Peripheral blood metabolite profiles associated with new onset atrial fibrillation.

BACKGROUND: Peripheral blood metabolite profiles have yielded mechanistic insights into various cardiovascular disease states. We hypothesized that peripheral blood metabolite profiles would be associated with new onset atrial fibrillation (AF). METHODS AND RESULTS: The study population comprised 1892 patients without AF at baseline, who, as part the MURDOCK Cardiovascular Disease Study molecular profiling cohort (n = 2023), had previously had determination of levels of 69 metabolites from frozen, fasting plasma specimens obtained during coronary angiography. We used Cox proportional hazards models to examine the association of 13 uncorrelated metabolite factors created from these data using principal components analysis (PCA) with new occurrences of AF during a median follow up of 2.8 (0.1-4.9) years. A total of 233 patients developed new AF (12.3%) during follow up. Patients with new onset AF were older (median 67 vs. 60 years); more often white (82 vs. 71%) and male (68 vs. 60%), and had more comorbidities than those who did not develop AF. After adjustment, PCA factor 1 (medium chain acylcarnitines; hazard ratio [HR]: 1.11 [1.01-1.22]), factor 2 (short chain dicarboxylacylcarnitines; HR: 1.21 [1.09-1.34]) and factor 5 (long chain acylcarnitines; HR: 1.19 [1.06-1.34]) were associated with new onset AF. CONCLUSION: Metabolite profiles were associated with new onset AF among patients referred for coronary angiography. Validation of these observations in broader patient populations may provide better mechanistic insight into the development of AF, and may provide new opportunities for prevention and treatment.

Variable Selection in Kernel Regression Using Measurement Error Selection Likelihoods.

This paper develops a nonparametric shrinkage and selection estimator via the measurement error selection likelihood approach recently proposed by Stefanski, Wu, and White. The Measurement Error Kernel Regression Operator (MEKRO) has the same form as the Nadaraya-Watson kernel estimator, but optimizes a measurement error model selection likelihood to estimate the kernel bandwidths. Much like LASSO or COSSO solution paths, MEKRO results in solution paths depending on a tuning parameter that controls shrinkage and selection via a bound on the harmonic mean of the pseudo-measurement error standard deviations. We use small-sample-corrected AIC to select the tuning parameter. Large-sample properties of MEKRO are studied and small-sample properties are explored via Monte Carlo experiments and applications to data.

Using ClinicalTrials.gov to understand the state of clinical research in pulmonary, critical care, and sleep medicine.

RATIONALE: ClinicalTrials.gov is the largest trial registry in the world. Strengthened registration requirements, including federal mandates in 2007, have increased study representation. A systematic evaluation of all registered studies has been limited by the absence of an aggregate data set and specialty-specific search terms. OBJECTIVES: We leveraged a newly transformed database containing annotated data from ClinicalTrials.gov to define the portfolio of interventional clinical research in pulmonary, critical care, and sleep medicine. METHODS: Analysis was restricted to studies registered after September 2007 through September 2010 and defined as "interventional" (n = 40,970). A specialty-specific study data set (n = 2,226) was created using disease condition terms provided by data submitters and medical subject heading terms generated by a National Library of Medicine algorithm. Trial characteristics were extracted and summarized using descriptive statistics. MEASUREMENTS AND MAIN RESULTS: Pulmonary, critical care, and sleep medicine trials composed 5.4% of all interventional studies registered over the 3-year period. In contrast, oncology and cardiovascular disease composed 21.9 and 8.4% of trials, respectively. Within pulmonary trials, asthma and chronic obstructive pulmonary disease were the most studied conditions (27.4 and 21.8% of studies, respectively), and measures of lung function or safety were the most frequent primary outcomes. Nearly two-thirds of trials indicated enrollment of 100 patients or fewer, and a majority of studies were phase II or III trials. The single largest funding source (43.5%) was industry, and study characteristics varied by funding source. CONCLUSIONS: We applied a novel approach to describe the portfolio of interventional clinical research in pulmonary medicine. Our results indicate a disparity between trial representation and the burden of respiratory disease. Resources should be targeted across the spectrum of pulmonary research to address this discrepancy.

Serious infection after acute myocardial infarction: incidence, clinical features, and outcomes.

OBJECTIVES: The aim of this study was to address the knowledge gap using the APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial database. We also assessed the association between serious infections and 90-day death or death/myocardial infarction (MI). BACKGROUND: Little is known about the incidence, location, etiological organisms, and outcomes of infection in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. METHODS: We analyzed data from 5,745 STEMI patients enrolled in the APEX-AMI trial. Detailed information on infection was collected for all patients. We described characteristics of patients according to infection and details of infection. Cox proportional hazards models were used to assess 90-day outcomes among patients with and without infections after adjusting for associated clinical variables and with infection as a time-dependent covariate. RESULTS: Overall, 138 patients developed a serious infection (2.4%), most of whom presented with a single-site infection. The median (25th, 75th percentile) time until diagnosis of infection was 3 (1, 6) days. The most commonly identified organism was Staphylococcus aureus, and the main location of infection was the bloodstream. These patients had more comorbidities and lower procedural success at index percutaneous coronary intervention than those without infections. Serious infection was associated with significantly higher rates of 90-day death (adjusted hazard ratio: 5.6; 95% confidence interval: 3.8 to 8.4) and death or MI (adjusted hazard ratio: 4.9; 95% confidence interval: 3.4 to 7.1). CONCLUSIONS: Infections complicating the course of patients with STEMI were uncommon but associated with markedly worse 90-day clinical outcomes. Mechanisms for early identification of these high-risk patients as well as design of strategies to reduce their risk of infection are warranted.

Transfer times and outcomes in patients with ST-segment-elevation myocardial infarction undergoing interhospital transfer for primary percutaneous coronary intervention: APEX-AMI insights.

BACKGROUND: Transfer delays for primary percutaneous coronary intervention may increase mortality in patients with ST-segment-elevation myocardial infarction. We examined the association between door 1-to-door 2 (D1D2) time, a measure capturing the entire transfer process, and outcomes in patients undergoing interhospital transfer for primary percutaneous coronary intervention. METHODS AND RESULTS: We evaluated the relationship between D1D2 time and the 90-day incidence of death, shock, and heart failure in the subset of 2075 (36.1%) of 5745 patients who underwent interhospital transfer for primary percutaneous coronary intervention in the Assessment of Pexelizumab in Acute Myocardial Infarction trial. There was no significant difference in the 90-day incidence of death, shock, and heart failure between the transferred and the nontransferred groups (10.3% versus 10.2%; P = 0.89). The median difference in symptom-to-balloon time between the 2 groups was 45 minutes (229 versus 184; P<0.001). The primary outcome per 30-minute delay was higher for patients with a D1D2 time ≤150 minutes (hazard ratio, 1.19: 95% confidence interval, 1.06 to 1.33; P = 0.004) but not for D1D2 times >150 minutes (hazard ratio, 0.99: 95% confidence interval, 0.96 to 1.02; P = 0.496). The association between longer D1D2 time and worsening outcome was no longer statistically significant after multivariable adjustment. CONCLUSIONS: Longer transfer times were associated with higher rate of death, shock, and heart failure among patients undergoing interhospital transfer from primary percutaneous coronary intervention, although this difference did not persist after adjusting for baseline characteristics.