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.

Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea.

BACKGROUND: B-type natriuretic peptide levels are higher in patients with congestive heart failure than in patients with dyspnea from other causes. METHODS: We conducted a prospective, randomized, controlled study of 452 patients who presented to the emergency department with acute dyspnea: 225 patients were randomly assigned to a diagnostic strategy involving the measurement of B-type natriuretic peptide levels with the use of a rapid bedside assay, and 227 were assessed in a standard manner. The time to discharge and the total cost of treatment were the primary end points. RESULTS: Base-line demographic and clinical characteristics were well matched between the two groups. The use of B-type natriuretic peptide levels reduced the need for hospitalization and intensive care; 75 percent of patients in the B-type natriuretic peptide group were hospitalized, as compared with 85 percent of patients in the control group (P=0.008), and 15 percent of those in the B-type natriuretic peptide group required intensive care, as compared with 24 percent of those in the control group (P=0.01). The median time to discharge was 8.0 days in the B-type natriuretic peptide group and 11.0 days in the control group (P=0.001). The mean total cost of treatment was 5,410 dollars (95 percent confidence interval, 4,516 dollars to 6,304 dollars) in the B-type natriuretic peptide group, as compared with 7,264 dollars (95 percent confidence interval, 6,301 dollars to 8,227 dollars) in the control group (P=0.006). The respective 30-day mortality rates were 10 percent and 12 percent (P=0.45). CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment.

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.

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.

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.

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.

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.

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.

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.

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.

Hypertension is an independent risk factor for contrast nephropathy after percutaneous coronary intervention.

BACKGROUND: The administration of radiographic contrast agents is an important cause of acute renal failure. We hypothesised that hypertension is an independent risk factor for the development of contrast nephropathy in patients undergoing percutaneous coronary intervention. METHODS: 1383 consecutive patients scheduled for elective or emergency percutaneous coronary intervention were randomly assigned to receive isotonic or half-isotonic hydration. Contrast nephropathy was defined as a rise in serum creatinine of at least 44 micromol/l (0.5 mg/dl) within 48 h of the procedure. Hypertension was defined as self-reported history of treated or untreated diagnosed high blood pressure. RESULTS: The prevalence of hypertension was 63%. Patients with hypertension were significantly older, were more often female, smoked less and had a higher incidence of 3-vessel disease than patients without hypertension. The estimated glomerular filtration rate was slightly lower in hypertensive patients. There was no difference in preventive hydration regimen, type and quantity of contrast medium used, or quantity of intravenous fluids given. Contrast nephropathy developed in 17 of 874 hypertensive patients (2%) compared to 2 of 509 patients (0.4%) without hypertension (p = 0.016). When contrast nephropathy was defined as a 25% rise in baseline creatinine, the disease developed in 103 patients (12%) with and 36 patients (7%) without hypertension (p = 0.005). After adjustment for confounders, arterial hypertension remained an independent predictor of contrast nephropathy (odds ratio 4.6, 95% CI 1.0-20.5, p = 0.046). CONCLUSION: Hypertension is an independent risk factor for the development of contrast nephropathy. Further preventive strategies to lower the incidence of contrast nephropathy in hypertensive patients are warranted.

Gender differences in acute congestive heart failure.

BACKGROUND: Little is known about sex differences in baseline characteristics and outcomes in patients with acute congestive heart failure (CHF). METHODS AND RESULTS: This prospective observational study evaluated gender differences among 217 consecutive patients (124 men and 93 women) presenting with acute CHF to the emergency department. The primary endpoint was all-cause mortality. Women were older, and had less pulmonary comorbidity, but more noticeable jugular venous distension, as well as higher diastolic blood pressure and troponin level at presentation. Among contributing causes of acute CHF, myocardial ischaemia and anaemia were more frequent in women. Adequate medical CHF therapy was initiated more rapidly in women. Initial resource utilisation, time to discharge, and mortality were similar. Important differences to the disadvantage of women were noted during long-term follow-up. Mean cumulative survival was 619 (95% CI, 533-705) days in women as compared with 669 (95% CI, 601-737; p = 0.0663) in men. However, after multivariate adjustment female sex was not an independent predictor of long-term mortality (hazard ratio 1.14, 95% CI, 0.68-1.90; p = 0.619). Total spending for treatment cost was 11,858 US dollars University of Basel, University Hospital, Department of Internal Medicine, Switzerland (95% CI, 8921-14794) in women compared to 15,965 US dollars (95% CI, 12328-18003; p = 0.115) in men after 1 year. Functional status was similar in women and men at 6 and 12 months. CONCLUSIONS: The trend towards lower survival in women seems primarily related to higher age and other factors rather than gender itself. Female sex is not an independent predictor of long-term mortality in acute CHF.

