968 resultados para INTERNATIONAL COHORT


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Ce manuscrit est une pré-publication d'un article paru dans International Journal of Drug Policy 2010; 21(6): 477-484.

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OBJECTIVE: Studies have shown that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT-2C receptor (HTR2C) are associated with antipsychotic agent-induced weight gain and the development of behavioural and psychological symptoms. We aimed to analyse whether variation in the HTR2C is associated with obesity- and mental health-related phenotypes in a large population-based cohort. METHOD: Six tagSNPs, which capture all common genetic variation in the HTR2C gene, were genotyped in 4978 men and women from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, an ongoing prospective population-based cohort study in the United Kingdom. To confirm borderline significant associations, the -759C/T SNP (rs3813929) was genotyped in the remaining 16 003 individuals from the EPIC-Norfolk study. We assessed social and psychological circumstances using the Health and Life Experiences Questionnaire. Genmod models were used to test associations between the SNPs and the outcomes. Logistic regression was performed to test for association of SNPs with obesity- and mental health- related phenotypes. RESULTS: Of the six HTR2C SNPs, only the T allele of the -759C/T SNP showed borderline significant associations with higher body mass index (BMI) (0.23 kg m(-2); (95% confidence interval (CI): 0.01-0.44); P=0.051) and increased risk of lifetime major depressive disorder (MDD) (Odds ratio (OR): 1.13 (95% CI: 1.01-1.22), P=0.02). The associations between the -759C/T and BMI and lifetime MDD were independent. As associations only achieved borderline significance, we aimed to validate our findings on the -759C/T SNP in the full EPIC-Norfolk cohort (n=20 981). Although the association with BMI remained borderline significant (beta=0.20 kg m(-2); 95% CI: 0.04-0.44, P=0.09), that with lifetime MDD (OR: 1.01; 95% CI: 0.94-1.09, P=0.73) was not replicated. CONCLUSIONS: Our findings suggest that common HTR2C gene variants are unlikely to have a major role in obesity- and mental health-related traits in the general population.

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Objectives: Human papillomavirus (HPV) infection is a major risk factor for cervical disease. Using baseline data from the HIV-infected cohort of Evandro Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors associated with an increased prevalence of HPV were assessed. Methods: Samples from 634 HIV-infected women were tested for the presence of HPV infection using hybrid capture 11 and polymerase chain reaction. Prevalence ratios (PR) were estimated using Poisson regression analysis with robust variance. Results: The overall prevalence of HPV infection was 48%, of which 94% were infected with a high-risk HPV. In multivariate analysis, factors independently associated with infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5, 95% confidence interval (CI) 1.1-2.1), current or prior drug use (PR 1.3, 95% CI 1.0-1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96-1.6), condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1-1.7), and nadir CD4+ T-cell count <100 cells/mm(3) (PR 1.6, 95% CI 1.2-2.1). Conclusions: The estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is warranted in all HIV-infected women, in particular those of younger age and advanced immunosuppression. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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Background. Predicting risk of posteruptive enamel breakdown (PEB) of molar-incisor hypomineralization (MIH) opacity is a difficult but important clinical task. Therefore, there is a need to evaluate these aspects through longitudinal studies.Objective. The aim of this longitudinal study was to analyse the relationship between colours of MIH opacity of children aged 6-12 (baseline) and other clinical and demographic variables involved in the increase in severity of MIH.Materials and methods. A blinded prospective 18-month follow-up was conducted with 147 individuals presenting mild MIH. Tooth-based incidence of increase in severity of MIH (PEB or atypical restorations) was used as dependent measurement. Enamel opacities were recorded according to colour shades of white, yellow and brown, allowing assessment of susceptibility to structural loss over time, according to colour of MIH opacity. Poisson regression models were used to adjust the results for demographic and clinical variables.Results. Brown and yellow MIH opacities were at higher risk for PEB and atypical restorations than those of white ones, even after adjustment for clinical and demographic variables.Conclusion. Teeth presenting mild MIH severity associated with yellow and brown enamel opacities were at high risk for increase in severity of MIH than lighter ones. This result could help clinicians determine a risk-based treatment for children with MIH.

