluating patients with heart failure (HF)., Methods: We evaluated the performance of a new automated NT-proBNP assay., Results: The VITROS NT-proBNP assay had mean within-run and total imprecision of 1.0% and 3.4% at NT-proBNP concentrations from 67-27,500 ng/l. Acceptable linearity, functional/analytical sensitivity were demonstrated. Anticoagulant/tube types had no effect on results. Excellent sample stability and no high-dose hook were observed. High correlation between the VITROS and Elecsys methods was demonstrated (r=0.995; P<.001), with 98.3% clinical concordance. VITROS NT-proBNP concentrations were significantly higher in HF subjects than those without (1210 versus 68 ng/l; P<.001) and associated with HF symptom severity (P<.001). The VITROS assay had AUC for HF of 0.95 (P<.001), and had excellent NPV for excluding HF., Conclusions: The automated VITROS NT-proBNP assay demonstrates excellent analytical and clinical performance for evaluating the presence and severity of HF.

Objectives: The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea., Background: Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF)., Methods: Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified., Results: Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration > or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death., Conclusions: Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.

The laboratory testing process, including the preanalytic, analytic, and postanalytic phases, is an area where errors frequently occur. These errors may impair the diagnostic process and compromise patient safety. Delay in diagnosis and failure to diagnose are common reasons for a medicolegal action. It is estimated that over 70% of medical decisions are made using laboratory data. For this reason, the laboratory is often involved either directly or indirectly in medical liability cases. The laboratory and hospital need to design systems that reduce the possibility of error and to rapidly identify and resolve the errors that do occur. Because the pre- and postanalytic processes extend into the clinical operations of the hospital, the laboratory can play an important role in promoting patient safety by assisting clinicians with test ordering, communicating test results appropriately, and aiding in the interpretation of results.

Purpose: Exercise-associated hyponatremia (EAH), as defined by a blood sodium concentration [Na+] less than 135 mmol/L, may lead to hypotonic encephalopathy with fatal cerebral edema. Understanding the pathogenetic role of antidiuresis may lead to improved strategies for prevention and treatment., Methods: Normonatremic marathon runners were tested pre- and post-race for creatine kinase, interleukin-6, cortisol, prolactin, and arginine vasopressin. Similar testing also was carried out in runners with encephalopathy caused by EAH, including 2 cases with fatal cerebral edema., Results: Normonatremic runners (n = 33; 2001) with a mean 3% decrease in body weight showed a 40-fold increase in interleukin-6 (66.6 +/- 11.9 pg/mL from 1.6 +/- 0.5 pg/mL, P = .001), which was significantly correlated with increases in creatine kinase (r = 0.88, P = <.0001), cortisol (r = 0.70, P = .0003), and prolactin (r = 0.67, P <.007), but not arginine vasopressin (r = 0.44, P = .07). Collapsed runners with EAH (n = 22; 2004) showed a mean blood urea nitrogen less than 15 mg/dL with measurable plasma levels of arginine vasopressin (>0.5 pg/mL) in 43% of cases. Two marathon runners with fatal cerebral edema additionally showed less than maximally dilute urines (>100 mmol/kg/H2O) and urine [Na+] greater than 25 mEq/L., Conclusions: Cases of EAH fulfill the essential diagnostic criteria for the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Runners with hypotonic encephalopathy at subsequent races were treated with intravenous hypertonic (3%) saline on the basis of this paradigm, which resulted in rapid clinical improvement without adverse effects. Release of muscle-derived interleukin-6 may play a role in the nonosmotic secretion of arginine vasopressin, thereby linking rhabdomyolysis to the pathogenesis of EAH.

Background: Combining testing for natriuretic peptides [amino-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP)] and cardiac troponin T (cTnT) may help predict mortality in patients with acute heart failure (HF)., Methods: We studied 209 patients with acute HF at an urban academic center and used ROC curves and multivariate analyses to examine the relationship of outcome to natriuretic peptide and cTnT concentrations at presentation., Results: Higher concentrations of natriuretic peptides and cTnT at presentation were predictors of death at 60 days and 1 year (P <0.001 and P <0.01, respectively, at both time points). Optimal cutoff points for NT-proBNP, BNP, and cTnT for predicting death by 60 days or 1 year were 5562 and 3174 ng/L, 428 and 352 ng/L, and 0.01 and 0.01 microg/L, respectively. Most decedents demonstrated increased concentrations of both natriuretic peptides and cTnT and had a 25% mortality rate at the 60-day time point (P <0.001). Mortality rates were low (<4%) among patients with either no increase or an increase in only 1 marker. Decedents with increases in both a natriuretic peptide and cTnT at presentation had the highest death rate at 1 year (45%, P <0.001). This combination was strongly predictive of death [NT-proBNP plus cTnT: hazard ratio (HR), 7.66; 95% confidence interval (CI), 3.06-17.8; BNP plus cTnT: HR, 6.82; 95% CI, 2.99-16.5]., Conclusions: A dual-marker strategy incorporating a natriuretic peptide and cTnT is superior to either marker alone for estimating short- and longer-term risk in patients with acute HF.

