Biomedical subjects

Jeffrey A Kline

Publications and source records attributed to Jeffrey A Kline.

At least 19 recordsLinked to original sources

PubMed2007

Tenecteplase to treat pulmonary embolism in the emergency department.

Tenecteplase, a mutant form of alteplase, possesses pharmacological properties that might favor its use for emergent fibrinolysis of acute pulmonary embolism. Contemporaneous search of the World's literature reveals 14 humans with acute pulmonary embolism treated with tenecteplase. Here, we summarize those cases and report the presentation features, dosing details and outcomes of eight additional patients with acute pulmonary embolism treated with tenecteplase in an academic emergency department. None of our eight patients had a significant hemorrhagic event after tenecteplase, and the outcomes of all eight appear to be acceptable. Taken together, we submit that the present case report and prior case reports are sufficient to comprise a phase I study of the safety and efficacy of tenecteplase to treat acute pulmonary embolism.

Aged↗

PubMed2006

Procalcitonin test in the diagnosis of bacteremia: a meta-analysis.

STUDY OBJECTIVE: We seek to evaluate the diagnostic performance of the procalcitonin test for the diagnosis of bacteremia in the emergency department (ED) population. METHODS: We conducted a search of MEDLINE, bibliographies of previous systemic reviews, and pertinent national meeting research abstracts. We included studies that assessed the diagnostic accuracy of procalcitonin for bacteremia, with blood culture as the reference standard. We included prospective investigations of adults and children with suspected infection studied in the ED or at admission. Two authors independently extracted data and assessed study quality; consensus was reached by conference. The analysis was based on the I2 statistic for heterogeneity, unweighted summary receiver-operating characteristic curve, and random-effects pooled sensitivity and specificity across studies using the same test threshold. RESULTS: The search yielded 348 publications and 1 unpublished study. Seventeen studies met the inclusion criteria and provided a sample of 2,008 subjects. There was a substantial degree of inconsistency (I2=64%). The unweighted summary receiver-operating characteristic curve provided the best overall estimate of test performance, with an area under the curve of 0.84 (95% confidence interval [CI] 0.75 to 0.90). Sensitivity analysis based on study quality did not significantly change the results. Subgroup analysis including only studies that used a test threshold of 0.5 or 0.4 ng/mL yielded pooled estimates for sensitivity and specificity of 76% (95% CI 0.66 to 0.84) and 70% (95% CI 0.60 to 0.79), respectively. CONCLUSION: We found the diagnostic performance of the procalcitonin test for identifying bacteremia in ED patients to be moderate. Future research designed to determine the utility of the procalcitonin test as a diagnostic tool used in isolation for detecting bacteremia in ambulatory patients is needed before widespread clinical use.

Adult↗

PubMed2006

Emergency medicine practitioner knowledge and use of decision rules for the evaluation of patients with suspected pulmonary embolism: variations by practice setting and training level.

BACKGROUND: Several clinical decision rules (CDRs) have been validated for pretest probability assessment of pulmonary embolism (PE), but the authors are unaware of any data quantifying and characterizing their use in emergency departments. OBJECTIVES: To characterize clinicians' knowledge of and attitudes toward two commonly used CDRs for PE. METHODS: By using a modified Delphi approach, the authors developed a two-page paper survey including 15 multiple-choice questions. The questions were designed to determine the respondents' familiarity, frequency of use, and comprehension of the Canadian and Charlotte rules. The survey also queried the frequency of use of unstructured (gestalt) pretest probability assessment and reasons why physicians choose not to use decision rules. The surveys were sent to physicians, physician assistants, and medical students at 32 academic and community hospitals in the United States and the United Kingdom. RESULTS: Respondents included 555 clinicians; 443 (80%) work in academic practice, and 112 (20%) are community based. Significantly more academic practitioners (73%) than community practitioners (49%) indicated familiarity with at least one of the two decision rules. Among all respondents familiar with a rule, 50% reported using it in more than half of applicable cases. A significant number of these respondents could not correctly identify a key component of the rule (23% for the Charlotte rule and 43% for the Canadian rule). Fifty-seven percent of all respondents indicated use of gestalt rather than a decision rule in more than half of cases. CONCLUSIONS: Academic clinicians were more likely to report familiarity with either of these two specific decision rules. Only one half of all clinicians reporting familiarity with the rules use them in more than 50% of applicable cases. Spontaneous recall of the specific elements of the rules was low to moderate. Future work should consider clinical gestalt in the evaluation of patients with possible PE.

