Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial

Background: Bevacizumab improves the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer. Our aim was to assess the use of bevacizumab in combination with oxaliplatin-based chemotherapy in the adjuvant treatment of patients with resected stage III or high-risk stage II colon carcinoma. Methods: Patients from 330 centres in 34 countries were enrolled into this phase 3, open-label randomised trial. Patients with curatively resected stage III or high-risk stage II colon carcinoma were randomly assigned (1: 1: 1) to receive FOLFOX4 (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on day 1; leucovorin 200 mg/m(2) plus fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on day 2) every 2 weeks for 12 cycles; bevacizumab 5 mg/kg plus FOLFOX4 (every 2 weeks for 12 cycles) followed by bevacizumab monotherapy 7.5 mg/kg every 3 weeks (eight cycles over 24 weeks); or bevacizumab 7.5 mg/kg plus XELOX (oxaliplatin 130 mg/m(2) on day 1 every 2 weeks plus oral capecitabine 1000 mg/m(2) twice daily on days 1-15) every 3 weeks for eight cycles followed by bevacizumab monotherapy 7.5 mg/kg every 3 weeks (eight cycles over 24 weeks). Block randomisation was done with a central interactive computerised system, stratified by geographic region and disease stage. Surgery with curative intent occurred 4-8 weeks before randomisation. The primary endpoint was disease-free survival, analysed for all randomised patients with stage III disease. This study is registered with ClinicalTrials.gov, number NCT00112918. Findings: Of the total intention-to-treat population (n=3451), 2867 patients had stage III disease, of whom 955 were randomly assigned to receive FOLFOX4, 960 to receive bevacizumab-FOLFOX4, and 952 to receive bevacizumab-XELOX. After a median follow-up of 48 months (range 0-66 months), 237 patients (25%) in the FOLFOX4 group, 280 (29%) in the bevacizumab-FOLFOX4 group, and 253 (27%) in the bevacizumab-XELOX group had relapsed, developed a new colon cancer, or died. The disease-free survival hazard ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1.17 (95% CI 0.98-1.39; p=0.07), and for bevacizumab-XELOX versus FOLFOX4 was 1.07 (0.90-1.28; p=0.44). After a minimum follow-up of 60 months, the overall survival hazard ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1.27 (1.03-1.57; p=0.02), and for bevacizumab-XELOX versus FOLFOX4 was 1.15 (0.93-1.42; p=0.21). The 573 patients with high-risk stage II cancer were included in the safety analysis. The most common grade 3-5 adverse events were neutropenia (FOLFOX4: 477 [42%] of 1126 patients, bevacizumab-FOLFOX4: 416 [36%] of 1145 patients, and bevacizumab-XELOX: 74 [7%] of 1135 patients), diarrhoea (110 [10%], 135 [12%], and 181 [16%], respectively), and hypertension (12 [1%], 122 [11%], and 116 [10%], respectively). Serious adverse events were more common in the bevacizumab groups (bevacizumab-FOLFOX4: 297 [26%]; bevacizumab-XELOX: 284 [25%]) than in the FOLFOX4 group (226 [20%]). Treatment-related deaths were reported in one patient receiving FOLFOX4, two receiving bevacizumab-FOLFOX4, and five receiving bevacizumab-XELOX. Interpretation: Bevacizumab does not prolong disease-free survival when added to adjuvant chemotherapy in resected stage III colon cancer. Overall survival data suggest a potential detrimental effect with bevacizumab plus oxaliplatin-based adjuvant therapy in these patients. On the basis of these and other data, we do not recommend the use of bevacizumab in the adjuvant treatment of patients with curatively resected stage III colon cancer.

Analysis of noise in aircraft cabins through the VHF channel

Purpose - The purpose of this paper is to present a method to analyze the noise in aircraft cabins through the VHF Aeronautical Communication Channel, aimed at examining an environment that has the possibility of communication problems between the aircraft crew and the professionals responsible for the controls on land. Design/methodology/approach - This analysis includes equipment normally used for identification and comparison of electromagnetic noise, the cabin and the environment that are present in an airport, as well as equipment for frequency analysis and intensity of those signals. The analysis is done in a reverse way, eliminating situations that are not common in the examined environment, until the identification of the situation with the irregularity. Findings - According to the results, the implementation of the Fourier transform for noise analysis in the cabin was efficient. These results demonstrate that through this transformation, the noise sources can be identified in the environments in cases where there is much spectrum pollution. Research limitations/implications - This kind of noise analysis is important, considering the importance of having good accuracy in airport environment analysis. Originality/value - The paper presents the main trends in the future of aviation communications, and describes the new applications that aim to minimize problems with the current VHF channel.

