Study to determine the cardiovascular risk ofthe population of Guimarães/Vizela, includingthe prevalence of arterial stiffness and early vascular aging syndrome

Tese de Doutoramento em Medicina.

Prodromal Questionnaire: translation, adaptation to Portuguese and preliminary results in ultra-high risk individuals and first episode psychosis

OBJECTIVE: The Prodromal Questionnaire (PQ) is a 92-item self-report screening tool for individuals at ultra-high risk (UHR) to develop psychosis. This study aims to present the translation to Portuguese and preliminary results in UHR and first episode (FE) psychosis in a Portuguese sample. METHODS: The PQ was translated from English to Portuguese by two bilingual researchers from the research program on early psychosis of the Instituto de Psiquiatria HCFMUSP, São Paulo, Brazil (ASAS - "Evaluation and Follow up of Adolescents and Young Adults in São Paulo") and back translated by two other researchers. The study participants (n = 11-) were evaluated through the Portuguese version of the Prodromal Questionnaire (PQ) and SIPS. RESULTS: The individuals at UHR (n = 7) presented a lower score than first episode patients (n = 4). The UHR mean scores and standard deviation on Portuguese version of the PQ were: 13.0 ± 10.0 points on positive symptoms subscale, and FE patients: 33.0 ± 10.0. CONCLUSION: The UHR and FE patients' of this study presented PQ scores similar to the ones found in the literature; what suggests that it is possible to use the PQ in Brazilian help-seeking individuals as a screening tool.

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

Is psychodynamic psychotherapy an effective intervention for individuals at ultra-high risk (UHR) of psychosis?: a case report

OBJECTIVE: To report a case and to discuss the use of psychodynamic psychotherapy (PD-P) to treat individuals at ultra-high risk (UHR) of psychosis. METHODS: An individual at UHR was followed up for 24 months. The baseline evaluation included a psychiatric interview, the Structured Interview for Prodromal Symptoms (SIPS), the Scale of Prodromal Symptoms (SOPS), and neuropsychological assessment. He underwent weekly sessions of PD-P for 12 months and was followed up for 12 months after the end of PD-P. The evaluations were at baseline, after 6-, 12-, and 24-month follow-up. No medication was prescribed during the 24-month follow-up. RESULTS: The prodromal symptoms remitted. The initial total score on the SIPS/SOPS was 37 points. After the first 12 months of PD-P, there was a reduction to 12 points on the SIPS/SOPS score, which stabilized in the 24-month follow-up. There was also a slight improvement in his performance on the neuropsychological evaluations. CONCLUSION: This case report suggests that PD-P can reduce prodromal symptoms; nevertheless, a better understanding of the specificity and efficacy of PD-P as an option of treatment for UHR individuals is needed.

A study of risk-aware program transformation

In the trend towards tolerating hardware unreliability, accuracy is exchanged for cost savings. Running on less reliable machines, functionally correct code becomes risky and one needs to know how risk propagates so as to mitigate it. Risk estimation, however, seems to live outside the average programmer’s technical competence and core practice. In this paper we propose that program design by source-to-source transformation be risk-aware in the sense of making probabilistic faults visible and supporting equational reasoning on the probabilistic behaviour of programs caused by faults. This reasoning is carried out in a linear algebra extension to the standard, `a la Bird-Moor algebra of programming. This paper studies, in particular, the propagation of faults across standard program transformation techniques known as tupling and fusion, enabling the fault of the whole to be expressed in terms of the faults of its parts.

Risk factors for suicide in multiple sclerosis: a case-control study

ABSTRACT Objective To evaluated the prevalence and the suicide risk in a Brazilian sample of patients with multiple sclerosis (MS) and to identify potential factors associated with the risk of suicide. A study was performed with outpatient with MS. The risk of suicide and the presence of psychiatric disorders were assessed by version 5.0 of the Mini-International Neuropsychiatric Interview (MINI). The sample of patients at risk for suicide was matched by sex and age to a control group of patients with MS. Results Eight point three percent of the patients had a past history of attempted suicide, and 8.3% had a current suicide risk, totaling 16.6%. The results of this study suggest that the risk factors associated with suicide in this population are depression, marital status single, widowed or divorced, and lower education level.

