Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction

BACKGROUND The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain. METHODS In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of pre-specified thresholds. RESULTS Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P = 0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P = 0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P = 0.53). CONCLUSIONS The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone.

Derivation and external validation of a simple prediction model for the diagnosis of type 2 Diabetes Mellitus in the Brazilian urban population

A risk score model was developed based in a population of 1,224 individuals from the general population without known diabetes aging 35 years or more from an urban Brazilian population sample in order to select individuals who should be screened in subsequent testing and improve the efficacy of public health assurance. External validation was performed in a second, independent, population from a different city ascertained through a similar epidemiological protocol. The risk score was developed by multiple logistic regression and model performance and cutoff values were derived from a receiver operating characteristic curve. Model`s capacity of predicting fasting blood glucose levels was tested analyzing data from a 5-year follow-up protocol conducted in the general population. Items independently and significantly associated with diabetes were age, BMI and known hypertension. Sensitivity, specificity and proportion of further testing necessary for the best cutoff value were 75.9, 66.9 and 37.2%, respectively. External validation confirmed the model`s adequacy (AUC equal to 0.72). Finally, model score was also capable of predicting fasting blood glucose progression in non-diabetic individuals in a 5-year follow-up period. In conclusion, this simple diabetes risk score was able to identify individuals with an increased likelihood of having diabetes and it can be used to stratify subpopulations in which performing of subsequent tests is necessary and probably cost-effective.

Predictive value for malignancy in the finding of microcalcifications on ultrasonography of thyroid nodules

Background. The am of this study was to determine the predictive value for malignancy of microcalcifications determined by ultrasonography in thyroid nodules. Methods. One hundred seventy-seven nodules were prospectively studied by ultrasonography and compared with their fine-needle aspirative biopsy. The association between the presence and type of calcification and cytologic findings was verified through the chi-square test or likelihood ratio. Results. Thirty nodules showed calcification, of which 17 had fine calcifications, 3 had fine and gross calcifications, and 10 had only coarse calcification. Seven (41.18%) of 17 fine calcified nodules were malignant on cytology, 8 (47.06%) were benign, 1 (5,88%) was indeterminate, and 1 was suspect for malignancy. We found statistical significance between the presence of fine calcifications and malignancy (p =.001) and, in the 13 malignant nodule group, 8 (61.50%) had fine calcifications. Conclusion. This study suggests that microcalcifications were highly specific for malignancy and were present in 61% of the malignant nodules. (c) 2008 Wiley Periodicals, Inc.

THE TEMPO AND MODE OF EVOLUTION OF TRANSPOSABLE ELEMENTS AS REVEALED BY MOLECULAR PHYLOGENIES RECONSTRUCTED FROM MOSQUITO GENOMES

Although many mathematical models exist predicting the dynamics of transposable elements (TEs), there is a lack of available empirical data to validate these models and inherent assumptions. Genomes can provide a snapshot of several TE families in a single organism, and these could have their demographics inferred by coalescent analysis, allowing for the testing of theories on TE amplification dynamics. Using the available genomes of the mosquitoes Aedes aegypti and Anopheles gambiae, we indicate that such an approach is feasible. Our analysis follows four steps: (1) mining the two mosquito genomes currently available in search of TE families; (2) fitting, to selected families found in (1), a phylogeny tree under the general time-reversible (GTR) nucleotide substitution model with an uncorrelated lognormal (UCLN) relaxed clock and a nonparametric demographic model; (3) fitting a nonparametric coalescent model to the tree generated in (2); and (4) fitting parametric models motivated by ecological theories to the curve generated in (3).

Screening for serious mental illness in the general population with the K6 screening scale: results from the WHO World Mental Health (WMH) survey initiative

Data are reported on the background and performance of the K6 screening scale for serious mental illness (SMI) in the World Health Organization (WHO) World Mental Health (WMH) surveys. The K6 is a six-item scale developed to provide a brief valid screen for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) SMI based on the criteria in the US ADAMHA Reorganization Act. Although methodological studies have documented good K6 validity in a number of countries, optimal scoring rules have never been proposed. Such rules are presented here based on analysis of K6 data in nationally or regionally representative WMH surveys in 14 countries (combined N = 41,770 respondents). Twelve-month prevalence of DSM-IV SMI was assessed with the fully-structured WHO Composite International Diagnostic Interview. Nested logistic regression analysis was used to generate estimates of the predicted probability of SMI for each respondent from K6 scores, taking into consideration the possibility of variable concordance as a function of respondent age, gender, education, and country. Concordance, assessed by calculating the area under the receiver operating characteristic curve, was generally substantial (median 0.83; range 0.76-0.89; inter-quartile range 0.81-0.85). Based on this result, optimal scaling rules are presented for use by investigators working with the K6 scale in the countries studied. Copyright (c) 2010 John Wiley & Sons, Ltd.

