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Objective: The Agency for Healthcare Research and Quality (AHRQ) Inpatient Quality Indicator (IQI) #11, abdominal aortic aneurysm (AAA) repair mortality rate, is a measure of hospital quality that is publically reported but has not been externally validated. Because the IQI #11 overall mortality rate includes both intact and ruptured aneurysms and open and endovascular repair, we hypothesized that IQI #11 overall mortality rate does not provide accurate assessment of mortality risk after AAA repair and that AAA mortality cannot be accurately assessed by a single quality measure., Methods: Using AHRQ IQI software version 4.2, we calculated observed (O) and expected (E) mortality rates for IQI #11 for all hospitals performing more than 10 AAA repairs per year in the Nationwide Inpatient Sample for the years 2007 to 2011. We used Spearman correlation coefficient to compare expected rates as determined by IQI #11 overall mortality rate risk adjustment methodology and observed rates for all AAA repairs in four cohorts stratified by aneurysm stability (ruptured vs intact) and method of repair (open vs endovascular)., Results: Among 187,773 AAA repairs performed at 1268 U.S. hospitals, hospitals' IQI #11 overall expected rates correlated poorly with their observed rates (E: 5.0% ± 4.4% vs O: 6.0% ± 9.8%; r = .49). For ruptured AAAs, IQI #11 overall mortality rate methodology underestimated the mortality risk of open repair (E: 34% ± 7.2% vs O: 40.1% ± 38.2%; r = 0.20) and endovascular repair (E: 24.8% ± 9% vs O: 27.3% ± 37.9%; r = 0.08). For intact AAA repair, IQI #11 overall mortality rate methodology underestimated the mortality risk of open repair (E: 4.3% ± 2.4% vs O: 6.3% ± 16.1%; r = .24) but overestimated the mortality risk of endovascular repair (E: 1.3% ± 0.8% vs O: 1.1% ± 3.7%; r = 0.25). Hospitals' observed mortality rates after intact AAA repair were not correlated with their mortality rates after ruptured AAA repair (r = 0.03)., Conclusions: IQI #11 overall mortality rate fails to provide accurate assessment of inpatient mortality risk after AAA repair. Thus, it is inappropriate to use IQI #11 overall mortality rate for quality reporting. The accuracy of separate quality measures that assess mortality risk after repair of ruptured and intact AAAs, stratified by the use of open or endovascular repair, should be examined., (Copyright © 2015 Society for Vascular Surgery. All rights reserved.)

Background: Rates of Clostridium difficile (CD) infections are increasing. Elderly patients may be at particular risk of recurrent CD infection. Little is known about the risk for CD readmission specifically in this age group., Methods: A 5% random sample of Medicare data (2009-2011) was queried for patients surviving a hospitalization for CD by ICD-9 code. Demographic (age, sex, gender), clinical (Elixhauser index, gastrointestinal comorbidities), and hospitalization (length of stay, ICU admission) characteristics as well as exposure to antibiotics and interim non-CD hospitalization were compared for those with and without a readmission for CD. A multivariable survival analysis was used to determine predictors of readmission., Results: Of 7,564 patients surviving a CD hospitalization, 8.5% were readmitted with CD in a median of 25 days (interquartile range (IQR) 14-57). In multivariable survival analyses, interim non-CD hospital exposure was the strongest predictor of CD readmission (hazard ration (HR) 3.75 95%, confidence interval (CI) 3.2-4.42). Oral and intravenous/intramuscular (IV/IM) antibiotic use, Elixhauser index, and CD as the primary diagnosis also increased the risk of CD readmission. Discharge to hospice, long-term care or a skilled nursing facility decreased the odds of CD readmission., Conclusion: Hospital exposure and antibiotic use put elderly patients at risk of CD readmission. Exposure to these factors should be minimized in the immediate post discharge period.

Background: Elderly Americans are at increased risk of head trauma, particularly fall related. The effect of warfarin on head trauma outcomes remains controversial., Methods: Medicare beneficiaries with head injuries from 2009 to 2011 were identified by International Classification of Diseases (ICD)-9 code. Preinjury warfarin use was determined using Part D claims. Multiple logistic regression models determined the association of preinjury warfarin on need for hospitalization, intensive care unit care, and occurrence of intracranial hemorrhage. Association between warfarin and in-hospital mortality was assessed using a Cox proportional hazard model., Results: Of 11,078 head injured patients, 5.2% were injured while on warfarin. Preinjury warfarin increased the odds of intracranial hemorrhage by 40% and doubled the risk of 30-day in-hospital mortality after adjusting for demographic and clinical factors., Conclusions: Warfarin at the time of head injury increases the risk of adverse outcomes in Medicare beneficiaries with head injuries. Caution should be used when initiating anticoagulation in elderly Americans at risk for trauma., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The clinical epidemiology of venous thromboembolism has changed recently because of advances in identification, prophylaxis, and treatment. We sought to describe secular trends in the occurrence of venous thromboembolism among residents of the Worcester, Massachusetts, metropolitan statistical area., Methods: Population-based methods were used to monitor trends in event rates of first-time or recurrent venous thromboembolism in 5025 Worcester, Massachusetts, metropolitan statistical area residents who were diagnosed with acute pulmonary embolism or lower-extremity deep vein thrombosis during 9 annual periods between 1985 and 2009. Medical records were reviewed by abstractors and validated by clinicians., Results: Age- and sex-adjusted annual event rates for first-time venous thromboembolism increased from 73 (95% confidence interval [CI], 64-82) per 100,000 in 1985/1986 to 133 (CI, 122-143) in 2009, primarily because of an increase in pulmonary embolism. The rate of recurrent venous thromboembolism decreased from 39 (CI, 32-45) in 1985/1986 to 19 (CI, 15-23) in 2003, and then increased to 35 (CI, 29-40) in 2009. There was an increasing trend in using noninvasive diagnostic testing, with approximately half of tests being invasive in 1985/1986 and almost all noninvasive by 2009., Conclusions: Despite advances in identification, prophylaxis, and treatment between 1985 and 2009, the annual event rate of venous thromboembolism has increased and remains high. Although these increases partially may be due to increased sensitivity of diagnostic methods, especially for pulmonary embolism, they also may imply that current prevention and treatment strategies are less than optimal., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend early oral beta-blocker administration in the management of acute coronary syndromes for patients who are not at high risk of complications., Methods: Data from patients enrolled between 2000 and 2007 in the Global Registry of Acute Coronary Events (GRACE) were used to evaluate hospital outcomes in 3 cohorts of patients admitted with ST-elevation myocardial infarction, based on beta-blocker use (early [first 24 hours] intravenous (IV) [± oral], only early oral, or delayed [after first 24 hours])., Results: Among 13,110 patients with ST-elevation myocardial infarction, 21% received any early IV beta-blockers, 65% received only early oral beta-blockers, and 14% received delayed (>24 hours) beta-blockers. Higher systolic blood pressure, higher heart rate, and chronic beta-blocker use were independent predictors of early beta-blocker use. Early beta-blocker use was less likely in older patients, patients with moderate to severe left ventricular dysfunction, and in those presenting with inferior myocardial infarction or Killip class II or III heart failure. IV beta-blocker use and delayed beta-blocker use were associated with higher rates of cardiogenic shock, sustained ventricular fibrillation/ventricular tachycardia, and acute heart failure, compared with oral beta-blocker use. In-hospital mortality was increased with IV beta-blocker use (propensity score adjusted odds ratio, 1.41; 95% confidence interval, 1.03-1.92) but significantly reduced with delayed beta-blocker administration (propensity adjusted odds ratio, 0.44; 95% confidence interval, 0.26-0.74)., Conclusions: Early beta-blocker use is common in patients presenting with ST-elevation myocardial infarction, with oral administration being the most prevalent. Oral beta-blockers were associated with a decrease in the risk of cardiogenic shock, ventricular arrhythmias, and acute heart failure. However, the early receipt of any form of beta-blockers was associated with an increase in hospital mortality., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The incidence of community-acquired Clostridium difficile (CACD) is increasing in the United States. Many CACD infections occur in the elderly, who are predisposed to poor outcomes. We aimed to describe the epidemiology and outcomes of CACD in a nationally representative sample of Medicare beneficiaries., Study Design: We queried a 5% random sample of Medicare beneficiaries (2009-2011 Part A inpatient and Part D prescription drug claims; n = 864,604) for any hospital admission with a primary ICD-9 diagnosis code for C difficile (008.45). We examined patient sociodemographic and clinical characteristics, preadmission exposure to oral antibiotics, earlier treatment with oral vancomycin or metronidazole, inpatient outcomes (eg, colectomy, ICU stay, length of stay, mortality), and subsequent admissions for C difficile., Results: A total of 1,566 (0.18%) patients were admitted with CACD. Of these, 889 (56.8%) received oral antibiotics within 90 days of admission. Few were being treated with oral metronidazole (n = 123 [7.8%]) or vancomycin (n = 13 [0.8%]) at the time of admission. Although 223 (14%) patients required ICU admission, few (n = 15 [1%]) underwent colectomy. Hospital mortality was 9%. Median length of stay among survivors was 5 days (interquartile range 3 to 8 days). One fifth of survivors were readmitted with C difficile, with a median follow-up time of 393 days (interquartile range 129 to 769 days)., Conclusions: Nearly half of the Medicare beneficiaries admitted with CACD have no recent antibiotic exposure. High mortality and readmission rates suggest that the burden of C difficile on patients and the health care system will increase as the US population ages. Additional efforts at primary prevention and eradication might be warranted., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Anticoagulants reduce the risk of venous thromboembolism (VTE) after total joint replacement. However, concern remains that pharmacologic VTE prophylaxis can lead to bleeding, which may impact on postoperative complications such as infections and reoperations., Methods and Findings: From the Global Orthopedic Registry (GLORY), we reviewed 3,755 patients in US who elected for primary total hip or knee arthroplasty, received either warfarin or low molecular weight heparin (LMWH) as VTE prophylactics, and had up-to-90-day follow-up after discharge. We compared incidence rates of VTE, infections and other complications between LMWH and warfarin groups, and used multivariate analyses with propensity score weighting to generate the odds ratio (OR). Patients receiving LMWH tended to be older and higher in the American Society of Anesthesiologists grade scores. In contrast, warfarin was used more frequently for hip arthroplasty with longer duration among patients with more pre-existing comorbidity (all P<0.02). A weight variable was created with propensity score to account for differences in covariate distributions. Propensity score-weighted analyses showed no differences in VTE complications. However, compared to warfarin, LMWH was associated with significantly higher rates of bleeding (6.2% vs. 2.1%; OR = 3.82, 95% confidence interval [CI], 2.64 to 5.52), blood transfusion (29.4% vs. 22.0%; OR = 1.75, 95% CI, 1.51 to 2.04), reoperations (2.4% vs. 1.3%; OR = 1.77, 95% CI, 1.07 to 2.93) and infections (1.6% vs. 0.6%; OR = 2.79, 95% CI, 1.42 to 5.45). Similar results were obtained from compliant uses of warfarin (26%) and LMWH (62%) according to clinical guidelines. While surgical site infections were mostly superficial, current study was underpowered to compare incidence rates of deep infections (<1.0%)., Conclusions: Surgical site infections and reoperations in 3 months following primary total joint arthroplasty may be associated with anticoagulant use that exhibited higher bleeding risk. Long-term complications and deep wound infections remain to be studied.