Context: In clinical trials, N-terminal pro-brain natriuretic peptide (NT-proBNP) testing has been shown to be valuable for diagnosis and triage of patients with acute decompensated heart failure. It is not yet clear what benefits might be expected from the initiation of NT-proBNP testing in an everyday clinical setting., Objective: To determine the effects of NT-proBNP testing on hospital length of stay as well as on 60-day morbidity and mortality in patients with acute decompensated heart failure before and after the test was implemented in the clinical laboratory., Design: We measured hospital length of stay and 60-day morbidity and mortality rates among patients with acute decompensated heart failure admitted before and after initiation of NT-proBNP testing in our hospital. Differences in demographics between preimplementation and postimplementation groups were compared with the chi2 test for categorical variables and the Wilcoxon rank sum test for continuous variables. Comparison between the hospital length of stay for each group was evaluated using the Mann-Whitney U test. Differences in rates of rehospitalization or death at 60 days following presentation were assessed using chi2 cross-tabulation., Results: Patients in the postimplementation group had similar clinical features as those in the preimplementation group. The hospital length of stay for patients in the postimplementation study group decreased both with respect to mean (1.86-day reduction) and median (1.3-day reduction) hospital stay (both, P = .03). Additionally, significantly lower rates of death (6.6% absolute risk reduction, P = .01), rehospitalization (12.1% absolute risk reduction, P = .005), and the composite of the 2 rates (18.7% absolute risk reduction, P = .008) were found following initiation of NT-proBNP testing., Conclusions: Implementation of NT-proBNP testing may result in significant reductions in hospital length of stay as well as improvements in rates of morbidity and mortality in patients with acute decompensated heart failure.

Background: Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction., Methods and Results: We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler-derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, > 60% of participants had increased cTnT > 99th percentile of normal (> 0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (> or = 0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=-0.70, P<0.001) and inversely with training mileage (r=-0.71, P<0.001). Compared with athletes training > 45 miles/wk, athletes who trained < or = 35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16+/-5% versus 25+/-4%, P<0.001), myocyte injury (cTnT 0.09 versus < 0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001)., Conclusions: Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Context: D-dimer concentration can be used to exclude a diagnosis of acute pulmonary embolism. However, clinicians frequently order unnecessary supplemental testing in patients with low concentrations of D-dimer. Elevations in natriuretic peptides have also been described in the setting of pulmonary embolism., Objective: We investigated the integrative role of D-dimer with amino-terminal pro-B-type natriuretic peptide for the evaluation of patients with and without acute pulmonary embolism., Design: Patients were selected for analysis from a previous study in which levels of D-dimer and amino-terminal pro-B-type natriuretic peptide were measured. The presence of pulmonary embolism was determined by computed tomographic angiography., Results: The median levels of D-dimer were significantly higher in patients with acute pulmonary embolism. Similarly, the median levels of amino-terminal pro-B-type natriuretic peptide were higher in patients with pulmonary embolism., Conclusions: The Roche Tina-quant D-Dimer immunoturbidimetric assay provides a high negative predictive value and can be used to exclude acute pulmonary embolism in patients with dyspnea. Measurement of amino-terminal pro-B-type natriuretic peptide in addition to D-dimer improves specificity for acute pulmonary embolism without sacrificing negative predictive value. A combination of both markers may offer reassurance for excluding acute pulmonary embolism, and thus avoid redundant, expensive confirmatory tests.

We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically significant increase in MMP-9 (P < .001) and D dimer (P < .001). Nonsignificant changes in S-100 b and BNP were observed. Premarathon and postmarathon values for a multimarker stroke index increased from 0.97 (normal) to 3.5 (low risk or more; P < .001). Two subjects had index values more than the high-risk cutoff value. Mean TnT premarathon and postmarathon levels increased (from <0.01 to 0.03 ng/mL; P < .0001). After the marathon, with a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's recommended cutoff for myocardial damage. Although biochemical evidence of myocardial damage following strenuous exercise may reflect myocardial stunning or subclinical ischemia, the changes in the stroke index and values for individual stroke markers may reflect a systemic inflammatory response to exertional rhabdomyolysis which is common, but the possibility of subclinical central nervous system damage cannot be excluded.

