Application and evaluation of automated semantic annotation of gene expression experiments.

MOTIVATION: Many microarray datasets are available online with formalized standards describing the probe sequences and expression values. Unfortunately, the description, conditions and parameters of the experiments are less commonly formalized and often occur as natural language text. This hinders searching, high-throughput analysis, organization and integration of the datasets. RESULTS: We use the lexical resources and software tools from the Unified Medical Language System (UMLS) to extract concepts from text. We then link the UMLS concepts to classes in open biomedical ontologies. The result is accessible and clear semantic annotations of gene expression experiments. We applied the method to 595 expression experiments from Gemma, a resource for re-use and meta-analysis of gene expression profiling data. We evaluated and corrected all stages of the annotation process. The majority of missed annotations were due to a lack of cross-references. The most error-prone stage was the extraction of concepts from phrases. Final review of the annotations in context of the experiments revealed 89% precision. A naive system, lacking the phrase to concept corrections is 68% precise. We have integrated this annotation pipeline into Gemma. AVAILABILITY: The source code, documentation and Supplementary Materials are available at http://www.chibi.ubc.ca/GEOMMTX. The results of the manual evaluations are provided as Supplementary Material. Both manual and predicted annotations can be viewed and searched via the Gemma website at http://www.chibi.ubc.ca/Gemma. The complete set of predicted annotations is available as a machine readable resource description framework graph.

Left Atrial Remodeling Assessed by Cardiac MRI after Conversion from Conventional Hemodialysis to In-Centre Nocturnal Hemodialysis.

BACKGROUND: Left atrial (LA) volume is a well-established cardiovascular prognosticator in patients with end-stage renal disease. Although dialysis intensification is associated with left ventricular mass regression, there are limited data regarding LA remodeling. Using cardiac magnetic resonance imaging (CMR), we examined changes in LA size and function relative to ventricular remodeling and cardiac biomarkers after dialysis intensification. METHODS: In this prospective 2-centre cohort study, 37 patients receiving conventional hemodialysis (CHD, 4 h/session, 3×/week) were converted to in-centre nocturnal hemodialysis (INHD 7-8 h/session, 3×/week); 30 patients remained on CHD. CMR and biomarkers were performed at baseline and repeated at 52 weeks. RESULTS: After 52 weeks, there were no significant changes in the LA volumes or LA ejection fraction (EF) within either the CHD or INHD group, and no significant differences between the two groups. Correlations existed between changes in LA and LV end-diastolic volume index (EDVi, Spearman's r = 0.69, p < 0.001), LA and LV end-systolic volume index (ESVi, r = 0.44, p = 0.001), LAEF and LVEF (r = 0.28, p = 0.04), LA and RV EDVi (r = 0.51, p < 0.001), LA and RV ESVi (r = 0.29, p = 0.039), and LA ESVi and LV mass index (r = 0.31, p = 0.02). At baseline, indexed LA volumes positively correlated with NT-proBNP, whereas LAEF negatively correlated with NT-proBNP and Troponin I. After 52 weeks, changes in biomarker levels did not correlate with changes in LA volume or EF. CONCLUSION: There was no significant change in LA size or systolic function after conversion to INHD. The significant correlations between LA and ventricular remodeling and cardiac biomarkers suggest common underlying pathophysiologic mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00718848.

Association Between Transthoracic Echocardiography Appropriateness and Echocardiographic Findings.

