Low-risk Stratum Research Articles

Comparison of the reliability and validity of four contemporary risk stratification schemes to predict thromboembolism in non-anticoagulated patients with atrial fibrillation

BackgroundThe risk of thromboembolic (TE) complications in atrial fibrillation (AF) patients is not homogeneous. Risk schemes can help target anticoagulant therapy for patients at highest risk of TE complications. ObjectivesTo test the predictive ability of 4 risk schemes: The Framingham, the 8th ACCP, the ACC/AHA/ESC 2006, and the CHA2DS2-VASc. Methods186 patients with non-valvular AF and off anticoagulant therapy were included. All subjects who experienced a stroke, transient ischemic attack, or peripheral embolism were identified. Each schema was divided into low, intermediate, and high-risk categories. Discrimination was assessed via the c-statistic. ResultsWe identified 10 TE events that occurred during 668 person-years off anticoagulation therapy. All risk schemes had fair discriminating ability (c-statistic ranged from 0.59 [for CHA2DS2-VASc] to 0.73 [for Framingham]). The proportion of patients assigned to individual risk categories varied widely across schemes. CHA2DS2-VASc categorized the fewest patients into low and intermediate-risk categories, whereas the Framingham schema assigned the highest patients into low-risk strata. There were no TE events in the low and intermediate-risk categories using CHA2DS2-VASc, whereas the most schemes assigned patients into intermediate-risk category had a event rate ranging from 2.5 (ACC/AHA/ESC and 8th ACCP schemes) to 6% (Framingham). The negative predictive value of TE events was of 100% for the no high-risk patients using CHA2DS2-VASc. ConclusionsCompared to ACC/AHA/ESC, 8th ACCP, and Framingham, CHA2DS2-VASc risk stratification schema may be better in discriminating between patients at a low and intermediate risk of TE complications.

The motor component does not convey all the mortality prediction capacity of the Glasgow Coma Scale in trauma patients

PurposeWe tested the hypothesis that the motor component of the Glasgow Coma Scale (GCS) conveys most of the predictive information of triage scores (Triage Revised Trauma Score [T-RTS] and the Mechanism, GCS, Age, arterial Pressure score [MGAP]) in trauma patients. MethodWe conducted a multicenter prospective observational study and evaluated 1690 trauma patients in 14 centers. We compared the GCS, T-RTS, MGAP, and Trauma Related Injury Severity Score (reference standard) using the full GCS or its motor component only using logistic regression model, area under the receiver operating characteristic curve, and reclassification technique. ResultsAlthough some changes were noted for the GCS itself and the Trauma Related Injury Severity Score, no significant change was observed using the motor component only for T-RTS and MGAP when considering (1) the odds ratio of variables included in the logistic model as well as their discrimination and calibration characteristics, (2) the area under the receiver operating characteristic curve (0.827 ± 0.014 vs 0.831 ± 0.014, P = .31 and 0.863 ± 0.011 vs 0.859 ± 0.012, P = .23, respectively), and (3) the reclassification technique. Although the mortality rate remained less than the predetermined threshold of 5% in the low-risk stratum, it slightly increased for MGAP (from 1.9% to 3.9%, P = .048). ConclusionThe use of the motor component only of the GCS did not change the global performance of triage scores in trauma patients. However, because a subtle increase in mortality rate was observed in the low-risk stratum for MGAP, replacing the GCS by its motor component may not be recommended in every situation.

Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study)

