Sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks in noncirrhotic subjects chronically infected with hepatitis C virus genotype 1: a randomized clinical trial.

OBJECTIVE: To investigate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or simeprevir (SMV) in a randomized, open-label, noninferiority trial of patients infected with hepatitis C virus genotype 1, who were previously unresponsive to pegylated interferon and ribavirin or were treatment naive. METHODS: Patients were randomly assigned to receive SOF (400 mg once daily) plus DCV (60 mg once daily) or SMV (150 mg once daily) for 12 weeks. The analysis included all participants who received at least one dose of the study drugs. The primary endpoint was sustained virologic response 12 weeks after ending treatment (SVR12; hepatitis C virus RNA measured using COBAS TaqMan RT-PCR (lower limit of detection and quantification of 12 UI/mL)). This study was registered at ClinicalTrials.gov (NCT02624063). RESULTS: A total of 125 of 127 enrolled and randomized patients started treatment (n = 65 SOF + DCV; n = 60 SOF + SMV). SVR12 was attained in 121 patients (96.8%): 65 (100%) receiving SOF + DCV (95% confidence interval (CI), 94.5 to 100) and 56 (93.3%) receiving SOF + SMV (95% CI, 83.8 to 98.2; absolute difference, 6.6%; 95% CI, -15.0 to 0). The most common adverse events were fatigue (n = 32, 25.6%), headache (n = 27, 21.6%), and mood swings (n = 24, 19.2%). No patients discontinued therapy. CONCLUSIONS: The overall SVR rate was 96.9%; SOF + DCV (100%) was higher than that of SOF + SMV (93.3%). Despite no statistically significant intergroup difference in SVR12 rates, the noninferiority of SOF + SMV to SOF + DCV could not be established because the difference in efficacy was clinically relevant.

A cost-effective melting temperature assay for the detection of single-nucleotide polymorphism in the MBL2 gene of HIV-1-infected children.

We report a fast (less than 3 h) and cost-effective melting temperature assay method for the detection of single-nucleotide polymorphisms in the MBL2 gene. The protocol, which is based on the Corbett Rotor Gene real time PCR platform and SYBR Green I chemistry, yielded, in the cohorts studied, sensitive (100%) and specific (100%) PCR amplification without the use of costly fluorophore-labeled probes or post-PCR manipulation. At the end of the PCR, the dissociation protocol included a slow heating from 60 degrees to 95 degrees C in 0.2 degrees C steps, with an 8-s interval between steps. Melting curve profiles were obtained using the dissociation software of the Rotor Gene-3000 apparatus. Samples were analyzed in duplicate and in different PCR runs to test the reproducibility of this technique. No supplementary data handling is required to determine the MBL2 genotype. MBL2 genotyping performed on a cohort of 164 HIV-1-positive Brazilian children and 150 healthy controls, matched for age and sex and ethnic origin, yielded reproducible results confirmed by direct sequencing of the amplicon performed in blind. The three MBL2 variants (Arg52Cys, Gly54Asp, Gly57Glu) were grouped together and called allele 0, while the combination of three wild-type alleles was called allele A. The frequency of the A/A homozygotes was significantly higher among healthy controls (0.68) than in HIV-infected children (0.55; P = 0.0234) and the frequency of MBL2 0/0 homozygotes was higher among HIV-1-infected children than healthy controls (P = 0.0296). The 0 allele was significantly more frequent among the 164 HIV-1-infected children (0.29) than among the 150 healthy controls (0.18; P = 0.0032). Our data confirm the association between the presence of the mutated MBL2 allele (allele 0) and HIV-1 infection in perinatally exposed children. Our results are in agreement with the literature data which indicate that the presence of the allele 0 confers a relative risk of 1.37 for HIV-1 infection through vertical transmission.

A cost-effective melting temperature assay for the detection of single-nucleotide polymorphism in the MBL2 gene of HIV-1-infected children