Ameloblastoma demographic, clinical and treatment study - analysis of 40 cases

Dental lesions represent about 1% of oral cavity tumors being ameloblastoma the most common one. It is a tumor of epithelial origin that mainly affects the jaw, and less commonly the maxilla. Its clinical presentation is that of an asymptomatic slow-growing tumor. Despite being a benign tumor, it has an invasive behavior with a high rate of recurrence if not treated properly. Objective: To describe the cases of ameloblastoma in a reference department. Methods: Retrospective analysis of 40 cases. The variables analyzed were: age, gender, ethnicity, tumor location, type of treatment, complications and recurrence. Results: The most affected gender was male - 21 cases (52.5%); with a predominance of Caucasians - 24 cases (60%). The mean age was 35.45 years; the most common location was in.the jaw - 37 cases (92.5%). Facial asymmetry was the most frequent complaint. Of the 40 cases, 33 were submitted to surgery. Of those submitted to surgery, 24 (72.72%) underwent segmental resection, with recurrence in 4 (12.12%) cases. Conclusion: Ameloblastoma may relapse when treatment is not performed with broad surgical resection of the lesion with wide safety margins.

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.

Work Precariousness and Risk of Accidents in Civil Construction: A study based on the Collective Work Analysis

This paper aims to describe the construction workers' activities, as well as their perceptions about risks and workload. The study, based on the Collective Work Analysis, is part of a broader public policies project for the improvement of SIVAT (Surveillance System of Work Accidents) - in the city of Piracicaba (Southeastern Brazil). Civil construction was prioritized given the epidemiological magnitude of the occurrence of work accidents and the limited efficacy of traditional surveillance initiatives in this sector due to informal employment practices, outsourcing, high staff turnover, etc. The workers have a high level of awareness concerning the risk of accidents, but they believe that the main preventive measures hinder or even make it impossible for them to carry out the tasks. Our findings question the efficacy of traditional training for adherence to safety practices, thus highlighting the need for a transformative pedagogy for preventive practices and the health promotion of workers.

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.

Assessment of nose protector for sport activities: finite element analysis

There has been a significant increase in the number of facial fractures stemming from sport activities in recent years, with the nasal bone one of the most affected structures. Researchers recommend the use of a nose protector, but there is no standardization regarding the material employed. Clinical experience has demonstrated that a combination of a flexible and rigid layer of ethylene vinyl acetate (EVA) offers both comfort and safety to practitioners of sports. The aim of the present study was the investigation into the stresses generated by the impact of a rigid body on the nasal bone on models with and without an EVA protector. For such, finite element analysis was employed. A craniofacial model was constructed from images obtained through computed tomography. The nose protector was modeled with two layers of EVA (1 mm of rigid EVA over 2 mm of flexible EVA), following the geometry of the soft tissue. Finite element analysis was performed using the LS Dyna program. The bone and rigid EVA were represented as elastic linear material, whereas the soft tissues and flexible EVA were represented as hyperelastic material. The impact from a rigid sphere on the frontal region of the face was simulated with a constant velocity of 20 m s-1 for 9.1 mu s. The model without the protector served as the control. The distribution of maximal stress of the facial bones was recorded. The maximal stress on the nasal bone surpassed the breaking limit of 0.130.34 MPa on the model without a protector, while remaining below this limit on the model with the protector. Thus, the nose protector made from both flexible and rigid EVA proved effective at protecting the nasal bones under high-impact conditions.

