Schistosomiasis mansoni and hydrographical conditions in São Carlos, São Paulo, Brazil.

BACKGROUND: In Brazil, schistosomiasis mansoni cases still occur, even in non-endemic areas. This study aimed to evaluate schistosomiasis mansoni cases and to delimit water collections investigated for infested planorbidae in São Carlos, São Paulo, Brazil. METHODS: A cross-sectional descriptive study and spatial analysis of schistosomiasis mansoni cases notified in the city from January 2005 to December 2017 was conducted. The study used geographical information system software to map residential and leisure exposures to water courses and bodies and related them to planorbidae surveys of São Paulo state. RESULTS: During the study period, 32 cases were notified. The main forms were intestinal and hepatosplenic. Twenty-eight cases were allochthonous, two autochthonous and two indeterminate. Eleven patients (33.3%) had contact with water collections in São Carlos, mainly the 29 and Broa reservoirs. Three of them had contact only with water collections in the region. A third of cases lived in the Água Fria and Água Quente microbasins, highly impacted by the presence of domestic sewage, and the whole region seems to be colonized by Biomphalaria tenagophila. CONCLUSIONS: The resolution of anthropogenic contamination of water bodies is crucial for controlling schistosomiasis mansoni autochthony in São Carlos.

Smartphone-Based Screening for Cardiovascular Diseases: A Trend?

Abstract Cardiovascular diseases are the leading cause of death in the world. People living in vulnerable and poor places such as slums, rural areas and remote locations have difficulty in accessing medical care and diagnostic tests. In addition, given the COVID-19 pandemic, we are witnessing an increase in the use of telemedicine and non-invasive tools for monitoring vital signs. These questions motivate us to write this point of view and to describe some of the main innovations used for non-invasive screening of heart diseases. Smartphones are widely used by the population and are perfect tools for screening cardiovascular diseases. They are equipped with camera, flashlight, microphone, processor, and internet connection, which allow optical, electrical, and acoustic analysis of cardiovascular phenomena. Thus, when using signal processing and artificial intelligence approaches, smartphones may have predictive power for cardiovascular diseases. Here we present different smartphone approaches to analyze signals obtained from various methods including photoplethysmography, phonocardiograph, and electrocardiography to estimate heart rate, blood pressure, oxygen saturation (SpO2), heart murmurs and electrical conduction. Our objective is to present innovations in non-invasive diagnostics using the smartphone and to reflect on these trending approaches. These could help to improve health access and the screening of cardiovascular diseases for millions of people, particularly those living in needy areas.

Use of ivermectin in the treatment of Covid-19: A pilot trial.

OBJECTIVES: In this randomized open-label trial pilot study we assessed the antiviral effects and safety of various doses of ivermectin in patients with mild clinical symptoms of COVID-19. METHODS: Patients were randomly assigned to receive standard of care (SOC) treatment at hospital admission; SOC plus ivermectin 100 mcg/kg; SOC plus ivermectin 200 mcg/kg; or SOC plus ivermectin 400 mcg/kg. The primary assessed endpoint was the proportion of patients who achieved two consecutive negative SARS-CoV-2 RT PCR tests within 7 days of the start of the dosing period. This study was registered at ClinicalTrials.gov (NCT04431466). RESULTS: A total of 32 patients were enrolled and randomized to treatment. SOC treatment together with ivermectin did not result in any serious adverse events. All patients exhibited a reduction in SARS-CoV-2 viral load within 7 days; however, those who received ivermectin had a more consistent decrease as compared to the SOC alone group, characterized by a shorter time for obtaining two consecutive negative SARS-CoV-2 RT PCR tests. CONCLUSIONS: Ivermectin is safe in patients with SARS-CoV-2, reducing symptomatology and the SARS-CoV-2 viral load. This antiviral effect appears to depend on the dose used, and if confirmed in future studies, it suggests that ivermectin may be a useful adjuvant to the SOC treatment in patients with mild COVID-19 symptoms.

Resistance training combined with blood flow restriction in cirrhosis: study protocol for a randomized controlled trial.

BACKGROUND: Patients affected by hepatic cirrhosis show reductions in muscle mass and function, with poor quality of life and functional performance. As such, resistance training with blood flow restriction (BFR-RT) could be a useful therapeutic tool for health promotion. Thus, we aim to verify the effects of this intervention on muscle strength, muscle mass, fiber Pennation angle, fascicle length, functional performance, quality of life, and fall risk scores in this population. METHODS: Thirty participants will be randomly distributed between 1) BFR-RT and 2) control (CTRL). Assessments will occur at three time points: before the training intervention (0 W), after 12 weeks (12 W), and at follow-up (24 W). The following variables will be assessed: Child-Pugh classification; MELD score; SF-36 questionnaire; fatigue severity index; 6-min walk test; timed-up and go; 30-s sitting and rising test; dietary record; one-repetition maximum (1-RM) strength test (knee extension exercise); and vastus lateralis' cross-sectional area, Pennation angle, and fascicle length. The BFR-RT group will undergo 12 weeks of knee extension exercise (1 × 30 repetitions and 3 × 15 repetitions at 20% 1-RM and 50% of total blood flow occlusion pressure), with two sessions per week. Data normality will be assessed using the Shapiro-Wilk test. In case of normal distribution, a one-way repeated measures analysis of variance will be implemented to test for differences in baseline values. A mixed model then will be applied for each dependent variable. In case of non-normal data distribution, a Kruskal-Wallis test will be implemented to test for differences in baseline values. Next, the Friedman test will be used to analyze repeated measures. Within- and between-group effect sizes will be calculated using Cohen's d for each outcome. Finally, the minimal clinically important difference will be analyzed with distribution-based methods. DISCUSSION: To our knowledge, this will be the first trial to investigate BFR-RT in patients with cirrhosis and evaluate the effects on neuromuscular parameters, functional performance, disease severity, and quality of life outcomes. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBec): RBR-395mfw. Registered on 25 August 2018.

Cost-effectiveness analysis is a mandatory strategy for health systems: evidence from a study involving therapies for hepatitis C.

Cost-effectiveness analysis is essential in health decision making. Several countries use it as synthesis of evidence to incorporate health technologies. The protease inhibitors (PI) boceprevir (BOC) and telaprevir (TVR) are indicated for chronic hepatitis C treatment and were incorporated in guidelines worldwide. Pre-marketing clinical trials showed higher sustained virological response rates in relation to previous therapies, but the incorporation of PIs generated a significant financial impact. The aim of this study was to discuss the relevance of cost-effectiveness analysis through a study that involved the inclusion of PIs in a clinical protocol. The analysis was part of a real-life study that included patients infected with hepatitis C virus genotype 1 treated in a tertiary university hospital in Brazil. Triple therapies (TT) with ribavirin (RBV), peginterferon α-2a (Peg-INF α-2a) and BOC or TVR were compared to dual therapy with RBV and Peg-INF α-2a. Sensitivity analysis of the cost-effectiveness ratio indicated an 88.2% chance of TTs presenting a higher cost per cure. The incremental cost-effectiveness ratios (ICER) exceeded the Brazilian gross domestic product (GDP) per capita by three times in all proposed scenarios. The sensitivity of ICER showed an 88.4% chance of TT not being cost-effective. The impact of PI incorporation was negative and the conduct about this could have been different if a previous cost-effectiveness analysis had been conducted.