To define the long-term outcome of patients presenting with acute coronary syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to test the hypothesis that the GRACE (Global Registry of Acute Coronary Events) risk score predicts mortality and death/MI at 5 years. In the GRACE long-term study, UK and Belgian centres prospectively recruited and followed ACS patients for a median of 5 years (1797 days). Primary outcome events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke and re-hospitalization for ACS. There were 736 deaths, 19.8% (482 CVDs, 13%) and 347 (9.3%) MIs (>24 h), 261 strokes (7.7%), and 452 (17%) subsequent revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2% had >1 admission, 9.2% had 5+ admissions. These events were despite high rates of guideline indicated therapies. The GRACE score was highly predictive of all-cause death, CVD, and CVD/MI at 5 years (death: χ(2) likelihood ratio 632; Wald 709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P < 0.0001; CVD/MI C-statistic 0.70, P < 0.0001). Compared with the low-risk GRACE stratum (ESC Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95% CI 1.63, 2.81] and those with high-risk (HR 6.36, 95% CI 4.95, 8.16) had two- and six-fold higher risk of later death (Cox proportional hazard). A landmark analysis after 6 months confirmed that the GRACE score predicted long-term death (χ(2) likelihood ratio 265.4; Wald 289.5, P < 0.0001). Although in-hospital rates of death and MI are higher following STEMI, the cumulative rates of death (and CVD) were not different, by class of ACS, over the duration of follow-up (Wilcoxon = 1.5597, df = 1, P = 0.21). At 5 years after STEMI 269/1403 (19%) died; after non-STEMI 262/1170 (22%) after unstable angina (UA) 149/850 (17%). Two-thirds (68%) of STEMI deaths occurred after initial hospital discharge, but this was 86% for non-STEMI and 97% for UA. The GRACE risk score predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI. Their morbidity burden is high (MI, stroke, readmissions) and the substantial late mortality in non-STE ACS is under-recognized. The findings highlight the importance of pursuing novel approaches to diminish long-term risk.

Simple score to identify colectomy risk in ulcerative colitis hospitalizations

Patients hospitalized for ulcerative colitis (UC) are at high risk for colectomy. Despite growing interest in research using administrative data in inflammatory bowel disease, there is no available tool in such research to stratify disease severity or identify patients at high risk for colectomy. Using the Nationwide Inpatient Sample (NIS) 2004, we identified patients hospitalized for UC flare through appropriate ICD-9-CM discharge diagnosis codes (556.x). Our primary outcome of interest was undergoing total colectomy (45.8). Multivariate logistic regression models were constructed to identify independent predictors of colectomy. From this, a cumulative risk score was developed. Hospitalizations were divided into 3 strata (low, intermediate, high) based on the odds of colectomy. There were a total of 15,142 hospitalizations with a discharge diagnosis of UC included in our study among whom 366 patients underwent total colectomy (2.4%). Anemia (odds ratio [OR] 2.13), requirement for blood transfusion (OR 2.22), malnutrition (OR 4.53), and total parenteral nutrition (OR 4.30) were independent predictors of colectomy as were transfer in from another hospital (OR 2.06) and admission to a teaching hospital (OR 1.73). The cumulative colectomy risk score ranged from 0-8, with significantly higher risk of colectomy in the high-risk stratum (13.7%) compared to the intermediate-risk (4.2%, P < 0.001) and low-risk (1.3%, P < 0.001) strata. The risk score performed well in its discriminative ability with an area under the curve of 0.70. We propose a simple and novel risk score to stratify the severity of UC hospitalizations and predict colectomy in this population.

Cardiovascular risk factor trends and options for reducing future coronary heart disease mortality in the United States of America

To examine the potential for reducing cardiovascular risk factors in the United States of America enough to cause age-adjusted coronary heart disease (CHD) mortality rates to drop by 20% (from 2000 baseline figures) by 2010, as targeted under the Healthy People 2010 initiative. Using a previously validated, comprehensive CHD mortality model known as IMPACT that integrates trends in all the major cardiovascular risk factors, stratified by age and sex, we calculated how much CHD mortality would drop between 2000 and 2010 in the projected population of the United States aged 25-84 years (198 million). We did this for three assumed scenarios: (i) if recent risk factor trends were to continue to 2010; (ii) success in reaching all the Healthy People 2010 risk factor targets, and (iii) further drops in risk factors, to the levels already seen in the low-risk stratum. If age-adjusted CHD mortality rates observed in 2000 remained unchanged, some 388,000 CHD deaths would occur in 2010. First scenario: if recent risk factor trends continued to 2010, there would be approximately 19,000 fewer deaths than in 2000. Although improved total cholesterol, lowered blood pressure in men, decreased smoking and increased physical activity would account for some 51,000 fewer deaths, these would be offset by approximately 32,000 additional deaths from adverse trends in obesity and diabetes and in blood pressure in women. Second scenario: If Healthy People 2010 cardiovascular risk factor targets were reached, approximately 188,000 CHD deaths would be prevented. Scenario three: If the cardiovascular risk levels of the low-risk stratum were reached, approximately 372,000 CHD deaths would be prevented. Achievement of the Healthy People 2010 cardiovascular risk factor targets would almost halve the predicted CHD death rates. Additional reductions in major risk factors could prevent or postpone substantially more deaths from CHD.

Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment: U.S. Preventive Services Task Force Recommendation Statement

New recommendation from the U.S. Preventive Services Task Force (USPSTF) on the use of nontraditional, or novel, risk factors in assessing the coronary heart disease (CHD) risk of asymptomatic persons. Systematic reviews were conducted of literature since 1996 on 9 proposed nontraditional markers of CHD risk: high-sensitivity C-reactive protein, ankle-brachial index, leukocyte count, fasting blood glucose, periodontal disease, carotid intima-media thickness, coronary artery calcification score on electron-beam computed tomography, homocysteine, and lipoprotein(a). The reviews followed a hierarchical approach aimed at determining which factors could practically and definitively reassign persons assessed as intermediate-risk according to their Framingham score to either a high-risk or low-risk strata, and thereby improve outcomes by means of aggressive risk-factor modification in those newly assigned to the high-risk stratum. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using the nontraditional risk factors studied to screen asymptomatic men and women with no history of CHD to prevent CHD events. (I statement).

Goal attainment for multiple cardiovascular risk factors in community‐based clinical practice (a Canadian experience)

The primary goal in the clinical management of atherosclerotic cardiovascular (CV) disease is to reduce major CV risk factors. A single risk factor approach has been traditionally used for demonstrating effectiveness of therapeutic interventions designed to reduce CV risk in clinical trials, but a global CV risk reduction approach should be adopted when assessing effectiveness in the clinical practice setting. To explore combined goal achievement for low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose and systolic-diastolic blood pressure, in patients with dyslipidemia on pharmacotherapy in community-based clinical practices across Canada. In a cross-sectional study, patients filling a prescription for any antihyperlipidemia therapy in selected pharmacies in Ontario, Quebec, British Columbia and Nova Scotia were recruited. Family physicians of the participating patients were requested to provide information from the patient's medical record. Ten-year CV risk was identified for each patient according to the Framingham criteria. High-risk patients comprised 52% of the patient population; 34% were moderate-risk and 14% were low-risk. Patients had a mean of 2.8 CV risk factors; high-risk 3.7, moderate-risk 2.3 and low-risk 1.2. LDL-C goal attainment was observed in 62%, 79% and 96% of patients in high-risk, moderate-risk and low-risk strata respectively. BP goal was achieved in high-risk patients 58%, moderate-risk 83% and low-risk 95%. Glucose levels were below the threshold in 91% of patients. Complete global CV risk reduction was achieved in only 21%, 66% and 92% of high-risk, moderate-risk and low-risk strata respectively. This study illustrates that many patients with dyslipidemia in the Canadian population, and in particular the high-risk patients, did not meet the therapeutic targets for specific CV risk factors according to the Canadian guidelines. Overall, 54% of patients failed to achieve a state of complete global CV risk reduction.

Abstract 3124: The Magnitude of Reclassification Indices for Individual Predictors of Global Cardiovascular Risk

Methods based on risk stratification have recently been proposed to evaluate and compare predictive risk models, but their performance in clinically relevant populations has not been demonstrated, including for well-known cardiovascular risk predictors. We fit models including traditional risk factors as well as high-sensitivity C-reactive protein (hsCRP) and parental history of myocardial infarction in prospective data from 24,558 women in the Women’s Health Study who experienced 766 cardiovascular events over an average 10-year follow-up. Fit of models with and without each risk factor was evaluated using both traditional methods, including the C index and goodness-of-fit test, and newly proposed methods for reclassification, which compare predicted risk strata for two models. Reclassification calibration compares observed to predicted risk for each model within reclassified risk strata; the net reclassification improvement (NRI) estimates the net proportion of cases moving to higher vs. lower risk strata; the clinical NRI estimates the NRI among those at intermediate risk; and the integrated discrimination improvement (IDI) compares the mean difference in predicted probabilities between cases and controls for two models. For each model set, the reclassification calibration statistic showed a significant lack of fit in models excluding each of these predictors, indicating that the predicted risk did not fit that observed in reclassified strata. Values of the NRI were 20% for age, 8–11% for hemoglobin A1c in diabetics, smoking, and systolic blood pressure, and 3–5% for lipids, hsCRP, and parental history. The clinical NRI for those initially at intermediate risk was 46% for age and ranged from 9–29% for other risk factors. The IDI was less than 2% for all predictors, including age. These data demonstrate the magnitude of several newly proposed reclassification measures for well-known cardiovascular risk factors. These measures can demonstrate the potential of new models and markers to change risk strata and alter treatment decisions, and should be considered as another means to compare models and assess the accuracy of absolute risk estimates and risk strata.

