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Featured researches published by John C. Stein.


JAMA | 2010

Trends and Characteristics of US Emergency Department Visits, 1997-2007

Ning Tang; John C. Stein; Renee Y. Hsia; Judith H. Maselli; Ralph Gonzales

CONTEXT The potential effects of increasing numbers of uninsured and underinsured persons on US emergency departments (EDs) is a concern for the health care safety net. OBJECTIVE To describe the changes in ED visits that occurred from 1997 through 2007 in the adult and pediatric US populations by sociodemographic group, designation of safety-net ED, and trends in ambulatory care-sensitive conditions. DESIGN, SETTING, AND PARTICIPANTS Publicly available ED visit data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 1997 through 2007 were stratified by age, sex, race, ethnicity, insurance status, safety-net hospital classification, triage category, and disposition. Codes from the International Classification of Diseases, Ninth Revision (ICD-9), were used to extract visits related to ambulatory care-sensitive conditions. Visit rates were calculated using annual US Census estimates. MAIN OUTCOME MEASURES Total annual visits to US EDs and ED visit rates for population subgroups. RESULTS Between 1997 and 2007, ED visit rates increased from 352.8 to 390.5 per 1000 persons (rate difference, 37.7; 95% confidence interval [CI], -51.1 to 126.5; P = .001 for trend); the increase in total annual ED visits was almost double of what would be expected from population growth. Adults with Medicaid accounted for most of the increase in ED visits; the visit rate increased from 693.9 to 947.2 visits per 1000 enrollees between 1999 and 2007 (rate difference, 253.3; 95% CI, 41.1 to 465.5; P = .001 for trend). Although ED visit rates for adults with ambulatory care-sensitive conditions remained stable, ED visit rates among adults with Medicaid increased from 66.4 in 1999 to 83.9 in 2007 (rate difference, 17.5; 95% CI, -5.8 to 40.8; P = .007 for trend). The number of facilities qualifying as safety-net EDs increased from 1770 in 2000 to 2489 in 2007. CONCLUSION These findings indicate that ED visit rates have increased from 1997 to 2007 and that EDs are increasingly serving as the safety net for medically underserved patients, particularly adults with Medicaid.


American Journal of Respiratory and Critical Care Medicine | 2013

Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients.

Ashish Agrawal; Michael A. Matthay; Kirsten Neudoerffer Kangelaris; John C. Stein; Jeffrey C. Chu; Brandon M. Imp; Alfredo Cortez; Jason Abbott; Kathleen D. Liu; Carolyn S. Calfee

RATIONALE Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores. OBJECTIVES To determine whether plasma angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8), and/or receptor for advanced glycation end products (sRAGE) predict ALI in critically ill patients. METHODS Plasma samples were drawn from critically ill patients (n = 230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI. MEASUREMENTS AND MAIN RESULTS Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (P = 0.0008, 0.004, respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those who developed ALI and those who did not (area under the receiver operating characteristic curve, 0.74 for each), and using the two together improved the area under the curve to 0.84 (vs. 0.74, P = 0.05). In contrast, plasma levels of sRAGE and vWF were not predictive of ALI. CONCLUSIONS Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.


Journal of the American College of Cardiology | 2013

Copeptin Helps in the Early Detection of Patients With Acute Myocardial Infarction Primary Results of the CHOPIN Trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction)

Alan S. Maisel; Christian Mueller; Sean-Xavier Neath; Robert H. Christenson; Nils G. Morgenthaler; James McCord; Richard M. Nowak; Gary M. Vilke; Lori B. Daniels; Judd E. Hollander; Fred S. Apple; Chad M. Cannon; John T. Nagurney; Donald Schreiber; Christopher R. deFilippi; Christopher Hogan; Deborah B. Diercks; John C. Stein; Gary F. Headden; Alexander T. Limkakeng; Inder S. Anand; Alan H.B. Wu; Jana Papassotiriou; Oliver Hartmann; Stefan Ebmeyer; Paul Clopton; Allan S. Jaffe; W. Frank Peacock

OBJECTIVES The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED). BACKGROUND Copeptin is secreted from the pituitary early in the course of AMI. METHODS This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99 th percentile 40 ng/l; 10% coefficient of variation 0.03 μg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results. RESULTS AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001). CONCLUSIONS Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws.