Adult↗

PubMed2006

End expiratory oxygen concentrations to predict central venous oxygen saturation: an observational pilot study.

BACKGROUND: A non-invasive surrogate measurement for central venous oxygen saturation (ScVO2) would be useful in the ED for assessing therapeutic interventions in critically ill patients. We hypothesized that either linear or nonlinear mathematical manipulation of the partial pressure of oxygen in breath at end expiration (EtO2) would accurately predict ScVO2. METHODS: Prospective observational study of a convenience sample of hemodialysis patients age > 17 years with existing upper extremity central venous catheters were enrolled. Using a portable respiratory device, we collected both tidal breathing and end expiratory oxygen and carbon dioxide concentrations, volume and flow on each patient. Simultaneous ScVO2 measurements were obtained via blood samples collected from the hemodialysis catheter. Two models were used to predict ScVO2: 1) Best-fit multivariate linear regression equation incorporating all respiratory variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume using the least squares method to estimate the pO2 that would occur at <20% of total lung capacity. RESULTS: From 21 patients, the correlation between EtO2 and measured ScVO2 yielded R2 = 0.11. The best fit multivariate equation included EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute difference from the measured ScVO2 of 8 +/- 6% (range -18 to +17%). The predicted ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling of the EtO2 curve did not accurately predict ScVO2 at any lung volume. CONCLUSION: We found no significant correlation between EtO2 and ScVO2. A linear equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for ScVO2.

Journal Article↗

PubMed2006

Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats.

Acute right ventricular (RV) failure following pulmonary embolism (PE) is a strong predictor of poor clinical outcome. Present studies test for an association between RV failure from experimental PE, inflammation, and upregulated chemokine expression. Additional experiments test if neutrophil influx contributes to RV dysfunction. PE was induced in male rats by infusing 24 microm microspheres (right jugular vein) producing mild hypertension (1.3 million beads/100 g, PE1.3), or moderately severe hypertension (2.0 million beads/100 g, PE2.0). Additional rats served as vehicle sham (0.01% Tween 20, Veh). In vivo RV peak systolic pressures (RVPSP) increased significantly, and then declined following PE2.0 (51 +/- 1 mm Hg 2 h; 49 +/- 1, 6 h; 44 +/- 1, 18 h). RV generated pressure of isolated, perfused hearts was significantly reduced in PE2.0 compared with PE1.3 or Veh. MCP-1 protein (ELISA) was elevated 21-fold and myeloperoxidase activity 95-fold in RV of PE2.0 compared with Veh or PE1.3. CINC-1, CINC-2, MIP-2, MCP-1, and MIP-1alpha mRNA also increased in RV of PE2.0. Histological analysis revealed massive accumulation of neutrophils (selective esterase stain) and monocyte/macrophages (CD68, ED-1) in RV of PE2.0 hearts in regions of myocyte damage. Electron microscopy showed myocyte necrosis and phagocytosis by inflammatory cells. LV function was normal and did not show increased inflammation after PE2.0. Treatment with anti-PMN antibody reduced RV MPO activity and prevented RV dysfunction. Conclusions-PE with moderately severe pulmonary hypertension (PE2.0) resulted in selective RV dysfunction, which was associated with increased chemokine expression, and infiltration of both neutrophils and monocyte/macrophages, indicating that a robust immune response occurred with RV damage following experimental PE. Experimental agranulocytosis reduced RV, suggesting that neutrophil influx contributed to RV damage.