Context: Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired., Objective: The objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles., Design: This was a prospective, observational cohort study., Setting: The study was conducted at primary care practices in 10 countries., Patients: Women aged 55 years or older participated in the study., Intervention: Self-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures., Main Outcome Measure: The main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age., Results: Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase., Conclusions: After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.

Fractures may be associated with higher morbidity in obese postmenopausal women than in nonobese women. We compared health-care utilization, functional status, and health-related quality of life (HRQL) in obese, nonobese, and underweight women with fractures. Information from the GLOW study, started in 2006, was collected at baseline and at 1, 2, and 3 years. In this subanalysis, self-reported incident clinical fractures, health-care utilization, HRQL, and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 nonobese, and 941 obese women with one or more incident clinical fractures during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities, and fracture type, was significantly greater in obese than nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score were significantly worse in obese than in nonobese women, both before and after fracture; but changes after fracture were similar across groups. Use of antiosteoporosis medication was significantly lower in obese than in nonobese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than nonobese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.

Antiosteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining two or more fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow-up, 73 of 5550 women in the AOM group (1.3%) and 123 of 21,368 in the non-AOM group (0.6%) reported occurrence of two or more fractures. The following variables were associated with treatment failure: lower Short Form 36 Health Survey (SF-36) score (physical function and vitality) at baseline, higher Fracture Risk Assessment Tool (FRAX) score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF-36 vitality score (odds ratio [OR] per 10-point increase, 0.85; 95% confidence interval [CI], 0.76-0.95; p = 0.004); two or more falls in the past year (OR, 2.40; 95% CI, 1.34-4.29; p = 0.011), and prior fracture (OR, 2.93; 95% CI, 1.81-4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients., (© 2014 American Society for Bone and Mineral Research.)

Unlabelled: We examined the use of pharmacologic agents for the primary prevention of osteoporosis among older women with osteopenia. We found that these individuals were not managed in concordance with the National Osteoporosis Foundation (NOF) guidelines and that self-perceived osteoporosis risk and lower bone density were strongly associated with receipt of treatment., Introduction: Although osteoporosis medications are used for the primary prevention of osteoporosis among persons with low bone mass (osteopenia), their use may be discordant with clinical practice guidelines., Methods: We studied women 55 years and older participating in the Global Longitudinal Study of Osteoporosis in Women (GLOW). Eligible participants had a dual energy x-ray absorptiometry (DXA) test performed at the University of Alabama at Birmingham hospital and had an osteopenia diagnosis based on their DXA test results. Participants' demographics, fracture risk factors, and exposure to osteoporosis medications were determined from the GLOW survey. We examined the proportions of women managed in concordance with the National Osteoporosis Foundation 2008 guidelines, and we assessed factors independently associated with osteoporosis treatment decisions. Women with a prior spine or hip fracture were excluded., Results: Among 597 eligible women from GLOW, the mean age ± standard deviation (SD) was 70 ± 7 years. Among all subjects, 309 (52%) were treated in concordance with the NOF 2008 guidelines. Greater self-perceived osteoporosis risk and lower bone mineral density were significantly and consistently associated with receipt of osteoporosis treatment, both for those considered appropriate and for those considered inappropriate for treatment based on the NOF guidelines., Conclusions: We found significant discordance between NOF 2008 guidelines and pharmacologic management of women with osteopenia. A person's self-perceived osteoporosis risk and bone mineral density were most strongly associated with receipt of osteoporosis medication use among women with low bone mass.

Objective: To assess patterns of anti-osteoporosis medication (AOM) use over 3 years among women at high risk of major fracture., Methods: The GLOW registry follows a cohort of more than 40,000 women aged ≥ 55 from 615 primary care practices in 10 countries. Self-administered surveys (baseline, 12, 24, and 36 months) collected data on patient characteristics, perception of fracture risk, and AOM use. FRAX scores were calculated from the baseline surveys and women classified as high risk if their FRAX 10-year probability of major fracture was ≥ 20%., Results: A total of 5774 women were classified as at high risk and had complete data over 3 years. At baseline, 2271 (39%) reported receiving AOM, 739 (13%) reported prior but not current use, and 2764 (48%) said they had never used AOM. Over 3 years, 85% of baseline non-users continued as non-users and 15% initiated AOM; among baseline users, 49% continued the same medication class, 29% stopped AOM, and 12% switched. Women who stopped AOM were less likely to self-report osteoporosis (HR 0.56, 95% CI 0.42-0.75) than women who continued AOM. Compared with non-users who did not begin treatment, women initiating AOM were more likely to report a diagnosis of osteoporosis (HR 11.3, 95% CI 8.2-15.5) or osteopenia (HR 4.1, 95% CI 2.9-5.7) and be very concerned about osteoporosis (HR 1.9, 95% CI 1.3-2.8)., Conclusions: Less than 40% of women at high risk of fracture reported taking AOM. Women who stopped AOM were less likely to believe they have osteoporosis. Women who initiated treatment appeared motivated primarily by a diagnosis of osteoporosis or osteopenia and concern about the condition.

