15 research outputs found

    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

    Oxygen kinetics: Pitfalls in clinical research

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28793/1/0000627.pd

    Variations in cardiac implantable electronic device surveillance and ancillary testing in the paediatric and congenital heart disease population: An international multi-centre survey from the Paediatric and Congenital Electrophysiology Society

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    Background: Expert guidance from scientific societies and regulatory agencies recommend a framework of principles for frequency of in-person evaluations and remote monitoring for patients with cardiac implantable electronic devices. However, there are limited data regarding adherence to recommendations among paediatric electrophysiologists, and there are no data regarding cardiac implantable electronic device-related ancillary testing. Methods: To assess current clinical practices for cardiac implantable electronic device in-person evaluation, remote monitoring, and cardiac implantable electronic device-related ancillary testing, the Paediatric and Congenital Electrophysiology Society members were surveyed. The main outcome measures were variations in frequency of in person evaluation, frequency of remote monitoring, and cardiac implantable electronic device-related ancillary testing. Results: All respondents performed in-person evaluation at least once a year, but \u3c50% of respondents performed an in-person evaluation within 2 weeks of cardiac implantable electronic device implantation. Remote monitoring was performed every 3 months for pacemakers and implantable cardioverter defibrillators by 71 and 75% respondents, respectively. Follow-up echocardiography was performed every 2-3 years by 53% respondents for patients with \u3e50% ventricular pacing. Majority of respondents (75%) did not perform either an exercise stress test or ambulatory Holter monitoring or chest X-ray (65%) after cardiac implantable electronic device implantation. Conclusion: This survey identified significant practice variations in cardiac implantable electronic device in- person evaluation, remote monitoring, and ancillary testing practices among paediatric electrophysiologists. Cardiac implantable electronic device management may be optimised by development of a paediatric-specific guidelines for follow-up and ancillary testing

    Effect of interhospital transfer on resource utilization and outcomes at a tertiary pediatric intensive care unit

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    Purpose: The study aimed to examine the effect of interhospital transfer on resource utilization and clinical outcomes at a tertiary pediatric intensive care unit (PICU) among patients with sepsis or respiratory failure. Materials and methods: Data on 2146 consecutive admissions with respiratory failure or sepsis to the PICU were analyzed. Data included demographics, admission source, and outcomes. Admission source was classified as interhospital transfer from the emergency departments (ED), wards, or PICUs of referring hospitals; or from the study hospital ED (direct). Results: Compared with direct admissions, inter-PICU transfers had higher crude mortality (odds ratio, 1.93; 95% confidence interval, 1.31-2.84) but not significant mortality difference (odds ratio, 1.16; 95% confidence interval, 0.71-1.86) after adjusting for illness severity, age, and sex. Conversely, ED transfers had lower PICU mortality than direct ED admissions. Children with transfer admissions stayed significantly longer and used more intensive care technology in the study PICU than children directly admitted (P \u3c .01). In comparisons within quartiles of mortality risk, inter-PICU transfers had longer hospitalization and higher mortality in all but the highest quartile. Conclusions: Interhospital transfer, particularly inter-PICU transfer, was associated with significant hospital resource consumption that often correlated with admission illness severity. Future prospective studies should identify determinants of pretransfer illness severity and investigate decision making underlying interhospital transfer. © 2009 Elsevier Inc. All rights reserved

    Characteristics and outcomes of interhospital transfers from level II to level I pediatric intensive care units

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    OBJECTIVE: To examine the characteristics, resource utilization, and outcomes for transfer admissions from level II to level I pediatric intensive care units (PICUs). DESIGN: Retrospective study. SETTING: A 16-bed level I PICU in a tertiary care children\u27s hospital. PATIENTS: All transfer admissions from level II PICUs from January 1, 1997, through December 31, 2003; admissions for cardiac surgery were excluded. Patient characteristics, resource utilization, and outcomes were described and then compared across predefined strata (low \u3c5%, moderate 5-30%, and high \u3e30%) of predicted probability of death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 168 transfer admissions, 45%, 30%, and 25% were in the low, moderate, and high mortality risk groups, respectively. Length of stay at the referring PICU was shortest for the high-risk admissions. The most frequent diagnoses among all risk groups were respiratory failure (49%) and sepsis (14%). High-risk admissions were more likely to receive advanced therapies such as extracorporeal membrane oxygenation (41.5% high risk vs. 39.2% moderate vs. 6.6% low risk, p \u3c .01) and renal replacement therapy (34.2% vs. 17.7% vs. 2.6%, p \u3c .01). The high-risk admissions had longer PICU length of stay and the highest death rates (34% vs. 10% vs. 4%, p \u3c .01) when compared with the moderate- and low-risk admissions, respectively. CONCLUSIONS: This study highlights significant differences in patient characteristics, resource utilization, and outcomes across mortality risk-stratified groups of critically ill and injured children transferred from level II to level I PICU care. Further studies are warranted to investigate decision making that prompt inter-PICU transfers. ©2006 The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

    Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique

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    Background: Several indirect calorimetry (IC) instruments are commercially available, but comparative validity and reliability data are lacking. Existing data are limited by inconsistencies in protocols, subject characteristics, or single-instrument validation comparisons. The aim of this study was to compare accuracy and reliability of metabolic carts using methanol combustion as the cross-laboratory criterion. Methods: Eight 20-minute methanol burn trials were completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O2 and CO2 recovery were calculated. Results: For accuracy, 1 Omnical, Cosmed Quark CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3 variables within 2% of the true value; both DeltaTracs and the Vmax Encore System (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking best (coefficient of variation [CV] < 1.26%). Both Cosmeds, Parvos, DeltaTracs, 1 Jaeger Oxycon Pro (Oxycon), Max-II Metabolic Systems (Max-II), and Vmax were reliable for at least 1 variable (CV ≤ 3%). For multiple regression, humidity and amount of combusted methanol were significant predictors of RER (R2 = 0.33, P <.001). Temperature and amount of burned methanol were significant predictors of O2 recovery (R2 = 0.18, P <.001); only humidity was a predictor for CO2 recovery (R2 = 0.15, P <.001). Conclusions: Omnical, Parvo, Cosmed, and DeltaTrac had greater accuracy and reliability. The small number of instruments tested and expected differences in gas calibration variability limits the generalizability of conclusions. Finally, humidity and temperature could be modified in the laboratory to optimize IC conditions
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