We report a fast (less than 3 h) and cost-effective melting temperature assay method for the detection of single-nucleotide polymorphisms in the MBL2 gene. The protocol, which is based on the Corbett Rotor Gene real time PCR platform and SYBR Green I chemistry, yielded, in the cohorts studied, sensitive (100 percent) and specific (100 percent) PCR amplification without the use of costly fluorophore-labeled probes or post-PCR manipulation. At the end of the PCR, the dissociation protocol included a slow heating from 60° to 95°C in 0.2°C steps, with an 8-s interval between steps. Melting curve profiles were obtained using the dissociation software of the Rotor Gene-3000 apparatus. Samples were analyzed in duplicate and in different PCR runs to test the reproducibility of this technique. No supplementary data handling is required to determine the MBL2 genotype. MBL2 genotyping performed on a cohort of 164 HIV-1-positive Brazilian children and 150 healthy controls, matched for age and sex and ethnic origin, yielded reproducible results confirmed by direct sequencing of the amplicon performed in blind. The three MBL2 variants (Arg52Cys, Gly54Asp, Gly57Glu) were grouped together and called allele 0, while the combination of three wild-type alleles was called allele A. The frequency of the A/A homozygotes was significantly higher among healthy controls (0.68) than in HIV-infected children (0.55; P = 0.0234) and the frequency of MBL2 0/0 homozygotes was higher among HIV-1-infected children than healthy controls (P = 0.0296). The 0 allele was significantly more frequent among the 164 HIV-1-infected children (0.29) than among the 150 healthy controls (0.18; P = 0.0032). Our data confirm the association between the presence of the mutated MBL2 allele (allele 0) and HIV-1 infection in perinatally exposed children. Our results are in agreement with the literature data which indicate that the presence of the allele 0 confers a relative risk of 1.37 for HIV-1 infection through vertical transmission.

[Study of preoperative risk factors for bacteriobilia in patients with acute calculosis cholecystitis]. / Estudos dos fatores de risco pré-operatórios para bacteriobilia em doentes portadores de colecistite aguda calculosa.

OBJECTIVE: to determine an association between the preoperative clinical status and the result of bile and gallbladder wall cultures. MATERIAL AND METHODS: 28 variables regarding history, physical examination and labatorial assessment in 38 patients with acute calculosis cholecystitis submitted to urgency surgery were prospectively studied during a 19-month period, between November 1995 and May 1997. Cultures for aerobic and anaerobic agents from both the gallbladder wall and the bile were performed, in three different culture media (BACTEC 9240, BHI and HEMOBAC). RESULTS: bacteria were isolated in at least one culture medium, in 68.2% of the patients. At univariate analysis, five preoperative factors were identified as predictors of bactibilia: over 55 years of age, a greater than 0.4 degrees C difference in the axillary-rectal temperature, a greater than 12.000 cels/m3 blood leukocyte count, a greater than 75% neutrophil percentage and a greater than 4% rod neutrophil percentage. Owing to the small sample size, statistical significance of the series could not be noted by logistic regression, although a trend to preoperative determination could be observed in 98% of the subjects with positive culture, by means of the model based on age and percentage of rod neutrophil. By analyzing predictive factors jointly, it was noted that patients with more than one predictive factor have a significantly greater possibility to yielding positive culture when compared to those with up to one predictive factor for bactibilia. CONCLUSIONS: We concluded that, in patients with acute calculosis cholecystitis, bactibilia may be predicted yet at the preoperative period, by using simple and easily obtained data.

Estudos dos fatores de risco pré-operatórios para bacteriobilia em doentes portadores de colecistite aguda calculosa / Study of preoperative risk factors for bactibilia in patients with calculosis acute cholecystitis

OBJETIVO: Determinar uma associaçäo entre o quadro clínico pré-operatório e os resultados das culturas de bile e da parece vesicular. CASUISTICA E METODOS: Foram estudadas 28 variáveis considerando-se história clínica, exame físico e investigaçäo laboratorial em 38 doentes portadores de colecistite aguda calculosa, submetidos à cirurgia de urgência. Este estudo prospectivo foi realizado em 19 meses, entre novembro de 1995 a maio de 1997. Foram realizadas culturas para agentes anaeróbios e aeróbios, em três diferentes meios de cultura (BACTEC 9240, BHI e HEMOBAC). RESULTADOS: Foram isoladas bactérias em pelo menos um meio de cultura em 68,2 por cento dos doentes. Pela anßlise univariada, foram identificadas cinco variáveis pré-operatórias como preditivas de bacteriobilia: idade acima de 55 anos, temperatura diferencial axilo-retal maior do que 0,4 C, leucocitose acima de 12000 cels/mmÝ, neutrofilia acima de 75 por cento e neutrófilos bastonetes acima de 4 por cento. Devido ao pequeno tamanho da amostra, näo pôde ser observada significância estatística por regressäo logística, embora pudesse ser observada em 98 por cento uma tendência para determinaçäo pré-operatória dos indivíduos com cultura positiva por meio do modelo baseado na idade e porcentagem de neutrófilos bastonetes. Pela análise em conjunto dos fatores preditivos, pôde-se observar que doentes com mais de um fator preditivo têm uma possibilidade significantemente maior para cultura positiva, quando comparado com aqueles com fator preditivo de bacteriobilia. CONCLUSAO: Conclui-se, portanto, que pela utilizaçäo de dados facilmente disponíveis em doentes com colecistite aguda calculosa, a bacteriobilia pode ser previsível no pré-operatório,

Reference values for lung function tests. I. Static volumes.