Objective: To examine when, where and how fractures occur in postmenopausal women., Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3., Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling., Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.

Background: Many hospitalized Medical Service patients are at risk for venous thromboembolism in the months after discharge. We conducted a multicenter randomized controlled trial to test whether a hospital staff member's thromboprophylaxis alert to an Attending Physician before discharge will increase the rate of extended out-of-hospital prophylaxis and, in turn, reduce the incidence of symptomatic venous thromboembolism at 90 days., Methods: From April 2009 to January 2010, we enrolled hospitalized Medical Service patients using the point score system developed by Kucher et al to identify those at high risk for venous thromboembolism who were not ordered to receive thromboprophylaxis after discharge. There were 2513 eligible patients from 18 study sites randomized by computer in a 1:1 ratio to the alert group or the control group., Results: Patients in the alert group were more than twice as likely to receive thromboprophylaxis at discharge as controls (22.0% vs 9.7%, P <.0001). Based on an intention-to-treat analysis, symptomatic venous thromboembolism at 90 days (99.9% follow-up) occurred in 4.5% of patients in the alert group, compared with 4.0% of controls (hazard ratio 1.12; 95% confidence interval, 0.74-1.69). The rate of major bleeding at 30 days in the alert group was similar to that of the control group (1.2% vs 1.2%, hazard ratio 0.94; 95% confidence interval, 0.44-2.01)., Conclusions: Alerting providers to extend thromboprophylaxis after hospital discharge in Medical Service patients increased the rate of prophylaxis but did not decrease the rate of symptomatic venous thromboembolism., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To test whether women aged 55 and older with increasing evidence of a frailty phenotype would have greater risk of fractures, disability, and recurrent falls than women who were not frail, across geographic areas (Australia, Europe, and North America) and age groups., Design: Multinational, longitudinal, observational cohort study., Setting: Global Longitudinal Study of Osteoporosis in Women (GLOW)., Participants: Women (N = 48,636) aged 55 and older enrolled at sites in Australia, Europe, and North America., Measurements: Components of frailty (slowness and weakness, poor endurance and exhaustion, physical activity, and unintentional weight loss) at baseline and report of fracture, disability, and recurrent falls at 1 year of follow-up were investigated. Women also reported health and demographic characteristics at baseline., Results: Women younger than 75 from the United States were more likely to be prefrail and frail than those from Australia, Canada, and Europe. The distribution of frailty was similar according to region for women aged 75 and older. Odds ratios from multivariable models for frailty versus nonfrailty were 1.23 (95% confidence interval (CI) = 1.07-1.42) for fracture, 2.29 (95% CI = 2.09-2.51) for disability, and 1.68 (95% CI = 1.54-1.83) for recurrent falls. The associations for prefrailty versus nonfrailty were weaker but still indicated statistically significantly greater risk of each outcome. Overall, associations between frailty and each outcome were similar across age and geographic region., Conclusion: Greater evidence of a frailty phenotype is associated with greater risk of fracture, disability, and falls in women aged 55 and older in 10 countries, with similar patterns across age and geographic region., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Venous thromboembolism (VTE) prophylaxis is suboptimal in American hospitals despite long-standing evidence-based recommendations. Data from observational studies indicate a lower uptake of effective prophylaxis in patients hospitalized with medical versus surgical conditions. Reluctance to use prophylaxis in medical patients has been attributed to difficulty in identifying at-risk patients and balancing risks of bleeding against occurrence of VTE. Several risk-assessment models (RAMs) have been proposed to assist physicians in identifying non-surgical patients who need prophylaxis. We conducted a systematic review of published RAMs, based on objective criteria, to determine whether any RAM is validated sufficiently to be employed in clinical practice. We identified 11 RAMs, six derived from primary data and five based on expert opinion. The number, types, and strength of association of VTE risk predictors were highly variable. The variability in methods and outcome measurement precluded pooled estimates of these different models. Published RAMs for VTE lack generalizability and adequate validation. As electronic health records become more ubiquitous, validated dynamic RAMs are needed to assess VTE risk at the point-of-care in real time.

Introduction: Many women at risk of fracture do not receive anti-osteoporosis medication (AOM), while others may be receiving unnecessary treatment., Purpose: To examine the characteristics associated with AOM use among women at low and high risks of fracture., Methods: The Global Longitudinal Study of Osteoporosis in Women (GLOW) is a prospective cohort study in which data were collected, via self-administered questionnaires, from 60,393 non-institutionalized women aged ≥ 55 years in 10 countries between October 1, 2006 and April 30, 2008. This is a cross-sectional analysis of baseline USA data, in which women were classified as having low fracture risk (<65 years; no FRAX risk factors) or high fracture risk (≥65 years; prior fracture or ≥ 2 other FRAX risk factors)., Results: Of 27,957 women, 3013 were at low risk of fracture and 3699 were at high risk. Only 35.7% of high-risk women reported AOM treatment, rising to 39.5% for those with self-reported osteopenia and 65.4% for those with self-reported osteoporosis. Conversely, 13.4% of low-risk women reported AOM, rising to 28.7% for osteopenia and 62.4% for osteoporosis. Characteristics associated with significantly higher AOM treatment rates among low- and high-risk women were: osteoporosis (odds ratios 75.3 and 18.1, respectively), osteopenia (17.9 and 6.3), concern about osteoporosis (2.0 and 1.8), higher perceived risk of fracture (2.3 and 1.6), and higher vitality score (1.7 and 1.6)., Conclusion: Use of AOM is frequently inconsistent with published guidelines in both high- and low-risk women. Characteristics other than FRAX fracture risk appear to influence this use, particularly the presence of self-reported osteoporosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The risk of stroke in patients hospitalized with an acute coronary syndrome (ACS) ranges from <1% to ≥ 2.5%. The aim of this study was to develop a simple predictive tool for bedside risk estimation of in-hospital ischemic stroke in patients with ACS to help guide clinicians in the acute management of these high-risk patients. Data were obtained from 63,118 patients enrolled from April 1999 to December 2007 in the Global Registry of Acute Coronary Events (GRACE), a multinational registry involving 126 hospitals in 14 countries. A regression model was developed to predict the occurrence of in-hospital ischemic stroke in patients hospitalized with an ACS. The main study outcome was the development of ischemic stroke during the index hospitalization for an ACS. Eight risk factors for stroke were identified: older age, atrial fibrillation on index electrocardiogram, positive initial cardiac biomarkers, presenting systolic blood pressure ≥ 160 mm Hg, ST-segment change on index electrocardiogram, no history of smoking, higher Killip class, and lower body weight (c-statistic 0.7). The addition of coronary artery bypass graft surgery and percutaneous coronary intervention into the model increased the prediction of stroke risk. In conclusion, the GRACE stroke risk score is a simple tool for predicting in-hospital ischemic stroke risk in patients admitted for the entire spectrum of ACS, which is widely applicable to patients in various hospital settings and will assist in the management of high-risk patients with ACS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Greater awareness of the relationship between co-morbidities and fracture risk may improve fracture-prediction algorithms such as FRAX., Materials and Methods: We used a large, multinational cohort study (GLOW) to investigate the effect of co-morbidities on fracture risk. Women completed a baseline questionnaire detailing past medical history, including co-morbidity history and fracture. They were re-contacted annually to determine incident clinical fractures. A co-morbidity index, defined as number of baseline co-morbidities, was derived. The effect of adding the co-morbidity index to FRAX risk factors on fracture prevention was examined using chi-squared tests, the May-Hosmer test, c index and comparison of predicted versus observed fracture rates., Results: Of 52,960 women with follow-up data, enrolled between October 2006 and February 2008, 3224 (6.1%) sustained an incident fracture over 2 years. All recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson's disease (age-adjusted hazard ratio [HR]: 2.2; 95% CI: 1.6-3.1; P<0.001). Co-morbidities that contributed most to fracture prediction in a Cox regression model with FRAX risk factors as additional predictors were: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, osteoarthritis, and heart disease., Conclusion: Co-morbidities, as captured in a co-morbidity index, contributed significantly to fracture risk in this study population. Parkinson's disease carried a particularly high risk of fracture; and increasing co-morbidity index was associated with increasing fracture risk. Addition of co-morbidity index to FRAX risk factors improved fracture prediction., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A survey was mailed to a representative sample of US orthopedic surgeons to assess protocols for the prevention of venous thromboembolism after lower extremity total joint arthroplasty. Practices were examined by type of operation, annual surgical volume, and opinions of consensus guidelines issued by the American Academy of Orthopaedic Surgeons and the American College of Chest Physicians. Although there was near-unanimous agreement that routine thromboprophylaxis should be the standard practice for patients who undergo hip or knee arthroplasty, surgeons were divided as to the exact management approach., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To determine the proportion of untreated women who reported receiving treatment after incident fracture and to identify factors that predict treatment across an international spectrum of individuals., Design: Prospective observational study. Self-administered questionnaires were mailed at baseline and 1 year., Setting: Multinational cohort of noninstitutionalized women recruited from 723 primary physician practices in 10 countries., Participants: Sixty thousand three hundred ninety-three postmenopausal women aged 55 and older were recruited with a 2:1 oversampling of women aged 65 and older., Measurements: Data collected included participant demographics, medical history, fracture occurrence, medications, and risk factors for fracture. Anti-osteoporosis medications (AOMs) included estrogen, selective estrogen receptor modulators, bisphosphonates, calcitonin, parathyroid hormone, and strontium., Results: After the first year of follow-up, 1,075 women reported an incident fracture. Of these, 17% had started AOM, including 15% of those with a single fracture and 35% with multiple fractures. Predictors of treatment included baseline calcium use (P = .01), baseline diagnosis of osteoporosis (P < .001), and fracture type (P < .001). In multivariable analysis, women taking calcium supplements at baseline (odds ratio (OR) = 1.67) and with a baseline diagnosis of osteoporosis (OR = 2.55) were more likely to be taking AOM. Hip fracture (OR = 2.61), spine fracture (OR = 6.61), and multiple fractures (OR = 3.79) were associated with AOM treatment. Age, global region, and use of high-risk medications were not associated with treatment., Conclusion: More than 80% of older women with new fractures were not treated, despite the availability of AOM. Important factors associated with treatment in this international cohort included diagnosis of osteoporosis before the incident fracture, spine fracture, and to a lesser degree, hip fracture., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Introduction: Acceptability of a prescribed treatment regimen is crucial to its clinical success, and the route of drug administration can play an important role in determining acceptability. This international survey explored physician and patient perceptions of injectable and oral treatments, and how these perceptions affect acceptability of treatments. Findings are discussed in the context of patient acceptance of treatments for venous thromboembolism (VTE) management., Methods: Physicians who are regular prescribers of VTE prophylaxis and a randomly selected patient population were recruited to take part in a questionnaire. Patients had to answer 23 questions and physicians gave their predictions of patients' responses., Results: In total, 568 physicians and 825 patients from 5 countries took part in the survey. More patients considered injectable treatments effective than considered oral treatments effective (87% versus 76%, respectively). This trend was well predicted by the physicians (98% and 61%, respectively). Additionally, 46% of patients would accept an injectable treatment program lasting >2months (rising to 67% for life-threatening diseases), a figure underestimated by physicians (11% and 46%, respectively). Overall, 73% of patients stated they would never miss an injection, where as 54% of physicians expected patients to miss one injection in a month of therapy., Conclusions: Physicians who are regular prescribers of VTE prophylaxis underestimate patients' ability to accept injectable treatments as an alternative to oral therapy. This survey suggests that injectable treatments may be an acceptable, and often preferred, option over oral administration of therapeutic and preventive medicines., (Copyright © 2011. Published by Elsevier Ltd.)