Estratificación y grado de control del riesgo cardiovascular en la población hipertensa española. Resultados del estudio DICOPRESS

Hypertension, together with other contributing risk factors, is a major risk for cardiovascular disease. The aim of this study was to assess the cardiovascular risk in the Spanish hypertensive population according to the 2003 European Society of Hypertension-European Society of Cardiology (ESH/ESC) guidelines criteria and to determine the control rate of the main cardiovascular risk factors (CVRF). Observational and transversal study including 22,639 patients with essential hypertension, who have been admitted to primary care units and hypertension units in Spain. Dyslipemia (52.1%), diabetes (36.6%) and smoking (22.3%) were the most prevalent CVRF. Cardiovascular risk stratification according to the ESH/ESC guidelines showed that more than 70% patients were considered at high added risk (36.9%) or at very high added risk (35.8%), whereas only 7.6% were classified in the low-risk stratum. Blood pressure was the worst controlled risk factor among hypertensive patients (80.6%). Total cholesterol was also poorly controlled in a high percentage of the analyzed population (66.4%). Diabetes was the best predictor of uncontrolled blood pressure with an odds ratio of 5.25 (99% confidence interval, 4.57-6.06). Coexistence of several cardiovascular risk factors, as well as the presence of target organ damage and associated cardiovascular conditions in the Spanish hypertensive population, increase the vascular risk, complicate the control in the hypertensive population and show the convenience of using ESH/ESC 2003 guidelines to estimate the cardiovascular risk.

Prognostic Models for Selecting Patients With Acute Pulmonary Embolism for Initial Outpatient Therapy

To assess the performance of two prognostic models in predicting short-term mortality in patients with pulmonary embolism (PE). We compared the test characteristics of two prognostic models for predicting 30-day outcomes (mortality, thromboembolic recurrences, and major bleeding) in a cohort of 599 patients with objectively confirmed PE. Patients were stratified into the PE severity index (PESI) risk classes I-V and the Geneva low-risk and high-risk strata. We compared the discriminatory power of both prognostic models. The PESI classified fewer patients as low risk (strata I and II) [36%; 216 of 599 patients; 95% confidence interval (CI), 32 to 40%] compared to the Geneva prediction rule (84%; 502 of 599 patients; 95% CI, 81 to 87%) [p < 0.0001]. Using either prediction rule, the low-risk groups showed statistically relevant 30-day mortality difference (PESI, 0.9%; 95% CI, 0.3 to 2.2; vs Geneva, 5.6%; 95% CI, 3.6 to 7.6) [p < 0.0001], although nonfatal recurrent venous thromboembolism or major bleeding rates were statistically similar (PESI, 2.8%; 95% CI, 0.6 to 5.0%; vs Geneva, 4.2%; 95% CI, 2.4 to 5.9%). The area under the receiver operating characteristic curve was higher for the PESI (0.76; 95% CI, 0.69 to 0.83) than for the Geneva score (0.61; 95% CI, 0.51 to 0.71) [p = 0.002]. The PESI quantified the prognosis of patients with PE better than the Geneva score. This study demonstrated that PESI can select patients with very low adverse event rates during the initial days of acute PE therapy and assist in selecting patients for treatment in the outpatient setting.