Procalcitonin and the early diagnosis of infective endocarditis.

BACKGROUND: Variability in the clinical presentation of infective endocarditis (IE) makes the diagnosis a clinical challenge. We hypothesized that serum procalcitonin, a marker of systemic bacterial infection, might be helpful in its diagnosis. METHODS AND RESULTS: We conducted a prospective cohort study in 67 consecutive patients admitted to the hospital with the suspicion of IE or in whom the suspicion arose during the hospital course. IE was diagnosed by an interdisciplinary team that included an infectious disease specialist and a cardiologist who applied the Duke criteria. IE was confirmed in 21 patients. Procalcitonin was significantly higher in patients with IE (median 6.56 ng/mL) than in those with other final diagnoses (median 0.44 ng/mL, P<0.001). The area under the receiver operating characteristic curve that used procalcitonin to predict IE was 0.856 (95% CI 0.750 to 0.962), compared with 0.657 (95% CI 0.511 to 0.802) for C-reactive protein. The optimum concentration of procalcitonin for the calculation of positive and negative predictive accuracy as obtained from the receiver operating characteristic curve was 2.3 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 81%, specificity 85%, negative predictive value 92%, and positive predictive value 72%. Multiple logistic regression analysis revealed that procalcitonin was the only significant independent predictor of IE on admission (OR 1.52, 95% CI 1.07 to 2.15, P=0.018). CONCLUSIONS: Procalcitonin may be a valuable additional diagnostic marker in patients with suspected IE.

Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients.

BACKGROUND: This study sought to evaluate the predictive value of C-reactive protein (CRP) on long-term mortality in non-ST-elevation acute coronary syndromes (NSTACS) that were treated with a very early aggressive revascularization strategy. METHODS AND RESULTS: We conducted a prospective cohort study in 1042 consecutive patients with NSTACS who were undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 hours. Levels of CRP were determined on admission. The patients were followed for a mean of 20 months. In-hospital mortality was significantly higher in patients with a CRP>10 mg/L (3.7% versus 1.2% with CRP<3 mg/L and versus 0.8% with CRP of 3 to 10 mg/L; relative risk for CRP>10 mg/L compared with CRP< or =10 mg/L was 4.2, 95% confidence interval [CI] was 1.6 to 11.0; P=0.004). The increase in mortality in patients with CRP>10 mg/L persisted during follow-up. Long-term mortality was 3.4% with CRP<3 mg/L, 4.4% with CRP between 3 and 10 mg/L, and 12.7% with CRP>10 mg/L (relative risk for CRP>10 mg/L compared with CRP< or =10 mg/L, 0.8; 95% CI, 2.3 to 6.2; P<0.001). In addition, Kaplan-Meier survival analysis demonstrated a significantly reduced survival at 4 years in patients with a CRP>10 mg/L (78% versus 88% for a CRP of 3 to 10 mg/L and versus 92% for CRP<3 mg/L; P<0.001 by log-rank). In a multivariate analysis, CRP was an independent predictor of long-term mortality. Patients with a CRP>10 mg/L had >4 times the risk of death (odds ratio, 4.1; 95% CI, 2.3 to 7.2). CONCLUSION: CRP is a strong independent predictor of short and long-term mortality after NSTACS that are treated with very early revascularization.

A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents.

OBJECTIVES: The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up. BACKGROUND: Randomized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days. METHODS: After successful coronary stent implantation, 700 patients with 899 lesions were randomly assigned to receive a four-week course of either 500 mg ticlopidine (n = 345) or 75 mg clopidogrel (n = 355) in addition to 100 mg aspirin. Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months. RESULTS: Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel (hazard ratio with ticlopidine compared with clopidogrel, 0.30; 95% confidence interval [CI], 0.14 to 0.66; p = 0.003). After adjustment for co-variables, ticlopidine reduced the risk of cardiovascular death by 63% compared with clopidogrel. The combined end point of cardiovascular death or nonfatal myocardial infarction was present in 19 patients assigned ticlopidine, compared with 40 patients assigned clopidogrel (hazard ratio, 0.45; p = 0.005). The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 (95% CI, 0.14 to 0.64; p = 0.002). CONCLUSIONS: After the placement of coronary artery stents in unselected patients, ticlopidine was associated with a significantly lower mortality than clopidogrel. This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies.