Aim: Information about the variation in the risk for venous thromboembolism (VTE) and in prophylaxis practices in France and around the world is scarce., Methods: The Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study is a multinational cross-sectional survey designed to assess the prevalence of VTE risk in the acute hospital care setting, and to determine the proportion of at-risk patients who receive effective prophylaxis, in accordance with the 2004 American College of Chest Physicians (ACCP) guidelines. This paper gives the results of the ENDORSE study in the French centres in comparison with the global worldwide results of the ENDORSE study and with other Western Europe countries., Results: In France, 18 randomized hospitals participated to the study between august 2006 and January 2007. 2844 patients were evaluated (917 from chirurgical wards and 1927 from medical wards). One thousand four hundred and nineteen patients (49.9%) were at VTE risk (78.3% in chirurgical wards and 36.4% in medical wards). Of the 1419 patients at VTE risk, 62.4% received ACCP-recommended VTE prophylaxis (71.2% in chirurgical wards and 53.5% in medical wards). VTE Prophylaxis in France (62.4%) is more frequent than worldwide in the international ENDORSE study (50.2%) and similar to the majority of the other western European countries and the USA. It is also more used in university hospitals (66.9%) than in other hospitals (58.9%). Prophylaxis in patients at risk for VTE was presented in 43% patients with acute heart failure, 53% with non-infectious acute respiratory failure, 57% in patients with pulmonary infection, 56% in patients with stroke, 55% in patients with active cancer and 48% in patients with non-pulmonary sepsis., Conclusions: The ENDORSE study has shown a high level of patients at risk for VTE in the population of hospitalized patients in France. The rate of prophylaxis for VTE remained low, in particular in Medicine wards. Our data reinforced the rationale for the use of hospital-wide strategies to assess patients' VTE risk and to implement measures that ensure that at-risk patients receive appropriate prophylaxis, in particularly in medical patients., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The Arab Middle East is a unique region of the developing world where little is known about the outcomes of patients hospitalized with an acute coronary syndrome (ACS), despite playing an important role in the global burden of cardiovascular disease. The primary objectives of this observational study were to compare patients with ACS hospitalized in the Arab Middle East to patients enrolled in a multinational non-Arabian ACS registry. The study cohort consisted of patients hospitalized in 2007 with an ACS including 4,445 from the Global Registry of Acute Coronary Events (GRACE) and 6,706 from the Gulf Registry of Acute Coronary Events (Gulf RACE). Average age of patients in Gulf RACE was nearly a decade younger than that in GRACE (56 vs 66 years). Patients in Gulf RACE were more likely to be men, diabetic, and smoke and less likely to be hypertensive compared to patients in GRACE. Patients in Gulf RACE had higher odds of receiving aspirin and a lower likelihood of receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β blockers, and clopidogrel during their index hospitalization. Although most eligible patients with ST-elevation myocardial infarction in Gulf RACE received thrombolytics, most of their counterparts in GRACE underwent a primary percutaneous coronary intervention. Multivariable adjusted in-hospital case-fatality rates were not significantly different between patients in Gulf RACE and those in GRACE. In conclusion, despite differences in patient characteristics and treatment practices, short-term mortality rates were comparable in patients with ACS enrolled in these 2 registries. Future studies should explore the effects of these differences on long-term prognosis and other pertinent patient outcomes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

There is no consensus about the toxicity of erythropoiesis-stimulating agents among hemodialysis patients. We aimed to calculate the risk of death according to anemia control and erythropoietin (EPO) dosing among end-stage renal disease patients undergoing hemodialysis. We retrospectively studied 156 end-stage renal disease patients on hemodialysis from a single renal unit during 12 months. Participants were classified according to anemia control into four groups: excellent (A), good (B), moderate (C) and bad (D) control. They were also classified according to EPO dosing into two groups: usual and high EPO dosing. The Cox proportional hazards regression model, adjusted for the difference in age, sex, time on dialysis, comorbidity, albumin, and Kt/V index, was performed to calculate the risk of death according to anemia control and EPO dosing profiles. Multivariate analysis by backward stepwise logistic regression was used to calculate the risk of death according to the variables that differed in the comparison between survivors and nonsurvivors. The hazard ratio of death was not significant according to anemia control profile C/D vs. A/B, but hazard ratio was 2.967 (95% confidence interval [CI] = 1.132-7.777; P = 0.027) for high EPO dosing profile patients. The multivariate analysis showed comorbidity (odds ratio [OR] = 8.958; 95% CI = 2.843-26.223; P < 0.001], high EPO dosing profile (OR = 5.172; 95% CI = 1.663-16,081; P = 0.005), age (OR = 1.056; 95% CI = 1.020-1.094; P = 0.002), and mean hemoglobin (OR = 0.435; 95% CI = 0.267-0.709; P = 0.001) to be predictive of death. Even though we cannot conclude that mortality risk is due to EPO toxicity, hemodialysis patients using high EPO dosing must be seen as at risk., (© 2011 The Authors; Hemodialysis International © 2011 International Society for Hemodialysis.)