Comparison of Peak Exercise Oxygen Consumption and the Heart Failure Survival Score for Predicting Prognosis in Women Versus Men

The Heart Failure Survival Score (HFSS) and peak exercise oxygen consumption (VO2) predict survival in ambulatory patients with heart failure and are used for selection for cardiac transplantation. However, the populations tested have predominately been men. To investigate if peak VO2 and the HFSS predict prognosis in women, we derived HFSS and measured peak VO2 in 274 women referred for cardiac transplantation and in 278 men matched by referral year. Seven HFSS parameters were obtained, including presence of coronary artery disease, left ventricular ejection fraction, heart rate, mean arterial blood pressure, peak VO2, presence of intraventricular conduction defects, and serum sodium. Subjects were divided into high-, medium-, and low-risk strata for HFSS and VO2 based on previous cutpoints. Survival curves were derived using Kaplan-Meier analysis and compared by log-rank analysis. Follow-up averaged 929 days. For women, 1-year event-free survival in the low- (>14), medium- (10.1 to 14), and high-risk (<10 ml/kg/min) VO2 strata was 93%, 84%, and 80%, respectively. For the HFSS, 1-year event-free survival in the low- (>or=8.10), medium- (7.20 to 8.09), and high-risk (<or=7.19) strata was 90%, 87%, and 67%, respectively. Survival curves for VO2 (p <0.01) and HFSS (p <0.001) demonstrated significant differences. In both genders, the low-risk groups for HFSS and VO2 can safely have transplantation deferred. Women had better survival than men for a given peak VO2. The HFSS was consistent between genders. In conclusion, peak VO2 and the HFSS are excellent parameters to predict survival in women with congestive heart failure. THE HFSS is more consistent than the peak VO2 between the genders.

Outcomes in off-pump vs. on-pump coronary artery bypass grafting stratified by pre-operative risk profile: an assessment using propensity score

To assess the benefit of off-pump coronary surgery stratified by the pre-operative risk profile. Prospective and multicentric cohort study. All consecutive patients undergoing a first coronary bypass procedure between November 2001 and November 2003 were potentially eligible. Pre-operative EuroSCORE and in-hospital outcomes were prospectively collected using strictly standardized criteria. To ensure optimal adjustment, a propensity score was constructed using clinically relevant variables and incorporating individual centres. Of 1602 patients who underwent a first coronary bypass, EuroSCORE could be calculated in 1585: 787 were of moderate/high pre-operative risk profile (EuroSCORE > 3), of which 347 underwent off-pump procedures, and 798 were of low pre-operative risk profile (EuroSCORE < or = 3), of which 349 underwent off-pump procedures. After risk adjusting for propensity score, off-pump patients had less major events (post-operative death, myocardial infarction, and need for reoperation). This benefit was higher in the low-risk stratum (OR ranged between 0.27 and 0.4; P = 0.02-0.07) than in the high-risk stratum (OR between 0.4 and 0.7; P, not significant). In real-life conditions, off-pump coronary surgery may be more effective than on-pump surgery. In contrast with previous reports, our results suggest that this benefit may be higher in patients with low pre-operative risk.

Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score

The effect of 5 percent human albumin on multiple organ dysfunction was investigated during the first 14 days of treatment to determine whether albumin resuscitation might benefit adult burn patients. Multicenter unblinded controlled trial with stratified block (two patients per block) randomization by center and mortality prediction at enrollment (high-risk stratum [predicted mortality, 50%-90%] and low-risk stratum [predicted mortality, <50%]). The primary outcome was the worst multiple organ dysfunction score (MODS), excluding the cardiovascular component, to Day 14. Eligible adults (>15 years) suffering from thermal injury not more than 12 hours before enrollment received fluid resuscitation with Ringer's lactate (n=23) or 5 percent human albumin plus Ringer's lactate (n=19) by protocol to achieve recommended (American Burn Association) resuscitation endpoints. Forty-two patients were randomly assigned. There were no significant differences (median [95% confidence intervals]) in age (36 [24-45] vs. 31 [25-39] years), burn size (39 [32-53] vs. 32 [26-34] total body surface area percentage), inhalation injury (n=12/19 vs. n=11/23), or baseline MODS (3 [1-5] vs. 1.5 [0-2]) between the treatment and control groups. In an intention-to-treat analysis, there was no significant difference between the treatment and control group in the lowest MODS from Day 0 to Day 14 (analysis of covariance, p=0.73). Treatment with 5 percent albumin from Day 0 to Day 14 does not decrease the burden of MODS in adult burn patients.