Rapid-cycling bipolar disorder: cross-national community study

Background The epidemiology of rapid-cycling bipolar disorder in the community is largely unknown. Aims To investigate the epidemiological characteristics of rapid cycling and non-rapid-cycling bipolar disorder in a large cross-national community sample. Method The Composite International Diagnostic interview (CIDI version 3.0) was used to examine the prevalence, severity, comorbidity, impairment, suicidality, sociodemographics, childhood adversity and treatment of rapid-cycling and non-rapid-cycling bipolar disorder in ten countries (n=54257). Results The 12-month prevalence of rapid-cycling bipolar disorder was 0.3%. Roughly a third and two-fifths of participants with lifetime and 12-month bipolar disorder respectively met criteria for rapid cycling. Compared with the non-rapid-cycling, rapid-cycling bipolar disorder was associated with younger age at onset, higher persistence, more severe depressive symptoms, greater impairment from depressive symptoms, more out-of-role days from mania/hypomania, more anxiety disorders and an increased likelihood of using health services. Associations regarding childhood, family and other sociodemographic correlates were less clear cut. Conclusions The community epidemiological profile of rapid-cycling bipolar disorder confirms most but not all current clinically based knowledge about the illness. Declaration of interest R.C.K. has been a consultant for GlaxoSmithKline Inc, Kaiser Permanente, Pfizer Inc, Sanofi-Aventis, Shire Pharmaceuticals and Wyeth-Ayerst; has served on advisory boards for Eli Lilly & Company and Wyeth-Ayerst, and has had research support for his epidemiological studies from Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals Inc, Pfizer Inc and Sanofi-Avertis.

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

Purpose: To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. Design: Observational cohort study. Participants: The study included 453 eyes from 252 individuals followed for an average of 46 +/- 14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. Methods: Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. Main Outcome Measures: Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. Results: Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC1 coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. Conclusions: The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 462-470 (C) 2010 by the American Academy of Ophthalmology.

Urothelial carcinoma transmission via kidney transplantation

Transmission of urothelial carcinoma via solid organ transplant has never been reported in the literature to our knowledge. We report a case of transmission of this tumour to a kidney recipient. The donor was a 37-year-old woman, victim of a subarachnoid haemorrhage. The recipient was a 21-year-old girl, with a history of chronic kidney disease secondary to neurogenic bladder. This fatality has been rarely described in literature, but never with this histological type of cancer. Nowadays, with the expanded criteria for donation, older people are accepted as donor because of the shortage of organs. However, this may increase the likelihood of the number of cancer transmission.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Anterior cingulate volumes associated with trait impulsivity in individuals with bipolar disorder

Objective: Impulsivity is associated with the clinical outcome and likelihood of risky behaviors among bipolar disorder (BD) patients. Our previous study showed an inverse relationship between impulsivity and orbitofrontal cortex (OFC) volume in healthy subjects. We hypothesized that BD patients would show an inverse relationship between impulsivity and volumes of the OFC, anterior cingulate cortex (ACC), medial prefrontal cortex, and amygdala, which have been implicated in the pathophysiology of BD. Methods: Sixty-three BD patients were studied (mean +/- SD age = 38.2 +/- 11.5 years; 79% female). The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity. Images were processed using SPM2 and an optimized voxel-based morphometry protocol. We examined the correlations between BIS scores and the gray matter (GM) and white matter (WM) volumes of the prespecified regions. Results: Left rostral ACC GM volume was inversely correlated with the BIS total score (t = 3.95, p(corrected) = 0.003) and the BIS motor score (t = 5.22, p(corrected) < 0.001). In contrast to our hypothesis, OFC volumes were not significantly associated with impulsivity in BD. No WM volume of any structure was significantly correlated with impulsivity. No statistical association between any clinical variable and the rostral ACC GM volumes reached significance. Conclusions: Based on our previous findings and the current results, impulsivity may have a different neural representation in BD and healthy subjects, and the ACC may be involved in the pathophysiology of abnormal impulsivity regulation in BD patients.

Genetic Analysis of Age-at-Onset for Cardiovascular Risk Factors in a Brazilian Family Study

Background/Aims: Statistical analysis of age-at-onset involving family data is particularly complicated because there is a correlation pattern that needs to be modeled and also because there are measurements that are censored. In this paper, our main purpose was to evaluate the effect of genetic and shared family environmental factors on age-at-onset of three cardiovascular risk factors: hypertension, diabetes and high cholesterol. Methods: The mixed-effects Cox model proposed by Pankratz et al. [2005] was used to analyze the data from 81 families, involving 1,675 individuals from the village of Baependi, in the state of Minas Gerais, Brazil. Results: The analyses performed showed that the polygenic effect plays a greater role than the shared family environmental effect in explaining the variability of the age-at-onset of hypertension, diabetes and high cholesterol. The model which simultaneously evaluated both effects indicated that there are individuals which may have risk of hypertension due to polygenic effects 130% higher than the overall average risk for the entire sample. For diabetes and high cholesterol the risks of some individuals were 115 and 45%, respectively, higher than the overall average risk for the entire population. Conclusions: Results showed evidence of significant polygenic effects indicating that age-at-onset is a useful trait for gene mapping of the common complex diseases analyzed. In addition, we found that the polygenic random component might absorb the effects of some covariates usually considered in the risk evaluation, such as gender, age and BMI. Copyright (C) 2008 S. Karger AG, Basel