Background: Blood donor screening is performed to accomplish several goals, including donor safety during collection and recipient safety during transfusion. Donors taking certain medications such as teratogens or platelet-inhibiting drugs are deferred from donation. Studies investigating the accuracy of the donor history are limited and only provide data on select groups of drugs. This study compares the results of an extended serum toxicology analysis to the medication use reported on the donor questionnaire., Study Design and Methods: Whole-blood samples were collected from 108 volunteer blood donors. A serum toxicology analysis was performed with high-performance liquid chromatography with photodiode array detection. The results were compared to those reported on the donor history questionnaire., Results: The medication history was consistent with the reported medications in 96 (89%) donors. Serum toxicology testing detected medications that were not reported on the donor history form in 12 (11%) donors. Most of the donors who did not accurately report their medication use (8 or 67%) were taking psychotropic medications., Conclusion: Eleven percent of the donors did not fully disclose their recent medication history. Although none of the omitted medications would have been grounds for deferral, the finding of underreporting questions the reliability of donor screening. Despite a negative medication history, blood donor centers cannot assume that donors are medication-free. This study reveals a bias to omit psychotropic medications such as antidepressants and anxiolytics.

Hypothesis: Drotrecogin alfa (activated), the pharmacologic form of activated protein C and the first Food and Drug Administration-approved drug for treatment of severe sepsis, is beneficial in experimental acute pancreatitis (AP)., Design: Animal study., Setting: Laboratory., Subjects: Male Sprague-Dawley rats., Interventions: Mild (intravenous cerulein) or severe (intravenous cerulein plus intraductal glycodeoxycholic acid) AP was induced in 72 rats, and coagulation evaluated. Rats with severe AP were randomized to treatment with drotrecogin alfa (activated), 100 microg/kg per hour, or isotonic sodium chloride., Main Outcome Measures: Histologic scoring of pancreatic necrosis, inflammation of the pancreas and lung (measured by myeloperoxidase concentration), coagulation measures, and 24-hour survival., Results: Severe consumptive coagulopathy, hemoconcentration, and leukocytosis were observed 6 hours after induction of severe AP, but not in mild AP. Treatment of AP with drotrecogin did not worsen coagulation measures. Although the degree of pancreatic necrosis was comparable in treated and untreated animals with severe AP, drotrecogin significantly reduced myeloperoxidase levels in the pancreas (P = .009) and lungs (P = .03). The 24-hour survival in severe AP was markedly improved in animals treated with drotrecogin (86% vs 38%; P = .05)., Conclusions: Animals with severe AP have severe consumptive coagulopathy, but administration of drotrecogin alfa (activated), 100 microg/kg per hour, does not worsen coagulation abnormalities. Drotrecogin treatment reduces inflammation in the pancreas and lungs and significantly improves survival. These results encourage clinical investigation of drotrecogin in the treatment of severe AP.

Reporting of laboratory critical values has become an issue of national attention as illustrated by recent guidelines described in the National Patient Safety Goals of the Joint Commission on Accreditation of Healthcare Organizations. Herein, we report the results of an analysis of 37,503 consecutive laboratory critical values at our institution, a large urban academic medical center. We evaluated critical value reporting by test, laboratory specialty, patient type, clinical care area, time of day, and critical value limits. Factors leading to delays in critical value reporting are identified, and we describe approaches to improving this important operational and patient safety issue.

We evaluated the CellaVision DM96 (CellaVision AB, Lund, Sweden), an automated digital cell morphology and informatics system for peripheral blood smears. Technologists agreed with 82% of the instrument's preclassifications. Correlation coefficients between final results released from the CellaVision and results obtained by direct microscopy were 0.96 (all neutrophils), 0.94 (lymphocytes), 0.88 (segmented neutrophils), 0.73 (eosinophils), 0.69 (bands), and 0.67 (monocytes). After correction for statistically and clinically insignificant variations, the CellaVision DM96 had 95% sensitivity and 88% specificity for immature myeloid cells. It was 100% sensitive and 94% specific for blasts, and 100% sensitive and 97% specific for unusual WBCs and nucleated RBCs. Advantages of the CellaVision DM96 over direct microscopy include the ability to review slides from a remote location, consultation and quality control on a cell-by-cell basis, and potential labor savings.