Background: Acutely ill hospitalized medical patients are at risk for VTE. We assessed the incidence of VTE in the observational International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) study and derived VTE risk assessment scores at admission and associative VTE scores during hospitalization., Methods: Data from 15,156 medical patients were analyzed to determine the cumulative incidence of clinically observed VTE over 3 months after admission. Multiple regression analysis identified factors associated with VTE risk., Results: Of the 184 patients who developed symptomatic VTE, 76 had pulmonary embolism, and 67 had lower-extremity DVT. Cumulative VTE incidence was 1.0%; 45% of events occurred after discharge. Factors independently associated with VTE were previous VTE, known thrombophilia, cancer, age > 60 years, lower-limb paralysis, immobilization ≥ 7 days, and admission to an ICU or coronary care unit (first four were available at admission). Points were assigned to each factor identified to give a total risk score for each patient. At admission, 67% of patients had a score ≥ 1. During hospitalization, 31% had a score ≥ 2; for a score of 2 or 3, observed VTE risk was 1.5% vs 5.7% for a score ≥ 4. Observed and predicted rates were similar for both models (C statistic, 0.65 and 0.69, respectively). During hospitalization, a score ≥ 2 was associated with higher overall and VTE-related mortality., Conclusions: Weighted VTE risk scores derived from four clinical risk factors at hospital admission can predict VTE risk in acutely ill hospitalized medical patients. Scores derived from seven clinical factors during hospitalization may help us to further understand symptomatic VTE risk. These scores require external validation.

Purpose: To determine if important geographic differences exist in treatment rates for osteoporosis and whether this variation can be explained by regional variation in risk factors., Methods: The Global Longitudinal Study of Osteoporosis in Women is an observational study of women ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires were used to collect data on patient characteristics, risk factors for fracture, previous fractures, anti-osteoporosis medication, and health status., Results: Among 58,009 women, current anti-osteoporosis medication use was lowest in Northern Europe (16%) and highest in U.S.A. and Australia (32%). Between 48% (U.S.A., Southern Europe) and 68% (Northern Europe) of women aged ≥65 years with a history of spine or hip fracture since age 45 were untreated. Among women with osteoporosis, the percentage of treated cases was lowest in Europe (45-52% versus 62-65% elsewhere). Women with osteopenia and no other risk factors were treated with anti-osteoporosis medication most frequently in U.S.A. (31%) and Canada (31%), and least frequently in Southern Europe (12%), Northern Europe (13%), and Australia (16%). After adjusting for risk factors, U.S. women were threefold as likely to be treated with anti-osteoporosis medication as Northern European women (odds ratio 2.8; 95% confidence interval 2.5-3.1) and 1.5 times as likely to be treated as Southern European women (1.5, 1.4-1.6). Up to half of women reporting previous hip or spine fracture did not receive treatment., Conclusions: The likelihood of being treated for osteoporosis differed between regions, and cannot be explained by variation in risk factors. Many women at risk of fracture do not receive prophylaxis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Although effective strategies are available for the management of chronic hypertension, less is known about treating patients with acute, severe elevations in blood pressure. Using data from the European registry for Studying the Treatment of Acute hyperTension (Euro-STAT), we sought to evaluate 'real-life' management practices and outcomes in patients who received intravenous antihypertensive therapy to treat an episode of acute hypertension., Methods: Euro-STAT is a European, hospital-based, observational study of consecutive adult patients treated with intravenous antihypertensive therapy while in the emergency department, perioperative unit or ICU. Enrolment took place between 1 July and 15 October 2009 in 11 hospitals in 7 European countries (Austria, Belgium, Germany, Italy, Spain, Sweden and the United Kingdom)., Results: The study population was composed of 791 consecutive patients (median age 69 years, 37% women). Median arterial blood pressure before treatment was 166 mmHg systolic blood pressure (IQR 141 to 190 mmHg) and 80 mmHg diastolic blood pressure (IQR 68 to 95). Nitroglycerine was the most commonly used antihypertensive treatment overall (40% of patients), followed by urapidil (21%), clonidine (16%) and furosemide (8%). Treatment was associated with hypotension in almost 10% of patients. Overall 30-day mortality was 4%, and new or worsening end-organ damage occurred in 19% of patients., Conclusions: High blood pressure requiring intravenous therapy is currently managed with a variety of agents in Europe, with those most commonly used being nitroglycerine, urapidil and clonidine. Patients with acute hypertension have substantial concomitant morbidity and mortality, and intravenous antihypertensive treatment is associated with hypotension in almost 10% of cases.

Background: venous thromboembolism prophylaxis is suboptimal in the US despite long-standing evidence-based recommendations. The aim of this subset analysis of the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study was to identify characteristics of hospitals with high guideline-recommended prophylaxis use., Methods: between September and November 2006, charts from eligible patients aged ≥ 40 years with an acute medical illness or age ≥ 18 years and undergoing a surgical procedure were reviewed from randomly selected US acute-care hospitals. Hospitals were ranked based on the proportion of at-risk patients who received American College of Chest Physicians-recommended types of prophylaxis. Hospital characteristics were compared to determine factors related to more frequent prophylaxis use. Hospitals were followed up 1 year after the chart audit., Results: overall, 9257 patients were evaluated from 81 hospitals. Appropriate types of prophylaxis were prescribed to more at-risk patients in hospitals in the highest quartile compared with the lowest quartile of prophylaxis use (74% vs 36%). All quartiles had a similar percentage of at-risk patients (61%-65%). Significantly more hospitals in the highest quartile had residency training programs (43% vs 5%), a larger median number of beds (277 vs 140), and had adopted hospital-wide prophylaxis protocols (76% vs 40%). In the follow-up survey, more hospitals overall had adopted hospital-wide written guidelines for venous thromboembolism prevention., Conclusions: these findings support the value of hospital-wide protocols and local audits for VTE prevention, as recommended by several national quality-of-care groups., (2010 Elsevier Inc. All rights reserved.)

Background: There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era., Methods: The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms., Results: Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003)., Conclusions: Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Study Objective: To assess antihypertensive treatment practices and outcomes for patients with acute severe hypertension requiring hospitalization., Design: Subanalysis of a multicenter, observational, cross-sectional study., Data Source: The STAT registry (data from 25 hospitals)., Patients: A total of 1184 consecutive adults with acute severe hypertension (systolic blood pressure [SBP] ≥ 180 mm Hg, diastolic blood pressure ≥ 110 mm Hg), without a neurologic reason for admission, receiving two or more intermittent intravenous antihypertensive doses or a continuous intravenous infusion within 24 hours of hospitalization., Measurements and Main Results: Patients started intravenous antihypertensive therapy 1.3 (median [interquartile range (IQR) 0.5-3.2]) hours after the qualifying SBP (median 204 [IQR 190-221] mm Hg). Labetalol (27%), metoprolol (21%), and nitroglycerin (20%) were the most frequent initial intravenous choices. For the 43% of patients administered two or more intravenous agents sequentially, the 24% receiving three or more, and the 8% receiving four or more, median SBPs at the time of the second, third, and fourth additions were 186 (IQR 168-211), 176 (IQR 152-196), and 164 (IQR 143-193) mm Hg, respectively. Most common continuous intravenous infusions were nitroglycerin (30%), nicardipine (13%), and labetalol (7%). After the first intravenous agent, an SBP decrease of 10-25% was achieved at 1 and 6 hours in 48% and 72%, respectively. Of the 6% without at least a 10% decrease in SBP during the entire hospitalization, labetalol (28%), hydralazine (21%), and metoprolol (17%) were the most frequent initial intravenous choices. Hypotension (SBP ≤ 90 mm Hg) occurred in 5% and was most common with intravenous nitroglycerin (39%). Oral antihypertensives were started within 1 and 6 hours after the first intravenous therapy in 13% and 34% of patients, respectively, with many patients (61%) receiving three or more oral agents during hospitalization., Conclusion: Pharmacologic treatment of acute severe hypertension in patients with nonneurologic causes is heterogeneous and often not consistent with Joint National Committee recommendations. Patients received numerous intravenous agents, experienced variable decreases in SBP, often failed to receive timely oral therapy, and a clinically relevant proportion developed hypotension.

