Prospective, comprehensive assessment of cardiac troponin T testing after coronary artery bypass graft surgery.

BACKGROUND: The significance and clinical role of cardiac troponin testing after coronary artery bypass grafting remain unclear. METHODS AND RESULTS: Cardiac troponin T (cTnT) was measured during the first 24 hours after coronary artery bypass graft surgery in 847 consecutive patients. Only 17 patients (2.0%) had new Q waves or left bundle-branch block after surgery; however, cTnT elevation was observed in nearly all subjects, with a median cTnT concentration of 1.08 ng/mL overall. Direct predictors of postoperative cTnT values included preoperative myocardial infarction (P<0.001), preoperative intraaortic balloon pump (P<0.001), intraoperative/postoperative intraaortic balloon pump (P<0.001), number of distal anastomoses (P=0.005), bypass time (P<0.001), and number of intraoperative defibrillations (P=0.009), whereas glomerular filtration rate (P<0.001), off-pump coronary artery bypass grafting (P=0.003), and use of warm cardioplegia (P=0.02) were inversely associated with cTnT values. A linear association was seen between cTnT levels and length of stay and ventilator hours, and in an analysis adjusted for the Society for Thoracic Surgery Risk Model, cTnT remained independently prognostic for death (odds ratio, 3.20; P=0.003), death or heart failure (odds ratio, 2.04; P=0.008), death or need for vasopressors (odds ratio, 2.70; P<0.001), and the composite of all 3 (odds ratio, 2.57; P<0.001). In contrast to consensus-endorsed cTnT cut points for postoperative evaluation, a cTnT <1.60 ng/mL had a negative predictive value of 93% to 99% for excluding various post-coronary artery bypass graft surgery complications. CONCLUSIONS: cTnT concentrations after coronary artery bypass graft surgery are nearly universally elevated, are determined by numerous factors, and are independently prognostic for impending postoperative complications when used at appropriate cut points.

[Frequency of respiratory viruses and clinical characteristics in children attending a care center in Mexico City]. / Frecuencia de virus respiratorios y características clínicas de niños que acuden a un hospital en México.

OBJECTIVE: To describe the frequency of respiratory viruses and clinical characteristics in children with respiratory signs and symptoms in a tertiary care center in Mexico. MATERIAL AND METHODS: Patients with a clinical diagnosis of respiratory infection and a positive immunofluorescence result (Light Diagnostics) from January 2004 to October 2006 were included. RESULTS: From the 986 nashopharyngeal samples, 138 (14%) were positive by immunofluorescence. The frequency was: 80% RSV, 8% parainfluenza 1, 5% parainfluenza 3, 2% adenovirus, 2% influenza A, 1% parainfluenza 2 and 1% influenza B. CONCLUSIONS: Respiratory viruses were detected in 14% of samples tested. RSV was the most frequently identified virus and was associated with pneumonia and bronchiolitis in children younger than 3 years old.

Electronic alerts to prevent venous thromboembolism among hospitalized patients.

BACKGROUND: Prophylaxis against deep-vein thrombosis in hospitalized patients remains underused. We hypothesized that the use of a computer-alert program to encourage prophylaxis might reduce the frequency of deep-vein thrombosis among high-risk hospitalized patients. METHODS: We developed a computer program linked to the patient database to identify consecutive hospitalized patients at risk for deep-vein thrombosis in the absence of prophylaxis. The program used medical-record numbers to randomly assign 1255 eligible patients to an intervention group, in which the responsible physician was alerted to a patient's risk of deep-vein thrombosis, and 1251 patients to a control group, in which no alert was issued. The physician was required to acknowledge the alert and could then withhold or order prophylaxis, including graduated compression stockings, pneumatic compression boots, unfractionated heparin, low-molecular-weight heparin, or warfarin. The primary end point was clinically diagnosed, objectively confirmed deep-vein thrombosis or pulmonary embolism at 90 days. RESULTS: More patients in the intervention group than in the control group received mechanical prophylaxis (10.0 percent vs. 1.5 percent, P<0.001) or pharmacologic prophylaxis (23.6 percent vs. 13.0 percent, P<0.001). The primary end point occurred in 61 patients (4.9 percent) in the intervention group, as compared with 103 (8.2 percent) in the control group; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent (95 percent confidence interval, 92.5 to 95.4 percent) and 90.6 percent (95 percent confidence interval, 88.7 to 92.2 percent), respectively (P<0.001). The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent (hazard ratio, 0.59; 95 percent confidence interval, 0.43 to 0.81; P=0.001). CONCLUSIONS: The institution of a computer-alert program increased physicians' use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk.