The utility of aminoterminal pro-brain natriuretic peptide (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p <0.001). NT-proBNP at cutpoints of >450 pg/ml for patients <50 years of age and >900 pg/ml for patients >or=50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p <0.001). An NT-proBNP level <300 pg/ml was optimal for ruling out acute CHF, with a negative predictive value of 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting.

Context: Recommendations for prevention and treatment of medical emergencies in participants in marathon races center on maintenance of adequate hydration status and administration of fluids. Recently, new recommendations for fluid replacement for marathon runners were promulgated by medical and athletic societies. These new guidelines encourage runners to drink ad libitum between 400 and 800 mL/h as opposed to the previous "as much as possible" advice., Objective: To assess the sodium and hydration (plasma osmolality) status of collapsed marathon runners after the promulgation of new hydration guidelines., Design: Plasma sodium and osmolality values of runners who presented to the medical tent at the finish line of the 2003 Boston Marathon were measured., Results: Using reference ranges derived from the general population, of 140 collapsed runners, 35 (25%) were hypernatremic (sodium, >146 mEq/L) and 6 (12%) were hyperosmolar (osmolality, >296 mOsm/kg H(2)O), whereas 9 (6%) were hyponatremic (sodium, <135 mEq/L) and 8 (16%) were hypo-osmolar (osmolality, <280 mOsm/kg H(2)O). Compared with a population of marathon runners who had experienced no medical difficulties, 9% of the runners were hypernatremic, 5% were hyponatremic, 8% were hypo-osmolar, and none were hyperosmolar., Conclusions: Our findings indicate a significant incidence of hypernatremia with hyperosmolality and hyponatremia with hypo-osmolality among collapsed runners despite the new fluid intake recommendations, suggesting that either further educational measures are required or that the new guidelines are not entirely adequate to prevent abnormalities in fluid balance. Furthermore, the immediate medical management of hypernatremia and hyponatremia is different. Administration of fluids to severely hyponatremic patients may result in fatal cerebral edema. Our findings caution against institution of treatment until laboratory tests determine the patient's sodium status.

We studied the role of ischemia-modified albumin (IMA) with standard biomarkers (myoglobin, creatine kinase-MB [CK-MB], troponin I [TnI]) in assessment of 200 patients with suspected myocardial ischemia admitted to the emergency department. Every case was reviewed by a cardiologist. A clinical diagnosis of ischemia was assigned and correlated with biomarker test results. Of the patients, 25 (13.0%) had myocardial ischemia. Receiver operating characteristic curves demonstrated IMA as highly sensitive but somewhat poorly specific for the presence of ischemia (area under curve, 0.63; P = .01). With a cut point of 90 U/mL, the Albumin Cobalt Binding Test had 80% sensitivity and 31% specificity for diagnosing ischemia and a negative predictive value of 92%. IMA was positive in 4 of 5 patients with electrocardiographic (ECG) evidence of ischemia and 16 of 20 patients with coronary ischemia but negative ECG. Among the same patients, the myoglobin-CK-MB-TnI triad had a sensitivity of 57%. The combination of IMA-myoglobin-CK-MB-TnI increased the sensitivity for detecting ischemia to 97%, with a negative predictive value of 92%. IMA is highly sensitive and has a high negative predictive value, which might improve the usefulness of standard biomarkers of myocardial ischemia.

Context: The consumption of fish high in omega-3 fatty acids is advocated by the American Heart Association to decrease the risk of coronary artery disease. However, fish contain environmental toxins such as mercury, polychlorinated biphenyls, and organochlorine pesticides, which may negate the beneficial cardiovascular effects of fish meals. Toxin levels vary depending on both the fish source and the specific toxin, and neither farm-raised nor wild fish are toxin free. Fish oil supplements also prevent the progression of coronary artery disease and reduce cardiovascular mortality. However, only sparse data exist on the level of toxins in fish oil. In a previous study we showed that the amount of mercury in 5 over-the-counter brands of fish oil was negligible., Objective: To determine the concentrations of polychlorinated biphenyls and other organochlorines in 5 over-the-counter preparations of fish oil., Design: The contents of 5 commercial fish oil brands were sent for organochlorine analysis., Results: The levels of polychlorinated biphenyls and organochlorines were all below the detectable limit., Conclusions: Fish oil supplements are more healthful than the consumption of fish high in organochlorines. Fish oils provide the benefits of omega-3 fatty acids without the risk of toxicity. In addition, fish oil supplements have been helpful in a variety of diseases, including bipolar disorder and depression.