Animals↗

PubMed2006

Multimarker panel to rule out acute coronary syndromes in low-risk patients.

OBJECTIVES: To test novel markers of acute coronary syndrome (ACS), monocyte chemoattractant protein-1 (MCP), myeloperoxidase (MPO), C-reactive protein (CRP), and brain natriuretic peptide (BNP) in low-risk emergency department (ED) patients who were evaluated for ACS in a chest pain unit (CPU). METHODS: A convenience sample of 414 patients underwent CPU evaluation, including provocative testing, and were followed prospectively for 45 days for ACS, which was defined as death, myocardial infarction (MI), revascularization, or >60% coronary artery stenosis prompting new medical treatment, adjudicated by three blinded reviewers. Published diagnostic thresholds were used to calculate diagnostic indices for each marker and for the multimarker panel. RESULTS: The prevalence of ACS was 7 in 414 (1.7%; 95% CI = 0.7% to 3.5%). Only MCP demonstrated a negative likelihood ratio [LR(-)] of less than 0.5, with a sensitivity of 85% (95% CI = 42% to 99%), specificity of 72% (95% CI = 67% to 76%), and LR(-) of 0.20 (95% CI = 0.04 to 0.71). For MPO, CRP, and BNP, LR(-) was 0.89 (95% CI = 0.26 to 2.05), 0.79 (95% CI = 0.40 to 1.01), and 0.90 (95% CI = 0.51 to 1.03), respectively. The sensitivity, specificity, and LR(-) of an abnormal multimarker panel were 86% (95% CI = 42% to 100%), 17% (95% CI = 13% to 21%), and 0.84 (95% CI = 0.15 to 3.12), respectively. CONCLUSIONS: The prevalence of ACS was very low but was similar to reports from other CPUs. BNP and CRP had high specificities, but had limited sensitivities, whereas MPO had a low specificity. Only MCP had a low LR(-) and should be studied further. The combined multimarker panel had an unexpectedly low sensitivity and specificity, yielding an LR(-) of 0.84, suggesting that the panel would not be an efficient screening test to decrease unnecessary CPU testing.

Acute Disease↗

PubMed2006

Frequency of thrombophilia-related genetic variations in patients with idiopathic pulmonary embolism in an urban emergency department.

BACKGROUND: The frequency of the thrombophilic genetic variants factor V Leiden (FVL) G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T in acutely symptomatic ambulatory patients with idiopathic pulmonary embolism (PE) has not been measured. METHODS: This prospective case-control study included patients presenting to urban emergency departments (EDs) with chest pain or shortness of breath. Cases were classified as idiopathic PE (49 patients with PE, but without overt risk factors for thrombosis). Control groups included (a) patients with nonidiopathic PE (152 patients with PE and risk factors); (b) patients in whom PE was excluded (91 patients who had PE ruled out with a structured protocol, including follow-up); and (c) patients in whom PE was not suspected (193 patients without a workup for PE, who were free of PE on follow-up). Blood DNA extracts were analyzed by PCR and restriction fragment length polymorphism analysis for the FVL, prothrombin, and MTHFR sequence variations. RESULTS: Either the FVL or prothrombin variant was found in 10% (95% confidence interval, 3%-22%) of patients with idiopathic PE compared with 13% (8%-20%) of nonidiopathic PE, 2% (5%-14%) of PE excluded, and 9% (5%-14%) of PE not suspected patients. Patients with idiopathic PE tended to have a higher frequency of homozygous MTHFR sequence variants, but mean (SD) plasma homocysteine concentrations were not increased [15.6 (5.4) micromol/L vs 12.8 (4.6) micromol/L for homozygous, and wild-type, respectively; P = 0.40]. CONCLUSIONS: The frequency of either the FVL or prothrombin sequence variant was not increased in idiopathic PE patients compared with nonidiopathic PE patients or patients who had PE excluded. These data suggest that genotyping to detect idiopathic PE would have limited clinical utility in the urban ED setting.