Background: Acute severe hypertension can be a life-threatening emergency. The objective of this study was to describe the frequency of rehospitalization for patients with acute severe hypertension and to identify clinical predictors of 90-day rehospitalization., Methods: In this observational cross-sectional study, consecutive patients were identified retrospectively (January 2007 to April 2008) through uniform data query of hospital pharmacy databases in 25 hospitals in the United States. Eligible patients were > or =18 years old, had systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg, and had received intravenous antihypertensive therapy within 24 hours of presentation. Data were collected on patient demographics, medical history, laboratory findings, antihypertensive therapies, resource utilization, hospital-associated events, readmission within 90 days of hospital discharge, and death up to 6 months following the index hospitalization., Results: The 90-day readmission rate was 35% (354/1,009) of patients discharged home alive and with known readmission status; 41% (144/354) were readmitted more than once. Of these 354 patients, readmission was for acute severe hypertension in 29% (n = 101). Eighteen (1.9%) patients died between hospital discharge and 90 days. Factors associated with readmission for hypertension included previous hospitalization for acute severe hypertension, history of drug abuse, and presenting with seizures or shortness of breath. Patients with an admitting diagnosis of hypertension were 94% more likely to be readmitted., Conclusions: More than one third of patients discharged home after hospitalization for severe hypertension were rehospitalized at least once within 90 days, more than one quarter for acute severe hypertension. Further studies are warranted to determine the impact of other variables on readmission rates and clinical outcomes in this population., (2010 Mosby, Inc. All rights reserved.)

Objective: To examine several dimensions of health-related quality of life (HRQL) in postmenopausal women who report previous fractures, and to provide perspective by comparing these findings with those in other chronic conditions (diabetes, arthritis, lung disease)., Patients and Methods: Fractures are a major cause of morbidity among older women. Few studies have examined HRQL in women who have had prior fractures and the effect of prior fracture location on HRQL. In this observational study of 57,141 postmenopausal women aged 55 years and older (enrollment from December 2007 to March 2009) from 17 study sites in 10 countries, HRQL was measured using the European Quality of Life 5 Dimensions Index (EQ-5D) and the health status, physical function, and vitality questions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)., Results: Reductions in EQ-5D health-utility scores and SF-36-measured health status, physical function, and vitality were seen in association with 9 of 10 fracture locations. Spine, hip, and upper leg fractures resulted in the greatest reductions in quality of life (EQ-5D scores, 0.62, 0.64, and 0.61, respectively, vs 0.79 without prior fracture). Women with fractures at any of these 3 locations, as well as women with a history of multiple fractures (EQ-5D scores, 0.74 for 1 prior fracture, 0.68 for 2, and 0.58 for >/=3), had reductions in HRQL that were similar to or worse than those in women with other chronic diseases (0.67 for diabetes, 0.69 for arthritis, and 0.71 for lung disease)., Conclusion: Previous fractures at a variety of bone locations, particularly spine, hip, and upper leg, or involving more than 1 location are associated with significant reductions in quality of life.

Aims: The authors sought to define which guideline-advocated therapies are associated with the greatest benefit with respect to 6-month survival in patients hospitalised with an acute coronary syndrome (ACS)., Methods and Results: The authors conducted a nested case-control study of ACS patients within the Global Registry of Acute Coronary Events cohort between April 1999 and December 2007. The cases were ACS patients who survived to discharge but died within 6 months. The controls were patients who survived to 6 months, matched for ACS diagnosis, age and the Global Registry of Acute Coronary Events risk score. Rates of use of evidence-based medications and coronary interventions (angiography, percutaneous coronary intervention and coronary artery bypass graft surgery) were compared. Logistic regression including matched variables was used, and the attributable mortality from incomplete application of each therapy was calculated. A total of 1716 cases and 3432 controls were identified. Coronary artery bypass graft surgery and percutaneous coronary intervention were associated with the greatest 6-month survival benefit (OR for death 0.60 (95% CI 0.39 to 0.90) and 0.57 (0.48 to 0.72), respectively). Statins and clopidogrel provided the greatest independent pharmacologic benefit (ORs for death 0.85 (0.73 to 0.99) and 0.84 (0.72 to 0.99)) with lesser effects seen with other pharmacotherapies., Conclusions: A diminishing benefit associated with each additional ACS therapy is evident. These data may provide a rational basis for selecting between therapeutic options when compliance or cost is an issue.

The aim of GRACE was to provide a large multinational registry of the full spectrum of patients with acute coronary syndromes (ACS) in order to define patient characteristics and outcomes and derive predictive risk scores. The study was designed and administered by an independent steering committee; data analyses were performed under the guidance of the steering committee at the Center for Outcomes Research of the University of Massachusetts. Regular feedback regarding local, regional and international guideline and performance measures was provided to individual hospitals and clusters of hospitals. Regional and international benchmark data were available to all sites. Main GRACE involved 123 hospitals in 14 countries in North and South America, Europe, Australia and New Zealand. GRACE2 (Expanded GRACE) comprised 154 hospitals in Europe, North and South America, Asia, Australasia and China. Continuous recruitment and follow-up took place between 1999 and 2009. The first 10 -20 patients per site (depending on hospital size) were enrolled each month, resulting in the recruitment of 102 341 patients, who were categorized as having ST-segment elevation myocardial infarction, non-ST-elevation myocardial infarction or unstable angina. Standardized case report forms (datafax or electronic) were completed by trained study coordinators, and included fields relating to demographic factors, comorbid conditions, treatments and in-hospital and post-discharge (6-month) events. Blood sampling, genetic analyses and longer-term follow-up were undertaken in GRACE substudies. Prospective individual patient follow-up was carried out. All sites were audited locally; 10% of individual patient records were audited in a 2-year cycle. Less than 1% of 20 key baseline fields, and less than 1% of discharge diagnosis and discharge status data, were missing. Six-month follow-up was 85% complete. Publications and risk scores are available at http://www.outcome.org/grace. Proposals for specific analyses were considered, in competition, by an independent publications committee.

Aims: To examine the extent of delay from initial hospital presentation to fibrinolytic therapy or primary percutaneous coronary intervention (PCI), characteristics associated with prolonged delay, and changes in delay patterns over time in patients with ST-segment elevation myocardial infarction (STEMI)., Methods and Results: We analysed data from 5170 patients with STEMI enrolled in the Global Registry of Acute Coronary Events from 2003 to 2007. The median elapsed time from first hospital presentation to initiation of fibrinolysis was 30 min (interquartile range 18-60) and to primary PCI was 86 min (interquartile range 53-135). Over the years under study, there were no significant changes in delay times to treatment with either strategy. Geographic region was the strongest predictor of delay to initiation of fibrinolysis >30 min. Patient's transfer status and geographic location were strongly associated with delay to primary PCI. Patients treated in Europe were least likely to experience delay to fibrinolysis or primary PCI., Conclusion: These data suggest no improvements in delay times from hospital presentation to initiation of fibrinolysis or primary PCI during our study period. Geographic location and patient transfer were the strongest predictors of prolonged delay time, suggesting that improvements in modifiable healthcare system factors can shorten delay to reperfusion therapy even further.

Limited data are available regarding the risk for venous thromboembolism (VTE) and VTE prophylaxis use in hospitalised medically ill patients. We analysed data from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this population according to diagnosis, baseline characteristics, and country. Data on patient characteristics, VTE risk, and prophylaxis use were abstracted from hospital charts. VTE risk and prophylaxis use were evaluated according to the 2004 American College of Chest Physicians (ACCP) guidelines. Multivariable analysis was performed to identify factors associated with use of ACCP-recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical patients across 32 countries. VTE risk varied according to medical diagnosis, from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of patients with acute heart failure, active non-infectious respiratory disease, or pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP-recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40-45% of cardiopulmonary disease patients (global rate, 39.5%). Large differences in prophylaxis use were observed among countries. Markers of disease severity, including central venous catheters, mechanical ventilation, and admission to intensive care units, were strongly associated with use of ACCP-recommended prophylaxis. In conclusion, VTE risk varies according to medical diagnosis. Less than 40% of at-risk hospitalised medical patients receive ACCP-recommended prophylaxis. Prophylaxis use appears to be associated with disease severity rather than medical diagnosis. These data support the necessity to improve implementation of available guidelines for evaluating VTE risk and providing prophylaxis to hospitalised medical patients.

Objective: To evaluate venous thromboembolism (VTE) risk in patients who underwent a major operation, including the use of, and factors influencing, American College of Chest Physicians-recommended types of VTE prophylaxis., Summary Background Data: The Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) survey, conducted in 358 hospitals in 32 countries, reported that globally, more than 40% of at-risk patients do not receive VTE prophylaxis. Limited data are available regarding VTE prophylaxis practices according to surgery type and patient characteristics., Methods: Patients aged >or=18 years undergoing major surgery were included in this prespecified subanalysis. VTE risk and use of prophylaxis were determined from hospital medical records according to the 2004 American College of Chest Physicians guidelines. Multivariable analyses were performed to identify factors associated with VTE prophylaxis use., Results: Of the 18,461 patients in ENDORSE who had undergone major surgery, 17,084 (92.5%) were at-risk for VTE and 10,638 (62.3%) received prophylaxis. Use of prophylaxis varied according to major surgery type from 86.0% for orthopedic surgery to 53.8% in urologic/gynecologic and 53.6% in other procedures. Major orthopedic surgery was most strongly associated with prophylaxis use (hip replacement: odds ratio 6.2, 95% confidence interval [CI] 5.0-7.6; knee replacement: odds ratio 5.9, 95% CI 4.6-7.8)., Conclusions: The majority of surgical patients are at high-risk for VTE. Despite long-standing recognition of the high-risk for VTE in surgical patients, thromboprophylaxis remains underutilized.

Aims: Brief episode(s) of ischaemia may increase cardiac tolerance to a subsequent major ischaemic insult ('preconditioning'). Nitrates can pharmacologically mimic ischaemic preconditioning in animals. In this study, we investigated whether antecedent nitrate therapy affords protection toward acute ischaemic events using data from the Global Registry of Acute Coronary Events., Methods and Results: The dataset comprised 52,693 patients from 123 centres in 14 countries: 42,138 (80%) were nitrate-naïve and 10,555 (20%) were on chronic nitrates at admission. In nitrate-naïve patients, admission diagnosis was ST-segment elevation myocardial infarction (STEMI) in 41%, whereas 59% presented with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). In contrast, only 18% nitrate users showed STEMI, whereas 82% presented with NSTE-ACS. Thus, among nitrate users clinical presentation was tilted toward NSTE-ACS by more than four-fold, STEMI occurring in less than one of five patients (P < 0.0001). After adjustment (age, sex, medical history, prior therapy, revascularization, previous angina), chronic nitrate use remained independent predictor of NSTE-ACS (OR 1.36; 95% CI 1.26-1.46; P < 0.0001). Furthermore, regardless of presentation, within both STEMI and NSTEMI populations, antecedent nitrate use was associated with significantly lower levels of CK-MB and troponin (P < 0.0001 for all)., Conclusion: In this large multinational registry, chronic nitrate use was associated with a shift away from STEMI in favour of NSTE-ACS and with less release of markers of cardiac necrosis. These findings suggest that in nitrate users acute coronary events may develop to a smaller extent. Randomized, placebo-controlled trials are warranted to establish whether nitrate therapy may pharmacologically precondition the heart toward ischaemic episodes.

Aims: In acute coronary syndromes (ACS), the optimal revascularization strategy for unprotected left main coronary disease (ULMCD) has been little studied. The objectives of the present study were to describe the practice of ULMCD revascularization in ACS patients and its evolution over an 8-year period, analyse the prognosis of this population and determine the effect of revascularization on outcome., Methods and Results: Of 43 018 patients enrolled in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007, 1799 had significant ULMCD and underwent percutaneous coronary intervention (PCI) alone (n = 514), coronary artery bypass graft (CABG) alone (n = 612), or no revascularization (n = 673). Mortality was 7.7% in hospital and 14% at 6 months. Over the 8-year study, the GRACE risk score remained constant, but there was a steady shift to more PCI than CABG over time. Patients undergoing PCI presented more frequently with ST-segment elevation myocardial infarction (STEMI), after cardiac arrest, or in cardiogenic shock; 48% of PCI patients underwent revascularization on the day of admission vs. 5.1% in the CABG group. After adjustment, revascularization was associated with an early hazard of hospital death vs. no revascularization, significant for PCI (hazard ratio (HR) 2.60, 95% confidence interval (CI) 1.62-4.18) but not for CABG (1.26, 0.72-2.22). From discharge to 6 months, both PCI (HR 0.45, 95% CI 0.23-0.85) and CABG (0.11, 0.04-0.28) were significantly associated with improved survival in comparison with an initial strategy of no revascularization. Coronary artery bypass graft revascularization was associated with a five-fold increase in stroke compared with the other two groups., Conclusion: Unprotected left main coronary disease in ACS is associated with high mortality, especially in patients with STEMI and/or haemodynamic or arrhythmic instability. Percutaneous coronary intervention is now the most common revascularization strategy and preferred in higher risk patients. Coronary artery bypass graft is often delayed and performed in lower risk patients, leading to good 6-month survival. The two approaches therefore appear complementary.

Background: Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this population., Methods: STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting., Results: One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension., Conclusion: This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.

Background: The Global Registry of Acute Coronary Events (GRACE)-a prospective, multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was designed to improve the quality of care for patients with an ACS. Expanded GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practices to an international reference cohort., Methods: We describe the objectives; study design; study and data management; and the characteristics, management, and hospital outcomes of patients > or =18 years old enrolled with a presumptive diagnosis of ACS., Results: From 2001 to 2007, 31,982 patients were enrolled at 184 hospitals in 25 countries; 30% were diagnosed with ST-segment elevation myocardial infarction, 31% with non-ST-segment myocardial infarction, 26% with unstable angina, and 12% with another cardiac/noncardiac final diagnosis. The median age was 65 (interquartile range 55-75) years; 24% were >75 years old, and 33% were women. In general, increases were observed over time across the spectrum of ACS (1) in the use in the first 24 hours and at discharge of aspirin, clopidogrel, beta-blockers, and angiotensin-converting enzyme inhibitors/receptor blockers; (2) in the use at discharge of statins; (3) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin; and (4) in the use of cardiac catheterization and percutaneous coronary intervention. An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infarction were also seen., Conclusions: Over the course of 7 years, general increases in the use of evidence-based therapies for ACS patients were observed in the expanded GRACE.

Background: Patients with non-ST-elevation acute coronary syndrome complicated by congestive heart failure (CHF) have a poor prognosis. The aims of this study were to describe the use of revascularization in non-ST-elevation acute coronary syndrome and CHF and to analyze its impact on survival., Methods and Results: In the Global Registry of Acute Coronary Events, 29 844 patients with non-ST-elevation acute coronary syndrome were enrolled at 120 hospitals in 14 countries between April 1999 and June 2007; 4953 had CHF at presentation. One fifth of the patients with CHF underwent revascularization versus 35% of those without CHF (P<0.001). Among CHF patients, revascularized patients had lower-risk baseline clinical characteristics than nonrevascularized patients and were more likely to receive evidence-based cardiac medications. Hospital rates were not affected by revascularization (adjusted hazard ratio 0.97, 95% confidence interval 0.72 to 1.33, P=0.87). Death from discharge to 6-month follow-up was lower in patients who underwent revascularization than in those who did not (odds ratio 0.51, 95% confidence interval 0.35 to 0.74, P<0.001). This difference persisted after adjustment for GRACE risk score variables, country, and propensity for revascularization (odds ratio 0.58, 95% confidence interval 0.40 to 0.85, P=0.005). When revascularization as a time-varying covariate was taken into account in an adjusted Cox regression, the rate of death was again lower in patients undergoing revascularization (hazard ratio 0.64, 95% confidence interval 0.45 to 0.93, P=0.02)., Conclusions: This observational study suggests a low use of in-hospital revascularization in non-ST-elevation acute coronary syndrome patients with CHF. The consistent reduction in postdischarge death in revascularized patients suggests that broader application of revascularization in this high-risk group may be beneficial.