Deep venous thrombosis: clinically silent in the intensive care unit

Purpose The reliability of clinical signs and the physical examination in the evaluation of deep venous thrombosis (DVT) in the critically ill is unknown. The purpose of this study was to determine the diagnostic properties of clinical examination for signs of DVT in a cohort of medical-surgical intensive care unit (ICU) patients using screening compression ultrasonography as a reference standard. Materials and Methods We prospectively included patients older than 18 years with an expected length of ICU stay of more than 72 hours. Patients underwent bilateral lower limb screening compression ultrasound twice weekly and structured physical examination twice weekly by 2 independent trained research coordinators blinded to the ultrasonography results. We classified patients according to 2 methods: method 1, a DVT Risk Stratification System of 3 categories and method 2, a DVT Risk Score, both of which use the history and physical examination to stratify patients for their risk of DVT. Results We included 239 patients in our study, 32 of whom had DVT based on the results of their compression ultrasound. We excluded 7 patients with DVT on ICU admission and 2 who did not undergo any structured examinations. We matched controls with cases (9:1) based on duration of ICU stay. Cases and controls were then allocated to low, moderate, and high risk strata for DVT. Using method 1, the area under the receiver operating characteristic curve (AUC) was 0.57 (95% CI, 0.33-0.78, P = .01). Using method 2, the AUC was 0.59 (95% CI, 0.42-0.75, P = .02). An AUC of 1.0 indicates an ideal test, and AUC of 0.50 indicates a test with no diagnostic utility. Conclusions The history and physical examination for DVT are not useful in detecting lower limb DVT in the ICU.

White-coat hypertension in adults

White-coat hypertension is defined by the coexistence of persistently high office blood pressure (BP) with normal self-measured or ambulatory blood pressure. The prognostic impact of white-coat hypertension is a subject of debate. Cardiovascular morbidity seems to be lower in white-coat hypertension than in ambulatory hypertension, and, according to some but not all studies, is not dissimilar between white-coat hypertension and clinical normotension. In a large collaborative study including individual data from four prospective cohort studies, the incidence of stroke tended to increase in the white-coat hypertension group in the long run, crossing the hazard curve of the ambulatory hypertension by the ninth year of follow-up. These data raise the hypothesis, to be tested in future studies, that white-coat hypertension might not be a benign condition for stroke in the long term. Further studies are needed in order to: (1) test whether white-coat hypertension is really a benign condition for stroke in the long term; (2) compare, in patients with white-coat hypertension, a regimen based on life-style measures without drugs and a standard regimen consisting of life-style measures with the possible addition of drugs. On the basis of current evidence, it is reasonable to suggest a treatment based on life-style measures in the low-risk stratum of patients with white-coat hypertension under the conditions of correct definition, absence of comorbid conditions and target-organ damage, and adequate follow-up

A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

BackgroundMeta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome.MethodsIn search for relevant studies published, two randomized clinical trials were found eligible.ResultsThe studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR) and 95% confidence interval (CI) data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02) suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score < 25. In this low-risk stratum, no effect of recombinant human activated protein C administration on 28-day mortality was observed. This observation appears to be consistent and homogenous. Heterogeneity between the two studies, however, was seen in patients with APACHE II score ≥ 25 in whom recombinant activated protein C was effective in PROWESS (n = 817; RR 0.71, CI 0.59–0.85) whereas a tendency toward harm was present in ADDRESS (n = 324; RR 1.21, CI 0.85–1.74). Even though the overall treatment effect in this high-risk population was still in favour of treatment with recombinant activated protein C (n = 1141; RR 0.80, CI 0.68–0.94), the observed heterogeneity suggests that the efficacy of recombinant human activated protein C is not robust. Not unlikely, the adverse tendency observed could have become significant with higher statistical power would ADDRESS not have been terminated prematurely.ConclusionThis meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial.

Low frequency of target organ damage in Taiwanese with white coat hypertension.