Acute Disease↗

PubMed2006

Interobserver agreement for the diagnosis of venous thromboembolism on computed tomography chest angiography and indirect venography of the lower extremities in emergency department patients.

OBJECTIVES: To determine interobserver agreement between radiologists for computed tomography (CT) angiography and venography. CT venography of the lower extremities combined with standard CT angiography of the chest may result in an increased overall diagnosis rate of venous thromboembolism (pulmonary embolism or deep venous thrombosis). METHODS: The study had a retrospective cohort design. The population consisted of emergency department patients who were evaluated for suspected pulmonary embolism. A random sample of 50 patients diagnosed and treated for venous thromboembolism and 50 age- and gender-matched patients whose CT angiograms and venograms were read as negative were enrolled. The original reading (R1) was compared with readings of two study radiologists: R2, a general radiologist, and R3, a radiologist with fellowship training in cross-sectional imaging. All readers were blinded to each other. RESULTS: Both R2 and R3 found both CT angiogram and venogram components technically adequate in 95% (95% CI = 89% to 98%) and 86% (95% CI = 78% to 92%) of studies, respectively. The agreement was very good for CT angiography (lowest agreement = 92%; lowest kappa = 0.83) and was good for CT venography (85%, kappa = 0.65). In nine cases, R1 read the CT angiogram as negative but the venogram as positive for DVT, whereas both R2 and R3 read both components as negative in four of these nine, suggesting a false-positive isolated DVT rate of 44% (95% CI = 19% to 73%). In no case did R1 read both scan components as negative when R2 and R3 agreed on presence of pulmonary embolism or DVT. CONCLUSIONS: Diagnosis of pulmonary embolism on CT angiography is more reliable than diagnosis of isolated DVT on CT venography.

Aged↗

PubMed2006

Prospective multicenter study of quantitative pretest probability assessment to exclude acute coronary syndrome for patients evaluated in emergency department chest pain units.

STUDY OBJECTIVE: We compare the diagnostic accuracy of 3 methods--attribute matching, physician's written unstructured estimate, and a logistic regression formula (Acute Coronary Insufficiency-Time Insensitive Predictive Instrument, ACI-TIPI)--of estimating a very low pretest probability (< or = 2%) for acute coronary syndromes in emergency department (ED) patients evaluated in chest pain units. METHODS: We prospectively studied 1,114 consecutive patients from 3 academic EDs, evaluated for acute coronary syndrome. Physicians collected data required for pretest probability assessment before protocol-driven chest pain unit testing. A pretest probability greater than 2% was considered "test positive." The criterion standard was the outcome of acute coronary syndrome (death, myocardial infarction, revascularization, or > 60% stenosis prompting new treatment) within 45 days, adjudicated by 3 independent reviewers. RESULTS: Fifty-one of 1,114 enrolled patients (4.5%; 95% confidence interval [CI] 3.4% to 6.0%) developed acute coronary syndrome within 45 days, including 4 of 991 (0.4%; 95% CI 0.1% to 1.0%) patients, discharged after a negative chest pain unit evaluation result, who developed acute coronary syndrome. Unstructured estimate identified 293 patients with pretest probability less than or equal to 2%, 2 had acute coronary syndrome, yielding sensitivity of 96.1% (95% CI 86.5% to 99.5%) and specificity of 27.4% (95% CI 24.7% to 30.2%). Attribute matching identified 304 patients with pretest probability less than or equal to 2%; 1 had acute coronary syndrome, yielding a sensitivity of 98.0% (95% CI 89.6% to 99.9%) and a specificity of 26.1% (95% CI 23.6% to 28.7%). ACI-TIPI identified 56 patients; none had acute coronary syndrome, yielding sensitivity of 100% (95% CI 93.0% to 100%) and specificity of 6.1% (95% CI 4.7% to 7.9%). CONCLUSION: In a low-risk ED population with symptoms suggestive of acute coronary syndrome, patients with a quantitative pretest probability less than or equal to 2%, determined by attribute matching, unstructured estimate, or logistic regression, may not require additional diagnostic testing.

Acute Disease↗

PubMed2006

Surrogate markers for adverse outcomes in normotensive patients with pulmonary embolism.

BACKGROUND: Although echocardiography has proven utility in risk stratifying normotensive patients with pulmonary embolism, echocardiography is not always available. OBJECTIVE: Test if a novel panel consisting of pulse oximetry, 12-lead electrocardiography, and serum troponin T would have prognostic equivalence to echocardiography and to examine the prognostic performance of age, previous cardiopulmonary disease, D-dimer, brain natriuretic peptide, and percentage of pulmonary vascular occlusion on chest computed tomography. DESIGN: Prospective cohort study. PATIENTS AND SETTING: Normotensive (systolic blood pressure of >100 mm Hg) emergency department and hospital inpatients with diagnosed pulmonary embolism who underwent cardiologist-interpreted echocardiography and other measurements within 15 hrs of anticoagulation. MEASUREMENTS AND MAIN RESULTS: End points were in-hospital circulatory shock or intubation, or death, recurrent pulmonary embolism, or severe cardiopulmonary disability (defined as echocardiographic evidence of severe right ventricular dysfunction with New York Heart Association class III dyspnea or 6-min walk test of <330 m) at 6-month follow-up. The two-one-sided test tested the hypothesis of equivalence with one-tailed alpha = 0.05 and Delta = 5%. Of 200 patients enrolled, data were complete for 181 (88%); 51 of 181 patients (28%) had an adverse outcome, including in-hospital complication (n = 18), death (n = 11), recurrent pulmonary embolism (n = 2), or cardiopulmonary disability (n = 20). Right ventricular dysfunction on initial echocardiogram was 61% sensitive (95% confidence interval, 46-74%) and 57% specific (48-66%). The panel was 71% sensitive (56-83%) and 62% specific (53-71%). The two-one-sided procedure demonstrated superiority of the panel to echocardiography for both sensitivity and noninferiority for specificity. No other biomarker demonstrated equivalence, noninferiority, or superiority for sensitivity and specificity. CONCLUSION: Normotensive patients with pulmonary embolism have a high rate of severe adverse outcomes during 6-month follow-up. A panel of three widely available tests can be used to risk stratify patients with pulmonary embolism when formal echocardiography is not available.

Age Factors↗

PubMed2006

Measurement of expired carbon dioxide, oxygen and volume in conjunction with pretest probability estimation as a method to diagnose and exclude pulmonary venous thromboembolism.

BACKGROUND: The classical alveolar pCO(2)-pO(2) relationship predicts that pulmonary embolism (PE) causes a low ratio of pCO(2)/pO(2) at end expiration. Our purpose was to define a simple protocol to collect expired pCO(2)/pO(2) to diagnose PE. Emergency department patients with suspected PE were enrolled. Clinical pretest probabilities for PE were estimated prior to diagnostic testing using the Canadian score and clinicians' unstructured estimate. Patients provided three 30-s periods of tidal breathing, separated by three deep exhalations. Expired pCO(2), pO(2) and breath volume were measured. All patients underwent standardized objective testing for PE including 90-day follow-up. Diagnosis (PE+) required anticoagulation for image-proven PE within 90 days. RESULTS: Of 200 patients enrolled, 178 were included in final analysis (24 PE+). The mean coefficient of variability for the deep-exhaled and end-tidal pCO(2)/pO(2) ratios were 6.8 +/- 6.7 and 7.5 +/- 6.8%, respectively. Mean pCO(2)/pO(2) ratios were stable throughout the collection periods in both methods. When compared with the deep-exhaled ratio, the end-tidal mean ratio demonstrated slightly better diagnostic utility by the area under the receiver operating characteristic curve. The end-tidal ratios were divided into four interval likelihood ratios and coupled with pretest probability from the two methods to generate three sets of posttest probabilities. Receiver operating characteristic analysis demonstrated good overall diagnostic performance (areas under the curves >0.88) for both posttest probability sets. CONCLUSION: This preliminary work demonstrates that the end-tidal pCO(2)/pO(2) averaged from 30 s of breathing can produce clinically relevant likelihood ratios for the diagnosis and exclusion of PE.