Comparison of HRT-3 glaucoma probability score and subjective stereophotograph assessment for prediction of progression in glaucoma

PURPOSE. To assess whether baseline Glaucoma Probability Score (GPS; HRT-3; Heidelberg Engineering, Dossenheim, Germany) results are predictive of progression in patients with suspected glaucoma. The GPS is a new feature of the confocal scanning laser ophthalmoscope that generates an operator-independent, three-dimensional model of the optic nerve head and gives a score for the probability that this model is consistent with glaucomatous damage. METHODS. The study included 223 patients with suspected glaucoma during an average follow-up of 63.3 months. Included subjects had a suspect optic disc appearance and/or elevated intraocular pressure, but normal visual fields. Conversion was defined as development of either repeatable abnormal visual fields or glaucomatous deterioration in the appearance of the optic disc during the study period. The association between baseline GPS and conversion was investigated by Cox regression models. RESULTS. Fifty-four (24.2%) eyes converted. In multivariate models, both higher values of GPS global and subjective stereophotograph assessment ( larger cup-disc ratio and glaucomatous grading) were predictive of conversion: adjusted hazard ratios (95% CI): 1.31 (1.15 - 1.50) per 0.1 higher global GPS, 1.34 (1.12 - 1.62) per 0.1 higher CDR, and 2.34 (1.22 - 4.47) for abnormal grading, respectively. No significant differences ( P > 0.05 for all comparisons) were found between the c-index values ( equivalent to area under ROC curve) for the multivariate models (0.732, 0.705, and 0.699, respectively). CONCLUSIONS. GPS values were predictive of conversion in our population of patients with suspected glaucoma. Further, they performed as well as subjective assessment of the optic disc. These results suggest that GPS could potentially replace stereophotograph as a tool for estimating the likelihood of conversion to glaucoma.

Models for genetic evaluation of Nelore cattle mature body weight

Records of 18,770 Nelore animals, born from 1975 to 2002, in 8 herds participating in the Nelore Cattle Breeding Program, were analyzed to estimate genetic parameters for mature BW. The mature BW were analyzed as a single BW taken closest to 4.5 yr of age for each cow in the data file, considering BW starting from 2 (W2Y_S), 3 (W3Y_S), or 4 (W4Y_S) yr of age or as repeated records, including all BW starting from 2 (W2Y_R), 3 (W3Y_R), or 4 (W4Y_R) yr of age. The variance components were estimated by restricted maximum likelihood, fitting univariate and bivariate animal models, including weaning weight. The heritability estimates were 0.29, 0.34, 0.36, 0.41, 0.44, and 0.46 for W2Y_S, W3Y_S, W4Y_S, W2Y_R, W3Y_R, and W4Y_R, respectively. The repeatability estimates for W2Y_R, W3Y_R, and W4Y_R were 0.59, 0.64, and 0.72, respectively. Larger accuracy values associated with the EBV were obtained in the repeated records models. The results indicated the bivariate repeated records model as the most appropriate for analyzing mature BW.

Genetic associations between accumulated productivity, and reproductive and growth traits in Nelore cattle

The total meat yield in a beef cattle production cycle is economically very important and depends on the number of calves born per year or birth season, being directly related to reproductive potential. Accumulated Productivity (ACP) is an index that expresses a cow`s capacity to give birth regularly at a young age and to wean animals of greater body weight. Using data from cattle participating in the ""Program for Genetic Improvement of the Nelore Breed"" (PMGRN - Nelore Brasil), bi-trait analyses were performed using the Restricted Maximum Likelihood method based on an ACP animal model and the following traits: age at first calving (AFC), female body weight adjusted for 365 (BW365) and 450 (BW450) days of age, and male scrotal circumference adjusted for 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730) days of age. Median estimated ACP heritability was 0.19 and the genetic correlations with AFC, BW365, BW450, SC365, SC450, SC550 and SC730 were 0.33, 0.70, 0.65, 0.08, 0.07, 0.12 and 0.16, respectively. ACP increased and AFC decreased over time, revealing that the selection criteria genetically improved these traits. Selection based on ACP appears to favor the heaviest females at 365 and 450 days of age who showed better reproductive performance as regards AFC. Scrotal circumference was not genetically associated with ACP. (C) 2007 Elsevier B.V. All rights reserved.

A general hazard model for lifetime data in the presence of cure rate

Historically, the cure rate model has been used for modeling time-to-event data within which a significant proportion of patients are assumed to be cured of illnesses, including breast cancer, non-Hodgkin lymphoma, leukemia, prostate cancer, melanoma, and head and neck cancer. Perhaps the most popular type of cure rate model is the mixture model introduced by Berkson and Gage [1]. In this model, it is assumed that a certain proportion of the patients are cured, in the sense that they do not present the event of interest during a long period of time and can found to be immune to the cause of failure under study. In this paper, we propose a general hazard model which accommodates comprehensive families of cure rate models as particular cases, including the model proposed by Berkson and Gage. The maximum-likelihood-estimation procedure is discussed. A simulation study analyzes the coverage probabilities of the asymptotic confidence intervals for the parameters. A real data set on children exposed to HIV by vertical transmission illustrates the methodology.