Impact of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis

Transforming growth factor beta (TGF-ß) plays an important role in carcinogenesis. Two polymorphisms in the TGF-ß1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-ß1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-ß1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-ß1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.

Stress induced risk-aversion is reverted by D2/D3 agonist in the rat

Stress exposure triggers cognitive and behavioral impairments that influence decision-making processes. Decisions under a context of uncertainty require complex reward-prediction processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system in brain areas sensitive to the deleterious effects of chronic stress, in particular the orbitofrontal cortex (OFC). Using a decision-making task, we show that chronic stress biases risk-based decision-making to safer behaviors. This decision-making pattern is associated with an increased activation of the lateral part of the OFC and with morphological changes in pyramidal neurons specifically recruited by this task. Additionally, stress exposure induces a hypodopaminergic status accompanied by increased mRNA levels of the dopamine receptor type 2 (Drd2) in the OFC; importantly, treatment with a D2/D3 agonist quinpirole reverts the shift to safer behaviors induced by stress on risky decision-making. These results suggest that the brain mechanisms related to risk-based decision-making are altered after chronic stress, but can be modulated by manipulation of dopaminergic transmission.

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

Risk factors for atherosclerosis in students of a private university in São Paulo - Brazil

OBJECTIVE: To characterize the risk profile for atherosclerosis (AS) in adolescents and young adults of a private university in São Paulo. METHODS: Clinical, nutritional, and laboratory parameters were evaluated in 209 students of both genders aged 17 to 25 years. In addition to determination of the lipid profile, the association of its abnormal values with other risk factors for AS was also investigated. RESULTS: Increased levels of total cholesterol, LDL-C and triglycerides (TG) were observed in 9.1%, 7.6% and 16.3% of the students, respectively, and decreased levels of HDL-C in 8.6% of them. Prevalence of the remaining risk factors analyzed was elevated: sedentary life style (78.9%); high intake of total fat (77.5%); high cholesterol intake (35.9%); smoking, hypertension (15.8%) and obesity (7.2%). There was an association between elevated LDL-C and TG levels and sedentary life style and body mass index. CONCLUSION: The high prevalence of risk factors for AS in young individuals draws attention to the need for adopting preventive plans.

Are apolipoproteins A and B better than lipoproteins for assessing risk of obstructive coronary heart disease?

OBJECTIVE: To evaluate whether apolipoproteins A-I (Apo A-I) and B (Apo B) have, higher ensitivity (SN), specificity (SP) and positive predictive value (PPV) than lipoproteins (LP), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides (TGL) in assessing the risk of coronary heart disease (CHD). METHODS: This is a transversal case-control study of 241 patients, who were divided into two groups: 1) 145 patients with CHD, and 2) 96 patients without coronary disease. A model of logistic regression to evaluate the relation between the LPs and CHD was developed in which variables with a p-alpha <0.1 were included. RESULTS: Apo A-I levels were higher in the patients without CHD, (OR 2.08, CI 1.20-3.57). There were no statistical differences between the values of Apo A-I and the remaining lipid fractions (Apo A-I: 67%; Apo B: 100%; PPV: TC= 71%; TGC=71%; HDL=71%; LDL=71%). The costs of the tests in Reais were as follows: Apo A-I: R$ 56.60; Apo B-100: R$ 56.60; TC: R$ 9.94; HDL: R$ 21.30; LDL: R$ 28.40; TGL: R$ 14.20. CONCLUSION: Levels of Apo A-I and Apo B have no advantage over conventional lipoproteins in predicting the risk of CHD, despite the statistical association between Apo A-I and CHD; in addition, their costs are higher than those of the conventional lipoproteins.

