Do socioeconomic factors explain why maternal smoking during pregnancy is more frequent in a more developed city of Brazil?

The prevalence of smoking during pregnancy in Ribeirão Preto, a rich Brazilian city, was significantly higher (21.4%) than in São Luís (5.9%), a less developed city. To assess which variables explain the difference in prevalence of smoking during pregnancy, data from two birth cohorts were used, including 2846 puerperae from Ribeirão Preto, in 1994, and 2443 puerperae from São Luís, in 1997/98. In multivariable analysis, risk of maternal smoking during pregnancy was higher in São Luís for mothers living in a household with five or more persons (OR = 1.72, 95%CI = 1.12-2.64), aged 35 years or older (OR = 1.98, 95%CI = 0.99-3.96), who had five or more children (OR = 2.10, 95%CI = 1.16-3.81), and whose companion smoked (OR = 2.20, 95%CI = 1.52-3.18). Age of less than 20 years was a protective factor (OR = 0.55, 95%CI = 0.33-0.92). In Ribeirão Preto there was association with maternal low educational level (OR = 2.18, 95%CI = 1.30-3.65) and with a smoking companion (OR = 3.25, 95%CI = 2.52-4.18). Receiving prenatal care was a protective factor (OR = 0.24, 95%CI = 0.11-0.49). Mothers from Ribeirão Preto who worked outside the home were at a higher risk and those aged 35 years or older or who attended five or more prenatal care visits were at lower risk of smoking during pregnancy as compared to mothers from São Luís. Smoking by the companion reduced the difference between smoking rates in the two cities by 10%. The socioeconomic variables in the model did not explain the higher prevalence of smoking during pregnancy in the more developed city.

TNF-a and IL-10 levels in tracheobronchial lavage of ventilated preterm infants and subsequent lung function

The role of airway inflammation in ventilated preterm newborns and the risk factors associated with the development of chronic lung disease are not well understood. Our objective was to analyze the association of the airway inflammatory response in ventilated preterm infants by serial measurements of TNF-a and IL-10 in tracheobronchial lavage (TBL) with perinatal factors and lung function measured early in life. A series of TBL samples were collected from ventilated preterm infants (less than 32 weeks of gestational age) and concentrations of TNF-a and IL-10 were measured by ELISA. Pulmonary function tests were performed after discharge by the raised volume rapid compression technique. Twenty-five subjects were recruited and 70 TBL samples were obtained. There was a significant positive association between TNF-a and IL-10 levels and length of time between the rupture of the amniotic membranes and delivery (r = 0.65, P = 0.002, and r = 0.57, P < 0.001, respectively). Lung function was measured between 1 and 22 weeks of corrected age in 10 patients. Multivariable analysis with adjustment for differences in lung volume showed a significant negative association between TNF-a levels and forced expiratory flow (FEF50; r = -0.6; P = 0.04), FEF75 (r = -0.76; P = 0.02), FEF85 (r = -0.75; P = 0.03), FEF25-75 (-0.71; P = 0.02), and FEV0.5 (r = -0.39; P = 0.03). These data suggest that TNF-a levels in the airways during the first days of life were associated with subsequent lung function abnormalities measured weeks or months later.

C-reactive protein in acute coronary syndrome: association with 3-year outcomes

Inflammatory markers have been associated with clinical outcome in patients with acute coronary syndrome (ACS). The present study evaluated the role of high-sensitivity C-reactive protein (CRP) measurements as a predictor of late cardiovascular outcomes after ACS. One hundred and ninety-nine ACS patients in a Coronary Care Unit from March to November 2002 were included and were reassessed clinically after ~3 years. Clinical variables and CRP levels were evaluated as predictors of major cardiovascular events (MACE, defined as the occurrence of cardiac death, ischemic stroke or myocardial infarction) and mortality. Statistical analyses included Cox multivariable analysis and survival curves (Kaplan-Meier). Of the 199 patients, 11 died within 1 month (5.5%). Of the 188 remaining patients, 22 died after a mean follow-up of 2.9 ± 0.5 years. Baseline CRP levels for patients with MACE (N = 57) were significantly higher than those of patients with no events (median = 0.67 mg/L; 25th-75th percentiles = 0.32 and 1.99 mg/L vs median = 0.45 mg/L; 25th-75th percentiles = 0.24 and 0.83 mg/L; P < 0.001). Patients with CRP levels >3 mg/L had a significantly lower survival than the other two groups (1-3 and <1 mg/L; P = 0.001, log-rank test). The odds ratio for MACE was 7.41 (2.03-27.09) for patients with CRP >3 mg/L compared with those with CRP <1 mg/L. For death by any cause, the hazard ratio was 4.58 (1.93-10.86). High CRP levels predicted worse long-term outcomes (MACE and death by any cause) in patients with ACS.