Women do have an improved long-term outcome after non-ST-elevation acute coronary syndromes treated very early and predominantly with percutaneous coronary intervention: a prospective study in 1,450 consecutive patients.

OBJECTIVES: This study sought to assess gender-based differences in long-term outcome after very early aggressive revascularization for non-ST-elevation acute coronary syndromes (NSTACS). BACKGROUND: The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC) II study suggested that women have less to gain from an early invasive strategy. METHODS: We conducted a prospective cohort study in 1,450 consecutive patients with NSTACS undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 h of admission. The combined primary end point was defined as death or nonfatal myocardial infarction (MI) and recorded for a mean of 20 months. RESULTS: Percutaneous coronary intervention was performed in more than 50% of patients in women and men and accompanied with stenting in 80%. The percutaneous coronary intervention:coronary artery bypass grafting ratio was 4:1 in men and 5:1 in women. The primary end point occurred in 29 (7.0%) women as compared with 108 (10.5%) men (hazard ratio for women, 0.65; 95% confidence interval [CI] 0.42 to 0.99; p = 0.045). Backward-stepwise multivariate Cox regression analysis identified female gender as an independent predictor of death or MI (hazard ratio for female gender, 0.51; 95% CI, 0.28 to 0.92; p = 0.024). Kaplan-Meier analysis showed that women had consistently lower event rates during the entire follow-up period (p = 0.037 by log-rank for death or MI). CONCLUSIONS: Women treated with very early aggressive revascularization with coronary stenting of the culprit lesion as the primary revascularization strategy have a better long-term outcome as compared with men.

Reference values for methacholine reactivity (SAPALDIA study).

BACKGROUND: The distribution of airway responsiveness in a general population of non-smokers without respiratory symptoms has not been established, limiting its use in clinical and epidemiological practice. We derived reference equations depending on individual characteristics (i.e., sex, age, baseline lung function) for relevant percentiles of the methacholine two-point dose-response slope. METHODS: In a reference sample of 1567 adults of the SAPALDIA cross-sectional survey (1991), defined by excluding subjects with respiratory conditions, responsiveness during methacholine challenge was quantified by calculating the two-point dose-response slope (O'Connor). Weighted L1-regression was used to estimate reference equations for the 95th , 90th , 75th and 50th percentiles of the two-point slope. RESULTS: Reference equations for the 95th , 90th , 75th and 50th percentiles of the two-point slope were estimated using a model of the form a + b* Age + c* FEV1 + d* (FEV1)2 , where FEV1 corresponds to the pre-test (or baseline) level of FEV1. For the central half of the FEV1 distribution, we used a quadratic model to describe the dependence of methacholine slope on baseline FEV1. For the first and last quartiles of FEV1, a linear relation with FEV1 was assumed (i.e., d was set to 0). Sex was not a predictor term in this model. A negative linear association with slope was found for age. We provide an Excel file allowing calculation of the percentile of methacholine slope of a subject after introducing age--pre-test FEV1--and results of methacholine challenge of the subject. CONCLUSION: The present study provides equations for four relevant percentiles of methacholine two-point slope depending on age and baseline FEV1 as basic predictors in an adult reference population of non-obstructive and non-atopic persons. These equations may help clinicians and epidemiologists to better characterize individual or population airway responsiveness.

High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration.

The objective of this study was to evaluate whether the interleukin (IL)-1 decoy receptor (R), a negative pathway of regulation of IL-1, is correlated with severity of infection in critically ill patients and reflects the activation of anti-inflammatory pathways by glucocorticoid hormones. Plasma samples were obtained from 101 consecutive, critically ill patients admitted to the intensive care unit with different severities of microbial infection, as defined by standardized criteria. Here, we report that the IL-1 type II decoy R(II) is elevated in critically ill patients, especially in severe, systemic infection and culture-positive infections. In patients with a marked systemic inflammatory response syndrome 4, a pronounced, sepsis-induced further increase of circulating IL-1 decoy RII levels was evident. Thirty-six patients treated with glucocorticoid hormones had significantly higher levels of IL-1 decoy RII, but lower IL-6 and C-reactive protein, than 67 untreated subjects. The usefulness of IL-1RII, in particular as a potential marker for the activation of anti-inflammatory pathways or for responsiveness to anti-inflammatory agents such as glucocorticoid hormones, deserves further analysis.