METHODS: Using data from a large multinational study, we examined the age and sex differences, and changing trends (1999-2007) therein, in the hospital use of evidence-based therapies in patients hospitalized with an ACS using data from the Global Registry of Acute Coronary Events (n=50 096).

RESULTS: After adjustment for several variables, in comparison with men below 65 years, patients in other age-sex strata had a significantly lower odds of receiving aspirin [odds ratios (ORs) for men 65-74, 75-84, and >/=85 years, women <65, 65-74, 75-84, and >/=85 years were 0.86, 0.84, 0.72, 0.80, 0.86, 0.68 and 0.46, respectively], angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ORs, 1.08, 1.01, 0,71, 0.83, 0.90, 0.89, and 0.63), beta blockers (ORs, 0.66, 0.52, 0.53, 0.67, 0.54, 0.53, and 0.52), statins (ORs, 0.72, 0.49, 0.29, 0.82, 0.68, 0.44, and 0.22), and undergoing coronary artery bypass graft surgery or a percutaneous coronary intervention (ORs, 0.79, 0.53, 0.21, 0.64, 0.57, 0.38, and 0.13) during their acute hospitalization. Age and sex differences in the receipt of these therapies remained relatively unchanged during the period under study.

CONCLUSION: Although there were increasing trends in the use of evidence-based medications and cardiac procedures over time, important gaps in the utilization of effective cardiac treatment modalities persist in elderly patients and younger women.

OBJECTIVE: To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS.

METHODS: Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment.

RESULTS: While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and highrisk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization.

CONCLUSION: Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada.

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.

METHODS AND RESULTS: A systematic review of the literature from 1960 to 2008, including publications that provided data on duration of prehospital delay in patients hospitalized with AMI, was conducted. A total of 44 articles (42 studies) were included in the present analysis. The majority of studies showed that in patients hospitalized with AMI, women and older persons were more likely to arrive at the hospital later than men and younger persons. Several factors associated with duration of prehospital delay, including sociodemographic, medical history, clinical, and contextual characteristics differed according to sex.

CONCLUSIONS: The elderly and women were more likely to exhibit longer delays in seeking medical care after the development of symptoms suggestive of AMI compared with other groups. Further research is needed to more fully understand the reasons for delay in these vulnerable groups.

Methods: We conducted a secondary analysis in 93,676 women enrolled in the observational arm of the Women’s Health Initiative. Constipation was evaluated at baseline by a self-administered questionnaire and rated as none, mild, moderate, severe. Baseline associations between constipation and risk factors for CV disease were determined using cross-tabulations and chi-square statistics. Estimates of the risk of CV events (cumulative end-point including mortality for coronary heart disease, MI, angina, PTCA, CABG, stroke and TIA) in the different constipation categories (vs. no constipation) were derived from Cox proportional hazard regression models. CV outcomes were centrally validated.

Results: The analysis included 76,870 women. Mean follow-up was 6.4 years (max. 9.3). Constipation was associated with age, race, smoking, diabetes, high cholesterol, family history of MI, hypertension, obesity, lack of physical activity, low fiber intake, and depression (all p<0.001). Women with moderate and severe constipation had a higher number of CV events (14.7 and 18.9/1000 person-years, respectively, vs. 9.6/1000 person-years in the no constipation group) and a higher risk of CV events (unadjusted HR, moderate vs. none: 1.53; CI: 1.39, 1.68); severe vs. none: HR: 1.97; CI: 1.66, 2.33). After adjustment for demographics, risk factors for CHD, dietary factors, medications and depression, women reporting moderate constipation still had a higher risk of CV events (HR:1.13; CI: 1.03,1.24) as did women with severe constipation (HR 1.28; CI: 1.08,1.53).

Conclusion: Moderate and severe constipation appear to be independently associated with an increased risk of CV events in menopausal women. Since constipation is easily assessed, it may be helpful in identifying women at risk, in whom preventive screening for coronary risk factors may be indicated.

AIM: To review the methodology of previously published studies of psychosocial interventions in ICD patients, according to CONSORT statement guidelines for non-pharmacological interventions, and provide recommendations for future research.

METHODS: We electronically searched the PubMed, PsycInfo and Cochrane databases. To be included, studies needed to be published in a peer-reviewed journal between 1980 and 2008, to involve a human population aged 18+ years and to have an experimental design.