Static lung volume (LV) measurements have a number of clinical and research applications; however, no previous studies have provided reference values for such tests using a healthy sample of the adult Brazilian population. With this as our main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), RV/TLC ratio and inspiratory capacity (IC) as dependent variables, and with age, height, weight, lean body mass and indexes of physical fitness as independent ones. Simpler demographic and anthropometric variables were as useful as more complex measurements in predicting LV values, independent of gender and age (R2 values ranging from 0.49 to 0.78, P < 0.001). Interestingly, prediction equations from North American and European studies overestimated the LV at low volumes and underestimated them at high volumes (P < 0.05). Our results, therefore, provide a more appropriate frame of reference to evaluate the normalcy of static lung volume values in Brazilian males and females aged 20 to 80 years.

Reference values for lung function tests: I. Static volumes

Static lung volume (LV) measurements have a number of clinical and research applications; however, no previous studies have provided reference values for such tests using a healthy sample of the adult Brazilian population. With this as our main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), RV/TLC ratio and inspiratory capacity (IC) as dependent variables, and with age, height, weight, lean body mass and indexes of physical fitness as independent ones. Simpler demographic and anthropometric variables were as useful as more complex measurements in predicting LV values, independent of gender and age (R2 values ranging from 0.49 to 0.78, P<0.001). Interestingly, prediction equations from North American and European studies overestimated the LV at low volumes and underestimated them at high volumes (P<0.05). Our results, therefore, provide a more appropriate frame of reference to evaluate the normalcy of static lung volume values in Brazilian males and females aged 20 to 80 years.

Risk of Helicobacter pylori transmission by upper gastrointestinal endoscopy.

BACKGROUND: Upper gastrointestinal endoscopy has been reported as a risk factor for the transmission of Helicobacter pylori. The aim of this study was to evaluate the possibility of transmission of H. pylori infection by upper gastrointestinal endoscopy in patients who had previously had such procedures in a low disinfection level environment. METHODS: The study included 1082 patients. Patients that had undergone upper gastrointestinal endoscopy or were treated with antibiotics 15 days before the index endoscopy were excluded. H. pylori infection was diagnosed by ultra-rapid urease test. Variables analyzed were age, gender, type of dyspepsia (organic or functional), and the number of previous upper gastrointestinal endoscopies. RESULTS: Overall prevalence of H. pylori infection was 60%. Patients ranged in age from 13 to 94 years (mean = 45.8, SD = 15.7) and the number of previous upper gastrointestinal endoscopies ranged from 0 to 20 (mean = 1.5, SD = 2.4). In 53.3% of the patients, upper gastrointestinal endoscopy revealed some mucosal lesion (organic dyspepsia). Prevalence of H. pylori infection was higher in patients with organic rather than functional dyspepsia (71.1% vs. 47.1%, p < 0.001). There was no statistically significant difference in the mean number of upper gastrointestinal endoscopies in patients with and without H. pylori infection. CONCLUSIONS: We concluded that there was no association between history of upper gastrointestinal endoscopy and current H. pylori infection in this study population.

Seroprevalence of Trypanosoma cruzi infection in students at the seven-fourteen age range, Londrina, PR, Brazil, in 1995.

Seropositivity for Chagas disease was evaluated in 834 children aged between 7 and 14 from the Municipal Teaching System in the district of Londrina, State of Paraná. A seroprevalence rate of 0.1% was found through the use of an indirect immunofluorescent test and an enzyme-linked immunosorbent assay. This low rate of seroprevalence provides evidence that the vectorial transmission of Chagas disease has been eliminated in Londrina. The main reason for the elimination of vectorial transmission of Trypanosoma cruzi infection, as evaluated by serological tests, may be a remarkable change in the economic structure of the northern region of Paraná in the 1960's. At that time coffee production was almost completely replaced by soy beans, wheat and grazing in the rural areas. This change deeply affected the rural ecology and caused an exodus of the population from rural to urban areas as well as a decrease in the total number of the population of that region. The measures introduced for controlling the disease through the Program of Chagas Disease Control established by the Fundação Nacional de Saúde of the Brazilian Ministry of Health, certainly, had a positive impact on the reduction of American trypanosomiasis prevalence in the area under study. However, it does not seem that this was the most relevant factor responsible for the elimination of vectorial transmission of Chagas disease in Londrina.