Breath Tests↗

PubMed2006

Prospective study of the diagnostic accuracy of the simplify D-dimer assay for pulmonary embolism in emergency department patients.

OBJECTIVE: To determine if a d-dimer assay (Simplify D-dimer; Agen Biomedical; Brisbane, Australia) can reliably exclude pulmonary embolism (PE) by producing a posttest probability of PE < 1% in low-risk, symptomatic emergency department (ED) patients. METHODS: Hemodynamically stable patients were evaluated for PE using a structured d-dimer-centered protocol; d-dimer testing was performed prior to imaging. Prior to testing, physicians completed an electronic data form that included their unstructured clinical estimate for the pretest probability of PE (< 15%, 15 to 40%, or > 40%) and the elements of the Charlotte rule and Canadian score for PE. Criterion standard was selective use of pulmonary vascular imaging and 90-day follow-up. RESULTS: We enrolled 2,302 patients (mean age, 45 +/- 16 years [+/- SD]; 31% male); 108 patients received a diagnosis of PE (4.7%; 95% confidence interval [CI], 3.6 to 5.6%). The overall sensitivity and specificity of the d-dimer assay were 80.6% (95% CI, 71.8 to 87.5%) and 72.5% (95% CI, 70.6 to 74.4%), respectively. The negative likelihood ratio and negative predictive value were 0.27 (95% CI, 0.18 to 0.39) and 98.7% (95% CI, 98.0 to 99.1%), respectively. The posttest prevalence of PE among low-risk patients with negative d-dimer results was 0.7% (95% CI, 0.3 to 1.4%) for the unstructured estimate, 1.2% (95% CI, 0.7 to 2.0%) for the Canadian score, and 1.1% (95% CI, 0.6 to 1.7%) for the Charlotte rule. CONCLUSIONS: The Simplify D-dimer assay had moderate sensitivity and relatively high specificity for PE in low-risk ED patients. The combination of a physician's unstructured estimate of pretest probability of PE of < 15% and a negative d-dimer result produced a posttest probability of PE of 0.7% (95% CI, 0.3 to 1.4%).

Adult↗

PubMed2006

Emergency department hypotension predicts sudden unexpected in-hospital mortality: a prospective cohort study.

OBJECTIVE: The prevalence and prognostic significance of nontraumatic hypotension measured in the emergency department (ED) have not been studied. We hypothesized that ED hypotension confers risk of in-hospital mortality. DESIGN: Prospective cohort study. SETTING: Large urban ED with 115,000 visits per year. PARTICIPANTS: Nontrauma ED patients aged > 17 years admitted to the hospital were prospectively identified on a random sample of 24-h blocks during 2004 to 2005. "Exposures" had any systolic BP (SBP) < 100 mm Hg in the ED; "nonexposures" all had SBP >/= 100 mm Hg in the ED. Deaths were classified as sudden and unexpected by independent observers using explicit criteria. OUTCOME MEASURES: Mortality rates were compared with confidence intervals (CIs), Kaplan-Meier survival curves, and multivariate logistic regression. RESULTS: A total of 4,790 patients were enrolled during the study period, with 887 patients (19%) in the exposure group. Exposures were more likely to die in the hospital compared with nonexposures (8% vs 3%; 95% CI for difference of 5%, 4 to 8%). Exposures were more likely to have sudden and unexpected death compared with nonexposures (2% vs 0.2%, 95% CI for difference of 1.8%, 1 to 3%). Kaplan-Meier estimates showed increased mortality in the exposure group at all time points (log-rank test, p < 0.001). Multivariate logistic regression revealed exposure to hypotension as an independent predictor of in-hospital mortality (odds ratio, 2.0; 95% CI, 1.3 to 2.8). CONCLUSION: Nontraumatic hypotension was documented in 19% of a random sample of ED patients admitted to the hospital. Patients exposed to hypotension had a significantly increased risk of death during hospitalization.