Interval increase in right-left ventricular diameter ratios at CT as a predictor of 30-day mortality after acute pulmonary embolism: initial experience.

PURPOSE: To retrospectively determine if the interval increase of right ventricular-left ventricular (RV/LV) diameter ratio from negative prior to positive current computed tomographic (CT) examination findings for pulmonary embolism (PE) is more accurate for predicting 30-day mortality than positive CT ratio alone, by using patient 30-day mortality as reference standard. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study had waiver of informed consent and retrospectively reviewed 50 patients (19 men, 31 women; mean age, 60 years) with negative prior and positive current CT findings for acute PE (median interval, 63 days). Interval increase was defined as percentage change in RV/LV diameter ratio by using reformatted four-chamber views. Receiver operating characteristic (ROC) analysis compared the interval increase with the RV/LV diameter ratio from the positive findings alone for PE-related and all-cause mortality. RESULTS: Twelve (24%) patients died in 30 days; nine were PE-related. The interval increase was significantly more accurate overall than the ratio from the positive study alone for PE-related (area under the ROC curve [AUC] = 0.95 vs 0.73, P = .003) and all-cause (AUC = 0.81 vs 0.66, P = .05) mortality. The respective sensitivity, specificity, positive predictive value, and negative predictive value were 0.78 (seven of nine; 95% confidence interval [CI]: 0.43, 1.00), 0.93 (38 of 41; 95% CI: 0.83, 1.00), 0.70 (seven of 10; 95% CI: 0.38, 1.00), and 0.95 (38 of 40; 95% CI: 0.87, 1.00) for PE-related mortality (interval increase, >18%) and 0.75 (nine of 12; 95% CI: 0.49, 1.00), 0.89 (34 of 38; 95% CI: 0.80, 0.99), 0.69 (nine of 13; 95% CI: 0.44, 0.95), and 0.92 (34 of 37; 95% CI: 0.83, 1.00) for all-cause mortality (interval increase, >15%). At target sensitivity (0.75), specificity of interval increase was significantly higher than from positive scans alone for both PE-related (0.93 vs 0.59, P = .001) and all-cause (0.89 vs 0.58, P = .05) mortality. CONCLUSION: The interval increase in four-chamber RV/LV diameter ratio is more accurate than the diameter ratio of the CT examination with with positive findings for PE alone for mortality prediction after acute PE.

Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

BACKGROUND: Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. METHODS AND RESULTS: Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring (P=0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring (P≤0.02 for both). CONCLUSIONS: In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease.

Prospective Relation of Circulating Adipokines to Incident Metabolic Syndrome: The Framingham Heart Study.

BACKGROUND: Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross-sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS. METHODS AND RESULTS: Participants in the community-based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002-2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin-A, fatty acid-binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow-up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index ≥25 kg/m2) and prevalent MetS, excess body weight without MetS (metabolically healthy obese), and normal-weight with MetS (metabolically obese, normal-weight) with normal-weight participants without MetS as a referent. Metabolically healthy obese individuals (n=1467) had higher circulating levels of fetuin-A and fatty acid-binding protein 4 but lower levels of leptin, leptin receptor, and adiponectin (P<0.001 for all). The adipokine panel was associated with incident MetS (263 new-onset cases; P=0.002). Higher circulating concentrations of retinol-binding protein 4 and fetuin-A were associated with incidence of MetS (odds ratio per 1-SD increment log marker, 1.21; 95% CI, 1.03-1.41 [P=0.02] and 1.17; 95% CI, 1.01-1.34 [P=0.03], respectively). CONCLUSIONS: In our community-based sample of young to middle-aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol-binding protein 4 and fetuin-A marked future cardiometabolic risk.