Cost-effectiveness analysis is a mandatory strategy for health systems: evidence from a study involving therapies for hepatitis C / Análise de custo-efetividade é uma estratégia essencial para os sistemas de saúde: as evidências de um estudo sobre terapias para hepatite C / El análisis de coste-efectividad es una estrategia esencial para los sistemas de salud: evidencias de un estudio sobre terapias para hepatitis C

Abstract: Cost-effectiveness analysis is essential in health decision making. Several countries use it as synthesis of evidence to incorporate health technologies. The protease inhibitors (PI) boceprevir (BOC) and telaprevir (TVR) are indicated for chronic hepatitis C treatment and were incorporated in guidelines worldwide. Pre-marketing clinical trials showed higher sustained virological response rates in relation to previous therapies, but the incorporation of PIs generated a significant financial impact. The aim of this study was to discuss the relevance of cost-effectiveness analysis through a study that involved the inclusion of PIs in a clinical protocol. The analysis was part of a real-life study that included patients infected with hepatitis C virus genotype 1 treated in a tertiary university hospital in Brazil. Triple therapies (TT) with ribavirin (RBV), peginterferon α-2a (Peg-INF α-2a) and BOC or TVR were compared to dual therapy with RBV and Peg-INF α-2a. Sensitivity analysis of the cost-effectiveness ratio indicated an 88.2% chance of TTs presenting a higher cost per cure. The incremental cost-effectiveness ratios (ICER) exceeded the Brazilian gross domestic product (GDP) per capita by three times in all proposed scenarios. The sensitivity of ICER showed an 88.4% chance of TT not being cost-effective. The impact of PI incorporation was negative and the conduct about this could have been different if a previous cost-effectiveness analysis had been conducted.

Resumo: A análise de custo-efetividade tem sido essencial para a tomada de decisões em saúde. Diversos países utilizam esse tipo de análise como síntese das evidências para incorporar as tecnologias em saúde. Os inibidores de protease (IPs) boceprevir (BOC) e telaprevir (TVR) são indicados para o tratamento da hepatite C crônica e foram incorporados nas diretrizes internacionais. Os ensaios clínicos pré-marketing demonstraram taxas mais altas de resposta virológica sustentada em relação às terapias anteriores, mas a incorporação dos IPs gerou um impacto financeiro significativo. O estudo teve como objetivo discutir a relevância da análise de custo-efetividade, através de um estudo que envolveu a inclusão de IPs em um protocolo clínico. A análise fez parte de um estudo de vida real que incluiu pacientes com infecção pelo vírus da hepatite C, genótipo 1, tratados em um hospital universitário terciário no Brasil. As terapias triplas (TTs) com ribavirina (RBV), peg-interferon α-2a (Peg-INF α-2a) e BOC ou TVR foram comparadas às terapias duplas com RBV e Peg-INF α-2a. A análise de sensibilidade da custo-efetividade indicou odds de 88,2% de TTs apresentarem custo mais elevado por paciente curado. Em todos os cenários propostos, as razões de custo-efetividade incremental (ICERs) superaram em três vezes o produto interno bruto (PIB) per capita brasileiro. A sensibilidade da ICER mostrou probabilidade de 88,4% das TTs não serem custo-efetivas. O impacto da incorporação dos IPs foi negativo, e a conduta teria sido diferente se tivesse sido realizada uma análise prévia de custo-efetividade.

Resumen: El análisis de coste-efectividad ha sido esencial para la toma de decisiones en salud. Diversos países utilizan este tipo de análisis como síntesis de evidencias para incorporar tecnologías en salud. Los inhibidores de proteasa (IPs) boceprevir (BOC) y telaprevir (TVR) se indican para el tratamiento de la hepatitis C crónica y fueron incorporados en directrices internacionales. Los ensayos clínicos pre-marketing demostraron tasas más altas de respuesta virológica sostenida, respecto a las terapias anteriores, pero la incorporación de los IPs generó un impacto financiero significativo. El objetivo del estudio fue discutir la relevancia del análisis de coste-efectividad, a través de un estudio que implicó la inclusión de IPs en un protocolo clínico. El análisis formó parte de un estudio de vida real que incluyó a pacientes con infección por el virus de la hepatitis C, genotipo 1, tratados en un hospital universitario terciario en Brasil. Las terapias triples (TTs) con ribavirina (RBV), peg-interferon α-2a (Peg-INF α-2a) y BOC o TVR se compararon con las terapias dobles con RBV y Peg-INF α-2a. El análisis de sensibilidad del coste-efectividad indicó odds de 88,2% de que las TTs presentaran un coste más elevado por paciente curado. En todos los escenarios propuestos, las razones de coste-efectividad incremental (ICERs) superaron tres veces el producto interno bruto (PIB) per cápita brasileño. La sensibilidad de la ICER mostró una probabilidad de que un 88,4% de las TTs no eran costo-efectivas. El impacto de la incorporación de los IPs fue negativo, y el resultado habría sido diferente si se hubiese realizado un análisis previo de coste-efectividad.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients.

INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases.

BACKGROUND: In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES: This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS: A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS: PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS: A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.

Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

BACKGROUND In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.

Distribution of HBV subgenotypes in Ribeirão Preto, Southeastern Brazil: a region with history of intense Italian immigration

Abstract Hepatitis B virus (HBV) is distributed worldwide, with geographical variations regarding prevalence of the different genotypes. The aim of this study was to determine the HBV genotypes and subgenotypes circulating in Southeast Brazil and compare the genetic sequences found with HBV sequences previously described in the world. Sequences from 166 chronic HBV carriers were analyzed using the fragment constituted by 1306 base pairs comprising surface and polymerase regions of the HBV genome. The sequences obtained were submitted to phylogenetic analysis. HBV subgenotypes A1, A2, D1-D4, F2a, and F4 were found. HBV genotype D was the most frequent, found in 99 patients (58.4%). Within this group, subgenotype D3 was the most prevalent, in 73 patients (42.9%). HBV genotype A was identified in 58 (36%) patients, subgenotype A1, in 48 (29.8%) subjects. Genotype F was identified in 9 (5.4%). According to the phylogenetic analysis, the sequences found were grouped with sequences from Europe, Asia and Middle East (subgenotypes D1, D2, D3) and sequences from Latin America and Africa (subgenotype A1). HBV D3 grouped in different clusters inside D3 clade, several of them with sequences isolated in Italy. We also identified eight families whose relatives were infected with the same HBV subgenotype, most with high similarity between sequences. In conclusion, the distribution of the HBV sequences obtained interweaved with sequences from other continents, corresponding to regions from where many immigrants came to this region, in accordance to the hypothesis that the HBV detected over there were brought during the colonization times.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study.

OBJECTIVE:: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS:: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS:: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION:: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Distribution of HBV subgenotypes in Ribeirão Preto, Southeastern Brazil: a region with history of intense Italian immigration.

Hepatitis B virus (HBV) is distributed worldwide, with geographical variations regarding prevalence of the different genotypes. The aim of this study was to determine the HBV genotypes and subgenotypes circulating in Southeast Brazil and compare the genetic sequences found with HBV sequences previously described in the world. Sequences from 166 chronic HBV carriers were analyzed using the fragment constituted by 1306 base pairs comprising surface and polymerase regions of the HBV genome. The sequences obtained were submitted to phylogenetic analysis. HBV subgenotypes A1, A2, D1-D4, F2a, and F4 were found. HBV genotype D was the most frequent, found in 99 patients (58.4%). Within this group, subgenotype D3 was the most prevalent, in 73 patients (42.9%). HBV genotype A was identified in 58 (36%) patients, subgenotype A1, in 48 (29.8%) subjects. Genotype F was identified in 9 (5.4%). According to the phylogenetic analysis, the sequences found were grouped with sequences from Europe, Asia and Middle East (subgenotypes D1, D2, D3) and sequences from Latin America and Africa (subgenotype A1). HBV D3 grouped in different clusters inside D3 clade, several of them with sequences isolated in Italy. We also identified eight families whose relatives were infected with the same HBV subgenotype, most with high similarity between sequences. In conclusion, the distribution of the HBV sequences obtained interweaved with sequences from other continents, corresponding to regions from where many immigrants came to this region, in accordance to the hypothesis that the HBV detected over there were brought during the colonization times.

