Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid Subgroup Analysis from a Randomized Phase 3 Study

Introduction: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma. Methods: Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC. Results: Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA. Conclusion: In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.

Homophobic discourse in blogs: Weaving of violence and network

This article aims at analyzing the effects of meaning installed in the discursive space of a blog, especially a formulation of discriminatory nature which was posted in November, 2011 and considerably discussed in other discursive spaces on the Internet. By means of French Discourse Analysis, we sought to track the memory networks and the ideological effects that are at play in the discourse on homosexuals posted by browsers-subjects and how they update the meanings already there in order to install effects of prejudice and hatred. Our interest is also to catch the meanings of violence inscribed in the electronic network and analyze the functioning of the language in motion in this space bordered by the imaginary in which it is possible to say anything. Hence, by means of the analyses performed in this study, we observed these effects of the subject's full freedom when he/she subscribes to the electronic network without fear of any punishment of any order. The discourses of intolerance and hatred posted on the blog by the subject give voice to a discursive confrontation observed by marks of agreement or indignation, supported by the discursive memory. Thus, we observed the interruption of regularities that break up with a supposed linearity in the discourse, putting the contradiction and the heterogeneous nature of the sayings on the net in motion.

Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-alpha (anti-TNF) combined therapy. Methods. We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received intliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. Results. Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1 CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study. (First Release July 1 2012; J Rheumatol 2012;39:1524-32; doi:10.3899/jrheum.120092)

DELAY IN THE DIAGNOSIS OF TUBERCULOSIS IN PRISONS: THE EXPERIENCE OF INCARCERATED PATIENTS

This study analyzed the causes of delay in the diagnosis of tuberculosis in the prison system, according to the experience of incarcerated patients. The theoretical and methodological framework of the French school of discourse analysis was used, which seeks to comprehend the processes of meaning production, in the relationship of language with ideology and the development of subjects in their positions. Semi-directed interviews were conducted with seven incarcerated tuberculosis patients in a hospital of Joao Pessoa, Paraiba, Brazil, between August and October 2009. The delay in the diagnosis of tuberculosis was related to the naturalization of the lack of care for the prisoner, to the interpretation of the prison as a place of death and suffering and to the deprivation of the right to health for the detainees as a result of their position in the asymmetric power relationships and ideological effects.

Clinical Evaluation of the Effectiveness of Different Bleaching Therapies in Vital Teeth

The aims of this in vivo study were to compare the effectiveness and color stability of at-home and in-office bleaching techniques and to evaluate whether the use of light sources can alter bleaching results. According to preestablished criteria, 40 patients were selected and randomly divided into four groups according to bleaching treatment: (1) at-home bleaching with 10% carbamide peroxide, (2) in-office bleaching with 35% hydrogen peroxide (HP) without a light source, (3) in-office bleaching with 35% HP with quartz-tungsten-halogen light, and (4) in-office bleaching with 35% HP with a light-emitting diode/laser. Tooth shade was evaluated using the VITA Classical Shade Guide before bleaching as well as after the first and third weeks of bleaching. Tooth shade was evaluated again using the same guide 1 and 6 months after the completion of treatment. The shade guide was arranged to yield scores that were used for statistical comparison. Statistical analysis using the Kruskal-Wallis test showed no significant differences among the groups for any time point (P > .01). There was no color rebound in any of the groups. The bleaching techniques tested were equally effective. Light sources are unnecessary to bleach teeth. (Int J Periodontics Restorative Dent 2012;32:303-309.)

Atenção primária à saúde e a construção de sentidos para a saúde bucal: leitura construcionista social sobre discursos de idosos

Dentistry is nowadays open to new ideas about the constructions of meanings for oral health. This openness tallies with the social production of health and shows the need to contextualize the social, historical and sundry knowledge in the development of oral health for different communities. The scope of this research is to build meanings for oral health with a group of elderly people. With this in mind, we propose an approximation between the discourses of the elderly on oral health and the Social Constructionist discourse. Thus, we interviewed 14 elderly people registered with a Family Health Unit in Ribeirao Preto in the State of Sao Paulo in the first semester of 2010. This enabled us to identify two Interpretative Repertoires with the use of Discourse Analysis, which showed the relationship between: 1 Lack of dental information and assistance in childhood; and 2 - Primary Healthcare constructing meaning for oral health. We concluded that Social Constructionism assists epistemologically for the construction of meaning for oral health and that Primary Healthcare is essential for valuing healthcare for the construction of meaning for oral health on the part of the elderly by fostering conditions for self care and healthy attitudes.