The clinical importance of white coat hypertension (WCH) remains to be clarified. This study investigated the target organ damage in Taiwanese with WCH. A total of 188 consecutive Taiwanese (88 men and 100 women), aged 26 to 75 years who had an abnormal office casual blood pressure (systolic blood pressure >/= 140 mm Hg or diastolic blood pressure >/= 90 mm Hg or both) and a normal ambulatory blood pressure (ABP) average (systolic ABP average < 140 mm Hg and diastolic ABP average < 90 mm Hg) at the outpatient clinic or from a mass survey were enrolled. Office casual blood pressure measurements were obtained by standard sphygmomanometric methods. Twenty-four-hour blood pressures were recorded by a commercial ambulatory pressure recorder (Del Mar Avionics, Model 1990 Pressurometer IV System). Hypertension-related target organ complications were assessed by electrocardiogram, chest X-ray, urinalysis and eye fundus examinations. Target organ damage was found in 6.4% of subjects with WCH. Roentgenographic left ventricular hypertrophy (LVH) was found in 1.1% of subjects and electrocardiographic LVH in 2.7%. Proteinuria was found in 1.6% of subjects and retinopathy in 1.1%. The frequencies of various target organ damage were not significantly associated with age, gender and the definition of normal ABP average as 135/85 mm Hg or 140/90 mm Hg. WCH represents a low-risk stratum for target organ damage in Taiwanese. These subjects should be identified and followed up regularly. The factors responsible for the low frequency of target organ damage in Taiwanese with WCH need further study.

Heart failure survival score continues to predict clinical outcomes in patients with heart failure receiving β-blockers

Background The Heart Failure Survival Score (HFSS) has been previously shown to effectively risk-stratify patients under evaluation for heart transplantation. However, this model was developed before broad use of beta blockade. We hypothesized that the prognostic tool would retain its ability to risk stratify patients treated with β-blockers. Methods We collected clinical data on 524 consecutive patients referred for heart transplantation from 1994 to 2001. Kaplan-Meier survival analysis and multivariable Cox regression analysis were performed with events defined as death, left ventricular assist device placement, or United Network of Organ Sharing 1 heart transplantation. Results Kaplan-Meier analysis of the patient population revealed effective discrimination by the survival score both for β-blocker treated and untreated patients (both p < 0.0001). Two-year event-free survival was 94% ± 2% and 84% ± 4% for β-blocker and no β-blocker patients in the low-risk HFSS strata. Cox proportional hazard modeling showed that HFSS strata (medium risk: HR 2.65, 95% CI 1.75–4.02, p < 0.001; high risk: HR 5.51, 95% CI 3.64–8.33, p < 0.001) and β-blocker treatment (HR 0.45, 95% CI 0.31–0.64, p < 0.001) were significant predictors of event-free survival. Receiver operating curves (area under the curve) for HFSS strata used to predict 2-year events were similar for β-blocker treated (0.78 ± 0.04) and untreated (0.80 ± 0.03) patients. Conclusions The HFSS provides effective risk stratification with or without β-blocker therapy. Consideration of β-blocker therapy with survival score strata improves outcome prediction in patients evaluated for heart transplantation.

A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery

The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed. CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%.

Persistent low immunization coverage among inner-city preschool children despite access to free vaccine.

To compare vaccination coverage among children 19 to 35 months of age from public housing developments where a free vaccine outreach program was in place with children residing elsewhere in the city. A household survey using a multistage cluster sampling method to compare community areas which accounted for 80% of measles cases during 1989 (high-risk stratum), areas which accounted for the remaining 20% of cases (low-risk stratum), and public housing developments (public housing stratum) having free, on-site vaccination services. Inner-city Chicago households, April to May 1994. Antigen-specific and series-specific coverage based on written records. Based on evaluation of 1244 children, citywide coverage for four doses of diphtheria-tetanus-pertussis vaccine, three doses of polio vaccine, and one dose of measles-containing vaccine (4:3:1) was 47% [95% confidence interval (CI), 40% to 55%]. Coverage was significantly lower among children residing in public housing (23%; 95% CI, 18% to 28%) compared with those residing in high-risk strata (45%; 95% CI, 38% to 52%) and low-risk strata (51%; 95% CI, 43% to 60%). Compared with white children (53%), coverage for the 4:3:1 series was lower among African-American children in public housing (29%) or outside public housing (36%). Moreover, 11% (95% CI, 8% to 14%) of children residing in public housing had never received any immunizations. African-American children throughout Chicago, particularly in public housing, remain at increased risk for vaccine-preventable diseases and should be targeted further for vaccination services. Vaccination coverage remains low several years after a major outbreak of measles and implementation of a free vaccine outreach program. Cluster surveys may be useful for monitoring vaccination coverage in high-risk urban settings.