Late diagnosis of abdominal aortic aneurysms substantiates underutilization of abdominal aortic aneurysm screening for Medicare beneficiaries

ObjectiveAbdominal aortic aneurysm (AAA) screening remains largely underutilized in the U.S., and it is likely that the proportion of patients with aneurysms requiring prompt treatment is much higher compared with well-screened populations. The goals of this study were to determine the proportion of AAAs that required prompt repair after diagnostic abdominal imaging for U.S. Medicare beneficiaries and to identify patient and hospital factors contributing to early vs late diagnosis of AAA.MethodsData were extracted from Medicare claims records for patients at least 65 years old with complete coverage for 2 years who underwent intact AAA repair from 2006 to 2009. Preoperative ultrasound and computed tomography was tabulated from 2002 to repair. We defined early diagnosis of AAA as a patient with a time interval of greater than 6 months between the first imaging examination and the index procedure, and late diagnosis as patients who underwent the index procedure within 6 months of the first imaging examination.ResultsOf 17,626 patients who underwent AAA repair, 14,948 met inclusion criteria. Mean age was 77.5 ± 6.1 years. Early diagnosis was identified for 60.6% of patients receiving AAA repair, whereas 39.4% were repaired after a late diagnosis. Early diagnosis rates increased from 2006 to 2009 (59.8% to 63.4%; P < .0001) and were more common for intact repair compared with repair after rupture (62.9% vs 35.1%; P < .0001) and for women compared with men (66.3% vs 59.0%; P < .0001). On multivariate analysis, repair of intact vs ruptured AAAs (odds ratio, 3.1; 95% confidence interval, 2.7-3.6) and female sex (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) remained the strongest predictors of surveillance. Although intact repairs were more likely to be diagnosed early, over one-third of patients undergoing repair for ruptured AAAs received diagnostic abdominal imaging greater than 6 months prior to surgery.ConclusionsDespite advances in screening practices, significant missed opportunities remain in the U.S. Medicare population for improving AAA care. It remains common for AAAs to be diagnosed when they are already at risk for rupture. In addition, a significant proportion of patients with early imaging rupture prior to repair. Our findings suggest that improved mechanisms for observational management are needed to ensure optimal preoperative care for patients with AAAs

Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

Fold change and p-value cutoffs significantly alter microarray interpretations

<p>Abstract</p> <p>Background</p> <p>As context is important to gene expression, so is the preprocessing of microarray to transcriptomics. Microarray data suffers from several normalization and significance problems. Arbitrary fold change (FC) cut-offs of >2 and significance p-values of <0.02 lead data collection to look only at genes which vary wildly amongst other genes. Therefore, questions arise as to whether the biology or the statistical cutoff are more important within the interpretation. In this paper, we reanalyzed a zebrafish (<it>D. rerio</it>) microarray data set using GeneSpring and different differential gene expression cut-offs and found the data interpretation was drastically different. Furthermore, despite the advances in microarray technology, the array captures a large portion of genes known but yet still leaving large voids in the number of genes assayed, such as leptin a pleiotropic hormone directly related to hypoxia-induced angiogenesis.</p> <p>Results</p> <p>The data strongly suggests that the number of differentially expressed genes is more up-regulated than down-regulated, with many genes indicating conserved signalling to previously known functions. Recapitulated data from Marques et al. (2008) was similar but surprisingly different with some genes showing unexpected signalling which may be a product of tissue (heart) or that the intended response was transient.</p> <p>Conclusions</p> <p>Our analyses suggest that based on the chosen statistical or fold change cut-off; microarray analysis can provide essentially more than one answer, implying data interpretation as more of an art than a science, with follow up gene expression studies a must. Furthermore, gene chip annotation and development needs to maintain pace with not only new genomes being sequenced but also novel genes that are crucial to the overall gene chips interpretation.</p

Family History of Schizophrenia and Bipolar Disorder as Risk Factors for Autism

The clinical and etiological relation between autism spectrum disorders (ASD) and schizophrenia is unclear. The degree to which these disorders share a basis in etiology has important implications for clinicians, researchers, and those affected. Our objective was to determine if a family history of schizophrenia and/or bipolar disorder was a risk factor for ASD. We conducted a case-control evaluation of histories of schizophrenia or bipolar disorder in first-degree relatives of probands in three samples, population registers in Sweden, Stockholm County, and Israel. Probands met criteria for ASD, and affection status of parents and siblings for schizophrenia and bipolar disorder were established

The nasal and oropharyngeal microbiomes of healthy livestock workers.

Little information exists on the microbiomes of livestock workers. A cross-sectional, epidemiological study was conducted enrolling 59 participants (26 of which had livestock contact) in Iowa. Participants were enrolled in one of four ways: from an existing prospective cohort study (n = 38), from the Iowa Department of Natural Resources Animal Feeding Operations database (n = 17), through Iowa county fairs (n = 3), and through snowball sampling (n = 1). We collected swabs from the nares and oropharynx of each participant to assess the microbiome via 16s rRNA sequencing. We observed livestock workers to have greater diversity in their microbiomes compared to those with no livestock contact. In the nares, there were 27 operational taxonomic units found to be different between livestock workers and non-livestock workers with the greatest difference seen with Streptococcus and Proteobacteria. In the oropharynx, livestock workers with swine exposure were more likely to carry several pathogenic organisms. The results of this study are the first to characterize the livestock worker nasal and oropharyngeal microbiomes

Gaps in preoperative surveillance and rupture of abdominal aortic aneurysms among Medicare beneficiaries

ObjectiveScreening and surveillance are recommended in the management of small abdominal aortic aneurysms (AAAs). Gaps in surveillance after early diagnosis may lead to unrecognized AAA growth, rupture, and death. This study investigates the frequency and predictors of rupture of previously diagnosed AAAs.MethodsData were extracted from Medicare claims for patients who underwent AAA repair between 2006 and 2009. Relevant preoperative abdominal imaging exams were tabulated up to 5 years prior to AAA repair. Repair for ruptured AAAs was compared with repair for intact AAAs for those with an early diagnosis of an AAA, defined as having received imaging at least 6 months prior to surgery. Gaps in surveillance were defined as no image within 1 year of surgery or no imaging for more than a 2-year time span after the initial image. Logistic regression was used to examine independent predictors of rupture despite early diagnosis.ResultsA total of 9298 patients had repair after early diagnosis, with rupture occurring in 441 (4.7%). Those with ruptured AAAs were older (80.2 ± 6.9 vs 77.6 ± 6.2 years; P < .001), received fewer images prior to repair (5.7 ± 4.1 vs 6.5 ± 3.5; P = .001), were less likely to be treated in a high-volume hospital (45.4% vs 59.5%; P < .001), and were more likely to have had gaps in surveillance (47.4% vs 11.8%; P < .001) compared with those receiving repair for intact AAAs. After adjusting for medical comorbidities, gaps in surveillance remained the largest predictor of rupture in a multivariate analysis (odds ratio, 5.82; 95% confidence interval, 4.64-7.31; P < .001).ConclusionsDespite previous diagnosis of AAA, many patients experience rupture prior to repair. Improved mechanisms for surveillance are needed to prevent rupture and ensure timely repair for patients with AAAs