Annals of Emergency Medicine | 2009

Ultrasonographically Guided Peripheral Intravenous Cannulation in Emergency Department Patients With Difficult Intravenous Access: A Randomized Trial

John C. Stein; Brian George; Gerin River; Anke Hebig; Daniel McDermott

STUDY OBJECTIVE We seek to compare ultrasonographically guided peripheral intravenous access to a non-ultrasonographically guided method in a randomized trial of emergency department patients with difficult intravenous access. METHODS A prospective cohort of patients with difficult intravenous access was established. Patients were randomized to 2 groups: (1) intravenous access obtained through an ultrasonographically guided technique or (2) intravenous access obtained through non-ultrasonographically guided methods. Outcomes measured were number of attempts after enrollment, time to cannulation from enrollment, and patient satisfaction. Groups were compared with nonparametric analysis. RESULTS Fifty-nine patients were randomized. Twenty-eight patients were randomized to the ultrasonography group and 31 to the no ultrasonography group. A median of 2 further intravenous attempts was required in each group before successful cannulation, corresponding to a difference of 0 attempts (95% confidence interval [CI] 0 to 1 attempts). Time to cannulation showed a median of 39 minutes in the ultrasonography group compared with 26 minutes for the no ultrasonography group, giving a median increase of 13 minutes for the ultrasonographically guided group (95% CI -5 to 28 minutes). Patients in the ultrasonography group had a median Likert satisfaction score of 8 compared with 7 for the no ultrasonography group, giving a median increase of 1 on this scale in the ultrasonography group (95% CI 0 to 2). CONCLUSION Ultrasonographically guided peripheral intravenous cannulation did not decrease the number of attempts or the time to successful catheterization, nor did it improve patient satisfaction compared with the group that did not use ultrasonography. Superiority of ultrasonographically guided peripheral intravenous cannulation is not supported by this study.


Annals of Emergency Medicine | 2010

Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: a meta-analysis

John C. Stein; Ralph Wang; Naomi Adler; John Boscardin; Vanessa L. Jacoby; Gloria Y. Won; Ruth B. Goldstein; Michael A. Kohn

STUDY OBJECTIVE Ectopic pregnancy is a common concern in emergency departments (EDs) and remains the leading cause of first-trimester mortality. Pelvic ultrasonography by emergency physicians has been investigated as a diagnostic test for ectopic pregnancy. We present a meta-analysis of the use of emergency physician ultrasonography in the evaluation of patients at risk of ectopic pregnancy. METHODS A structured search was performed of both MEDLINE and EMBASE. Inclusion criteria were that (1) the study reported original research on ED patients at risk for ectopic pregnancy; (2) an emergency physician performed and interpreted the initial pelvic ultrasonography; and (3) follow-up was conducted on all patients. Sensitivity was defined as the proportion of patients with ectopic pregnancy for which ED ultrasonography demonstrated no intrauterine pregnancy. A random-effects model was used to obtain summary test characteristics. RESULTS The initial search showed 576 publications, abstract review yielded 60 with potential relevance, and 10 studies were included. There was a total of 2,057 patients, of whom 152 (7.5%) had ectopic pregnancy. The pooled sensitivity estimate was 99.3% (95% confidence interval [CI] 96.6% to 100%), negative predictive value was 99.96% (95% CI 99.6% to 100%), and negative likelihood ratio was 0.08 (95% CI 0.025 to 0.25), all without significant heterogeneity. CONCLUSION The results of this meta-analysis suggest that in a wide variety of clinical settings, the use of bedside ultrasonography performed by emergency physicians as a diagnostic test for ectopic pregnancy provides excellent sensitivity and negative predictive value. Visualization of an intrauterine pregnancy by an emergency physician is generally sufficient to rule out ectopic pregnancy.


Annals of Intensive Care | 2011

FGF-23 and PTH levels in patients with acute kidney injury: A cross-sectional case series study

MaryAnn Zhang; Raymond K. Hsu; Chi-yuan Hsu; Kristina Kordesch; Erica Nicasio; Alfredo Cortez; Ian McAlpine; Sandra Brady; Hanjing Zhuo; Kirsten Neudoerffer Kangelaris; John C. Stein; Carolyn S. Calfee; Kathleen D. Liu