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Introduction: Peritonitis remains the main cause of peritoneal dialysis (PD) technique failure worldwide, despite significant reductions in infection rates observed over the past decades. Several studies have described risk factors for peritonitis, technique failure and mortality. However, there are scarce data regarding predictors of complications during and after a peritonitis episode. The aim of our study was to analyze predictors of peritonitis-related outcome in the Brazilian Peritoneal Dialysis study (BRAZPD) cohort.Methods: All adult incident patients recruited in the BRAZPD Study between December 2004 and October 2007, who remained at least 90 days on PD and presented their first peritonitis episode (n = 474 patients) were included in the study. The endpoints analyzed were non-resolution, death due to a peritonitis episode and long-term technique survival after a peritonitis episode.Results: In the multivariable regression, non-resolution was independently associated with older age (odds ratio (OR) 1.02; p < 0.01), collagenosis as the primary renal disease (OR 4.6; p < 0.05) and Pseudomonas spp as etiological agent (OR 2.9; p < 0.05). Patients who were transferred from APD to CAPD during peritonitis therapy presented a higher risk of non-response (OR 2.5; p < 0.05). The only factor associated with death during a peritonitis episode was older age (OR 1.04; p < 0.05). Exposure to vancomycin and male gender were the independent predictors of long-term technique failure (OR 2.2; p < 0.01).Conclusion: Apart from confirming previous observations of the negative impact of older age and Pseudomonas spp peritonitis on outcomes, we observed that collagenosis may negatively impact response to treatment and exposure to vancomycin may possibly reduce long-term technique survival. It is important to emphasize that the association of vancomycin with technique failure does not prove causality. These findings shed light on new factors predicting outcome when peritonitis is diagnosed.

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OBJECTIVE: To evaluate treatment of Brazilian patients with gestational trophoblastic disease (GTD).STUDY DESIGN: A retrospective cohort study with analysis of medical reports performed in 10 Brazilian referral centers from January 2000 to December 2011.RESULTS: Of 5,250 patients 3 died (0.06%) at the time of uterine evacuation. Spontaneous remission of GTD (group G1) was observed in 4,103 cases, and 1,144 (21.8%) progressed to gestational trophoblastic neoplasia (GTN) (G2). In G1 2,716 (66.2%) had complete hydatidiform mole (HM) and 1,210, partial HM (29.5%); 3,772 patients (92.7%) recovered as noted in December 2012. In G2, of 1,118 patients treated, initial histopathological results of previous gestation were complete HM (77.5% [n = 886]), partial HM (8.8% [n = 100]), and choriocarcinoma (8.0% [n = 92]); 930 (81.3%) were low-risk, 200 (17.5%) were high-risk GTN, and 14 had placental site trophoblastic tumor (PSTT) (1.2%); cure was achieved in 1,078 cases (96.4%), but 26 patients (2.3%) died (4 low-risk [0.4%], 19 high-risk [9.5%], and 3 PSTT [21.4%]).CONCLUSION: The highest death rates were due to high-risk GTN and PSTT. Patients with molar pregnancy should be referred to a referral center for an early diagnosis and prompt treatment of GTN in order to reduce the morbidity and mortality found in advanced stages.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Background. Ideal training methods that could ensure best peritoneal dialysis (PD) outcome have not been defined in previous reports. The aim of the present study was to evaluate the impact of training characteristics on peritonitis rates in a large Brazilian cohort.Methods. Incident patients with valid data on training recruited in the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD II) from January 2008 to January 2011 were included. Peritonitis was diagnosed according to International Society for Peritoneal Dialysis guidelines; incidence rate of peritonitis (episodes/patient-months) and time to the first peritonitis were used as end points.Results. Two thousand two hundred and forty-three adult patients were included in the analysis: 59 +/- 16 years old, 51.8% female, 64.7% with <= 4 years of education. The median training time was 15 h (IQI 10-20 h). Patients were followed for a median of 11.2 months (range 3-36.5). The overall peritonitis rate was 0.29 per year at risk (1 episode/41 patient-months). The mean number of hours of training per day was 1.8 +/- 2.4. Less than 1 h of training/day was associated with higher incidence rate when compared with the intervals of 1-2 h/day (P = 0.03) and > 2 h/day (P = 0.02). Patients who received a cumulative training of > 15 h had significantly lower incidence of peritonitis compared with < 15 h (0.26 per year at risk versus 0.32 per year at risk, P = 0.01). The presence of a caregiver and the number of people trained were not significantly associated with peritonitis incidence rate. Training in the immediate 10 days after implantation of the catheter was associated with the highest peritonitis rate (0.32 per year), compared with training prior to catheter implantation (0.28 per year) or > 10 days after implantation (0.23 per year). More experienced centers had a lower risk for the first peritonitis (P = 0.003).Conclusions. This is the first study to analyze the association between training characteristics and outcomes in a large cohort of PD patients. Low training time (particularly < 15 h), smaller center size and the timing of training in relation to catheter implantation were associated with a higher incidence of peritonitis. These results support the recommendation of a minimum amount of training hours to reduce peritonitis incidence regardless of the number of hours trained per day.

