Enhanced didactic methods of smoking cessation training for medical students--a randomized study.

BACKGROUND: It is essential that medical students are adequately trained in smoking cessation. A web-based tobacco abstinence training program might supplement or replace traditional didactic methods. METHODS: One-hundred and forty third-year medical students were all provided access to a self-directed web-based learning module on smoking cessation. Thereafter, they were randomly allocated to attend 1 of 4 education approaches: (a) web-based training using the same tool, (b) lecture, (c) role playing, and (d) supervised interaction with real patients. RESULTS: Success of the intervention was measured in an objective structured clinical examination. Scores were highest in Group 4 (35.9 ± 8.7), followed by Groups 3 (35.7 ± 6.5), 2 (33.5 ± 9.4), and 1 (28.0 ± 9.6; p = .007). Students in Groups 4 (60.7%) and 3 (57.7%) achieved adequate counseling skills more frequently than those in Groups 2 (34.8%) and 1 (30%; p = .043). There was no difference in the scores reflecting theoretical knowledge (p = .439). Self-assessment of cessation skills and students' satisfaction with training was significantly better in Groups 3 and 4 as compared with 1 and 2 (p < .001 and p = .006, respectively). CONCLUSIONS: Role playing and interaction with real patients are equally efficient and both more powerful learning tools than web-based learning with or without a lecture.

Biomarkers: past, present, and future.

In recent decades biomarkers have become accepted tools in clinical practice [1]. Although there is no widely accepted definition of what constitutes a biomarker, for the context of this review we consider a biomarker to be a protein or other macromolecule that is associated with a biological process or regulatory mechanism. Hence measurement of this biomarker in blood, for example, might provide quantitative information that could be clinically helpful regarding this biological process or regulatory mechanism. In this paper we review recent advances with the use of biomarkers in three major clinical areas: diagnosis of myocardial infarction, diagnosis and management of heart failure, and diagnosis and management of inflammatory conditions in general and systemic infections in particular. Although these may look like unrelated medical challenges, recent clinical research in these areas by our groups and others has opened up opportunities and challenges that seem fundamental for biomarkers in general.

Accuracy of chest radiographs in the emergency diagnosis of heart failure.

The purpose of this study was to determine the diagnostic accuracy of chest radiographic findings of heart failure (HF) in current patients presenting with dyspnea in the emergency department. In a secondary analysis of the BASEL study, initial chest radiographs of 277 patients with acute dyspnea were evaluated by two radiologists blinded to the adjudicated diagnosis (56% had the final diagnosis of HF). Predefined radiographic criteria of HF were used. Statistical analysis included receiver-operating characteristic (ROC) analysis and calculation of a logistic regression model including B-type natriuretic peptide (BNP) levels. The reader's overall impression showed the highest area under the ROC curve for the diagnosis of HF in both supine and erect patient positions (0.855 and 0.857). Among individual radiographic findings, peribronchial cuffing in the supine position (0.829) showed the highest accuracies. The lowest accuracy was found for the vascular pedicle width in the supine position (0.461). Logistic regression analysis showed no significant differences between the reader's overall impression, the radiographic model, and BNP testing. In our study, the combination of radiographic features provided valuable information and was of comparable accuracy as BNP-testing for the diagnosis of HF.

Multimarker strategy for risk prediction in patients presenting with acute dyspnea to the emergency department.

