Coelho T.,Hospital Of Santo Antonio |
Maia L.F.,Hertie Institute for Clinical Brain Research |
Da Silva A.M.,Hospital Of Santo Antonio |
Cruz M.W.,Hospital Universitario Clementino Fraga Filho |
And 13 more authors.
Neurology | Year: 2012
Objectives: To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods: In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo. Coprimary endpoints were the Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) popuation (n = 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n = 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population. Results: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p = 0.068) and change in TQOL (2.0 vs 7.2; p = 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p = 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p = 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p < 0.0001). Adverse events were similar between groups. Conclusions: Although the coprimary endpoints were not met in the ITT population, tafamidis was associated with no trend toward more NIS-LL responders and a significant reduction in worsening of most neurologic variables, supporting the hypothesis that preventing TTR dissociation can delay peripheral neurologic impairment. Classification of evidence: This study provides Class II evidence that 20 mg tafamidis QD was associated with no difference in clinical progression in patients with TTR-FAP, as measured by the NIS-LL and the Norfolk QOL-DN score. Secondary outcomes demonstrated a significant delay in peripheral neurologic impairment with tafamidis, which was well tolerated over 18 months. Copyright © 2012 by AAN Enterprises, Inc.
Nucci M.,Hospital Universitario Clementino Fraga Filho |
Anaissie E.,University of Arkansas for Medical Sciences |
Betts R.F.,University of Rochester |
Dupont B.F.,University of Paris Descartes |
And 5 more authors.
Clinical Infectious Diseases | Year: 2010
Background. Patients with candidemia frequently have a central venous catheter (CVC) in place, and its early removal is considered the standard of care. Methods. We performed a subgroup analysis of 2 phase III, multicenter, double-blind, randomized, controlled trials of candidemia to examine the effects of early CVC removal (within 24 or 48 h after treatment initiation) on the outcomes of 842 patients with candidemia. Inclusion criteria were candidemia, age >16 years, CVC at diagnosis, and receipt of ≥1 dose of the study drug. Six outcomes were evaluated: treatment success, rates of persistent and recurrent candidemia, time to mycological eradication, and survival at 28 and 42 days. Univariate and multivariate analyses were performed, controlling for potential confounders. Results. In univariate analysis, early CVC removal did not improve time to mycological eradication or rates of persistent or recurrent candidemia but was associated with better treatment success and survival. These benefits were lost in multivariate analysis, which failed to show any beneficial effect of early CVC removal on all 6 outcomes and identified Acute Physiology and Chronic Health Evaluation II score, older age, and persistent neutropenia as the most significant variables. Our findings were consistent across all outcomes and time points (removal within 24 or 48 h and survival at 28 and 42 days). The median time to eradication of candidemia was similar between the 2 study groups. Conclusions. In this cohort of 842 adults with candidemia followed up prospectively, early CVC removal was not associated with any clinical benefit. These findings suggest an evidence-based re-evaluation of current treatment recommendations. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Guerra R.L.,Federal University of Rio de Janeiro |
Dorman S.E.,Center for Tuberculosis Research |
Luiz R.R.,Hospital Universitario Clementino Fraga Filho |
Conde M.B.,Federal University of Rio de Janeiro
International Journal of Tuberculosis and Lung Disease | Year: 2013
SETTING: Primary health care unit in Rio de Janeiro City, Brazil. OBJECTIVE: To estimate and compare the cost-effectiveness of strategies used for passive case finding of pulmonary tuberculosis (PTB) cases using tests available at the primary care level. DESIGN: Data on PTB suspects were reviewed, and a decision model was developed using sputum smear microscopy and chest radiography (CXR) according to three different strategies for PTB detection. A cost-effectiveness analysis was performed to estimate the cost per correct PTB diagnosis. Mycobacterial culture was used to calculate the effectiveness of the strategies. Unit costs of health resource utilisation were obtained from the payer's perspective (the Brazilian Public Health System). RESULTS: For the evaluation of 254 PTB suspects, the total costs of strategies ranged from US$5369 to US$5944; the probability of a correct PTB diagnosis ranged from 0.66 to 0.86; the number of visits required to complete the diagnostic process ranged from two to three, and cost per PTB case identified ranged from US$47.93 to US$53.07. The cost-effectiveness of the three strategies studied varied between US$56.69 and US$72.55 per correct PTB case detected. CONCLUSION: A strategy in which sputum smears and CXR were requested for all PTB suspects at the initial evaluation was cost-effective, had a high probability of correct PTB diagnosis and could be accomplished in two visits. © 2013 The Union.
Garnica M.,Federal University of Rio de Janeiro |
Nucci M.,Federal University of Rio de Janeiro |
Nucci M.,Hospital Universitario Clementino Fraga Filho
Current Fungal Infection Reports | Year: 2013
Fusarium spp. are molds widely distributed in nature as soil saprophytes. Human infections by Fusarium spp. occur both in immunocompetent and immunocompromised hosts. The most common forms in immunocompetent individuals are onychomycosis and keratitis. By contrast, disseminated fusariosis affects the immunocompromised host, especially hematopoietic cell transplant recipients and patients with acute leukemia. Severe neutropenia and T-cell immunodeficiency are the most important predisposing factors. Infection in compromised hosts is frequently fatal, and successful outcome is largely determined by the degree and persistence of immunosuppression and the extent of infection. The frequency of invasive fusariosis is increasing in some regions, especially in South America. © 2013 Springer Science+Business Media New York.
Fernandes N.C.,Federal University of Rio de Janeiro |
De Andrade L.R.,Hospital Universitario Clementino Fraga Filho
Anais Brasileiros de Dermatologia | Year: 2010
Reticulate acropigmentation of Dohi is a rare dyschromic disorder of autosomal dominant inheritance. Most cases have been originally described in Japan. The case of a girl with lesions of typical distribution and morphology is reported. Skin biopsy was not considered essential for diagnosis. After literature review, it was concluded that this is the third case of the disorder reported in Brazil. ©2010 by Anais Brasileiros de Dermatologia.
Stelling M.P.,Federal University of Rio de Janeiro |
Lages Y.M.V.,Federal University of Rio de Janeiro |
Tovar A.M.F.,Federal University of Rio de Janeiro |
Mourao P.A.S.,Federal University of Rio de Janeiro |
And 2 more authors.
Glycobiology | Year: 2013
Human embryonic stem (hES) cell production of heparan sulfate influences cell fate and pluripotency. Human ES cells remain pluripotent in vitro through the action of growth factors signaling, and the activity of these factors depends on interaction with specific receptors and also with heparan sulfate. Here, we tested the hypothesis that matrix-associated heparan sulfate is enough to maintain hES cells under low fibroblast growth factor-2 concentration in the absence of live feeder cells. To pursue this goal, we compared hES cells cultured either on coated plates containing live murine embryonic fibroblasts (MEFs) or on a matrix derived from ethanol-fixed MEFs. hES cells were analyzed for the expression of pluripotency markers and the ability to form embryoid bodies. hES cells cultured either on live mouse fibroblasts or onto a matrix derived from fixed fibroblasts expressed similar levels of Oct-4, SOX-2, Nanog, TRA-1-60 and SSEA-4, and they were also able to form cavitated embryoid bodies. Heparan sulfate-depleted matrix lost the ability to support the adherence and growth of hES cells, confirming that this glycosaminoglycan, bound to the extracellular matrix, is enough for the growth and attachment of hES cells. Finally, we observed that the ethanol-fixed matrix decreases by 30% the levels of Neu5Gc in hES cells, indicating that this procedure reduces xeno-contamination. Our data suggest that matrix-bound heparan sulfate is required for the growth and pluripotency of hES cells and that ethanol-fixed MEFs may be used as a "live cell"-free substrate for stem cells. © The Author 2012.
Roimicher L.,Hospital Universitario Clementino Fraga Filho
Rheumatology (Oxford, England) | Year: 2011
To compare the use of radiolabelled human monoclonal anti-TNF-α scintigraphy with clinical examination and MRI of hands and wrists joints in patients with active RA. Eight patients with active RA, 28-joint DAS (DAS-28) ≥ 3.2 and a healthy volunteer underwent whole body and hand/wrist scintigraphy after the administration of anti-human TNF-α labelled with technetium-99m ((99m)Tc). One hundred and ninety-eight joints were examined. Patients were also given clinical examinations in addition to MRI of the hands and wrists. Of the 198 joints examined, signs of inflammation were detected by MRI in 49 (24.7%) and by scintigraphy in 48 (24.2%) joints, with agreement between the two methods in 44 joints. In five joints, MRI was positive and scintigraphy negative. In another four joints, scintigraphy was positive and MRI negative for signs of inflammation. MRI and scintigraphy were in agreement for negative results for 145 joints. The sensitivity and specificity of scintigraphy was 89.8 and 97.3%, respectively. When clinical parameters (presence of swelling and tenderness of joints) were compared with the MRI findings, lower correlation coefficients were observed (sensitivity of 59.2% and 65.3%, respectively). Scintigraphy using (99m)Tc-anti-TNF-α showed high correlation with the presence of inflammatory signs detected by MRI in the hands and wrists of patients with active RA, and demonstrated a greater sensitivity than clinical examination. These results can assist in better understanding of anti-cytokine therapy and support the achievement of evidence-based biologic therapy.