BackgroundFibroblast growth factor-23 (FGF-23), a novel regulator of mineral metabolism, is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. However, whether FGF-23 has an analogous role in acute kidney injury is unknown. The goal of this study was to measure FGF-23 levels in critically ill patients with acute kidney injury to determine whether FGF-23 levels were elevated, as in chronic kidney disease.MethodsPlasma FGF-23 and intact parathyroid hormone (PTH) levels were measured in 12 patients with acute kidney injury and 8 control subjects.ResultsFGF-23 levels were significantly higher in acute kidney injury cases than in critically ill subjects without acute kidney injury, with a median FGF-23 level of 1948 RU/mL (interquartile range (IQR), 437-4369) in cases compared with 252 RU/mL (IQR, 65-533) in controls (p = 0.01). No correlations were observed between FGF-23 and severity of acute kidney injury (defined by the Acute Kidney Injury Network criteria); among patients with acute kidney injury, FGF-23 levels were higher in nonsurvivors than survivors (median levels of 4446 RU/mL (IQR, 3455-5443) versus 544 RU/mL (IQR, 390-1948; p = 0.02). Severe hyperparathyroidism (defined as intact PTH >250 mg/dL) was present in 3 of 12 (25%) of the acute kidney injury subjects versus none of the subjects without acute kidney injury, although this result did not meet statistical significance.ConclusionsWe provide novel data that demonstrate that FGF-23 levels are elevated in acute kidney injury, suggesting that FGF-23 dysregulation occurs in acute kidney injury as well as chronic kidney disease. Further studies are needed to define the short- and long-term clinical effects of dysregulated mineral metabolism in acute kidney injury patients.


Journal of Ultrasound in Medicine | 2009

A Survey of Bedside Ultrasound Use by Emergency Physicians in California

John C. Stein; Gerin River; Irina Kalika; Anke Hebig; Daniel Price; Vanessa L. Jacoby; Roy A. Filly

Objective. The purpose of this study was to investigate the current practice of emergency physician–performed bedside ultrasound examinations in California and to assess differences between academic and community practice. Methods. We queried all emergency departments (EDs) in California to determine whether bedside ultrasound was used by emergency physicians. Among EDs that were using bedside ultrasound, we administered a survey to assess use patterns, credentialing criteria, and quality assurance (QA) programs. Results. We contacted all eligible EDs (n = 293) by telephone and had a 100% response rate for our primary question: 101 EDs (34%) reported use of bedside ultrasound. Of these 101 EDs, 97 (96%) responded to the secondary survey, showing the following: (1) 48% of physicians at each site were credentialed to use ultrasound in at least 1 modality; (2) 70% of EDs used American College of Emergency Physicians (ACEP) criteria for credentialing guidelines; and (3) 33% had an ultrasound QA program. Comparing practice settings, 68% of academic departments used bedside ultrasound compared with 29% of community departments (difference, 39%; 95% confidence interval [CI], 23% to 54%; P < .0001). In academic departments, a mean of 60% of physicians were credentialed, compared with 41% in community EDs (difference, 19%; 95% CI, 2.5% to 35%; P = .036). Conclusions. Most California EDs do not use bedside ultrasound. Although most EDs using ultrasound report that they follow ACEP emergency ultrasound guidelines, most do not have a QA program as recommended by these guidelines. Compared with community EDs, academic EDs are more likely to use bedside ultrasound, have physicians credentialed in ultrasound use, and have QA programs.


Journal of the American Board of Family Medicine | 2012

Development and Validation of a Clinical Decision Rule for the Diagnosis of Influenza

Mark H. Ebell; Anna M. Afonso; Ralph Gonzales; John C. Stein; Blaise Genton; Nicolas Senn

Introduction: A clinical decision rule to improve the accuracy of a diagnosis of influenza could help clinicians avoid unnecessary use of diagnostic tests and treatments. Our objective was to develop and validate a simple clinical decision rule for diagnosis of influenza. Methods: We combined data from 2 studies of influenza diagnosis in adult outpatients with suspected influenza: one set in California and one in Switzerland. Patients in both studies underwent a structured history and physical examination and had a reference standard test for influenza (polymerase chain reaction or culture). We randomly divided the dataset into derivation and validation groups and then evaluated simple heuristics and decision rules from previous studies and 3 rules based on our own multivariate analysis. Cutpoints for stratification of risk groups in each model were determined using the derivation group before evaluating them in the validation group. For each decision rule, the positive predictive value and likelihood ratio for influenza in low-, moderate-, and high-risk groups, and the percentage of patients allocated to each risk group, were reported. Results: The simple heuristics (fever and cough; fever, cough, and acute onset) were helpful when positive but not when negative. The most useful and accurate clinical rule assigned 2 points for fever plus cough, 2 points for myalgias, and 1 point each for duration <48 hours and chills or sweats. The risk of influenza was 8% for 0 to 2 points, 30% for 3 points, and 59% for 4 to 6 points; the rule performed similarly in derivation and validation groups. Approximately two-thirds of patients fell into the low- or high-risk group and would not require further diagnostic testing. Conclusion: A simple, valid clinical rule can be used to guide point-of-care testing and empiric therapy for patients with suspected influenza.


Circulation-cardiovascular Quality and Outcomes | 2012

Impact of Door-to-Activation Time on Door-to-Balloon Time in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarctions A Report From the Activate-SF Registry

James M. McCabe; Ehrin J. Armstrong; Kurt S. Hoffmayer; Prashant D. Bhave; John S. MacGregor; Priscilla Y. Hsue; John C. Stein; Scott Kinlay; Peter Ganz

Background—Little is known about the components of door-to-balloon time among patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We assessed the role of time from hospital arrival to ST-segment elevation myocardial infarction diagnosis (door-to-activation time) on door-to-balloon time in contemporary practice and evaluated factors that influence door-to-activation times. Methods and Results—Registry data on 347 consecutive patients diagnosed with a ST-segment elevation myocardial infarction in the emergency department over 30 months at 2 urban primary percutaneous coronary intervention centers were analyzed. The primary study end point was the time from hospital arrival to catheterization laboratory activation by the emergency department physician, and we assessed factors associated with this period. Door-to-balloon time and its other components were secondary study end points. The median door-to-activation time was 19 minutes (interquartile range, 9–54). Variation in door-to-activation times explained 93% of the variation in door-to-balloon times and demonstrated the strongest correlation with door-to-balloon times (r=0.97). Achieving a door-to-activation time of ⩽20 minutes resulted in an 89% chance of achieving a door-to-balloon time of ⩽90 minutes compared with only 28% for patients with a door-to-activation time >20 minutes. Factors significantly associated with door-to-activation time include the following: prehospital ECG use (61% shorter, 95% confidence interval, −50 to −72%; P<0.001) and computed tomography scan use in the emergency department (245% longer, 95% confidence interval, +50 to +399%; P=0.001). Conclusions—The interval from hospital arrival to ST-segment elevation myocardial infarction diagnosis and catheterization laboratory activation (door-to-activation time) is a strong driver of overall door-to-balloon times. Achieving a door-to-activation time ⩽20 minutes was key to achieving a door-to-balloon time ⩽90 minutes. Delays in door-to-activation time are not associated with delays in other aspects of the primary percutaneous coronary intervention process.


American Journal of Cardiology | 2012

Electrocardiographic Criteria for ST-Elevation Myocardial Infarction in Patients With Left Ventricular Hypertrophy

Ehrin J. Armstrong; Ameya Kulkarni; Prashant D. Bhave; Kurt S. Hoffmayer; John S. MacGregor; John C. Stein; Scott Kinlay; Peter Ganz; James M. McCabe

Patients with electrocardiographic (ECG) left ventricular hypertrophy (LVH) have repolarization abnormalities of the ST segment that may be confused with an ischemic current of injury. We analyzed the ACTIVATE-SF database, a registry of consecutive emergency department ST-segment elevation (STE) myocardial infarction diagnoses from 2 medical centers. Univariate analysis was performed to identify ECG variables associated with presence of an angiographic culprit lesion. Recursive partitioning was then applied to identify a clinical decision-making rule that maximizes sensitivity and specificity for presence of an angiographic culprit lesion. Seventy-nine patients with ECG LVH underwent emergency cardiac catheterization for primary angioplasty. Patients with a culprit lesion had greater magnitude of STE (3.0 ± 1.8 vs 1.9 ± 1.0 mm, p = 0.005), more leads with STE (3.1 ± 1.6 vs 2.0 ± 1.8 leads, p = 0.002), and a greater ratio of STE to R-S-wave magnitude (median 25% vs 9.2%, p = 0.003). Univariate application of ECG criteria had limited sensitivity and a high false-positive rate for identifying patients with an angiographic culprit lesion. In patients with anterior territory STE, using a ratio of ST segment to R-S-wave magnitude ≥25% as a diagnostic criteria for STE myocardial infarction significantly improved specificity for an angiographic culprit lesion without decreasing sensitivity (c-statistic 0.82), with a net reclassification improvement of 37%. In conclusion, application of an ST segment to R-S-wave magnitude ≥25% rule may augment current criteria for determining which patients with ECG LVH should undergo primary angioplasty.

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Ralph Gonzales

University of California

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Ehrin J. Armstrong

University of Colorado Denver

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Peter Ganz

University of California

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Ralph Wang

University of California

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Prashant D. Bhave

University of Iowa Hospitals and Clinics

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Scott Kinlay

Brigham and Women's Hospital

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