Primary healthcare and the construction of meanings of oral health: a social constructionist interpretation of discourses of the elderly

Dentistry currently reveals itself to be open to new ideas about the construction of meanings for oral health. This openness leads to the social production of health revealing the contextualization of the social and historical aspects of the sundry knowledge in the development of oral health for different communities. With this research, we seek to build meanings for oral health with a group of elderly people. With this objective in mind, we propose an approximation between discourses on oral health mentioned by the elderly and the Social Constructionist discourse. We interviewed 14 elderly people enrolled in a Family Health Unit in Ribeirao Preto, State of Sao Paulo, in the first semester of 2010, and identified two interpretative repertoires through Discourse Analysis, which showed the relationship between 1 Lack of information and dental assistance in childhood, and 2 - Primary Health Care building the meaning of oral health. We concluded that Social Constructionism works epistemologically for the construction of meanings for oral health and that primary health is essential for appreciation and health care that enables the construction of meanings in oral health by the elderly that create conditions for self-care and healthy attitudes.

Micropolítica do trabalho dos profissionais de saúde na UBS: visão sobre necessidades de saúde das famílias

Este estudo teve como objetivo compreender as potencialidades e limitações do processo de trabalho da enfermagem de uma Unidade Básica de Saúde para o reconhecimento das necessidades de saúde da população. A vertente metodológica utilizada foi a pesquisa social, na perspectiva qualitativa, tendo como base de análise dos discursos a hermêutica-dialética, e como alicerce a Teoria da Interpretação Práxica da Enfermagem em Saúde Coletiva. Os dados foram coletados por meio da entrevista semiestruturada e os processos de trabalho das equipes foram analisados através do Fluxograma Analisador do Modelo de Atenção de um Serviço de Saúde. Concluiu-se que há limitações no cotidiano do processo de trabalho da equipe de enfermagem à medida em que o reconhecimento e enfrentamento das necessidades de saúde perpassavam pela identificação de agravos instalados, deixando em segundo plano os determinantes sociais das más condições de vida associadas ao processo saúde-doença.

Transcriptional Alterations Related to Neuropathology and Clinical Manifestation of Alzheimer's Disease

Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR >= 1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak <= II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.

Representations of workplace psychological harassment in print news media

OBJECTIVE: To analyze discourses on workplace psychological harassment in print media. METHODOLOGICAL PROCEDURES: Documental study on workplace psychological harassment that analyzed news stories published in three major newspapers of the State of Sao Paulo (southeastern Brazil) between 1990 and 2008. Discourse analysis was performed to identify discursive practices that reflect the phenomenon of psychological harassment in today's society, explanations for its occurrence and impact on workers' health. RESULT ANALYSIS: This theme emerged in the media through the dissemination of books, academic research production and laws. It was initially published in general news then in jobs and/or business sections. Discourses on compensation and precautionary business practices and coping strategies are widespread. Health-related aspects are foregone under the prevailing money-based rationale. Corporate cultures are permissive regarding psychological harassment and conflicts are escalated while working to achieve goals and results. Indifference, embarrassment, ridicule and demean were common in the news stories analyzed. CONCLUSIONS: The causal explanations of workplace harassment tend to have a psychological interpretation with emphasis on individual and behavioral characteristics, and minimizing a collective approach. The discourses analyzed trivialized harassment by creating caricatures of the actors involved. People apprehend its psychological content and stigmatization which contributes to making workplace harassment an accepted practice and trivializing work-related violence.

Family health team knowledge concerning the health needs of people with tuberculosis

The purposes of the study were to get to know conceptions on tuberculosis and health needs and to describe the care provided to people with tuberculosis, according to health professionals' perspective. Qualitative study developed at family health units in Capao Redondo, Sao Paulo. The data were collected through open interviews in January 2010 and submitted to discourse analysis, resulting in three categories: meanings attributed to tuberculosis and health needs and care characteristics. The conceptions regarding the disease are supported by the multi-causal theory of the health-disease process. The care is characterized by interventions that go beyond the biological dimension. The precarious living conditions define the needs of most people with tuberculosis, and can be more important to the ill than the very diagnosis of the disease, influencing treatment adherence, and should gain relevance in care.