5-Methyltetrahydrofolate-homocysteine methyltransferase gene polymorphism (MTR) and risk of head and neck cancer

The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC). The frequency of MTR A2756G (rs1805087) polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis) was used for comparisons between groups and multiple logistic regression (multivariate analysis) was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05), AG genotype (P = 0.019) and G allele (P = 0.028) may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008). The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7%) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5% in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): £2.93 mm (RR = 0.54; 95%CI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm² (RR = 0.66; 95%CI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm³ (RR = 0.74; 95%CI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95%CI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): ≤108.8 mg/dL (RR = 0.53; 95%CI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

La PCSK9 humaine, une molécule aux multiples facettes métaboliques et une cible thérapeutique prometteuse : études de régulation in vitro et in vivo

La proprotéine convertase subtilisine/kexine-9 (PCSK9) a été identifiée comme le troisième locus impliqué dans l’hypercholestérolémie autosome dominante (ADH). Les deux autres gènes impliqués dans l’ADH encodent le récepteur des lipoprotéines de faible densité (LDLR) et l’apolipoprotéine B. La PCSK9 est une convertase qui favorise la dégradation du LDLR dans les hépatocytes et augmente le niveau plasmatique de cholestérol des LDL (LDL-C). Les mutations « gain de fonction » de la PCSK9 sont associées à un phénotype d’hypercholestérolémie familiale, tandis que les variantes « perte de fonction » sont associées à un LDL-C réduit et à un risque coronarien plus faible. Pour élucider le rôle physiologique de la PCSK9, nous avons étudié sa régulation génique. En utilisant le RT-PCR quantitatif dans des hépatocytes humains, nous avons analysé la régulation de PCSK9 sous différentes conditions modulant l’expression des gènes impliqués dans le métabolisme du cholestérol. Nous avons démontré que l’expression de la PCSK9 était induite par les statines de manière dose-dépendante et que cette induction était abolie par le mévalonate. De plus, le promoteur de PCSK9 contenait deux motifs conservés pour la régulation par le cholestérol : le sterol regulatory element (SRE) et un site Sp1. La PCSK9 circule dans le plasma sous des formes mature et clivée par la furine. Grâce à notre anticorps polyclonal, nous avons mis au point un test ELISA mesurant la PCSK9 plasmatique totale. Une étude transversale a évalué les concentrations plasmatiques de PCSK9 chez des sujets sains et hypercholestérolémiques, traités ou non par des statines ou une combinaison statine/ezetimibe. Chez 254 sujets sains, la valeur moyenne de PCSK9 (écart-type) était de 89,5 (31,9) µg/L. La concentration plasmatique de la PCSK9 corrélait avec celle de cholestérol total, du LDL-C, des triglycérides (TG), de la glycémie à jeun, l’âge et l’indice de masse corporelle. Le séquençage de PCSK9 chez des sujets aux extrêmes de la distribution des concentrations de PCSK9 de notre cohorte a révélé la présence d’une nouvelle variation « perte de fonction » : R434W. Chez 200 patients hypercholestérolémiques, la concentration de PCSK9 était plus élevée que chez les sujets sains (P<0,04). Elle a augmenté avec une dose croissante de statine (P<0,001), et a augmenté encore plus suite à l’ajout d’ezetimibe (P<0,001). Chez les patients traités, ceux présentant une hypercholestérolémie familiale (HF; due à une mutation du LDLR) avaient des concentrations plus élevées de PCSK9 que les non-HF (P<0,005), et la réduction de LDL-C corrélait positivement avec la concentration de PCSK9 atteinte de la même manière dans les deux sous-catégories (P<0,02 et P<0,005, respectivement). Par ailleurs, une incubation des cellules HepG2 (hépatocytes) et Caco-2 (entérocytes) avec de l’ezetimibe a provoqué une augmentation de l’ARNm de PCSK9 et de NPC1L1 de 1,5 à 2 fois (P<0,05), mais aucune variation significative de PCSK9 sécrétée n’a été observée, suggérant que ces lignées cellulaires ne sont pas un modèle idéal. Nous avons également mesuré le niveau de PCSK9 chez 1 739 Canadiens-français âgés de 9, 13 et 16 ans. La valeur moyenne (écart-type) de PCSK9 dans cette cohorte était de 84,7 (24,7) µg/L, légèrement plus basse que dans la cohorte d’adultes (89,5 (31,9) µg/L). Chez les garçons, la PCSK9 circulante diminuait avec l’âge, tandis que c’était l’inverse chez les filles. Il y avait des associations positives et significatives entre la PCSK9 et la glycémie à jeun, l’insulinémie, le HOMA-IR, et les paramètres lipidiques (TC, LDL-C, TG, HDL-C, apoAI et apoB). Dans l’analyse multivariée, une hausse de 10% de l’insulinémie à jeun était associée à une augmentation de 1 à 2% de PCSK9. La régulation de PCSK9 est typique de celle d’un gène impliqué dans le métabolisme des lipoprotéines et est probablement la cible du facteur de transcription «sterol regulatory element-binding protein » (SREBP-2). La concentration plasmatique de la PCSK9 est associée avec l’âge, le sexe, et de multiples marqueurs métaboliques chez les enfants et les adultes. La détection de la PCSK9 circulante chez les sujets HF et non-HF signifie que ce test ELISA spécifique à PCSK9 pourrait servir à suivre la réponse à la thérapie chez un grand éventail de sujets. PCSK9 semble être une cible thérapeutique prometteuse dans le traitement de l’hypercholestérolémie et de la maladie cardiovasculaire.