Comparison of a single end point to determine optimal initial warfarin dosing (5 mg versus 10 mg) for venous thromboembolism.

There remains considerable controversy regarding optimal initial warfarin dosing in patients with acute venous thromboembolism. Therefore, an open-label, randomized trial comparing 2 warfarin initiation nomograms (5 vs 10 mg) was conducted in patients with acute venous thromboembolism. All participants received fondaparinux for > or = 5 days as a "bridge" to warfarin. The primary end point was defined as the number of days necessary to achieve 2 consecutive international normalized ratio laboratory test values > 1.9. A total of 50 patients were enrolled and randomly assigned to each of the treatment arms. The median time to 2 consecutive international normalized ratios was 5 days in the 2 groups. There was no statistical difference in achieving the primary end point using either the 5- or the 10-mg nomogram (p = 0.69). These results should provide clinicians with increased warfarin dosing options in patients presenting with acute venous thromboembolism.

Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension.

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism.

BACKGROUND: In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. Right ventricular (RV) enlargement on chest CT has previously been shown to correlate with an unstable hospital course, but its role as a predictor of death is unknown. METHODS AND RESULTS: We evaluated 431 consecutive patients (mean age, 59+/-16 years; 55% women) with acute PE confirmed by multidetector-row chest CT. With the use of multiplanar reformats of axial CT data, CT 4-chamber (4-CH) views were reconstructed and right and left ventricular dimensions (RV(D), LV(D)) were measured. RV enlargement, defined as RV(D)/LV(D) >0.9, was present in 276 (64.0%; 95% CI, 59.5% to 68.6%) patients. Thirty-day mortality rate was 15.6% (95% CI, 11.3% to 19.9%) in patients with and 7.7% (95% CI, 3.5% to 12.0%) without RV enlargement (log rank, P=0.018). The hazard ratio of RV(D)/LV(D) >0.9 for predicting 30-day death was 3.36 (95% CI, 1.13 to 9.97; P=0.029). On multivariable analysis, RV enlargement predicted 30-day death (hazard ratio, 5.17; 95% CI, 1.63 to 16.35; P=0.005) after adjusting for pneumonia (hazard ratio, 2.95; 95% CI, 1.19 to 3.83; P=0.002), cancer (hazard ratio, 2.13; 95% CI, 1.19 to 3.83; P=0.011), chronic lung disease (hazard ratio, 2.00; 95% CI, 1.04 to 3.86; P=0.039), and age (hazard ratio, 1.03; 95% CI, 1.01 to 1.05; P=0.005). CONCLUSIONS: In patients with acute PE, RV enlargement on reconstructed CT 4-CH view helps predict early death.

Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism.

BACKGROUND: We investigated the prognostic role of right ventricular enlargement on multidetector-row chest CT in acute pulmonary embolism (PE). METHODS AND RESULTS: We studied 63 patients with CT-confirmed PE who underwent echocardiography within the ensuing 24 hours. Adverse clinical events, defined as 30-day mortality or the need for cardiopulmonary resuscitation, mechanical ventilation, pressors, rescue thrombolysis, or surgical embolectomy, were present in 24 patients. We performed off-line CT measurements of right and left ventricular dimensions (RV(D), LV(D)) with axial and 2-dimensional reconstructed 4-chamber (4-CH) views. The proportion of patients with RV(D)/LV(D)>0.9 on the axial view was similar in patients with (70.8%) and those without adverse events (71.8%; P=0.577). In contrast, RV(D)/LV(D)>0.9 on the 4-CH view was more common in patients with (80.3%) than without (51.3%; P=0.015) adverse events. The area under the curve of RV(D)/LV(D) from the axial and 4-CH views for predicting adverse events was 0.667 and 0.753, respectively. Sensitivity and specificity of RV(D)/LV(D)>0.9 for predicting adverse events were 37.5% and 92.3% on the axial view and 83.3% and 48.7% on the reconstructed 4-CH view, respectively. RV(D)/LV(D)>0.9 on the 4-CH view was an independent predictor for adverse events (OR, 4.02; 95% CI, 1.06 to 15.19; P=0.041) when adjusted for age, obesity, cancer, and recent surgery. CONCLUSIONS: Right ventricular enlargement on the reconstructed CT 4-CH views predicts adverse clinical events in patients with acute PE. Ventricular CT measurements obtained from 4-CH views are superior to those from axial views for identifying high-risk patients.