RESULTS: Twelve studies met the eligibility criteria. Samples were generally small. Interventions were very heterogeneous; most studies used cognitive behavioural therapy (CBT) and exercise programs either as unique interventions or as part of a multi-component program. Overall, studies showed a favourable effect on anxiety (6/9) and depression (4/8). CBT appeared to be the most effective intervention. There was no effect on the number of shocks and arrhythmic events, probably because studies were not powered to detect such an effect. Physical functioning improved in the three studies evaluating this outcome. Lack of information about the indication for ICD implantation (primary vs. secondary prevention), limited or no information regarding use of anti-arrhythmic (9/12) and psychotropic (10/12) treatment, lack of assessments of providers' treatment fidelity (12/12) and patients' adherence to the intervention (11/12) were the most common methodological limitations.

CONCLUSIONS: Overall, this review supports preliminary evidence of a positive effect of psychosocial interventions on anxiety and physical functioning in ICD patients. However, these initial findings must be interpreted cautiously because of important methodological limitations. Future studies should be designed as large RCTs, whose design takes into account the specific challenges associated with the evaluation of behavioural interventions.

Similarly strong evidence indicates that smoking cessation alone can result in a 36% reduction in the crude relative risk of mortality in smokers who quit versus those who do not.5 The risk decreases rapidly: after only 1 year of cessation, quitters have a lower relative risk (RR=0.63) of death from coronary heart disease (CHD) than do nonquitters, which decreases even further (RR=0.38) after 3 years of cessation. Consequently, efforts to find effective treatments to enhance smoking cessation are of great importance.

METHODS: Antipsychotic prescribing was assessed for a nationwide, cross-sectional population of 16 586 newly admitted NH residents in 2006. We computed facility-level antipsychotic rates based on the previous year's (2005) prescribing patterns. Poisson regressions with generalized estimating equations were used to identify the likelihood of resident-level antipsychotic medication use in 2006, given 2005 facility-level prescribing pattern and NH resident indication for antipsychotic therapy (psychosis, dementia, and behavioral disturbance).

RESULTS: More than 29% (n = 4818) of study residents received at least 1 antipsychotic medication in 2006. Of the antipsychotic medication users, 32% (n = 1545) had no identified clinical indication for this therapy. Residents entering NHs with the highest facility-level antipsychotic rates were 1.37 times more likely to receive antipsychotics relative to those entering the lowest prescribing rate NHs, after adjusting for potential clinical indications (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.24-1.51). The elevated risk associated with facility-level prescribing rates was apparent for only NH residents with dementia but no psychosis (RR, 1.40; 95% CI, 1.23-1.59) and residents without dementia or psychosis (RR, 1.54; 95% CI, 1.24-1.91).

CONCLUSIONS: The NH antipsychotic prescribing rate was independently associated with the use of antipsychotics in NH residents. Future research is needed to determine why such a prescribing culture exists and whether it could result in adverse health consequences.

METHODS AND FINDINGS: We conducted a prospective nested case-control study of DENV infections during infancy. Clinical data and blood samples were collected from 4,441 mothers and infants in up to two pre-illness study visits, and surveillance was performed for symptomatic and inapparent DENV infections. Pre-illness plasma samples were used to measure the associations between maternally derived anti-DENV3 antibody-neutralizing and -enhancing capacities at the time of DENV3 infection and development of infant DHF. The study captured 60 infants with DENV infections across a wide spectrum of disease severity. DENV3 was the predominant serotype among the infants with symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity at birth positively correlated with the age of symptomatic primary DENV3 illness in infants. At the time of symptomatic DENV3 infection, essentially all infants had low anti-DENV3 neutralizing activity (50% plaque reduction neutralizing titers [PRNT(50)]

CONCLUSIONS: This prospective nested case-control study of primarily DENV3 infections during infancy has shown that infants exhibit a full range of disease severity after primary DENV infections. The results support an initial in vivo protective role for maternally derived antibody, and suggest that a DENV3 PRNT(50) >50 is associated with protection from symptomatic DENV3 illness. We did not find a significant association between DENV3 ADE activity at illness onset and the development of DHF compared with less severe symptomatic illness. The results of this study should encourage rethinking or refinement of the current ADE pathogenesis model for infant DHF and stimulate new directions of research into mechanisms responsible for the development of DHF during infancy.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00377754

METHODS: In a cross-sectional development cohort (5729 patients), statistically significant predictors of the logarithm of erythrocyte sedimentation rate (lnESR) were identified. After computation of the mDAS28, a cross-sectional validation cohort (5578 patients) was used to evaluate internal, criterion, and construct validities. The ability of the mDAS28 to discriminate between disease states was also assessed. A second validation cohort (longitudinal, 336 pairs of patient visits) was used to assess sensitivity to change.

RESULTS: Significant predictors of lnESR included tender and swollen joints with 28 counts, patient's and physician's assessments of global health, and patient's assessment of pain (visual analog scale 0-100 mm) and a physical function (modified Health Assessment Questionnaire 0-3; mHAQ). Satisfactory internal validity (alpha = 0.72) and strong criterion validity compared to the DAS28, the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) (r = 0.87-0.96) were found. Predictive validity was demonstrated by good correlation with the mHAQ (r = 0.58). The mDAS28 showed substantial agreement with the DAS28, SDAI, and CDAI in discriminating between disease states (kappa = 0.70-0.77) and moderate to substantial agreement between response levels (kappa = 0.52-0.73). Both mDAS28 and DAS28 measures classified patients similarly in remission compared to the SDAI and CDAI. The mDAS28 was superior in detecting change (standardized response mean = 0.58) followed by the DAS28, CDAI, and SDAI.

CONCLUSION: The mDAS28 is a valid and sensitive tool to assess disease activity in epidemiological research, as an alternative to the DAS28, when acute-phase reactant values are unavailable.

Abstract presented at the 42nd Annual Meeting of the Society for Epidemiologic Research, Anaheim, California, June 23-26, 2009.

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.

METHODS AND RESULTS: In this multinational registry, 5093 STEMI patients received a stent: 1313 (26%) a DES and 3780 (74%) only BMS. Groups differed in baseline characteristics, type, or timing of percutaneous coronary intervention, with a higher baseline risk for patients receiving BMS. Two-year follow-up was available in 55 and 60% of the eligible BMS and DES patients, respectively. Unadjusted mortality was lower during hospitalization, similar for the first 6 months after discharge, and higher from 6 months to 2 years, for DES patients compared with that of BMS patients. Overall, unadjusted 2-year mortality was 5.3 vs. 3.9% for BMS vs. DES patients (P = 0.04). In propensity- and risk-adjusted survival analyses (Cox model), post-discharge mortality was not different up to 6 months (P = 0.21) or 1 year (P = 0.34). Late post-discharge mortality was higher in DES patients from 6 months to 2 years (HR 4.90, P = 0.01) or from 1 to 2 years (HR 7.06, P = 0.02). Similar results were observed when factoring in hospital mortality.

CONCLUSION: The observation of increased late mortality with DES vs. BMS suggests that DES should probably be avoided in STEMI, until more long-term data become available.

METHOD: Systematic review of the literature from 1990 to 30 October 2007 including English publications comparing dengue and OFI.

RESULTS: Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children only, and four assessed adults only. Patients with dengue had significantly lower platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of petechiae than OFI patients. Higher frequencies of myalgia, rash, haemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher haematocrits were reported in adult patients with dengue but not in children. Most multivariable models included platelet count, WBC, rash, and signs of liver damage; however, none had high statistical validity and none considered changes in clinical features over the course of illness.

CONCLUSIONS: Several individual clinical and laboratory variables distinguish dengue from OFI; however, some variables may be dependent on age. No published multivariable model has been validated. Study design, populations, diagnostic criteria, and data collection methods differed widely across studies, and the majority of studies did not identify specific aetiologies of OFIs. More prospective studies are needed to construct a valid and generalizable algorithm to guide the differential diagnosis of dengue in endemic countries.

METHODS: The study population consisted of 13,663 residents of the Worcester metropolitan area who were hospitalized with AMI at all greater Worcester medical centers during 15 annual periods between 1975 and 2005.

RESULTS: The average age of the hospitalized study sample was 69 years, and 58% were men. The overall proportion of patients with AMI who developed CHB was 4.1%. The incidence rates of CHB complicating AMI declined appreciably over time, with the greatest decline in these incidence rates occurring during the most recent years under study. In 2005, 2.0% of patients hospitalized with AMI developed CHB compared to 5.1% in the initial study year of 1975. Patients with AMI who developed CHB had higher inhospital death rates (43.2%) than did those who did not develop CHB (13.0%) (P < .001). The hospital death rates associated with CHB declined appreciably over time, particularly during the most recent years under study. Several patient characteristics were associated with an increased risk for developing CHB during hospitalization for myocardial infarcation.

CONCLUSIONS: Our findings indicate recent encouraging declines in the incidence rates of CHB complicating AMI and improving trends in the hospital prognosis of these patients.