AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION

SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.

RISK FACTORS OF HIV-1 VERTICAL TRANSMISSION (VT) AND THE INFLUENCE OF ANTIRETROVIRAL THERAPY (ART) IN PREGNANCY OUTCOME

In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.

INCIDENCE OF DIARRHEA BY Clostridium difficile IN HEMATOLOGIC PATIENTS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS: RISK FACTORS FOR SEVERE FORMS AND DEATH

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.

GIS capacity building for risk management to help developing countries:Case of climate change problem in Amhara rural region (Ethiopia)

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Mutilação Genital Feminina: o que Sabem os Profissionais de Saúde?

Portugal is considered by the World Health Organization (WHO) a risk country for the practice of Female Genital Mutilation (FGM). Objectives: To evaluate the knowledge that health professionals from Maternity Dr. Alfredo da Costa (MAC) have regarding FGM. Population and Methods: Analysis of surveys delivered to health professionals from MAC (a hospital dedicated to reproductive health), between April and June 2008, addressing issues related to the knowledge about FGM. Results: Authors collected 112 valid surveys involving 38 doctors, 48 nurses and 26 medical auxiliaries/administrative personnel. From the respondents, 106 (95%) had heard about FMG practice before, the media being the most reported source of information; 59 (53%) replied they could be able to recognize FGM cases in their clinical practice; however, only 31 (28%) claimed to know the FGM type classiication and 32 (29%) admitted to be prepared to recognize and manage these situations in their own clinical practice; 9 had been consulted explicitly by a FGM practice complication and 1 doctor had admitted having been asked to perform/execute FGM; 13 (12%) recognized that the Portuguese legislation its this practice. Regarding the practice of FGM, 100 (89%) of respondentes stated that it should not be maintained and 97 (87%) stated that it should not be tolerated. However, 42 (38%) considered that if these practices were a reality, then they should be medical assisted. Discussion: Health professionals can play an important role in eliminating the practice of FGM, not only by the proper clinical management of this situation, but also by preventing those communities at risk to resort to FGM. Most health professionals are not prepared to deal with FGM in their clinical practice. It is important to promote a better knowledge on the subject and to create protocols for proper clinical management.

TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN IMMUNOCOMPETENT PATIENT

Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicansand spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient.

Is It Possible to Simplify Risk Stratification Scores for Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty?

INTRODUCTION: There are several risk scores for stratification of patients with ST-segment elevation myocardial infarction (STEMI), the most widely used of which are the TIMI and GRACE scores. However, these are complex and require several variables. The aim of this study was to obtain a reduced model with fewer variables and similar predictive and discriminative ability. METHODS: We studied 607 patients (age 62 years, SD=13; 76% male) who were admitted with STEMI and underwent successful primary angioplasty. Our endpoints were all-cause in-hospital and 30-day mortality. Considering all variables from the TIMI and GRACE risk scores, multivariate logistic regression models were fitted to the data to identify the variables that best predicted death. RESULTS: Compared to the TIMI score, the GRACE score had better predictive and discriminative performance for in-hospital mortality, with similar results for 30-day mortality. After data modeling, the variables with highest predictive ability were age, serum creatinine, heart failure and the occurrence of cardiac arrest. The new predictive model was compared with the GRACE risk score, after internal validation using 10-fold cross validation. A similar discriminative performance was obtained and some improvement was achieved in estimates of probabilities of death (increased for patients who died and decreased for those who did not). CONCLUSION: It is possible to simplify risk stratification scores for STEMI and primary angioplasty using only four variables (age, serum creatinine, heart failure and cardiac arrest). This simplified model maintained a good predictive and discriminative performance for short-term mortality.

Epidemiological studies of Streptococcus pneumoniae carriage in the post-vaccination era among two risk groups: children and the elderly

Dissertation presented to obtain the Ph.D. degree in Biology/ Molecular Biology

PREVALENCE, RISK FACTORS AND SYMPTOMS ASSOCIATED TO INTESTINAL PARASITE INFECTIONS AMONG PATIENTS WITH GASTROINTESTINAL DISORDERS IN NAHAVAND, WESTERN IRAN

We studied the prevalence of intestinal parasites (IPs), their risk factors and associated symptoms among patients with gastrointestinal disorders. A total of 1,301 participants aged 22 days-90 years were enrolled in this study. We used a structured questionnaire to obtain socio-demographic and stool examination to investigate intestinal parasite infections. Data analysis was performed using SPSS16. The overall prevalence of intestinal parasites (IPs) was 32.2% (419/1,301). Three hundred and fifty nine cases/1,301 (27.6%) were infected with a single parasite and 60/1,301 cases (4.6%) presented polyparasitism. The most common IP was Blastocystis sp. 350/1,301 (26.9%), followed by Entamoeba coli 38/1,301 (2.92%), Giardia lamblia 30/1,301 (2.3%) and Cryptosporidium spp. 17/1,301 (1.3%). Regarding the socio-demographic variables, educational status (p = 0.001), contact with domestic animals and soil (p = 0.02), age above 15 years (p = 0.001) and seasons (p = 0.001) were significantly associated to intestinal parasitic infections. Concerning clinical characteristics, the presence of IPs was significantly associated to diarrhea (OR = 1.57; CI 95% = 1.24-1.98; p < 0.001) and dysentery (OR = 1.94; CI 95% = 1.03-3.66; p < 0.04). Our findings suggest that IPs are one of the main causal agents of gastrointestinal disorders. Improving the knowledge on local risk factors such as poverty, low level of education, poor sanitation, contact with soil and contact with domestic animal is warranted.

Endemic Methicillin-Resistant Staphylococcus Aureus: Nurses' Risk Perceptions and Attitudes

Dissemination of methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most difficult challenges for prevention, control, and treatment of health care-associated infections. A survey and interviews were conducted on nurses from a hospital center. We found that most nurses' perceived risk of acquiring MRSA related to themselves (72%), other nurses (88.5%), and patients (97.8%). This perception influences attitudes, leading to compliance with the existing recommendations.

Understanding the internet banking adoption by Portuguese customers - a unified theory of acceptance and use of technology and perceived risk application.

Trabalho de Projeto apresentado como requisito parcial para obtenção do grau de Mestre em Estatística e Gestão de Informação

Metodologia Value-at-risk: aplicação a uma carteira de obrigações de tesouro portuguesas

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Estatística e Gestão de Informação

The Use of Statins in People at Risk of Developing Diabetes Mellitus: Evidence and Guidance for Clinical Practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.