Amélioration des résultats cliniques en chirurgie cardiaque

Des éléments contributifs à plusieurs facettes de la chirurgie cardiaque ont été étudiés dans la présente thèse. Le premier manuscrit adresse la problématique de l’accident cérébro-vasculaire (ACV) post-opératoire. Nous avons analysé de façon rétrospective la médication prise en pré-opératoire de 6813 patients nécessitant une chirurgie de revascularisation coronarienne. Le but étant d’établir si la présence d’une médication précise (aspirine, inhibiteur de l’enzyme de conversion de l’angiotensine, statine, bêta-bloqueur) peut agir en pré-opératoire pour diminuer le risque d’ACV. En analyse multivariée, la combinaison de la prise de bêta-bloqueurs avec une statine a produit un ratio de cote de 0,37, suggérant un effet protecteur très important. Dans le deuxième manuscrit, je présente une étude ciblant les patients avec insuffisance mitrale ischémique modérée. Trente et un patients furent randomisés entre un traitement par pontages seuls vs pontages et annuloplastie mitrale restrictive. L’insuffisance mitrale a disparu en post-opératoire immédiat en présence de l’annuloplastie alors qu’aucun effet immédiat de la revascularisation coronarienne n’était noté sur l’insuffisance mitrale. Un an suivant la chirurgie, une insuffisance mitrale légère est réapparue chez le groupe ayant subi l’annuloplastie alors que les patients du groupe pontages seuls ont remodelé leur ventricule gauche et diminué l’importance de leur insuffisance mitrale au même niveau que le groupe annuloplastie. Aucun des marqueurs d’évolution clinique, tant au niveau symptomatique qu’au niveau de la survie ne diffère entre les groupes. La troisième étude est un suivi sur 20 ans des patients ayant eu des remplacements valvulaires mitraux ou aortiques avec une prothèse mécanique Carbomedics. Cette étude démontre une excellente survie avec un taux de complications valvulaires hémorragiques, thrombotiques, thrombo-emboliques, et d’endocardite favorable comparé aux autres types de prothèse et une absence de bris mécanique.

Estudio del liderazgo organizacional a través del análisis de conglomerados y factores

Esta investigación se basa en las herramientas multivariables como lo son el análisis por conglomerados y análisis de factores, aplicados en el estudio del liderazgo organizacional, de modo que podamos evidenciar el uso de estos métodos cuando se están evaluando variables no homogéneas.

Recidiva de câncer labial em pacientes atendidos no hospital DR. Luiz Antônio (Natal-RN) entre 1997-2004