Adolescent↗

PubMed2005

Estimating the pretest probability threshold to justify empiric administration of heparin prior to pulmonary vascular imaging for pulmonary embolism.

Expertly interpreted pulmonary vascular imaging (either ventilation-perfusion scan or computed tomography chest angiography) is not uniformly available at most hospitals, including those in the US. When evaluating a patient with suspected pulmonary embolism during times when pulmonary vascular imaging is not available, clinicians frequently face the decision of whether to administer heparin while awaiting availability of imaging. In this report, we analyze published data to quantitate the probability of death or disability from untreated pulmonary embolism versus the probability of serious bleeding for one, two and seven days of heparin therapy. For these three time points, we estimate the pretest probability of pulmonary embolism to justify the empiric administration of heparin.

Data Interpretation, Statistical↗

PubMed2005

Electronic medical record review as a surrogate to telephone follow-up to establish outcome for diagnostic research studies in the emergency department.

BACKGROUND: Follow-up for diagnostic research studies might be facilitated if medical record review (MRR) could be used instead of telephone calls. OBJECTIVES: The authors hypothesized that MRR would yield similar accuracy to telephone follow-up. METHODS: This was a secondary analysis of 2,178 initially disease-free patients who were followed after enrollment in a diagnostic study of either acute coronary syndrome (45 days) or pulmonary embolism (90 days) conducted in an urban teaching emergency department (ED). Disease status (positive or negative) was defined explicitly. Using structured data forms, trained researchers performed MRR using a comprehensive electronic database, and formulated an opinion about disease status. Trained researchers, blinded to the MRR, then dialed telephone numbers, asked questions from a script, and categorized disease status. The criterion standard was adjudication by consensus of two of three physicians who independently determined disease status based on explicit criteria and access to all follow-up data. RESULTS: Adjudicators found that 13 of 2,178 patients developed disease during follow-up; all 13 true positives occurred among the 2,054 (94.3%) of patients who acknowledged intent to return to the study hospital. Telephone follow-up was successful in 81% of patients, and found all 13 true positives (sensitivity 100%) but with three additional false-positive cases. MRR disclosed 12 of 13 cases of disease (sensitivity 92%) with no false-positive cases. Further review of the one false-negative case from MRR revealed that it occurred after the prescribed time limit for follow-up. CONCLUSIONS: Under limited circumstances, accurate clinical follow-up for diagnostic studies conducted in the ED can be obtained by medical record review.

Acute Disease↗

PubMed2005

Pretest probability assessment derived from attribute matching.

BACKGROUND: Pretest probability (PTP) assessment plays a central role in diagnosis. This report compares a novel attribute-matching method to generate a PTP for acute coronary syndrome (ACS). We compare the new method with a validated logistic regression equation (LRE). METHODS: Eight clinical variables (attributes) were chosen by classification and regression tree analysis of a prospectively collected reference database of 14,796 emergency department (ED) patients evaluated for possible ACS. For attribute matching, a computer program identifies patients within the database who have the exact profile defined by clinician input of the eight attributes. The novel method was compared with the LRE for ability to produce PTP estimation <2% in a validation set of 8,120 patients evaluated for possible ACS and did not have ST segment elevation on ECG. 1,061 patients were excluded prior to validation analysis because of ST-segment elevation (713), missing data (77) or being lost to follow-up (271). RESULTS: In the validation set, attribute matching produced 267 unique PTP estimates [median PTP value 6%, 1st-3rd quartile 1-10%] compared with the LRE, which produced 96 unique PTP estimates [median 24%, 1st-3rd quartile 10-30%]. The areas under the receiver operating characteristic curves were 0.74 (95% CI 0.65 to 0.82) for the attribute matching curve and 0.68 (95% CI 0.62 to 0.77) for LRE. The attribute matching system categorized 1,670 (24%, 95% CI = 23-25%) patients as having a PTP < 2.0%; 28 developed ACS (1.7% 95% CI = 1.1-2.4%). The LRE categorized 244 (4%, 95% CI = 3-4%) with PTP < 2.0%; four developed ACS (1.6%, 95% CI = 0.4-4.1%). CONCLUSION: Attribute matching estimated a very low PTP for ACS in a significantly larger proportion of ED patients compared with a validated LRE.