BACKGROUND: Multimarker approaches improve risk prediction in patients presenting with acute coronary syndrome. We hypothesized that simultaneous assessment of B-type natriuretic peptide (BNP), cardiac troponin I (cTNI) and C-reactive protein (CRP) enables clinicians to better predict risk among patients with acute dyspnea presenting to the emergency department. METHODS AND RESULTS: In this post-hoc analysis of the B-Type natriuretic peptide for Acute Shortness of Breath Evaluation (BASEL) study, above biomarkers were available in 305 patients. Death occurred in 123 (40%) patients within 24 months of follow-up. Using prospectively defined cut-off points (BNP>100 pg/mL; cTNI>0.8 microg/L; CRP>5 mg/L) and categorizing patients by the number of elevated cardiac biomarkers, the 24 months risk of death increased in proportion to the number of cardiac biomarkers elevated (p<0.001 for trend). Elevated biomarkers significantly predicted increased risk of death at 24 months of follow-up in univariate Cox models (BNP: RR 4.78, 95%CI: 2.51-9.14; p<0.001; cTNI: RR: 2.29, 95%CI: 1.61-3.26, p<0.001; CRP: RR 1.98, 95%CI: 1.28-3.08; p=0.002). Multivariable Cox regression analysis revealed that elevated levels of BNP (p<0.001) and TNI levels (p<0.002) indicated increased risk of death during long-term follow-up, while only a statistical trend was seen for elevated CRP (p=0.09). Comparably, risk of death or rehospitalization significantly increased with the number of elevated biomarkers. CONCLUSIONS: Our findings suggest that a simple multimarker approach with simultaneous assessment of BNP, and cTNI demonstrates potential to assist clinicians in predicting risk of death and/or rehospitalization in patients presenting with acute dyspnea in the emergency department.

Medical and economic long-term effects of B-type natriuretic peptide testing in patients with acute dyspnea.

BACKGROUND: The objective of this prospective study was to assess the medical and economic long-term effects of using B-type natriuretic peptide (BNP) concentrations in the management of patients with acute dyspnea. METHODS: We performed follow-up analysis of the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation, a randomized study including 452 patients who presented to the emergency department with acute dyspnea. Participants were randomly assigned to a diagnostic strategy involving the rapid measurement of BNP concentrations (n = 225) or standard assessment (n = 227). Mortality was assessed at 720 days, morbidity and economic data at 360 days. RESULTS: BNP testing induced several important changes in initial patient management, including a reduction in the initial hospital admission rate, the use of intensive care, and initial time to discharge. At 720 days, 172 deaths had occurred. Cumulative all-cause 720-day mortality was not different between the BNP group (37%) and the control group (36%, P = 0.6). Morbidity as reflected by days spent in-hospital at 360 days was significantly lower in the BNP group [median 12 days ([interquartile range 2-28 days)] compared with the control group [median 16 (7-32)] days, P = 0.025]. Functional status was similar in both groups. Economic outcome as quantified by total treatment cost at 360 days was significantly improved in the BNP group (mean 10,144 dollars vs 12,748 dollars in the control group, P = 0.008). CONCLUSIONS: Rapid BNP testing in patients with acute dyspnea has no effect on long-term mortality. However, morbidity as quantified by days spent in-hospital and economic outcome are still improved at 360 days.

QRS and QTc interval prolongation in the prediction of long-term mortality of patients with acute destabilised heart failure.

OBJECTIVES: To quantify the prognostic utility of QRS and QTc interval prolongation in patients presenting with acute destabilised heart failure (ADHF) to the emergency department (ED). DESIGN: Prospective cohort study among patients enrolled in the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study. QRS and QT intervals were measured in 173 consecutive patients with ADHF. QT interval was corrected using the Bazett formula. The primary end point was all-cause mortality during the 720-day follow-up. RESULTS: QRS interval was prolonged (> or =120 ms) in 27% of patients, and QTc interval was prolonged (> or =440 ms) in 72% of patients. Baseline demographic and clinical characteristics were comparable in patients with normal and prolonged QRS or QTc intervals. A total of 78 patients died during follow-up. Interestingly, the 720-day mortality was similar in patients with prolonged and normal QTc (44% vs 42%, p = 0.546), but was significantly higher in patients with prolonged QRS interval than in those with normal QRS (59% vs 37%, p = 0.004). In Cox proportional hazards analysis, prolonged QRS interval was associated with a nearly twofold increase in mortality (HR 1.94, 95% CI 1.22 to 3.07; p = 0.005). This association persisted after adjustment for variables routinely available in the ED. CONCLUSIONS: Prolonged QRS interval, but not prolonged QTc interval, is associated with increased long-term mortality in patients with ADHF.