Introduction: Cancer of the lip is very common in tropical countries, being noticeable the squamous cell carcinoma as the main histological type. Objective: Evaluate the socialdemographic profile, habits, occupation, clinical characteristics of the cancer lesions and the aftermath of treatment of the patients treated on the Luiz Antônio Hospital (Natal-RN). Design: Retrospective cohort. Methods: We analyzed 181 medical records of patients from the Luiz Antônio Cancer Hospital (Natal-RN) in the period between 1997 and 2004. The statistic evaluation of time between the diagnosis and the relapse or the cure of the patient were done through the Kaplan-Meier method and the comparison of survivor functions were done through the Log-rank test. Later, was estimated the proportional risk model of Cox. Results: The study population were composed by 69,1% males, 95,2% unlettered, the mean age of 66,5 years, 89,0% of smokers and 64,1% had an occupation involving sun exposure. In regard to the clinical characteristics, most lesions were in the lower lip (77,9%), the size of the tumor was smaller than 2 cm (51,8%), 92,6% had localized lesions. Were verified 16,3% of local relapse and 13% of regional. Almost the totally of the cases corresponded to squamous cell carcinoma (97,2%). We observed smaller accumulated probability of not occurrence of local relapse when the base and borders were free of lesions (p=0,041), as well as a smaller probability of regional relapse when the sort of treatment was surgery, associated with other therapeutics modalities (p=0,001). The patients with advanced pathologic stage (p=0,016), treated with surgery associated with other therapeutics modalities (p=0,001) and diameter above 4cm (p=0,019) presented a bigger possibility of any kind of relapse. The multivariable analysis pointed the complex treatments (surgery plus other therapeutics modalities) as a predictor variable for occurrence of new local lesions (p=0,001) and total (p=0,046), besides the age above 70 years to the regional relapse (p=0,050). Conclusion: Cancer of the lip occur in the lower lip, in males, smokers and individuals exposed to Sun light. The relapse was frequent, even being localized and without great consequences to the patient s health. The probability of relapse is related to the size and borders of the lesion and to the histological exam, as well as to the patient s age and complexity of the treatment chosen

Early nephrology consultation can have an impact on outcome of acute kidney injury patients

Background. Patients who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality and morbidity. The objectives of this study were to compare clinical and laboratory characteristics of AKI patients evaluated and not evaluated by nephrologists in ICU and generate the hypothesis of the relationship between timing of nephrology consultation and outcome.Methods. We explored associations among presence and timing of nephrology consultation with ICU stay and in-ICU mortality in 148 ICU patients with AKI at a Brazilian teaching hospital from July 2008 to May 2010. Multivariable logistic regression was used to adjust confounding and selection bias.Results. AKI incidence was 30% and 52% of these AKI patients were evaluated by nephrologists. At multivariable analysis, AKI patients evaluated by nephrologists showed higher Acute Tubular Necrosis-Index Specific Score and creatinine level, more dialysis indications, lower urine output and longer ICU stay. The mortality rate was similar to AKI patients who were not evaluated. Nephrology consultation was delayed (>= 48 h) in 62.3% (median time to consultation, 4.7 days). Lower serum creatinine levels (P - 0.009) and higher urine output (P = 0.002) were associated with delayed consultation. Delayed consultation was associated with increased ICU mortality (65.4 versus 88.2%, P < 0.001).Conclusions. In AKI, patients evaluated by nephrologists seem to be more seriously ill than those not evaluated and present similar mortality rate. The delayed nephrology consultation can be associated with increased ICU mortality.

Knowledge and attitudes of health care workers from intensive care units regarding nosocomial transmission of influenza: a study on the immediate pre-pandemic period

The transmission of influenza in health care settings is a major threat to patients, especially those with severe diseases. The attitude of health care workers (HCWs) may influence the transmission of countless infections. The current study aimed to quantify knowledge and identify attitudes of HCWs involved in intensive care units (ICUs) regarding the risk of nosocomial influenza transmission. A questionnaire was applied through interviews to HCWs who worked in one of the five ICUs from a teaching hospital. Questions about influenza were deliberately dispersed among others that assessed several infectious agents. Forty-two HCWs were interviewed: nine physicians, ten nurses and 23 nursing technicians or auxiliaries. Among the 42 HCWs, 98% were aware of the potential transmission of influenza virus in the ICUs, but only 31% would indicate droplet precautions for patients with suspected infection. Moreover, only 31% of them had been vaccinated against influenza in the last campaign (2008). Nursing technicians or auxiliaries were more likely to have been vaccinated, both by univariate and multivariable analysis. When asked about absenteeism, only 10% of the study subjects stated that they would not go to work if they had an influenza-like illness. Those findings suggest that, in non-pandemic periods, influenza control in hospitals requires strategies that combine continuous education with changes in organizational culture.