Critical analysis of the regulations regarding the disposal of medication waste

Expired or unused medication at people's homes is normally disposed of in normal garbage, sewage system or, in certain cases, returned to the public health system. There is still no specific legislation regarding this leftover medication to regulate and orient the handling and correct disposal of medication waste. However, there is defined regulation regarding health services' solid waste. This article has the objective of discussing management models for the disposal of medication waste and the recommendations made by pertinent national and international legislation. By means of literature reviews, the management structure for medication waste of international legislation and the regulations regarding the environment, as well as the national legislation for the solid waste from health services was analyzed. Through the analysis it was possible to present better clarifications as to the possible impacts to the environment, to the public's health and alternatives in order to obtain the efficient disposal of medication, reducing and/or avoiding sanitary risk, guaranteeing the quality and safety of public health.

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.

Questionário Atitudes de Segurança: adaptação transcultural do Safety Attitudes Questionnaire - Short Form 2006 para o Brasil

O objetivo deste estudo foi realizar a adaptação transcultural do Safety Attitudes Questionnaire - Short Form 2006 para o Brasil. O instrumento foi aplicado em seis hospitais de três Regiões do Brasil. Foi realizada a validade de conteúdo, face e de construto. A análise da confiabilidade do instrumento foi realizada por meio da análise da consistência interna dos itens por meio do alfa de Cronbach. A amostra do estudo foi composta por 1.301 profissionais das enfermarias clínicas e cirúrgicas de seis hospitais. A análise confirmatória mostrou que o ajuste do modelo final dos 41 itens foi considerado satisfatório. Aversão do instrumento em Português apresentou alfa de 0,89. As correlações item/total entre os domínios foram consideradas de moderada a forte, com exceção do domínio percepção do estresse. Conclui-se, portanto, que a versão do instrumento adaptada para o Português é considerada válida e confiável nesta amostra.

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF

Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2-0-3.0). Patients and investigators were masked to treatment allocation. Between Dec 18,2006, and June 17,2009,14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2.79% rivaroxaban vs 2.96% warfarin; hazard ratio [HR] 0-94,95% CI 0.77-1.16) and those without (1.44% vs 1.88%; 0.77, 0.58-1-01; interaction p=0.23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13.31% rivaroxaban vs 13.87% warfarin; HR 0.96,95% CI 0.87-1-07) and those without (16.69% vs 15.19%; 1.10, 0.99-1.21; interaction p=0.08). Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF.

Neutron activation analysis for assessing chemical composition of dry dog foods

Brazil holds the second largest population of domestic dogs in the world, with 33 million dogs, only behind the United States. The annual consumption of dog food in the country is 1.75 million tons, corresponding to the World's sixth in trade turnover. Dog food is supposed to be a complete and balanced diet, formulated with high quality ingredients. All nutrients and minerals required for an adequate nutrition of dogs are added to the formulation to ensure longevity and welfare. In this context, the present study aimed at assessing the chemical composition of dry dog foods commercialized in Brazil. Thirty-four samples were acquired in the local market of Piracicaba and analyzed by instrumental neutron activation analysis (INAA) to determine the elements As, Br, Ca, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se, U, and Zn. In general, the concentrations of Ca, Fe, K, Na, and Zn complied with the values required by the Association of American Feed Control Officials (AAFCO). To evaluate the safety of dog food commercialized in Brazil, further investigation is necessary to better understand the presence of toxic elements found in this study, i.e. Sb and U. INAA was useful for the screening analysis of different types and brands of dry dog foods for the determination of both essential and toxic elements.

Cross-cultural adaptation of the Safety Attitudes Questionnaire - Short Form 2006 for Brazil

The objective of this study was to perform a cross-cultural adaptation of the Safety Attitudes Questionnaire - Short Form 2006 for Brazil. The instrument was applied in six hospitals in three regions of Brazil. Content, face, and construct validity was performed. Analysis of the instrument's reliability was performed by verifying the items' internal consistency through Cronbach's alpha. The sample was composed of 1301 professionals working in clinical and surgical wards of six hospitals. Confirmatory analysis showed that the model including 41 items was satisfactory. The Portuguese version presented an alpha of 0.89. The item-total correlations among the domains were moderate to strong, except for the domain Stress Recognition. We concluded that the instrument's version adapted to Portuguese and applied in our sample is valid and reliable.

Safety assessment of oral photodynamic therapy in rats

Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue.