Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

Objective. We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study.Methods. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >= 21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008.Results. of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.Conclusion. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Circuit board accident - organizational dimension hidden by prescribed safety

This study analyzes an accident in which two maintenance workers suffered severe burns while replacing a circuit breaker panel in a steel mill, following model of analysis and prevention of accidents (MAPA) developed with the objective of enlarging the perimeter of interventions and contributing to deconstruction of blame attribution practices. The study was based on materials produced by a health service team in an in-depth analysis of the accident. The analysis shows that decisions related to system modernization were taken without considering their implications in maintenance scheduling and creating conflicts of priorities and of interests between production and safety; and also reveals that the lack of a systemic perspective in safety management was its principal failure. To explain the accident as merely non-fulfillment of idealized formal safety rules feeds practices of blame attribution supported by alibi norms and inhibits possible prevention. In contrast, accident analyses undertaken in worker health surveillance services show potential to reveal origins of these events incubated in the history of the system ignored in practices guided by the traditional paradigm.

Safety illusion and error trap in a collectively-operated machine accident

Workplace accidents involving machines are relevant for their magnitude and their impacts on worker health. Despite consolidated critical statements, explanation centered on errors of operators remains predominant with industry professionals, hampering preventive measures and the improvement of production-system reliability. Several initiatives were adopted by enforcement agencies in partnership with universities to stimulate production and diffusion of analysis methodologies with a systemic approach. Starting from one accident case that occurred with a worker who operated a brake-clutch type mechanical press, the article explores cognitive aspects and the existence of traps in the operation of this machine. It deals with a large-sized press that, despite being endowed with a light curtain in areas of access to the pressing zone, did not meet legal requirements. The safety devices gave rise to an illusion of safety, permitting activation of the machine when a worker was still found within the operational zone. Preventive interventions must stimulate the tailoring of systems to the characteristics of workers, minimizing the creation of traps and encouraging safety policies and practices that replace judgments of behaviors that participate in accidents by analyses of reasons that lead workers to act in that manner.

Studies of gastric mucosa regeneration and safety promoted by Mouriri pusa treatment in acetic acid ulcer model

Ethnopharmacological Relevance: Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used by people living in the Cerrado to treat gastrointestinal disturbances. This medicinal plant has shown intense gastroprotective action in rodent gastric lesion, but still there are no data about its healing effect on gastric mucosa.Aim of the Study: To evaluate the methanolic extract (MeOH) obtained from Mouriri pusa leaves for its effect on the cicatrisation process of gastric ulcer.Mterials and Methods: The healing effects on gastric ulcers inducted by subserosal injection of acetic acid were evaluated by macroscopic and microscopic measures, imunohistochemistry and cell counting in rats treated with MeOH extract of Mouriri pusa (250 mg/kg, p.o./daily) for 14 or 30 days. The toxicity of Mouriri pusa was also evaluated by body and organ weight measure and clinical biochemical parameters.Results: Mouriri pusa treatments lasting 14 and 30 days showed elevated mucus secretion (PAS) and thicker regenerative gastric mucosa, denoting increased cell proliferation, which was confirmed by PCNA immunohistochemical analysis. Moreover, there was important cell recruitment (neutrophils and mast cells) to the site of the ulcer, which is an important factor in ulcer healing. No toxic effect was observed in all parameters evaluated. Phenolic compounds present in the MeOH extract like tannins, flavonoids and epicatechin are the probable agents involved in the healing effects of this medicinal plant.Conclusions: These findings showed a potential effect of Mouriri pusa in increasing regeneration of damaged gastric mucosa with safety for human use. (C) 2007 Elsevier B.V. All rights reserved.

Characterization of operational safety in offshore oil wells

The main concern of activities developed in oil and gas well construction is safety. But safety during the well construction process is not a trivial subject. Today risk evaluation approaches are based in static analyses of existent systems. In other words, those approaches do not allow a dynamic analysis that evaluates the risk for each alteration of the context. This paper proposes the use of Quantitative and Dynamic Risk Assessment (QDRA) to assess the degree of safety of each planned job. The QDRA can be understood as a safe job analysis approach, developed with the purpose of quantifying the safety degree in entire well construction and maintenance activities. The QDRA is intended to be used in the planning stages of well construction and maintenance, where the effects of hazard on job sequence are important unknowns. This paper also presents definitions of barrier, and barriers integrated set (BIS), and a modeling technique showing their relationships. (c) 2006 Elsevier B.V. All rights reserved.