Intermittent pneumatic compression and deep vein thrombosis prevention. A meta-analysis in postoperative patients.

Our objective was to overview the effectiveness of intermittent pneumatic compression (IPC) devices to prevent deep vein thrombosis (DVT) in postoperative patients, using meta-analysis methodology. We searched the Medline, metaRegister of Controlled Trials, and Cochrane database for studies published between 1970 and October 2004. Our inclusion criteria were: 1) randomized controlled trial of IPC versus no prophylaxis, 2) at least 20 patients per group, 3) at least one diagnostic DVT imaging test in all patients, and 4) clinical follow-up for at least the duration of hospitalization. A total of 2,270 patients were included in 15 eligible studies: 1,125 and 1,145 in the IPC and no prophylaxis group, respectively. The included studies formed a total of 16 treatment groups and were conducted in orthopedic (5), general surgical (4),oncologic (3), neurosurgical (3) and urologic (1) patient populations. In comparison to no prophylaxis, IPC devices reduced the risk of DVT by 60% (relative risk 0.40, 95% CI 0.29 - 0.56; p < 0.001). Contemporary randomized trials should be undertaken to test the utility of IPC in hospitalized medical patients as well as combined pharmacological plus IPC prophylaxis in both medical and surgical patients.

Gender differences in the administration of prophylaxis to prevent deep venous thrombosis.

We investigated gender differences in the prescription of prophylaxis against deep vein thrombosis (DVT) in 2,619 patients who developed acute DVT while being hospitalized for reasons other than DVT or were diagnosed with acute DVT as outpatients but who had been hospitalized within 30 days prior to DVT diagnosis. Men were 21% more likely than women to receive prophylaxis (OR 1.21, 95% CI 1.03-1.43; p=0.021) after adjusting for DVT risk factors, including surgery, trauma, prior DVT, age, and cancer.

CT pulmonary angiography for acute pulmonary embolism: cost-effectiveness analysis and review of the literature.

Pulmonary embolism (PE) continues to be a diagnostic challenge. Clinical assessment tools, D-dimer testing, ventilation perfusion (V/Q) scanning, ultrasound of the lower limbs, computed tomography (CT), and pulmonary angiography are all adequate methods used in the diagnosis of acute PE. With several options available to physicians, variation in regional costs and practices, and conflicting views on imaging modality performance data, there is considerable uncertainty regarding the most cost-effective strategy. Cost-effectiveness analysis is a helpful tool for determining the most effective diagnostic strategy when several viable options exist. Although limited by a number of necessary assumptions, cost-effective analyses offer a feasible solution to a diagnostic process by using an evidence-based approach. Current evidence shows that CT is a cost-effective alternative to V/Q scanning, particularly when sensitivity is sufficiently high. The purpose of this article is to review the cost-effective role of CT in the diagnosis of acute PE.

Clinical validity of a negative computed tomography scan in patients with suspected pulmonary embolism: a systematic review.