The integration of BNP and NT-proBNP into clinical medicine.

B-type natriuretic peptide (BNP) and NTproBNP have been shown to be extremely helpful in the diagnosis and management of patients with heart failure (HF). These neurohormones are predominately secreted from the left and the right cardiac ventricle in response to volume and pressure overload. BNP and NT-proBNP can be seen as quantitative markers of HF summarizing the extent of systolic and diastolic left ventricular dysfunction. Research data from clinical studies and six years of clinical experience with BNP allow us to provide clear recommendations regarding the integration of BNP/NT-proBNP into clinical medicine. With multiple additional indications in prospect, current evidence clearly supports the use of BNP and NT-proBNP in three clinical settings: patients with acute dyspnoea, prior to discharge in patients hospitalised with acute HF, and the longterm management of patients with HF.

Gender-specific risk stratification with B-type natriuretic peptide levels in patients with acute dyspnea: insights from the B-type natriuretic peptide for acute shortness of breath evaluation study.

OBJECTIVES: We examined whether B-type natriuretic peptide (BNP) levels allow gender-specific risk stratification in patients with acute dyspnea. BACKGROUND: B-type natriuretic peptide levels determined in patients with heart failure correlate with the severity of disease and prognosis. Gender differences in risk prediction are poorly examined. METHODS: The BASEL (B-type natriuretic peptide for Acute Shortness of Breath Evaluation) Study enrolled 190 female and 262 male patients presenting with acute dyspnea. RESULTS: At 24 months, cumulative mortality was comparable in women and men (38% vs. 35%, p = 0.66). Cox regression analyses revealed that BNP levels >500 pg/ml indicated a 5.1-fold increase in mortality for women (95% confidence interval [CI] 3.0 to 8.5, p < 0.001) versus a 1.8-fold increase in men (95% CI 1.2 to 2.6; p = 0.007). The area under the receiver-operating characteristic curve (AUC) for BNP to predict death was significantly higher in female (AUC: 0.80, 95% CI 0.73 to 0.86) than in male patients (AUC: 0.64, 95% CI 0.57 to 0.71; p = 0.001 for the comparison of AUC(women) versus AUC(men)). Women with BNP >500 pg/ml displayed a higher mortality as compared with men with BNP >500 pg/ml (68% vs. 46%, p = 0.015). Interaction analysis showed that BNP is a stronger predictor of death in women than in men (p = 0.008). CONCLUSIONS: B-type natriuretic peptide plasma levels seem to be stronger predictors of death in women than in men.

The impact of platelet count on mortality in unstable angina/non-ST-segment elevation myocardial infarction.

BACKGROUND: Expanding the knowledge of pathogenesis of arteriosclerosis points at a central role of platelets in the development of acute coronary syndromes. Therefore, we sought to determine the impact of platelet count on long-term outcome in unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) receiving contemporary treatment. METHODS: This prospective cohort study included 1616 consecutive patients with UA/NSTEMI. All patients underwent coronary angiography and, if appropriate, subsequent catheter-based revascularization within 24 hours of admission. Patients were divided in quintiles according to platelet count. The primary end point was all-cause mortality during long-term follow-up of up to 60 months. RESULTS: During follow-up (median 17 months, interquartile range 6-31 months), 89 deaths and 74 nonfatal myocardial infarctions occurred. Patients with higher platelet counts were younger, more often female, and had lower height and weight as compared with patients with lower platelet counts. Mortality was significantly lower among patients in the second quintile of platelet count (181-210 x 10(9)/L) as compared with the other quintiles (hazard ratio 0.39, 95% CI 0.19 to 0.81, P = .011). Kaplan-Meier survival analysis showed cumulative 4-year mortality rates of 12.5%, 3.8%, 10.4%, 9.8%, and 11.4% for patients in the first, second, third, fourth, and fifth quintiles. This association persisted after multivariate adjustment. No association of platelet count and nonfatal myocardial infarctions was observed. CONCLUSIONS: We found a nonlinear association between platelet count and long-term mortality. The lowest mortality was observed in patients with a platelet count between 181 and 210 x 10(9)/L.