BACKGROUND: The association between appropriate use criteria and echocardiographic findings in patients with chronic cardiovascular diseases is unknown. METHODS: As a substudy of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) trial, 9,230 transthoracic echocardiographic (TTE) examinations from six Ontario academic hospitals were linked to a registry of echocardiographic findings. The TTE studies were rated appropriate), rarely appropriate, or may be appropriate according to the 2011 appropriate use criteria. TTE findings of appropriately ordered examinations were compared with those of rarely appropriate examinations for specific disease subsets, including heart failure and valvular heart disease. RESULTS: There were 7,574, 1,087, and 569 TTE examinations ordered for appropriate, rarely appropriate, and may be appropriate indications, and of the 7,574 appropriate studies, 6,399 were ordered for specific indications and 1,175 for general indications. TTE examinations ordered for general indications had lower rates of left ventricular dysfunction (19.6% vs 9.1%, P < .001) and moderate to severe aortic stenosis (15.5% vs 2.6%, P < .001). Of the 2,395 TTE examinations ordered for patients with heart failure, appropriately ordered studies were more likely to result in left ventricular segmental abnormality (37.0% vs 24.9%, P = .012) but similar rates of right ventricular dilatation (15.4% vs 14.7%, P = .79), right ventricular dysfunction (14.8% vs 11.3%, P = .22), and moderate to severe mitral regurgitation (12.1% vs 9.2%, P = .35). Of the 2,859 studies ordered to assess valvular heart disease, appropriately ordered studies were significantly more likely to find moderate to severe valvular pathology, including aortic stenosis (30.4% vs 24.6%, P = .008), aortic regurgitation (8.9% vs 1.6%, P < .001), mitral stenosis (6.7% vs 3.1%, P = .002), and mitral regurgitation (16.1% vs 6.1%, P < .001), but similar rates of tricuspid regurgitation (11.2% vs 13.0%, P = .60). CONCLUSIONS: Overall, appropriately ordered TTE examinations for heart failure and valvular heart disease were significantly more likely to have abnormal findings than rarely appropriate examinations. TTE studies ordered for general indications had fewer, although still a significant proportion, of abnormalities compared with studies ordered for specific indications.

Primary prevention of cardiovascular disease: global cardiovascular risk assessment and management in clinical practice.

AIMS: For the primary prevention of cardiovascular disease, the Framingham Risk Score (FRS) is the most well-known risk prediction method. However, there are limited data regarding physicians' method of risk assessment and guideline adherence in clinical practice. METHODS AND RESULTS: In the PARADIGM (Primary cARe AuDIt of Global risk Management) study (March 2009-10), 105 primary care physicians across Canada prospectively collected data for 3015 patients (mean age 56 years, 59% men) without known cardiovascular disease, diabetes, or lipid-lowering medications at baseline. For each patient, the treating physician determined their cardiovascular risk, and reported the risk stratification method and subsequent treatment decisions. Kappa statistics assessed the agreement between the study-calculated FRS and the treating physician's reported risk assessment. The FRS was the most commonly reported risk assessment method, but was used in only 34.0% of patients. Regardless of the method used (even if the FRS was reportedly used), there was only fair agreement between the risk stratification as reported by the physician and the study-calculated FRS. Moreover, physicians recommended statin initiation in 92% of all patients that they identified as high risk; however, according to the study-calculated FRS, only 56% of the truly high-risk patients were recommended statin therapy. CONCLUSION: For the primary prevention of cardiovascular disease, these findings indicate a need to improve risk assessment and stratification, as misclassification directly contributes to suboptimal risk factor management in real-world clinical practice. Future studies should establish the optimal risk stratification method with quality improvement strategies for its subsequent implementation. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/ct2/show/NCT00950703; NCT00950703.

Association between environmental factors and onset of psoriatic arthritis in patients with psoriasis.

OBJECTIVE: To investigate the association between potential environmental exposures and the development of psoriatic arthritis (PsA) in patients with psoriasis. METHODS: In this case-control study, the cases were patients with recent-onset PsA. The controls were psoriasis patients without arthritis. The occurrence of the following environmental exposures was recorded through a standardized questionnaire: smoking, alcohol consumption, infections, injuries, physically demanding occupational tasks, stressful life events, vaccinations, and female hormonal exposures. The association between each exposure to environmental events and disease status was assessed through logistic regression after adjustment for age, sex, education level, and duration and severity of psoriasis. RESULTS: There were 159 subjects in each group. The following exposures remained significantly associated with PsA following multivariate logistic regression: lifting cumulative loads of at least 100 pounds/hour (odds ratio [OR] 2.8, 95% confidence interval [95% CI] 1.51-5.05), infections that required antibiotics (OR 1.7, 95% CI 1.00-2.77), smoking (OR 0.6, 95% CI 0.36-0.89), and injuries (OR 2.1, 95% CI 1.11-4.01). The results were not appreciably changed with the inclusion of each of these factors in a single regression model; however, the level of significance for injuries had become borderline. No association was found between PsA and alcohol consumption, vaccination, stressful life events, and female hormonal exposures. CONCLUSION: Lifting heavy loads and infections that required antibiotics were associated with the occurrence of arthritis among patients with psoriasis. There was an inverse association between smoking and PsA. Further studies are necessary to determine whether these and other environmental factors are moderated by predisposing genetic factors.