CONTEXT: The clinical validity of using computed tomography (CT) to diagnose peripheral pulmonary embolism is uncertain. Insufficient sensitivity for peripheral pulmonary embolism is considered the principal limitation of CT. OBJECTIVE: To review studies that used a CT-based approach to rule out a diagnosis of pulmonary embolism. DATA SOURCES: The medical literature databases of PubMed, MEDLINE, EMBASE, CRISP, metaRegister of Controlled Trials, and Cochrane were searched for articles published in the English language from January 1990 to May 2004. STUDY SELECTION: We included studies that used contrast-enhanced chest CT to rule out the diagnosis of acute pulmonary embolism, had a minimum follow-up of 3 months, and had study populations of more than 30 patients. DATA EXTRACTION: Two reviewers independently abstracted patient demographics, frequency of venous thromboembolic events (VTEs), CT modality (single-slice CT, multidetector-row CT, or electron-beam CT), false-negative results, and deaths attributable to pulmonary embolism. To calculate the overall negative likelihood ratio (NLR) of a VTE after a negative or inconclusive chest CT scan for pulmonary embolism, we included VTEs that were objectively confirmed by an additional imaging test despite a negative or inconclusive CT scan and objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months. DATA SYNTHESIS: Fifteen studies met the inclusion criteria and contained a total of 3500 patients who were evaluated from October 1994 through April 2002. The overall NLR of a VTE after a negative chest CT scan for pulmonary embolism was 0.07 (95% confidence interval [CI], 0.05-0.11); and the negative predictive value (NPV) was 99.1% (95% CI, 98.7%-99.5%). The NLR of a VTE after a negative single-slice spiral CT scan for pulmonary embolism was 0.08 (95% CI, 0.05-0.13); and after a negative multidetector-row CT scan, 0.15 (95% CI, 0.05-0.43). There was no difference in risk of VTEs based on CT modality used (relative risk, 1.66; 95% CI, 0.47-5.94; P = .50). The overall NLR of mortality attributable to pulmonary embolism was 0.01 (95% CI, 0.01-0.02) and the overall NPV was 99.4% (95% CI, 98.7%-99.9%). CONCLUSION: The clinical validity of using a CT scan to rule out pulmonary embolism is similar to that reported for conventional pulmonary angiography.

Invasive therapy along with glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival in non-ST-segment elevation acute coronary syndromes: a meta-analysis and review of the literature.

Current evidence suggests that routine invasive therapy in the setting of unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) reduces the incidence of composite end points (i.e., death, myocardial infarction, or angina.). The 2002 American College of Cardiology/American Heart Association guidelines recommend invasive therapy in high-risk patients, although it is unknown if such an approach improves survival. We conducted a meta-analysis on 5 studies in 6,766 UA/NSTEMI patients who were randomized to either routine invasive versus conservative therapy in the era of glycoprotein IIb/IIIa inhibitors and intracoronary stents. Compared with conservative therapy, an invasive approach suggested a reduction in mortality at 6 to 12 months (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.63 to 1.03) and at 24 months (RR 0.77, 95% CI 0.60 to 0.99). The composite end point of death or myocardial infarction was reduced throughout all periods of follow-up: at 30 days (RR 0.61, 95% CI 0.45 to 0.84), at 6 months (RR 0.75, 95% CI 0.63 to 0.89), and at 12 months (RR 0.78, 95% CI 0.65 to 0.92). For the same composite end point at 6 to 12 months, men benefited from invasive therapy (RR 0.68, 95% CI 0.57 to 0.81), as did troponin-positive patients (RR 0.74, 95% CI 0.59 to 0.94). The results for women (RR 1.07, 95% CI 0.82 to 1.41) and troponin-negative patients (RR 0.82, 95% CI 0.59 to 1.14) were equivocal. Routine invasive therapy in UA/NSTEMI patients along with adjunctive use of glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival. Enhanced risk stratification is needed in women and troponin-negative patients so that invasive therapy may be more effectively recommended in these groups.

Time trends in warfarin-associated hemorrhage.

The annual incidence of warfarin-related bleeding at Brigham and Women's Hospital increased from 0.97/1,000 patient admissions in the first time period (January 1995 to October 1998) to 1.19/1,000 patient admissions in the second time period (November 1998 to August 2002) of this study. The proportion of patients with major and intracranial bleeding increased from 20.2% and 1.9%, respectively, in the first time period, to 33.3% and 7.8%, respectively, in the second.