Use of B-type natriuretic peptide in the detection of myocardial ischemia.

BACKGROUND: Exercise electrocardiography (ECG) has high specificity but limited sensitivity for the detection of myocardial ischemia. The aim of this study was to determine whether measurement of B-type natriuretic peptide (BNP) can improve the diagnostic accuracy of exercise ECG. METHODS: A total of 256 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography were enrolled. Levels of BNP were determined before and 1 minute after maximal exercise. RESULT: Inducible myocardial ischemia on perfusion images was detected in 127 patients (49.6%). Median BNP levels at rest and after peak exercise were higher in patients with than without inducible ischemia (71 pg/mL vs 38 pg/mL, P < .001; and 88 vs 52 pg/mL, P < .001, respectively). Compared with patients in the lowest peak exercise BNP quartile, those in the highest quartile of peak exercise BNP had more than 3 times the risk of inducible ischemia (adjusted relative risk 3.3, 95% CI 1.3-8.6, P = .015). Using 110 pg/mL as a cutoff, the combination of exercise ECG and peak exercise BNP level distinguished between ischemic and nonischemic patients more accurately than the exercise ECG alone (67% vs 60%, P = .024). Although the increase in accuracy was similar for the combination of exercise ECG with baseline BNP or DeltaBNP, overall, peak exercise BNP seemed to be the preferred measurement. CONCLUSIONS: B-type natriuretic peptide levels are associated with inducible myocardial ischemia. The use of BNP levels improves the diagnostic accuracy of exercise ECG.

Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea.

BACKGROUND: B-type natriuretic peptide (BNP) is a quantitative marker of heart failure that seems to be helpful in its diagnosis. METHODS: We performed a prospective randomized study (B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation) including 452 patients who presented to the emergency department with acute dyspnea to estimate the long-term cost-effectiveness of BNP guidance. Participants were randomly assigned to a diagnostic strategy involving the measurement of BNP levels (n = 225) or assessment in a standard manner (n = 227). Nonparametric bootstrapping was used to estimate the distribution of incremental costs and effects on the cost-effectiveness plane during 180 days of follow-up. RESULTS: Testing of BNP induced several important changes in management of dyspnea, including a reduction in the initial hospital admission rate, the use of intensive care, and total days in the hospital at 180 days (median, 10 days [interquartile range, 2-24 days] in the BNP group vs 14 days [interquartile range, 6-27 days] in the control group; P = .005). At 180 days, all-cause mortality was 20% in the BNP group and 23% in the control group (P = .42). Total treatment cost was significantly reduced in the BNP group (7930 dollars vs 10,503 dollars in the control group; P = .004). Analysis of incremental 180-day cost-effectiveness showed that BNP guidance resulted in lower mortality and lower cost in 80.6%, in higher mortality and lower cost in 19.3%, and in higher or lower mortality and higher cost in less than 0.1% each. Results were robust to changes in most variables but sensitive to changes in rehospitalization with BNP guidance. CONCLUSION: Testing of BNP is cost-effective in patients with acute dyspnea.

Inflammation and long-term mortality in acute congestive heart failure.

BACKGROUND: Systemic inflammation has long been recognized as a precipitator of acute congestive heart failure (CHF). The impact of inflammation on prognosis in acute CHF, however, is unknown. METHODS: This study evaluated the prognostic role of inflammation among 214 consecutive patients presenting with acute CHF to the emergency department. Patients were stratified according to C-reactive protein (CRP) levels determined on admission. The primary end point was all-cause mortality during 24-month follow-up. RESULTS: The median CRP level was 13.0 mg/L, with an intertertile range of 6.0 to 25.0 mg/L. Initial and long-term outcomes were significantly different to the detriment of patients with higher CRP levels. Patients in the highest CRP tertile significantly more often required admission to the intensive care unit (33% vs 14% in patients in the first tertile, P = .028) and died inhospital (15% vs 2% in patients in the first tertile, P = .027). Cumulative 24-month mortality rates were 33.5% in the first, 42.4% in the second, and 53.6% in the third tertile (P = .0265 by log-rank test). After multivariate adjustment, CRP remained an independent predictor of death (hazard ratio 1.4, 95% CI 1.1-1.8 for each step up in tertile, P = .044). CONCLUSIONS: Inflammation is a significant and independent predictor of long-term mortality in patients with acute CHF.

High prevalence of newly detected hypertension in hospitalized patients: the value of inhospital 24-h blood pressure measurement.

OBJECTIVE: Screening for hypertension in hospitalized patients could reduce the number of individuals with unrecognized hypertension. We hypothesized that 24-h blood pressure monitoring is an adequate tool to detect unrecognized hypertension among inpatients. METHODS: Clinically stable inpatients in the Department of Internal Medicine, Department of Visceral Surgery and Department of Orthopaedics were included in the cross-sectional study. Every patient underwent inhospital 24-h blood pressure measurement. Previously unknown hypertension was defined as 24-h blood pressure of at least 125/80 mmHg in the absence of known hypertension. Forty-two patients had an additional 24-h blood pressure measurement after discharge, to compare mean inhospital and outpatient 24-h blood pressure values. RESULTS: In 314 consecutive inpatients, 24-h blood pressure measurement was performed. Among 139 patients without known hypertension, 53 were hypertensive. The mean routine and 24-h blood pressures in these patients were 135/77 and 137/82 mmHg, respectively. Thirty-seven of these patients had normal routine blood pressure and could be detected only by 24-h blood pressure measurement. Patients with unknown hypertension had a marked cardiovascular risk profile, 26 being at high or very high cardiovascular risk. However, documented cardiovascular disease was present in only seven patients, suggesting that effective treatment could prevent a considerable number of cardiovascular events. The agreement between inhospital and outpatient 24-h blood pressure measurement in 42 patients was good. CONCLUSIONS: By performing inhospital 24-h blood pressure measurement, a considerable number of patients with previously unknown hypertension can be detected.

Use of B-type natriuretic peptide in the management of acute dyspnea in patients with pulmonary disease.

BACKGROUND: In patients with pulmonary disease, it is often challenging to distinguish exacerbated pulmonary disease from congestive heart failure (CHF). The impact of B-type natriuretic peptide (BNP) measurements on the management of patients with pulmonary disease and acute dyspnea remains to be defined. METHODS: This study evaluated the subgroup of 226 patients with a history of pulmonary disease included in the BASEL Study. Patients were randomly assigned to a diagnostic strategy with (n = 119, BNP group) or without (n = 107, clinical group) the use of BNP levels provided by a rapid bedside assay. Time to discharge and total cost of treatment were recorded as the primary end points. RESULTS: Baseline characteristics were similar in patients assigned to the BNP and control groups. Comorbidity was extensive, including coronary artery disease and hypertension in half of patients. The primary discharge diagnosis was CHF and exacerbated obstructive pulmonary disease in 39% and 33%, respectively. The use of BNP levels significantly reduced the need for hospital admission (81% vs 91%, P = .034). Median time to discharge was 9.0 days in the BNP group as compared with 12.0 days (P = .001) in the clinical group. Median total cost of treatment was $4841 in the BNP group as compared with $5671 in the clinical group (P = .008). Inhospital mortality was 8% in both groups. CONCLUSIONS: CHF is a major cause of acute dyspnea in patients with a history of pulmonary disease. Used in conjunction with other clinical information, rapid measurement of BNP reduced time to discharge and total treatment cost of these patients.