Nucci M.,Hospital Universitario Clementino Fraga Filho |
Nucci M.,University of Arkansas for Medical Sciences |
Nouer S.A.,Hospital Universitario Clementino Fraga Filho |
Nouer S.A.,University of Arkansas for Medical Sciences |
And 4 more authors.
Clinical Infectious Diseases | Year: 2010
Background. The European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) definition of invasive aspergillosis used in clinical trials lacks sensitivity. We hypothesize that giving lower weight to the prespecified radiologic findings in patients with a positive serum galactomannan index test result will improve the definition's diagnostic sensitivity. Methods. The medical records of 121 patients with 125 cases of invasive aspergillosis treated at a referral cancer institute from January 2003 through December 2009 were reviewed. Aspergillosis was diagnosed as EORTC-MSG proven or probable (controls, 83) or probable invasive aspergillosis without prespecified radiologic criteria (cases, 42). The latter differed from the former by the inclusion of patients whose pulmonary infiltrates, although well described in invasive aspergillosis, do not fulfill EORTC-MSG invasive aspergillosis requirements. The host, clinical, and mycologic characteristics and survival of cases and controls served as end points. Results. A total of 114 (91%) of 125 patients had multiple myeloma. Patients had a median age was 65 years (range, 26-81 years), and 74 were male. All had received antineoplastic therapy, including stem cell transplantation (58 [46%]). Aspergillosis involved lungs (88 patients), sinuses (9 patients), or both (28 patients). Except for higher median baseline platelet count and shorter duration of neutropenia among cases, there were no statistically significant differences between groups on all predefined end points, including 4-, 6-, and 12-week survival. Eleven of 26 cases were reclassified as controls on the basis of subsequent imaging. Conclusions. Except for less well-circumscribed consolidations, the host, clinical, radiologic, and mycologic characteristics and outcome of patients with probable invasive aspergillosis but without prespecified radiologic criteria are similar to those with EORTC-MSG invasive aspergillosis. Enrolling such patients in clinical trials of novel therapies will increase the pool of eligible study participants and improve trial speed and efficiency. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Pomin V.H.,Hospital Universitario Clementino Fraga Filho |
Piquet A.A.,Hospital Universitario Clementino Fraga Filho |
Pereira M.S.,Hospital Universitario Clementino Fraga Filho |
Mourao P.A.S.,Hospital Universitario Clementino Fraga Filho
Carbohydrate Polymers | Year: 2012
Chondroitin sulfate is a biomedical glycosaminoglycan (GAG) mostly used as a dietary supplement. We undertook analysis on some formulations of chondroitin sulfates available for oral administration. The analysis was based on agarose-gel electrophoresis, strong anion-exchange chromatography, digestibility with specific GAG lyases, uronic acid content, NMR spectroscopy, and size-exclusion chromatography. Keratan sulfate was detected in batches from shark cartilage, averaging ∼16% of the total GAG. Keratan sulfate is an inert material, and hazardous effects due to its presence in these formulations are unlikely to occur. However, its unexpected high percentage compromises the desired amounts of the real ingredient specified on the label claims, and forewarns the pharmacopeias to update their monographs. The techniques they recommended, especially cellulose acetate electrophoresis, are inefficient in detecting keratan sulfate in chondroitin sulfate formulations. In addition, this finding also alerts the manufacturers for improved isolation procedures as well as the supervisory agencies for better audits. Analysis based on strong anion-exchange chromatography is shown to be more reliable than the methods presently suggested by standard pharmacopeias. © 2012 Elsevier Ltd. All rights reserved.
Nucci M.,Hospital Universitario Clementino Fraga Filho
Current Fungal Infection Reports | Year: 2011
Persistent candidemia refers to the continued isolation of the same Candida species in the blood of a candidemic patient. Its incidence and clinical consequences are not well understood because of the lack of a homogeneous definition for persistent candidemia and the absence of prospective studies in which blood cultures were performed at prespecified times. Data from randomized clinical trials indicate that between 8% and 15% of candidemic patients have persistently positive blood cultures at the end of treatment, and the few studies that have attempted to evaluate the impact of persistent candidemia on outcomes have lacked appropriate analysis to conclude whether persistent candidemia is associated with worse outcome. On the other hand, assuming that it represents therapeutic failure, major causes for persistent candidemia include host factors (probably the most important), drug resistance, low serum levels of drugs, endovascular infection, deep-tissue abscesses, and infection associated with prosthetic material. © 2010 Springer Science+Business Media, LLC.