Acute Disease↗

PubMed2005

D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed.

BACKGROUND: Pregnancy is known to increase the D-dimer concentration above the conventional normal threshold of 0.50 mg/L, leading to an increased false-positive D-dimer test when venous thromboembolism (VTE) is clinically suspected in a pregnant patient. Our aim was to determine the effect of normal pregnancy on the D-dimer concentration. METHODS: Healthy women who were seeking to become pregnant and had no preexisting condition known to increase the D-dimer concentration were identified. Quantitative D-dimer measurements (MDA turbidimetric assay) and fibrinogen assays were performed before conception, at each trimester, and at 4 weeks postpartum. Patients were excluded for fetal loss or preeclampsia. RESULTS: A total of 50 women were enrolled in the study, and blood samples were obtained at preconception and all trimesters from 23 women. The mean (SD) preconception D-dimer concentration was 0.43 (0.49) mg/L, and 79% of women had a D-dimer concentration <0.50 mg/L. D-Dimer increased with each trimester such that only 22% of women in the second trimester and none (of 23) in the third trimester (95% confidence interval, 0-14%) had a D-dimer concentration <0.50 mg/L. We found no correlation between either the D-dimer and fibrinogen concentrations or between the increases in D-dimer and fibrinogen with pregnancy. CONCLUSIONS: Normal pregnancy causes a progressive increase in circulating D-dimer. The D-dimer test has no use in ruling out VTE in the third trimester if a cutoff of 0.50 mg/L is used. A large management study is needed to establish new thresholds for the D-dimer to rule out VTE in each trimester.

Adult↗

PubMed2005

Derivation and validation of a Bayesian network to predict pretest probability of venous thromboembolism.

STUDY OBJECTIVE: A Bayesian network can estimate a numeric pretest probability of venous thromboembolism on the basis of values of clinical variables. We determine the accuracy with which a Bayesian network can identify patients with a low pretest probability of venous thromboembolism, defined as less than or equal to 2%. METHODS: Using commercial software, we derived a population of Bayesian networks from 25 input variables collected on 3,145 emergency department (ED) patients with suspected venous thromboembolism who underwent standardized testing, including pulmonary vascular imaging, and 90-day follow-up (11.0% of patients were venous thromboembolism positive). The best-fit Bayesian network was selected using a genetic algorithm. The selected Bayesian network was tested in a validation population of 1,423 ED patients prospectively evaluated for venous thromboembolism, including 90-day follow-up (8.0% were venous thromboembolism positive). The Bayesian network probability estimate was normalized to a score of 0% to 100%. RESULTS: Of 1,423 patients in the validation cohort, 711 (50%; 95% confidence interval [CI] 47% to 52%) had a score less than or equal to 2% that predicted a low pretest probability. Of these 711 patients, 700 (98.5%; 95% CI 97.2% to 99.2%) had no venous thromboembolism at follow-up. CONCLUSION: A Bayesian network, derived and independently validated in ED populations, identified half of the validation cohort as having a low pretest probability (< or =2%); 98.5% of these patients were correctly classified by the network.

Adult↗