The HLA-G 14-base pair deletion allele and the deletion/deletion genotype are associated with persistent HBe antigenemia in chronic hepatis B infection.

BACKGROUND AND AIMS: HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection. METHODS: We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals. Chronic hepatitis HLA-G typing was performed using PCR-amplified DNA hybridized with specific primers. RESULTS: The frequencies of the insertion/deletion alleles and genotypes were very similar in patients and controls. After patient stratification according to the evolutionary form of the chronic HBV infection, the frequencies of the deletion allele (P=0.0460; OR=1.26; 95%CI=1.01-1.45) and of the deletion/deletion genotype (P=0.0356; OR=2.08; 95%CI=1.05-4.09) were overrepresented in HBeAg-positive patients when compared to HBeAg-negative patients. No differences were observed when HBV inactive carriers were compared to HBeAg-negative chronic hepatitis patients. CONCLUSIONS: Because the 14-bp deletion allele has been associated with increased HLA-G production and because HLA-G may down regulate the cytotoxic activity of TCD8 and NK cells, patients exhibiting the 14-bp deletion allele at single or double doses are at increased risk for developing chronic forms of HBV associated with persistent viremia and worse prognoses.

IL-18, TNF, and IFN-γ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury.

This study evaluated the association of polymorphisms in the IL-18 (-607C/A and -137C/G), IFNγ (+874 A/T), and TNF (-238 A/G and -308 A/G) genes with susceptibility to HBV infection and severity of liver injury. A total of 259 chronic HBV-infected patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy individuals were studied. Four Single Nucleotide Polymorphisms (SNPs) were amplified by Polymerase Chain Reaction (PCR). Liver biopsy was performed in 212 HBV-infected patients and classified according to severity of liver fibrosis (scores 0-4) and necroinflammatory activity (HAI scores 0-18). TNF-308*A allele (P < 0.001; OR = 2.16) and TNF -308 AA genotype (P = 0.026; OR = 5.43) were associated with susceptibility to HBV infection. An association was found between severe liver fibrosis when compared to mild fibrosis and the following polymorphisms: Alleles IL-18 -137*G (P = 0.004; OR = 3.45), TNF -308*A (P < 0.001; OR = 3.39), and IFNγ +874*T (P = 0.029; OR = 1.85) and IL-18 -137 GG genotype (P = 0.009; OR = 3.70). No significant association was found between IL-18 (-607 A/C) polymorphism and severity of liver fibrosis. Alleles IL-18 -137*G (P = 0.028; OR = 2.64) and TNF-308*A (P = 0.002; OR = 3.06) and IL-18 -137 GG genotype (P = 0.011; OR = 4.20) were associated with severe necroinflammatory activity (HAI>12) when compared to mild necroinflammatory activity (HAI 1-8). The results suggest that IL-18 -137C/G, TNF-308 G/A and IFNγ +874 A/T SNPs were associated to more severe liver injury in chronic HBV infection. TNF -308*A allele and TNF -308 AA genotype could play a role in the susceptibility to HBV infection.

Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in southeastern Brazil: predominance of HBeAg negative cases.

INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60% of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4% of the patients, among whom the risk of vertical/intrafamily transmission was 43.2% (p = 0.02). The consumption of alcohol in amounts exceeding 20 g a day was observed in 21.3% of the subjects and was more frequent among men (33%) (p < 0.001). Among patients with cirrhosis, 54.1% were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4%) than in the HBeAg-negative group (10.2%) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.

Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in southeastern Brazil: predominance of HBeAg negative cases / Características clínicas, demográficas e epidemiológicas dos pacientes com hepatite B em seguimento em hospital universitário no sudeste do Brasil: predominância de casos HBeAg negativos

INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60 percent of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4 percent of the patients, among whom the risk of vertical/intrafamily transmission was 43.2 percent (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3 percent of the subjects and was more frequent among men (33 percent) (p < 0.001). Among patients with cirrhosis, 54.1 percent were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4 percent) than in the HBeAg-negative group (10.2 percent) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.