Risk factors for Hospital-Acquired Pneumonia in nonventilated adults

Although most recent publications focus on Ventilator-associated Pneumonia, Non-Ventilator-associated Hospital-acquired pneumonia (NVHAP) is still worrisome. We studied risk factors for NVHAP among patients admitted to a small teaching hospital. Sixty-six NVHAP case patients and 66 controls admitted to the hospital from November 2005 through November 2006 were enrolled in a case-control study. Variables under investigation included: demographic characteristics, comorbidities, procedures, invasive devices and use of medications (Sedatives, Antacids, Steroids and Antimicrobials). Univariate and multivariable analysis (hierarchical models of logistic regression) were performed. The incidence of NVHAP in our hospital was 0.68% (1.02 per 1,000 patients-day). Results from multivariable analysis identified risk factors for NVHAP: age (Odds Ratio[OR]=1.03, 95% Confidence Interval[CI]=1.01-1.05, p=0.002), use of Antacids (OR=5.29, 95%CI=1.89-4.79, p=0.001) and Central Nervous System disease (OR=3.13, 95%CI=1.24-7.93, p=0.02). Although our findings are coherent with previous reports, the association of Antacids with NVHAP recalls a controversial issue in the physiopathology of Hospital-Acquired Pneumonia, with possible implications for preventive strategies.

Molar Pregnancy in Adolescents

OBJECTIVE: To describe the clinical presentation of hydatidiform molar pregnancy in women under the age of 20 years. In addition, we sought to understand if this adolescent population manifests differences in clinical factors compared to an adult population that may affect outcome.STUDY DESIGN: We used a database from the New England Trophoblastic Disease Center to analyze clinical data from all women followed for molar pregnancy between 1970 and 2009 with complete follow-up information. This population was stratified by age and clinical parameters including presenting signs, molar histology and development of gestational trophoblastic neoplasia (GTN). Univariable and multivariable logistic regression was employed to discern clinical factors that associated with adolescent age. The Partners Human Research Committee approved this study.RESULTS: We identified 1,494 women diagnosed with hydatidiform mole (HM), of which 220 (14.7%) were adolescents defined as age <20 years. The most common presenting clinical signs were vaginal bleeding and an enlarged uterus compared to dates. Median gestational age at diagnosis was 13.4 weeks, not different from that in the adult population. Similarly, no difference in presenting human chorionic gonadotropin was observed between the adult and adolescent populations. Adolescents presented with a significant overrepresentation of complete mole (86% vs. 75%, p < 0.001) compared to adults. Complete mole was associated with a heightened risk of developing GTN (OR 2.6, 95% CI 1.9-3.5), and despite the association of complete mole with young maternal age, univariable analysis showed no difference in the rate of GTN observed between adolescents and adults (24% vs. 30%, p = 0.08). Multivariable analysis controlling for molar histology demonstrated that adolescent age was associated with a decreased risk of GTN (hazard ratio 0.67, 95% CI 0.48 0.93).CONCLUSION: Adolescents account for a substantial proportion of the population with HM. They commonly present with vaginal bleeding. Though this population develops a complete mole with a higher frequency than adults, adolescents appear to have a significantly decreased risk of developing GTN. (J Reprod Med 2012; 57:225-230)

Transtornos mentais comuns e uso de psicofármacos: impacto das condições socioeconômicas

OBJETIVO: Avaliar a influência das condições socioeconômicas na associação entre transtornos mentais comuns, uso de serviços de saúde e de psicofármacos. MÉTODOS: Estudo transversal populacional conduzido na cidade de Botucatu, SP, com amostragem probabilística, estratificada e por conglomerados. Foram realizadas entrevistas domiciliares com 1.023 sujeitos de 15 anos ou mais de idade, entre 2001 e 2002. Transtorno mental comum foi avaliado utilizando o Self Reporting Questionnaire (SRQ-20). O uso de serviços foi investigado com relação à quinzena anterior à entrevista e uso de psicotrópicos, nos três dias anteriores. Utilizou-se regressão logística para análise multivariável, considerando o efeito do desenho. RESULTADOS: No total da amostra, 13,4% (IC 95%: 10,7;16,0) procuraram serviços de saúde na quinzena anterior à entrevista. A procura de serviços de saúde se associou ao sexo feminino (OR=2,0) e à presença de transtorno mental comum (OR=2,2). Na amostra 13,3% (IC 95%: 9,2;17,5) referiram ter usado ao menos um psicotrópico, destacando-se os antidepressivos (5,0%) e os benzodiazepínicos (3,1%). Na análise multivariável, sexo feminino e presença de transtorno mental comum mantiveram-se associados ao uso de benzodiazepínicos. Renda per capita mostrou-se direta e independentemente associada ao uso de psicofármacos, conforme aumento da renda. CONCLUSÕES: Menor renda associou-se à presença de transtorno mental comum, mas não ao uso de psicotrópicos. A associação entre transtorno mental comum e uso de psicotrópicos e maior renda reforça a hipótese da existência de iniqüidades no acesso à assistência médica na população estudada.

Walking for leisure among adults from three Brazilian cities and its association with perceived environment attributes and personal factors

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)