Epidemiology and outcomes of ventilator-associated pneumonia in a large US database

OBJECTIVES: To evaluate risk factors for ventilator-associated pneumonia (VAP), as well as its influence on in-hospital mortality, resource utilization, and hospital charges. DESIGN: Retrospective matched cohort study using data from a large US inpatient database. PATIENTS: Patients admitted to an ICU between January 1998 and June 1999 who received mechanical ventilation for > 24 h. MEASUREMENTS: Risk factors for VAP were examined using crude and adjusted odds ratios (AORs). Cases of VAP were matched on duration of mechanical ventilation, severity of illness on admission (predicted mortality), type of admission (medical, surgical, trauma), and age with up to three control subjects. Mortality, resource utilization, and billed hospital charges were then compared between cases and control subjects. RESULTS: Of the 9,080 patients meeting study entry criteria, VAP developed in 842 patients (9.3%). The mean interval between intubation, admission to the ICU, hospital admission, and the identification of VAP was 3.3 days, 4.5 days, and 5.4 days, respectively. Identified independent risk factors for the development of VAP were male gender, trauma admission, and intermediate deciles of underlying illness severity (on admission) [AOR, 1.58, 1.75, and 1.47 to 1.70, respectively]. Patients with VAP were matched with 2,243 control subjects without VAP. Hospital mortality did not differ significantly between cases and matched control subjects (30.5% vs 30.4%, p = 0.713). Nevertheless, patients with VAP had a significantly longer duration of mechanical ventilation (14.3 +/- 15.5 days vs 4.7 +/- 7.0 days, p < 0.001), ICU stay (11.7 +/- 11.0 days vs 5.6 +/- 6.1 days, p < 0.001), and hospital stay (25.5 +/- 22.8 days vs 14.0 +/- 14.6 days, p < 0.001). Development of VAP was also associated with an increase of > $40,000 USD in mean hospital charges per patient ($104,983 USD +/- $91,080 USD vs $63,689 USD+/- $75,030 USD, p < 0.001). CONCLUSIONS: This retrospective matched cohort study, the largest of its kind, demonstrates that VAP is a common nosocomial infection that is associated with poor clinical and economic outcomes. While strategies to prevent the occurrence of VAP may not reduce mortality, they may yield other important benefits to patients, their families, and hospital systems.     

Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population

Objectives

To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population.

Methods

Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants.End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis.

Results

Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles).

Conclusions

OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.     

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins

Objective

The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins.

Methods

Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative markers.

Results

Lipid profile analysis revealed a reduction in the plasma concentrations of cholesterol and triglycerides, which were mainly associated with a significant reduction in the plasma concentration of circulating apoB-containing lipoproteins rather than with changes in their relative chemical composition. All patients displayed a pattern A phenotype of LDL subfractions and a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P < 0.001). The switch towards predominantly larger HDL particles was due to an increase in their relative cholesteryl ester content. Excess weight loss also led to a significant decrease in the plasma concentration of oxidised LDL (∼−25%; P < 0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp-PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound Lp-PLA2.

Conclusion

Our data indicate that the weight loss induced by bariatric surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL-2 subfraction.     

Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples

Background: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals.Objective: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989–1991 (visit 1) and 1998–1999 (visit 3).Methods: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation.Results: The Spearman’s correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population.Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, especially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.Citation: Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. 2014. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 122:946–954; http://dx.doi.org/10.1289/ehp.1306674     

Chronic fatigue syndrome and personality: A case-control study using the alternative five factor model

Neuroticism is the personality dimension most frequently associated with chronic fatigue syndrome (CFS). Most studies have also shown that CFS patients are less extraverted than non-CFS patients, but results have been inconsistent, possibly because the facets of the extraversion dimension have not been separately analyzed. This study has the following aims: to assess the personality profile of adults with CFS using the Alternative Five-Factor Model (AFFM), which considers Activity and Sociability as two separate factors of Extraversion, and to test the discriminant validity of a measure of the AFFM, the Zuckerman–Kuhlman Personality Questionnaire, in differentiating CFS subjects from normal-range matched controls. The CFS sample consisted of 132 consecutive patients referred for persistent fatigue or pain to the Department of Medicine of a university hospital. These were compared with 132 matched normal population controls. Significantly lower levels of Activity and significantly higher levels of Neuroticism-Anxiety best discriminated CFS patients from controls. The results are consistent with existing data on the relationship between Neuroticism and CFS, and clarify the relationship between Extraversion and CFS by providing new data on the relationship of Activity to CFS.     

Chromosome microarray analysis should be offered to all invasive prenatal diagnostic testing following a normal rapid aneuploidy test result

Chromosomal microarray analysis (CMA) has now replaced karyotyping in the analysis of prenatal cases with a fetal structural anomaly, whereas in those pregnancies undergoing invasive prenatal diagnosis with a normal fetal ultrasound, conventional karyotyping is still performed. The aims of this study were to establish the diagnostic yield of CMA in prenatal diagnosis, and to provide new data that might contribute to reconsider current practices. We reviewed 2905 prenatal samples with a normal rapid aneuploidy detection test referred for evaluation by CMA testing. Our study revealed pathogenic and reported susceptibility copy number variants associated with syndromic disorders in 4.8% (n = 138/2905) of cases, being 2.8% (n = 81/2905) the estimated added diagnostic value of CMA over karyotyping. Clinically significant CMA abnormality was detected in 5.4% (107/1975) of the fetuses with ultrasound anomalies and in 1.4% (5/345) of those considered as low-risk pregnancies. Our series shows that in prenatal samples, CMA increases 2-fold the diagnostic yield achieved by conventional karyotyping.