Risk factors for atherosclerosis in an elderly out patient population in the City of São Paulo

OBJECTIVE: To analyze in out clinic elderly patients of both sexes for the prevalence of risk factors for atherosclerosis and study their association with the complications of atherosclerosis. METHODS: Five hundred and sixteen outpatients, 152 men and 364 women, 60 years or older, were studied. The prevalences of hypertension, dyslipidemia, diabetes mellitus, cigarette smoking and obesity were determined in both sexes and compared using the chi-square test. The association between these factors and the presence of atherosclerotic complications was analyzed by logistic regression. RESULTS: The comparative analysis of the factors in both sexes showed that hypertension, total cholesterol > or = 240mg/dL, LDL-cholesterol > or = 160mg/dL, and body mass index >27.5 were more frequent among women, but HDL-cholesterol <35mg/dL and cigarette smoking were more frequent among men, and no difference occurred between sexes in relation to the frequency of triglycerides > or = 250mg/dL and diabetes mellitus. After adjustment of the variables in the regression model, we observed that in the total of elderly patients, risk factors for complications of atherosclerosis were: triglycerides > or = 250mg/dL, hypertension, and male sex. Among men, the risk factors were: LDL-cholesterol > or = 160mg/dL, diabetes mellitus, HDL-cholesterol <35mg/dL and hypertension. Among women, the risk factors were: tryglicerides > or = 250mg/dL and hypertension. CONCLUSION: The results showed that, in the elderly, the risk factors for atherosclerosis persist, but with different behaviors between men and women. The study suggests that the relative importance of the risk factors can change with the aging process.

Arrhythmogenic cardiomyopathy of the right ventricle. Predictive value of QT interval dispersion to assess arrhythmogenic risk and sudden death

OBJECTIVE: To determine in arrhythmogenic right ventricular cardiomyopathy the value of QT interval dispersion for identifying the induction of sustained ventricular tachycardia in the electrophysiological study or the risk of sudden cardiac death. METHODS: We assessed QT interval dispersion in the 12-lead electrocardiogram of 26 patients with arrhythmogenic right ventricular cardiomyopathy. We analyzed its association with sustained ventricular tachycardia and sudden cardiac death, and in 16 controls similar in age and sex. RESULTS: (mean ± SD). QT interval dispersion: patients = 53.8±14.1ms; control group = 35.0±10.6ms, p=0.001. Patients with induction of ventricular tachycardia: 52.5±13.8ms; without induction of ventricular tachycardia: 57.5±12.8ms, p=0.420. In a mean follow-up period of 41±11 months, five sudden cardiac deaths occurred. QT interval dispersion in this group was 62.0±17.8, and in the others it was 51.9±12.8ms, p=0.852. Using a cutoff > or = 60ms to define an increase in the degree of the QT interval dispersion, we were able to identify patients at risk of sudden cardiac death with a sensitivity of 60%, a specificity of 57%, and positive and negative predictive values of 25% and 85%, respectively. CONCLUSION: Patients with arrhythmogenic right ventricular cardiomyopathy have a significant increase in the degree of QT interval dispersion when compared with the healthy population. However it, did not identify patients with induction of ventricular tachycardia in the electrophysiological study, showing a very low predictive value for defining the risk of sudden cardiac death in the population studied.

Myocardial revascularization with coronary endarterectomy. Stratification of risk factors for early mortality

OBJECTIVE: To determine the risk factors for mortality related to myocardial revascularization when performed in association with coronary endarterectomy. METHODS: We assessed retrospectively 353 patients who underwent 373 coronary endarterectomies between January '89 and November '98, representing 3.73% of the myocardial revascularizations in this period of time. The arteries involved were as follows: right coronary artery in 218 patients (58.45%); left anterior descending in 102 patients (27.35%); circumflex artery in 39 patients (10.46%); and diagonal artery in 14 patients (3.74%). We used 320 (85.79%) venous grafts and 53 (14.21%) arterial grafts. RESULTS: In-hospital mortality among our patients was 9.3% as compared with 5.7% in patients with myocardial revascularizations without endarterectomy (p=0.003). Cause of death was related to acute myocardial infarction in 18 (54.55%) patients. The most significant risk factors for mortality identified were as follows: diabetes mellitus (p=0.001; odds ratio =7.168), left main disease (<0.001; 9.283), female sex (0.01; 3.111), acute myocardial infarction (0.02; 3.546), ejection fraction <35% (<0.001; 5.89), and previous myocardial revascularization (<0.001; 4.295). CONCLUSION: Coronary endarterectomy is related to higher mortality, and the risk factors involved are important elements of a poor outcome.