Double-Tagging Polymerase Chain Reaction with a Thiolated Primer and Electrochemical Genosensing based on Gold Nanocomposite Sensor for Food Safety

A novel material for electrochemical biosensing based on rigid conducting gold nanocomposite (nano-AuGEC) is presented. Islands of chemisorbing material (gold nanoparticles) surrounded by nonreactive, rigid, and conducting graphite epoxy composite are thus achieved to avoid the stringent control of surface coverage parameters required during immobilization of thiolated oligos in continuous gold surfaces. The spatial resolution of the immobilized thiolated DNA was easily controlled by merely varying the percentage of gold nanoparticles in the composition of the composite. As low as 9 fmol (60 pM) of synthetic DNA were detected in hybridization experiments when using a thiolated probe. Moreover, for the first time a double tagging PCR strategy was performed with a thiolated primer for the detection of Salmonella sp., one of the most important foodborne pathogens affecting food safety. Ibis assay was performed by double-labeling the amplicon during the PCR with a -DIG and -SH set of labeled primers. The thiolated end allows the immobilization of the amplicon on the nano-AuGEC electrode, while digoxigenin allows the electrochemical detection with the antiDIG-HRP reporter in the femtomole range. Rigid conducting gold nanocomposite represents a good material for the improved and oriented immobilization of biomolecules with excellent transducing properties for the construction of a wide range of electrochemical biosensors such as immunosensors, genosensors, and enzymosensors.

Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study

Objective: To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women.Design: In this double-blind, randomized, placebo-controlled study, a total of 80 women (mean age =55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250 mg of standardized soy extract (Glycine max AT) a total of 100 mg/day of isoflavone (n=40) or placebo (n=40). Exclusion criteria included: contra-indication for hormone therapy (HT), chronic gastrointestinal diseases, and users of HT within the preceding 6-months. For 10-months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured. The t-test, Wilcoxon test and ANOVA were used in the statistical analysis.Results: At baseline, the mean number of hot flushes was 9.6 +/- 3.9 per day in the isoflavone group and 10.1 +/- 4.9 in the placebo group (p>0.05). After 10 months, there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1 +/- 2.3 and 5.9 +/- 4.3, respectively) (p<0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo, in reducing hot flush severity (69.9% and 33.7%, respectively) (p<0.001). Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups. No serious adverse event related to isoflavone treatment was reported.Conclusions: the soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance, providing a safe and effective alternative therapeutic for postmenopausal women. (C) 2007 Elsevier B.V.. All rights reserved.

Efficacy and safety of itraconazole pulse therapy: Brazilian multicentric study on toenail onychomycosis caused by dermatophytes

Background Itraconazole is a large spectrum triazole with known efficacy in both continuous and pulse therapy for various mycoses.Objectives Evaluate the efficacy and tolerability of itraconazole pulse therapy for onychomycosis of the toenails due to dermatophytes, in a prospective, open, non-comparative and multicentric investigation.Patients and methods the trial was completed by 72 patients of an initial total of 89. Treatment consisted of four cycles of itraconazole, 200 mg twice a day, for seven consecutive days each month. Patients were evaluated clinically, mycologically and biochemically before, during and at the end of the investigation, and were divided into two groups according to the measure of normal portion of the most affected nail (target nail), as follows: Group 1. 0-5.9 mm; and Group 2: more than 6 mm.Results Improvement was satisfactory and progressive. Results were statistically significant, when comparing the three moments of the study: pre-treatment, end of therapy (fourth month) and follow-up (ninth month) in both groups.Conclusions Itraconazole pulse therapy was efficient and safe for the treatment of onychomycosis caused by dermatophytes, although a much higher daily dosage than the known continuous administration was used. Group 1, with nails initially more extensively affected, had a more evident improvement, by the mean variation in millimeters of normal portion of the target nail. This group showed a very satisfactory response, although not reaching total cure, thus demonstrating the great importance of early treatment of this disease. A residual therapeutic effect is maintained even after suspension of the drug. Group 2 obtained better total cure rates, and four pulses were, in general, sufficient, whereas more cycles would have been beneficial for the Group 1 patients with more extensive involvement. (C) 1998 Elsevier B.V. B.V. All rights reserved.

Demonstration of the cellular viability and safety of Enterococcus faecium CRL 183 in long-term experiments

Enterococcus faecium CRL 183, a strain isolated from NSLAB cheese starter, has been the focus of much research on its potential probiotic capacity, although its survival through the gastrointestinal tract has not been demonstrated so far. In order to determine the capacity of E. faecium CRL 183 to survive such conditions, this strain was administered daily to rats for 30 weeks. The experimental animals were divided into Group I: those that did not receive E. faecium, Group II: those that received a pure culture of E. faecium CRL 183 and Group III: animals that received E. faecium CRL 183 in the form of a fermented soy-based product. Faecal samples were collected at the beginning and at the 50%, 75% and 100% stages of the experimental period. Isolation and counts of Enterococcus were carried out on KF selective media. To distinguish the various Enterococcus species in the faeces, biochemical (API Strep 20) and molecular (PCR) tests were performed. Initially, E. faecium was absent from the intestinal flora of the rats; however, after 15 weeks of administration, E. faecium could be recovered from the faeces of Groups II and III, demonstrating that E. faecium CRL 183 was able to survive gastrointestinal transit under the study conditions. This is further evidence of the probiotic qualities of this strain. The safety of the strain was also investigated with regard to body weight and serum biochemical analysis.