[Trypanosoma cruzi infection in blood donor candidates]. / Infecção por Trypanosoma cruzi em candidatos a doador de sangue.

INTRODUCTION: Transmission of American trypanossomiasis by transfusion has been reduced by expansion of control measures of blood quality in Brazil. A research project was, therefore, undertaken to evaluate soropositivity for Trypanosoma cruzi infection on blood donors and to compare this rate with those found in 1958 and 1975 in blood banks. METHOD: A transversal study was carried out on blood donors in Londrina, Paraná, Brazil. ELISA and Immunofluorescence were the serological test techniques used in the diagnosis of Trypanosoma cruzi infection. RESULTS AND CONCLUSION: A serumprevalence rate of 1.3% was found with a tendency for positive serum findings for Trypanosoma cruzi infection on blood donors to decrease over Aime (1958, 1975, and 1995).

Plasma levels of tumor necrosis factor-alpha in patients with visceral leishmaniasis (Kala-azar). Association with activity of the disease and clinical remission following antimonial therapy.

Evaluation of TNF-alpha in patients with Kala-azar has drawn increasing interest due to its regulatory role on the immune system, in addition to its cachetizing activity. The objective of this study was to examine the association between plasma levels of TNF-alpha, measured by immunoreactivity (ELISA) and bioactivity (cytotoxicity assay with L-929 cells), and clinical manifestations of visceral leishmaniasis. Plasma samples from 19 patients with Kala-azar were obtained before, during and at the end of antimonial therapy. TNF-alpha determinations was done by using the cytotoxicity assay (all patients) and the enzyme-linked immunoassay (ELISA-14 patients). A discrepancy between results obtained by ELISA and cytotoxicity assay was observed. Levels of circulating TNF-alpha, assessed by ELISA, were higher in patients than in healthy controls, and declined significantly with improvement in clinical and laboratory parameters. Plasma levels before treatment were 124.7 +/- 93.3 pg/ml (mean +/- SD) and were higher than at the end of therapy 13.9 +/- 25.1 pg/ml (mean +/- SD) (p = 0.001). In contrast, plasma levels of TNF-alpha evaluated by cytotoxicity assay did not follow a predicted course during follow-up. Lysis, in this case, might be not totally attributed to TNF-alpha. The discrepancy might be attributed to the presence of factor(s) known to influence the release and activity of TNF-alpha.

[The optimization of the use of economic resources for vaccination against hepatitis B in professionals in the health area]. / Otimização do emprego de recursos econômicos para vacinação contra hepatite B em profissionais da área de saúde.

In order to optimize the employment of financial resources to be allocated for hepatitis B vaccination programs involving health care workers, two different aspects were studied: the need of a pre-vaccination screening and the efficacy of low-doses schedules of HBV vaccine by the intradermal (ID) route. The economical analysis (a cost-minimization study) showed that when the prevalence of immune individuals is higher than 11% it is more cost-effective to perform pre-vaccination screening. This situation was observed in the employees group. For students and doctors vaccination without screening was the best approach. Regarding the schedules, 3 doses of HBV vaccine by the intramuscular (IM) route (group A) were compared to first dose by the ID route and second and third doses by the IM route (group B) and to first and second doses by the ID route and the last dose by the IM route (group C). After the third dose, soroconversion rates in groups A and B (92% and 93%, respectively) and geometric mean titers of antiHBs (1278 UI/L and 789.6 UI/L) were similar, and both were different from group A (p < 0.05), showing that alternative vaccination schedules may be cost-effective.

Mycobacterium avium complex (MAC) isolated from AIDS patients and the criteria required for its implication in disease.

Before the AIDS pandemia, the Mycobacterium avium complex (MAC) was responsible in most cases for the pneumopathies that attack patients with basic chronic pulmonary diseases such as emphysema and chronic bronchitis. In 1981, with the advent of the acquired immunodeficiency syndrome (AIDS), MAC started to represent one of the most frequent bacterial diseases among AIDS patients, with the disseminated form of the disease being the major clinical manifestation of the infection. Between January 1989 and February 1991, the Section of Mycobacteria of the Adolfo Lutz Institute, São Paulo, isolated MAC from 103 patients by culturing different sterile and no-sterile processed specimens collected from 2304 patients seen at the AIDS Reference and Training Center and/or Emilio Ribas Infectology Institute. Disseminated disease was diagnosed in 29 of those patients on the basis of MAC isolation from blood and/or bone marrow aspirate. The other 74 patients were divided into categories highly (5), moderately (26) and little suggestive of disease (43) according to the criteria of DAVIDSON (1989). The various criteria for MAC isolation from sterile and non-sterile specimens are discussed.