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Introduction: The aim was to confirm that PSF (probability of stone formation) changed appropriately following medical therapy on recurrent stone formers.Materials and Methods: Data were collected on 26 Brazilian stone-formers. A baseline 24-hour urine collection was performed prior to treatment. Details of the medical treatment initiated for stone-disease were recorded. A PSF calculation was performed on the 24 hour urine sample using the 7 urinary parameters required: voided volume, oxalate, calcium, urate, pH, citrate and magnesium. A repeat 24-hour urine sample was performed for PSF calculation after treatment. Comparison was made between the PSF scores before and during treatment.Results: At baseline, 20 of the 26 patients (77%) had a high PSF score (> 0.5). Of the 26 patients, 17 (65%) showed an overall reduction in their PSF profiles with a medical treatment regimen. Eleven patients (42%) changed from a high risk (PSF > 0.5) to a low risk (PSF < 0.5) and 6 patients reduced their risk score but did not change risk category. Six (23%) patients remained in a high risk category (> 0.5) during both assessments.Conclusions: The PSF score reduced following medical treatment in the majority of patients in this cohort.

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Pancreatitis is a rare and a life-threatening SLE manifestation in childhood-onset systemic lupus erythematosus (c-SLE). The objective of this study was to systematically classify pancreatitis in c-SLE according to the International Study Group of Pediatric Pancreatitis (INSPPIRE) and determine the overall prevalence, clinical features, laboratory and first episode outcomes. A multicenter cohort study in 10 Pediatric Rheumatology centers, including 852 cSLE patients. Pancreatitis was diagnosed in 22/852 (2.6%) cSLE patients. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%) and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration [1(0-10) vs. 4(0-23) years, p < 0.0001] and higher median of SLEDAI-2K [21(0-41) vs. 2(0-45), p < 0.0001]. The frequencies of fever (p < 0.0001), weight loss (p < 0.0001), serositis (p < 0.0001), nephritis (p < 0.0001), arterial hypertension (p < 0.0001), acute renal failure (p < 0.0001), macrophage activation syndrome (p < 0.0001) and death (p = 0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (p < 0.0001) and the median of prednisone dose [55(15-60) vs. 11(1-90)mg/day, p < 0.0001] were significantly higher in patients with pancreatitis. Of note, the two patients with acute recurrent pancreatitis had two episodes, with pain-free interval of 1 and 4 years. This was the first study characterizing pancreatitis using the INSPPIRE standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease.

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Objective  Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. Methods  All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. Results  A total of 497 children started ART and were followed for 972 person-years. Median age (interquartile range; IQR) was 8 years (4–11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from −2.1 (−2.7 to −1.3) and −2.6 (−3.6 to −1.8) to −1.4 (−2.1 to −0.8) and −1.8 (−2.4 to −1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions  Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.

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Background In the 19th century, eminent French sociologist Emile Durkheim found suicide rates to be higher in the Protestant compared with the Catholic cantons of Switzerland. We examined religious affiliation and suicide in modern Switzerland, where assisted suicide is legal. Methods The 2000 census records of 1 722 456 (46.0%) Catholics, 1 565 452 (41.8%) Protestants and 454 397 (12.2%) individuals with no affiliation were linked to mortality records up to December 2005. The association between religious affiliation and suicide, with the Protestant faith serving as the reference category, was examined in Cox regression models. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adjusted for age, marital status, education, type of household, language and degree of urbanization. Results Suicide rates per 100 000 inhabitants were 19.7 in Catholics (1664 suicides), 28.5 in Protestants (2158 suicides) and 39.0 in those with no affiliation (882 suicides). Associations with religion were modified by age and gender (P < 0.0001). Compared with Protestant men aged 35–64 years, HRs (95% CI) for all suicides were 0.80 (0.73–0.88) in Catholic men and 1.09 (0.98–1.22) in men with no affiliation; and 0.60 (0.53–0.67) and 1.96 (1.69–2.27), respectively, in men aged 65–94 years. Corresponding HRs in women aged 35–64 years were 0.90 (0.80–1.03) and 1.46 (1.25–1.72); and 0.67 (0.59–0.77) and 2.63 (2.22–3.12) in women aged 65–94 years. The association was strongest for suicides by poisoning in the 65–94-year-old age group, the majority of which was assisted: HRs were 0.45 (0.35–0.59) for Catholic men and 3.01 (2.37–3.82) for men with no affiliation; 0.44 (0.36–0.55) for Catholic women and 3.14 (2.51–3.94) for women with no affiliation. Conclusions In Switzerland, the protective effect of a religious affiliation appears to be stronger in Catholics than in Protestants, stronger in older than in younger people, stronger in women than in men, and particularly strong for assisted suicides.

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Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability.