Resultados preliminares de tres años de eventos adversos con implantes mamarios de poliuretano Silimed® / Three-year preliminary results of adverse events with Silimed® polyurethane breast implant

Antecedentes. Se solicita a los fabricantes que garanticen los estándares de calidad actuales, actualicen el plan de investigación del dispositivo y actualicen los informes de eficacia/seguridad. El objetivo de este estudio es estimar la seguridad y eficacia de los implantes mamarios de Silimed disponibles para la venta. Métodos. Este es un ensayo de fase IV, abierto, no aleatorizado, realizado en Río de Janeiro/Brasil. Los participantes se seleccionaron consecutivamente. Los principales criterios de elegibilidad son: recibir los implantes mamarios de Silimed para el aumento estético hasta 21 días antes de la visita de inclusión; no tener condiciones que aumenten el riesgo de eventos adversos a corto plazo. Las intervenciones son los implantes mamarios de poliuretano de Silimed. Los resultados de seguridad se consideran eventos adversos y el plan de análisis es estimar la incidencia de eventos adversos de Kaplan-Meier. Resultados. Se analizaron un total de 213 con seguimiento hasta 36 meses. La edad media era de 33,04 años. El riesgo de extracción del implante fue del 0,0% a los 36 meses. La estimación del riesgo de Kaplan-Meier para el seroma fue del 1,3%, no hubo casos de contractura capsular clínicamente relevante (Backer III/ IV), reintervención, infección y ruptura del implante. Conclusiones. Las tasas de eventos se consideraron prometedoras. Los informes futuros del estudio en curso mejorarán la interpretación de los datos actuales. Identificador de ClinicalTrials.gov: NCT03356132.

Background. Manufacturers are requested to ensure the current quality standards, update the device's investigation plan and update efficacy/safety reports. The aim of this study is to estimate the safety and efficacy of Silimed's breast implants available for sale. Methods: This is a phase IV, open label, non-randomized trial, performed at Rio de Janeiro/Brazil. Participants were selected consecutively. Main eligibility criteria are: received Silimed's breast implant(s) for aesthetic augmentation up to 21 days before the inclusion visit; not having conditions that increases adverse event short term risk. Interventions are Silimed's polyurethanebreast implants. Safety outcomes are considered adverse events and the analysis plan is to estimate Kaplan-Meier incidence of adverse events. Results. A total of 213 were analyzed with follow-up up to 36 months. The average age was 33.04 years. The risk for implant removal was 0.0% at 36 months. The Kaplan-Meier risk estimate for seroma was 1.3%, there were no cases of clinically relevant capsular contracture (Backer III/IV), reoperation, infection and implant rupture. Conclusions. Rates of events were considered promising. Future reports from the ongoing study will improve the interpretation of current data. Clinical Trials. gov Identifier: NCT03356132.

Exploring the parasite load and molecular diversity of Trypanosoma cruzi in patients with chronic Chagas disease from different regions of Brazil.

Chagas disease is still a major public health issue in many Latin American countries. One of the current major challenges is to find an association between Trypanosoma cruzi discrete typing units (DTUs) and clinical manifestations of the disease. In this study, we used a multilocus conventional PCR and quantitative real time PCR (qPCR) approaches to perform the molecular typing and parasite load quantification directly from blood specimens of 65 chronic Chagas disease patients. All patients were recruited at the same health center, but their place of birth were widely distributed in different geographic regions of Brazil. Of the 65 patients, 35 (53.8%) presented positive amplification by real time qPCR, being 20 (30.7%) with the clinical indeterminate form and 15 (23.1%) with the cardiac form of the disease. The parasite load median for all positive patients was 2.54 [1.43-11.14] parasite equivalents/mL (par. Eq./mL), with the load ranging from 0.12 to 153.66 par. Eq./mL. Noteworthy, the parasite load was significantly higher in patients over 70 years old (median 20.05 [18.29-86.86] par. Eq./mL). Using guanidine-EDTA blood samples spiked with reference T. cruzi strains, belonging to the six DTUs, it was possible to genotype the parasite up to 0.5 par. Eq./mL, with high specificity. Of the patients with positive qPCR, it was possible to identify the T. cruzi DTU in 28 patients (80%). For the remaining patients (20%), at least a partial result was obtained. Analysis of specimens showed prevalences of TcVI, TcII and mixed infection TcVI+TcII equal to 40%, 17.1% and 14.3%, respectively. In addition, two patients were infected by TcV, and one patient was coinfected by TcIII+TcVI, These last three patients were in stage A of chronic chagasic cardiomyopathy (CCC), and they were born at the Bahia State (northeast region of Brazil). When T. cruzi genotypes were compared with the parasite load, more elevated parasite loads were observed in patients infected by TcII in general (parasite load median of 7.56 par. Eq./mL) in comparison to patients infected by TcVI (median of 2.35 par. Eq./mL). However, while the frequency of CCC was 50% in patients infected by TcVI and TcV, only 16.7% of patients infected by TcII evolved to CCC. Taking together, our results contribute to update the epidemiological knowledge of T. cruzi DTUs in Brazil, and highlight the age of patient and infection by TcII as important features that lead to the observation of higher parasitemia levels.

Daily 800 mg versus 600 mg Efavirenz for HIV Patients Treating Tuberculosis with a Rifampicin-Based Regimen: An Open Label Randomized Controlled Trial.

OBJECTIVES: Pharmacokinetics studies recommend increasing efavirenz dosage in tuberculosis/HIV patients using rifampicin. We aimed to evaluate efficacy and safety of 600 versus 800 mg of efavirenz in tuberculosis/HIV patients using rifampicin. DESIGN: We conducted an open label, multicentre, randomized trial from 2006 to 2012. The primary outcome was the proportion of undetectable viral load (HIV-VL) within six months. Secondary outcomes were time to achieve primary endpoint, trajectories of HIV-VL, proportion of any adverse events (AE), proportion of severe and serious AE (SSAE), and time to treatment interruption due to SSAE. METHODS: Efavirenz-naïve patients were randomized 30 days after rifampicin-containing regimens initiation to receive 600 (comparison arm) or 800 mg (intervention arm) efavirenz-based regimens and followed-up for 180 days. RESULTS: Sixty-five and 67 participants were respectively included in the comparison and intervention arms with 64.6% (52.5%-65.1%) and 62.7% (50.7%-73.3%) attaining undetectable HIV-VL in six months. Median time to attain undetectable HIV-VL was 70 days in both arms, with HIV-VL overlapping trajectories during follow-up. Cough, acne, and dizziness were more frequent in the intervention arm. SSAE were observed in 19.1% (13.8%-25.8%) and 25.0% (18.9%-33.2%), respectively. Survival curves up to the first SSAE-attributed treatment interruption were similar. None of the differences were statistically significant. CONCLUSION: Efficacy of efavirenz was similar regardless of dosage. Differences regarding safety occurred as mild and transient events, which did not interfere with treatment. Similar efficacy and safety (SSAE) and lower tolerance (minor AE) in the intervention group favour the use of 600 mg efavirenz in patients using rifampicin.

Tuberculosis Treatment Outcomes and Factors Associated with Each of Them in a Cohort Followed Up between 2010 and 2014.

Tuberculosis treatment has undergone recent changes in Brazil. Objective. To assess whether favorable outcomes on tuberculosis therapy improved in recent years. Methods. Retrospective observational study, based on primary data of tuberculosis patients, followed at INI-FIOCRUZ, from January 2012 to December 2014. Results. The outcomes observed were as follows: cure (80%), default (14%), treatment failure (5%), and death (1%). HIV infection without antiretroviral therapy [OR 0.34 (0.15-0.79)], tuberculosis diagnosis based on sputum smear [OR 0.22 (0.07-0.74)], drug use [OR 0.22 (0.11-0.46)], and/or treatment interruption due to adverse reactions [OR 0.23 (0.08-0.67)] decreased the chance of cure. Predictors of default, that is, use of noninjecting drugs [OR 3.00 (95% CL 1.31-6.88)], treatment interruption due to adverse reactions [OR 6.30 (1.81-21.95)], low schooling [OR 2.59 (2.15-5.82)], higher age [OR 0.44 (0.23-0.82)], and female gender [OR 0.28 (0.11-0.71)], reduced the chance of treatment default. Tuberculosis diagnosis based on sputum smear [OR 7.77 (1.94-31.09)] and/or arterial hypertension [OR 4.07 (1.25-13.18)] was associated with treatment failure. Conclusion. Mortality and default were low considering the prevalence of HIV infection; however cure was not significantly increased.

Performance of Polymerase Chain Reaction Analysis of the Amniotic Fluid of Pregnant Women for Diagnosis of Congenital Toxoplasmosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Congenital infection caused by Toxoplasma gondii can cause serious damage that can be diagnosed in utero or at birth, although most infants are asymptomatic at birth. Prenatal diagnosis of congenital toxoplasmosis considerably improves the prognosis and outcome for infected infants. For this reason, an assay for the quick, sensitive, and safe diagnosis of fetal toxoplasmosis is desirable. GOAL: To systematically review the performance of polymerase chain reaction (PCR) analysis of the amniotic fluid of pregnant women with recent serological toxoplasmosis diagnoses for the diagnosis of fetal toxoplasmosis. METHOD: A systematic literature review was conducted via a search of electronic databases; the literature included primary studies of the diagnostic accuracy of PCR analysis of amniotic fluid from pregnant women who seroconverted during pregnancy. The PCR test was compared to a gold standard for diagnosis. RESULTS: A total of 1.269 summaries were obtained from the electronic database and reviewed, and 20 studies, comprising 4.171 samples, met the established inclusion criteria and were included in the review. The following results were obtained: studies about PCR assays for fetal toxoplasmosis are generally susceptible to bias; reports of the tests' use lack critical information; the protocols varied among studies; the heterogeneity among studies was concentrated in the tests' sensitivity; there was evidence that the sensitivity of the tests increases with time, as represented by the trimester; and there was more heterogeneity among studies in which there was more time between maternal diagnosis and fetal testing. The sensitivity of the method, if performed up to five weeks after maternal diagnosis, was 87% and specificity was 99%. CONCLUSION: The global sensitivity heterogeneity of the PCR test in this review was 66.5% (I(2)). The tests show low evidence of heterogeneity with a sensitivity of 87% and specificity of 99% when performed up to five weeks after maternal diagnosis. The test has a known performance and could be recommended for use up to five weeks after maternal diagnosis, when there is suspicion of fetal toxoplasmosis.