Mycobacterium avium complex (MAC): an unusual potential pathogen in cerebrospinal fluid of AIDS patients.

Mycobacterium avium complex (MAC) is frequently isolated from patients with late complications of Acquired Immunodeficiency Syndrome (AIDS), especially in North America and Europe. However, its isolation from the central nervous system (CNS) has been seldom reported in these countries. MAC infections in AIDS patients in African and Latin American countries are believed to be uncommon. We report the isolation of MAC from cerebrospinal fluid (CSF) of 11 AIDS patients out of 1723 (0.63%) seen at "Centro de Referência e Treinamento-AIDS", São Paulo and discuss the significance of its isolation.

Nosocomial and community acquired bacteremia: variables associated with outcomes.

Bacteremia is related to high morbidity and lethality. The present investigation was conducted to evaluate the variables associated with outcomes of bacteremia at a University Hospital in São Paulo, Brazil. Patients with bacteremia were identified through positive blood cultures performed at the microbiology laboratory between August 1985 and July 1986. Their charts were reviewed and the following variables were considered: age, sex, presence of underlying disease, where was the bacteremia acquired, source of infection, presence of shock and appropriateness of antimicrobial therapy. In the period of the study, there were 362 cases of bacteremia out of 16,636 admissions to the hospital. The lethality rate was 33.4%, six times higher than the mortality rate for non-bacteremic patients. Age greater than 40 years, presence of severe underlying disease, nosocomial acquisition, respiratory tract as the source of bacteremia, presence of shock and, being infected with Pseudomonas sp were significantly associated with fatal outcome. Appropriate antimicrobial therapy reduced the incidence of shock and improved survival of patients with bacteremia. This study provides information on outcome of patients with bacteremia at a University Hospital in Brazil and, settles the variables associated with poor outcome in these patients.

Rhinovirus antibodies in an isolated Amazon Indian tribe.

In early 1985, the Parakana-Apiterewa, a small, primitive Indian tribe, was contacted in the southern Amazon Basin. The tribe was thought to have been totally isolated from civilization until recent development of their land. Blood specimens were collected in 1985, shortly after the discovery of the tribe, and analyzed for the presence of rhinovirus-neutralizing antibody to nine different immunotypes. Six to forty-seven percent of the serum samples tested contained antibody to at least one immunotype of rhinovirus. The prevalence of rhinovirus antibody in the Parakana-Apiterewa Indians was similar to that reported in United States populations, suggesting that there had been considerable direct or indirect contact in the past between tribe members and persons in the outside world.

Risk factors for nosocomial urinary tract and postoperative wound infections in renal transplant patients: a matched-pair case-control study.

A matched-pair case-control study was done on 4 groups of renal transplant patients who acquired nosocomial infections: 1) urinary tract infection, 2) postoperative wound infection, 3) urinary tract plus postoperative wound infection and 4) the entire group of patients. For urinary tract infection patients a prolonged period of hemodialysis before hospitalization was considered a risk factor. Renal transplantation with an HLA-1 (identical) donor graft was a characteristic related to the control group. High levels of plasma creatinine and prolonged vesical catheterization were risk factors for acquiring postoperative wound infection. The latter was also considered to be a risk factor for both infections, as well as the inadequate use of antibiotic prophylaxis and the number of antibiotics used. For the entire group of patients surgical wall hematoma was a risk factor. In this group the independent risk factors analyzed by multivariate logistic regression were renal transplantation with a cadaver donor graft, prolonged vesical catheterization and prolonged use of antibiotics. Careful management of the cadaver donor allograft, decreasing the changes of contamination, decreasing the interval of urinary catheter maintenance and use of antibiotics in the postoperative period are measures that can contribute to lessen the incidence of these nosocomial infections in renal transplant recipients.

[Epidemiology of bacteremias at a university hospital]. / Epidemiologia das bacteremias em hospital universitário.

The epidemiological aspects of bacteremias were determined in a university hospital, according to service, age, sex and place of acquisition (nosocomial or community-acquired). From August 1985 through July 1986 the incidence rate of bacteremias at the Sao Paulo Hospital was 21.7/1000 admissions. Such a high rate is probably related to the characteristics of the patients admitted to the hospital. The incidence was higher in the extremes of age and was similar in either sex. Approximately 60% of the bacteremias were nosocomial including 9.1% that were present at admission in patients transferred from other hospitals. The most frequent isolated pathogen was S. aureus. The most important source of bacteremia was the respiratory tract followed by the gastrointestinal and urinary tracts.