INTRODUÇÃO: No Brasil, a hepatite B é comum. No entanto, há diferenças regionais no que diz respeito ao grau de endemicidade, as formas de transmissão mais encontradas e a presença dos diferentes estágios evolutivos da doença crônica. O objetivo deste trabalho foi o de conhecer características clínicas, demográficas e epidemiológicas de pacientes cronicamente infectados pelo vírus da hepatite B (HBV), residentes na região de Ribeirão Preto, no sudeste do Brasil. MÉTODOS: Foi realizada a análise retrospectiva de 529 prontuários de indivíduos com monoinfecção pelo HBV. RESULTADOS: Mais de 60 por cento eram masculinos, a média de idade foi de 38 anos. O padrão sorológico HBeAg negativo foi encontrado em 84,4 por cento dos pacientes, entre os quais o risco para transmissão vertical/intrafamiliar foi de 43,2 por cento (p = 0,02). Verificou-se uso de álcool em quantidades maiores que 20g ao dia em 21,3 por cento dos indivíduos, sendo mais frequente entre os homens (33 por cento) (p < 0,001). Entre os pacientes com cirrose, 54,1 por cento faziam uso abusivo de bebidas alcoólicas (p = 0,04), sendo todos estes do gênero masculino. A presença de cirrose foi maior no grupo HBeAg positivo (24,4 por cento) que no grupo HBeAg negativo (10,2 por cento) (p < 0,001). CONCLUSÕES: Observaram-se elevadas proporções de indivíduos com infecção pelo HBV com padrão sorológico HBeAg negativo, entre os quais houve maior risco para a transmissão vertical/intrafamiliar. O uso abusivo de álcool esteve associado a indivíduos do sexo masculino e, neste grupo, à cirrose hepática. Observou-se tendência ao aumento no número de casos HBeAg negativo ao longo do tempo.

Relato de experiência: o uso de simulações no processo de ensino-aprendizagem em medicina / Report on an experience with simulations in the teaching: learning process in medicine

Este trabalho relata a experiência, construída ao longo de dois anos, com o uso de estações de simulação da prática profissional no processo de ensino-aprendizagem do curso de graduação em Medicina da Universidade Federal de São Carlos. Seu referencial pedagógico está ancorado na concepção construtivista da aprendizagem e parte da premissa de que aprender não é reproduzir a realidade, mas ser capaz de elaborar uma representação pessoal sobre esta e seus conteúdos. Assim, a partir da vivência de situações simuladas, os estudantes são estimulados a ressignificar seus conhecimentos construindo novos saberes. Na Unidade Educacional Estações de Simulação da Prática Profissional, o estudante se defronta com pacientes simulados e tem a oportunidade de aprender fazendo, errando e aprendendo com os próprios erros. Ao refletir sobre o erro, constrói seu aprendizado por meio da identificação de lacunas de conhecimento e fundamenta cognitivamente suas capacidades. Professores acompanham o desenvolvimento dos estudantes, atuando ora como avaliadores, ora como facilitadores, ora como consultores. Esta estratégia pedagógica pode ser um instrumento poderoso para o desenvolvimento de competência na área clínica.

This article reports on a two-year experience with Professional Practice Simulations (PPS) as a teaching/learning process in the undergraduate medical course at the Federal University in Sao Carlos, Brazil. This medical school's pedagogical approach is based on the constructivist conception of learning and the premise that learning is not reproducing reality, but being capable of elaborating a personal representation of reality and its contents. From this perspective, after experiencing simulated situations, students are encouraged to re-signify their previous scope of information, building new significant knowledge. In this educational unit (PPS), students interact with simulated patients and have the opportunity to learn by doing and analyzing their mistakes. While students reflect on their errors, they can identify the gaps in their knowledge and cognitively substantiate their skills. Teachers interact with students as evaluators, facilitators, or consultants. This pedagogical strategy can be a powerful tool for developing clinical skills.

Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis.

Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76 kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.