Background: The time course of events after acute coronary syndromes might influence the timing and duration of therapeutic interventions. We investigated the impact of risk status and ST-segment category at presentation., Methods: The timing of death, reinfarction, stroke and major bleeding within 6 months of acute coronary syndromes was determined in 46,829 patients enrolled in the Global Registry of Acute Coronary Events (GRACE). Acute coronary syndromes were classified by elevation (n = 17,668), depression (n = 8,542), or neither (n = 20,619) in the ST segment. GRACE risk scores and hazard ratios (HR) were determined for three time periods: 0-4, 5-15 and 16-180 days., Results: ST-segment elevation was associated with a higher early risk of death than was ST-segment depression (0-4 days, HR 1.89, 95% CI 1.60-2.24 versus 5-15 days, HR 1.26, 95% CI 1.05-1.50), but after 15 days the risk was reversed (16-180 days, HR 0.85, 95% CI 0.75-0.97). Throughout the study, patients with ST-segment deviation had a higher mortality risk than those without. Within each ST category, the highest GRACE risk scores were associated with a 10-40-fold greater risk of death than the lowest scores (all categories P <0.0001). Most deaths occurred after day 4 (57%, 74%, and 78% for ST-segment elevation, depression and neither, respectively)., Conclusion: The timing of events after acute coronary syndromes was affected by ST category and influenced by GRACE risk score within each electrocardiographic category of acute coronary syndromes. Risk stratification should, therefore, include multiple risk factors rather than ST shift alone.

Venous thromboembolism (VTE) is a major US health problem. However, the total number of US inpatients who are at risk for VTE is unknown. Our objective was to estimate the number of US acute-care hospital inpatients who were at risk for VTE according to criteria established by the Seventh American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic and Thrombolytic Therapy guidelines for VTE prevention. Using the 2003 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP), patient diagnoses and procedures were examined to identify major surgery patients (age > or = 18 years, length of hospital stay > or = 2 days) and medical patients (age > or = 40 years, length of hospital stay > or = 2 days). ACCP guidelines were used to estimate the number of surgical and medical patients at risk of developing VTE. Of an estimated 38,220,659 discharges in 2003, 7,786,390 (20%) were surgical inpatients; 44% of which were at low risk for VTE, while 15%, 24%, and 17% were at moderate, high, and very high risk for VTE, respectively. Of the remaining 15,161,586 medical patients, 7,742,419 (51%) met ACCP VTE risk criteria. Over 12 million patients, comprising 31% of US hospital discharges in 2003, were at risk of VTE. Given the existence of internationally-accepted evidence-based guidelines for prevention of VTE, research is required to establish if this patient population is receiving recommended VTE prophylaxis., (2007 Wiley-Liss, Inc)

Objective: To analyze in-hospital mortality after pancreatectomy using a large national database., Summary and Background Data: Pancreatic resections, including pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy, remain the only potentially curative interventions for pancreatic cancer. The goal of this study was to define factors affecting outcomes after pancreatectomy for neoplasm., Methods: A retrospective analysis was performed using all patients undergoing pancreatic resections for neoplastic disease identified from the Nationwide Inpatient Sample from 1998 to 2003. Crude in-hospital mortality was analyzed by chi. A multivariable model was constructed to adjust for age, sex, hospital teaching status, hospital surgical volume, year of resection, payer status, and selected comorbid conditions., Results: In all, 279,445 patient discharges were identified with a primary diagnosis of pancreatic neoplasm. A total of 39,463 (14%) patients underwent resection during that hospitalization. In-hospital mortality was 5.9% with a significant decrease from 7.8% to 4.6% from 1998 to 2003 by trend analysis (P < 0.0001). Resections done at low (<5 procedures/year)- and medium (5-18/year)-volume centers had higher mortality compared with those at high (>18/year)-volume centers (low-volume odds ratio = 3.3; 95% confidence interval, 2.3-4.; medium-volume, odds ratio = 2.1; 95% confidence interval, 1.5-3.0). The proportion of procedures performed at high volume centers increased from 30% to 39% over the 6-year time period (P < 0.0001) by trend test., Conclusions: This large observational study demonstrates an improvement in operative mortality for patients undergoing pancreatectomy for neoplastic disease from 1998 to 2003. In addition, a greater proportion of pancreatectomies were performed at high-volume centers in 2003. The regionalization of pancreatic surgery may have partially contributed to the observed decrease in mortality rates.

Background: Limited data suggest that ST elevation (ST elevation) in aVR is associated with higher mortality and more extensive coronary artery disease in the setting of non-ST elevation acute coronary syndromes (ACS)., Methods: In the prospective Global Registry of Acute Coronary Events (GRACE) electrocardiographic substudy, the admission electrocardiograms were analyzed by a blinded core laboratory. We performed multivariable analysis to determine (1) the independent prognostic significance of ST elevation in aVR and (2) its association with significant (> or = 50% stenosis) left main or 3-vessel disease (LM/3-vd)., Results: Among 5064 patients with non-ST elevation ACS, 4696 had no ST elevation in aVR, 292 (5.8%) had minor (0.5-1 mm) ST elevation in aVR, and 76 (1.5%) had major (>1 mm) ST elevation in aVR; their in-hospital mortality rates were 4.2%, 6.2%, and 7.9%, respectively (P for trend =.03). At 6 months follow-up, the cumulative mortality rates were 7.6%, 12.7%, and 18.3%, respectively (log-rank P for trend <.001). However, minor and major ST elevation in aVR were not independent predictors of in-hospital or 6-month death after adjusting for other validated prognosticators in the GRACE risk model. Of the 2416 patients without prior coronary bypass surgery who underwent cardiac catheterization, the prevalence of LM/3-vd was 26.1%, 36.2%, and 55.9% for the groups with no, minor, and major ST elevation in aVR, respectively (P for trend <.001). After adjusting for other clinical characteristics, major ST elevation in aVR remained an independent predictor of LM/3-vd (adjusted odds ratio, 2.68; 95% confidence interval, 1.29-5.58; P = .008)., Conclusion: ST elevation in aVR is less prevalent than reported in previous smaller studies. Although it is associated with higher unadjusted in-hospital and 6-month mortality, it does not provide incremental prognostic value beyond comprehensive risk stratification using the validated GRACE risk model. However, ST elevation greater than 1 mm in aVR may be useful in the early identification of LM/3-vd in ACS patients with ST depression.

Background: We evaluated the association between invasive and non-invasive management and hospital and 6-month outcomes in patients with a prior coronary artery bypass graft (CABG) who experienced an acute coronary syndrome., Methods: Data were analysed from patients with a prior CABG who developed an acute coronary syndrome and were enrolled in the Global Registry of Acute Coronary Events. From 44,991 patients included in the study, 3853 fulfilled the inclusion criteria. Of these, 3356 received non-invasive treatment approaches while 497 underwent invasive treatment (percutaneous coronary intervention [PCI] within 48 h of admission)., Results: The primary composite endpoint of death, non-fatal myocardial infarction, and recurrent ischaemia during hospitalization was similar in patients in the non-invasive and invasive groups (31% vs 30%, respectively; P=0.53). The rates of hospital mortality (non-invasive 3.4% vs invasive 3.2%) and non-fatal myocardial infarction (3.4% vs 5.1%, respectively) were similar. At 6-month follow-up, the mortality rate was 6.5% in the non-invasive group vs 3.4% in the invasive group (P<0.02); the combined endpoint of death or myocardial infarction was lower in the invasive group (P<0.01). Multivariable analysis showed that, at 6-month follow-up, the combined endpoint of death, non-fatal myocardial infarction, and rehospitalization for heart disease was similar (P=0.10). A greater proportion of patients in the invasive group required unscheduled diagnostic and therapeutic invasive procedures compared with those in the non-invasive group (angiography 15.4% vs 8.1%; PCI 10% vs 5.0%; both P<0.001)., Conclusions: The results from this observational study show no statistically significant differences in hospital outcomes between acute coronary syndrome patients with a prior CABG who undergo invasive or non-invasive treatment. Invasively treated patients experienced higher rates of readmission and additional cardiac procedures than non-invasively treated patients but a lower incidence of cardiovascular complications at 6 months.