Routine blood pressure measurements do not predict adverse events in hospitalized patients.

PURPOSE: Countless blood pressure measurements are performed every day for almost every hospitalized patient. We analyzed the value of routine blood pressure measurements on patient care in an unselected group of hospitalized patients. METHODS: The study included 639 patients who were admitted to the hospital with a broad range of medical conditions. Two independent investigators reviewed the medical charts of the patients. Routine blood pressure values were abstracted from the patient charts and evaluated with respect to the occurrence of adverse clinical events in the study group. Changes in blood pressure between the last measurement just before adverse clinical events and the mean blood pressure values 72 hours before the adverse events were calculated and compared with mean normal day-to-day variations in blood pressure. RESULTS: In every patient, a mean of 1.6 +/- 0.6 routine blood pressure measurements per day were performed. Of the 639 patients in the study, 122 (19%) had clinical complications. The most commonly occurring complications were gastrointestinal bleeding (n = 15), falls (n = 13), other bleeding (n = 12) and pneumonia (n = 8). In patients who experienced clinical complications, pre-event systolic and diastolic blood pressure changes of at least 10 mm Hg occurred in 41% and 24% of the group, respectively, but this was not different from the normal day-to-day variations observed in patients who had no clinical complications. The results also were similar for patients who died or who had a severe adverse event that required admission to an intensive care unit. CONCLUSION: Routine blood pressure measurements in a general hospital patient population do not predict clinical adverse events.

Can airway obstruction be estimated by lung auscultation in an emergency room setting?

OBJECTIVE: Lung auscultation is a central part of the physical examination at hospital admission. In this study, the physicians' estimation of airway obstruction by auscultation was determined and compared with the degree of airway obstruction as measured by FEV(1)/FVC values. METHODS: Two hundred and thirty-three patients consecutively admitted to the medical emergency room with chest problems were included. After taking their history, patients were auscultated by an Internal Medicine registrar. The degree of airway obstruction had to be estimated (0=no, 1=mild, 2=moderate and 3=severe obstructed) and then spirometry was performed. Airway obstruction was defined as a ratio of FEV(1)/FVC <70%. The degree of airway obstruction was defined on FEV(1)/FVC as mild (FEV(1)/FVC <70% and >50%), moderate (FEV(1)/FVC <50% >30%) and severe (FEV(1)/FVC <30%). RESULTS: One hundred and thirty-five patients (57.9%) had no sign of airway obstruction (FEV(1)/FVC >70%). Spirometry showed a mild obstruction in 51 patients (21.9%), a moderate obstruction in 27 patients (11.6%) and a severe obstruction in 20 patients (8.6%). There was a weak but significant correlation between FEV(1)/FVC and the auscultation-based estimation of airway obstruction in Internal Medicine Registrars (Spearman's rho=0.328; P<0.001). The sensitivity to detect airway obstruction by lung auscultation was 72.6% and the specificity only 46.3%. Thus, the negative predictive value was 68% and the positive predictive value 51%. In 27 patients (9.7%), airway obstruction was missed by lung auscultation. In these 27 cases, the severity of airway obstruction was mild in 20 patients, moderate in 5 patients and severe in 2 patients. In 82 patients (29.4%) with no sign of airway obstruction (FEV(1)/FVC >70%), airway obstruction was wrongly estimated as mild in 42 patients, as moderate in 34 patients and as severe in 6 patients, respectively. By performing multiple logistic regression, normal lung auscultation was a significant and independent predictor for not having an airway obstruction (OR 2.48 (1.43-4.28); P=0.001). CONCLUSION: Under emergency room conditions, physicians can quite accurately exclude airway obstruction by auscultation. Normal lung auscultation is an independent predictor for not having an airway obstruction. However, airway obstruction is often overestimated by auscultation; thus, spirometry should be performed.