Organização dos serviços de saúde e a gestão do cuidado à tuberculose

Este estudo teve como objetivo analisar a discursividade de gestores sobre a relação entre a organização dos serviços de saúde e a gestão do cuidado à tuberculose (TB) em um município da região metropolitana de João Pessoa/PB. Conduzido pela pesquisa qualitativa no campo analítico da Análise de Discurso de linha francesa, participaram 16 trabalhadores de saúde que atuavam como integrantes de equipes gestoras. Os depoimentos transcritos foram organizados com uso do software Atlas.ti versão 6.0. Após leitura minuciosa do material empírico procurou-se observar nos discursos os processos parafrásicos, polissêmicos e metafóricos, os quais possibilitaram a identificação da seguinte formação discursiva: organização dos serviços de saúde e a relação com a gestão do cuidado à TB; o plano e a prática. Nos discursos dos gestores evidencia-se a fragmentação das ações de controle da tuberculose, a falta de articulação entre os serviços e os setores, o cumprimento de atividades específicas à TB, bem como a falta de planejamento estratégico para gestão do cuidado da doença. Nesse sentido, para que a organização dos serviços de saúde seja efetiva, se faz necessário que a tuberculose seja prioridade na agenda da gestão e reconhecida como um problema social.

A modernização ecológica conquistando hegemonia nos discursos ambientais: o caso da Zona Franca de Manaus

A Zona Franca de Manaus (ZFM) foi criada em 1967 pelo governo da ditadura militar brasileira, de acordo com um discurso nacionalista que apresentava a região amazônica como um território estratégico que era preciso ocupar e desenvolver. Apesar de a visão do grande vazio não ter sido apagada do imaginário popular, desde os anos de 1970 tem ganhado força a percepção da floresta como herança cultural e biológica a ser preservada. Estas mudanças nos discursos mais gerais sobre a Amazônia foram acompanhadas por um deslocamento do discurso de legitimação dos incentivos fiscais gozados pelas indústrias de Manaus, em um movimento relacionado ao processo de construção de hegemonia no campo ambiental, marcado pela emergência da chamada modernização ecológica. Utilizando a análise crítica do discurso, este artigo mostra como se constituiu o argumento de que as empresas em Manaus protegem a floresta, assentado em um roteiro de dupla ameaça: de desemprego e de desmatamento. As informações e dados foram levantados por meio de pesquisa bibliográfica, entrevistas semiestruturadas e observações diretas em reuniões e eventos corporativos. Fizeram parte do corpus, ainda, as transcrições oficiais de 64 pronunciamentos em plenário dos três senadores e oito deputados federais do Amazonas em 2007; 125 matérias publicadas no caderno de Economia do jornal A Crítica entre 1º de janeiro e 30 de junho, e quatro edições da revista institucional Suframa Hoje, no mesmo ano.

Investigando processos de autoria na produção do relatório de Iniciação Científica de um graduando em Química

Neste trabalho, analisamos o relatório de Iniciação Científica produzido por um aluno de graduação em Química, a partir da perspectiva da Análise de Discurso de linha francesa, como vem sendo divulgada por Eni Orlandi, especialmente quanto à noção de autoria. Orlandi distingue três tipos de repetição no processo de autoria: empírica, formal e histórica. Percebemos, na produção do relatório, o exercício da repetição empírica e formal, além do uso da repetição histórica, que demonstra a posição de autor ocupada pelo aluno. Essa investigação nos levou à percepção sobre a influência da Iniciação Científica na apropriação da linguagem científica, e indicou que esse processo se deu por meio da troca com os pares, da imitação de modelos, e, sobretudo, da vivência da pesquisa.

Investigação sobre as configurações sociais do subcampo do esporte paralímpico no Brasil: os processos de classificação de atletas

Este trabalho tem por objetivo investigar e delimitar formas de interação e disputas sociais presentes no movimento paralímpico brasileiro, relativos aos processos de classificação de atletas, com base em conceitos de Pierre Bourdieu. A metodologia utilizada fundamentou-se em entrevistas semiestruturadas com quatro atletas (com deficiência física ou visual, praticantes de diversas modalidades: natação, goalball, rugby e basquete em cadeira de rodas) e quatro dirigentes (2 atuantes em funções técnicas e 2 em funções administrativas do Comitê Paralímpico Brasileiro). A análise de dados apoiou-se no método Discurso do Sujeito Coletivo e suas ferramentas metodológicas (expressões-chave; ideias centrais; ancoragens; instrumentos de análise de discurso). Destacam-se como resultados: os protocolos de classificação, assim como a atuação e formação de novos classificadores, são motivo de tensões sociais neste espaço; Os classificadores exercem importante poder simbólico no subcampo; Demais agentes, como treinadores e atletas, têm suas possibilidades de ascensão diminuídas por condições sociais desfavoráveis..