TNFRSF1B Gene Variants in Clinicopathological Aspects and Prognosis of Patients with Cutaneous Melanoma.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3'-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3'-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.

Somatic Copy Number Alterations and Associated Genes in Clear-Cell Renal-Cell Carcinoma in Brazilian Patients.

Somatic copy number aberrations (CNAs) have been associated with clear-cell renal carcinoma (ccRCC) pathogenesis and are a potential source of new diagnostic, prognostic and therapeutic biomarkers. Recurrent CNAs include loss of chromosome arms 3p, 14q, 9p, and gains of 5q and 8q. Some of these regional CNAs are suspected of altering gene expression and could influence clinical outcomes. Despite many studies of CNAs in RCC, there are currently no descriptions of genomic copy number alterations in a Brazilian ccRCC cohort. This study was designed to evaluate the chromosomal profile of CNAs in Brazilian ccRCC tumors and explore clinical associations. A total of 92 ccRCC Brazilian patients that underwent nephrectomy at Barretos Cancer Hospital were analyzed for CNAs by array comparative genomic hybridization. Most patients in the cohort had early-stage localized disease. The most significant alterations were loss of 3p (87.3%), 14q (35.8%), 6q (29.3%), 9p (28.6%) and 10q (25.0%), and gains of 5q (59.7%), 7p (29.3%) and 16q (20.6%). Bioinformatics analysis revealed 19 genes mapping to CNA significant regions, including SETD2, BAP1, FLT4, PTEN, FGFR4 and NSD1. Moreover, gain of 5q34-q35.3 (FLT4 and NSD1) and loss of 6q23.2-q23.3 (MYB) and 9p21.3 (MLLT3) had gene expression levels that correlated with TCGA data and was also associated with advanced disease features, such as larger tumors, Fuhrman 3, metastasis at diagnosis and death. The loss of region 14q22.1 which encompasses the NIN gene was associated with poor overall survival. Overall, this study provides the first CNA landscape of Brazilian patients and pinpoints genomic regions and specific genes worthy of more detailed investigations. Our results highlight important genes that are associated with copy number changes involving large chromosomal regions that are potentially related to ccRCC tumorigenesis and disease biology for future clinical investigations.

Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population.

Ultraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele "A" were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3, CREB1, and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients' clinicopathological features.

The Brazilian TP53 mutation (R337H) and sarcomas.

Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.

Clinical, dietary and demographic characteristics interfering on quality of life of cancer patients.

OBJECTIVE: To estimate the dietary intake of cancer patients and its relation with clinical and demographic characteristics, and to assess the contribution of dietary intake, appetite/symptoms and clinical and demographic characteristics to their quality of life. METHODS: The consumption of energy and macronutrients of patients was estimated. The relation between dietary intake and clinical and demographic characteristics was evaluated by analysis of variance. The intake of energy and macronutrient of the patients was compared to the nutritional recommendations using 95% confidence interval. The Cancer Appetite and Symptom Questionnaire (CASQ) and the European Organization for Research and Treatment of Cancer (EORTC QLQ C-30) were used to assess appetite/symptoms and quality of life, respectively. The psychometric properties of the instruments were estimated. A structural equation model was prepared. RESULTS: In this study, 772 cancer patients (63.1% women) participated. There was a significant relation between dietary intake and work activity, economic class, specialty field of cancer, type of treatment and nutritional status. Patients' energy and macronutrients intake was below recommended values. Both CASQ and EORTC QLQ C-30 were refined to fit the data. In the structural model, impaired appetite, more symptoms, presence of metastasis, being female and of higher economic classes were characteristics that significantly contributed to interfering in patients' quality of life. CONCLUSION: The dietary intake of oncology patients did not reach the recommended values. Different characteristics impacted on quality of life of patients and should be considered in clinical and epidemiological protocols.

Cross-cultural psychometric assessment of an appetite questionnaire for patients with cancer.

OBJECTIVE: To evaluate the psychometric properties, along with cross-cultural invariance analysis, of the Cancer Appetite and Symptom Questionnaire (CASQ). METHOD: Data from 555 United Kingdom (UK) cancer patients were used to evaluate the psychometric properties of the CASQ. Construct validity was assessed through factorial and convergent validity. We conducted a confirmatory factor analysis using as indices the chi-square ratio by degrees of freedom (χ2/df), the comparative fit index (CFI), the goodness of fit index (GFI), and the root mean square error of approximation (RMSEA). Convergent validity was estimated by the items' average variance extracted (AVE). Reliability was estimated by composite reliability and internal consistency. Factorial invariance analysis of the CASQ was evaluated by multigroup analysis (∆χ2) using the UK and Brazilian samples. RESULTS: All items showed adequate psychometric sensitivity in the UK sample. One item was removed and four correlations were included between errors with an appropriate fit of the model (χ2/df = 2.674, CFI = 0.966, GFI = 0.964, RMSEA = 0.055). The reliability of the CASQ was adequate and the convergent validity was low. The factorial structure of the CASQ differed across countries, and a lack of measurement invariance for the two countries was observed (λ: ∆χ2 = 64.008, p < 0.001; i: ∆χ2 = 3515.047, p < 0.001; Res: ∆χ2 = 4452.504, p < 0.001). CONCLUSION: The CASQ showed adequate psychometric properties in the UK sample. The ability to estimate loss of appetite and the presence of symptoms was different between UK and Brazilian patients.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30: factorial models to Brazilian cancer patients.

Objective To evaluate the psychometric properties of the seven theoretical models proposed in the literature for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), when applied to a sample of Brazilian cancer patients. Methods Content and construct validity (factorial, convergent, discriminant) were estimated. Confirmatory factor analysis was performed. Convergent validity was analyzed using the average variance extracted. Discriminant validity was analyzed using correlational analysis. Internal consistency and composite reliability were used to assess the reliability of instrument. Results A total of 1,020 cancer patients participated. The mean age was 53.3±13.0 years, and 62% were female. All models showed adequate factorial validity for the study sample. Convergent and discriminant validities and the reliability were compromised in all of the models for all of the single items referring to symptoms, as well as for the "physical function" and "cognitive function" factors. Conclusion All theoretical models assessed in this study presented adequate factorial validity when applied to Brazilian cancer patients. The choice of the best model for use in research and/or clinical protocols should be centered on the purpose and underlying theory of each model.

Cross-cultural psychometric assessment of an appetite questionnaire for patients with cancer / Avaliação psicométrica transcultural de um questionário de apetite para pacientes com câncer

Abstract Objective To evaluate the psychometric properties, along with cross-cultural invariance analysis, of the Cancer Appetite and Symptom Questionnaire (CASQ). Method Data from 555 United Kingdom (UK) cancer patients were used to evaluate the psychometric properties of the CASQ. Construct validity was assessed through factorial and convergent validity. We conducted a confirmatory factor analysis using as indices the chi-square ratio by degrees of freedom (χ2/df), the comparative fit index (CFI), the goodness of fit index (GFI), and the root mean square error of approximation (RMSEA). Convergent validity was estimated by the items' average variance extracted (AVE). Reliability was estimated by composite reliability and internal consistency. Factorial invariance analysis of the CASQ was evaluated by multigroup analysis (∆χ2) using the UK and Brazilian samples. Results All items showed adequate psychometric sensitivity in the UK sample. One item was removed and four correlations were included between errors with an appropriate fit of the model (χ2/df = 2.674, CFI = 0.966, GFI = 0.964, RMSEA = 0.055). The reliability of the CASQ was adequate and the convergent validity was low. The factorial structure of the CASQ differed across countries, and a lack of measurement invariance for the two countries was observed (λ: ∆χ2 = 64.008, p < 0.001; i: ∆χ2 = 3515.047, p < 0.001; Res: ∆χ2 = 4452.504, p < 0.001). Conclusion The CASQ showed adequate psychometric properties in the UK sample. The ability to estimate loss of appetite and the presence of symptoms was different between UK and Brazilian patients.

Resumo Objetivos Avaliar as propriedades psicométricas, juntamente com a análise de invariância transcultural, do Questionário de Apetite e Sintoma para Pacientes com Câncer (Cancer Appetite and Symptom Questionnaire, CASQ). Métodos Dados de 555 pacientes com câncer do Reino Unido foram utilizados para avaliar as propriedades psicométricas do CASQ. A validade de construto foi estimada por meio das validades fatorial e convergente. Realizou-se análise fatorial confirmatória utilizando como índices a razão de qui-quadrado pelos graus de liberdade (χ2/gl), o comparative fit index (CFI), o goodness of fit index (GFI) e o root mean square error of aproximation (RMSEA). A validade convergente foi estimada pela variância extraída média (VEM). A confiabilidade foi estimada pela confiabilidade composta e consistência interna. A análise de invariância fatorial do CASQ foi avaliada por análise multigrupos (∆χ2) usando as amostras do Reino Unido e do Brasil. Resultados Todos os itens apresentaram adequada sensibilidade psicométrica na amostra do Reino Unido. Um item foi removido e foram incluídas quatro correlações entre erros, o que resultou em ajustamento adequado do modelo à amostra (χ2/df = 2,674, CFI = 0,966, GFI = 0,964, RMSEA = 0,055). A confiabilidade do CASQ foi adequada e a validade convergente foi baixa. A estrutura fatorial do CASQ diferiu entre os países, e uma falta de invariância foi observada para os dois países (λ: ∆χ2 = 64,008, p < 0,001; i: ∆χ2 = 3515,047, p < 0,001; Res: ∆χ2 = 4452,504, p < 0,001). Conclusão O CASQ apresentou adequadas propriedades psicométricas na amostra do Reino Unido. A capacidade de estimar a falta de apetite e a presença de sintomas foi diferente entre pacientes do Reino Unido e do Brasil.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30: factorial models to Brazilian cancer patients / European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30: modelos fatoriais em pacientes brasileiros com câncer

ABSTRACT Objective To evaluate the psychometric properties of the seven theoretical models proposed in the literature for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), when applied to a sample of Brazilian cancer patients. Methods Content and construct validity (factorial, convergent, discriminant) were estimated. Confirmatory factor analysis was performed. Convergent validity was analyzed using the average variance extracted. Discriminant validity was analyzed using correlational analysis. Internal consistency and composite reliability were used to assess the reliability of instrument. Results A total of 1,020 cancer patients participated. The mean age was 53.3±13.0 years, and 62% were female. All models showed adequate factorial validity for the study sample. Convergent and discriminant validities and the reliability were compromised in all of the models for all of the single items referring to symptoms, as well as for the "physical function" and "cognitive function" factors. Conclusion All theoretical models assessed in this study presented adequate factorial validity when applied to Brazilian cancer patients. The choice of the best model for use in research and/or clinical protocols should be centered on the purpose and underlying theory of each model.

RESUMO Objetivo Avaliar as propriedades psicométricas dos sete modelos teóricos propostos na literatura para o European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), quando aplicados em uma amostra de pacientes brasileiros com câncer. Métodos As validades de conteúdo e de construto (fatorial, convergente, discriminante) foram avaliadas. Foi realizada análise fatorial confirmatória. A validade convergente foi avaliada pela variância média extraída. A validade discriminante foi analisada por meio de análise correlacional. A consistência interna e a confiabilidade composta foram utilizadas para avaliar a confiabilidade do instrumento. Resultados Participaram do estudo 1.020 pacientes com câncer. A média de idade foi 53,3±13,0 anos, e 62% eram do sexo feminino. Todos os modelos mostraram validade fatorial adequada para a amostra de estudo. As validades convergente e discriminante e a confiabilidade foram comprometidas em todos os modelos para todos os itens isolados referentes aos sintomas, bem como para os fatores "função física" e "função cognitiva". Conclusão Todos os modelos teóricos avaliados neste estudo apresentaram validade fatorial adequada para pacientes brasileiros com câncer. A escolha do melhor modelo para uso em pesquisa e/ou protocolos clínicos deve ser baseada na finalidade e na teoria subjacente de cada modelo.

Clinical, dietary and demographic characteristics interfering on quality of life of cancer patients / Características clínicas, dietéticas e demográficas que interferem na qualidade de vida de pacientes com câncer

ABSTRACT Objective To estimate the dietary intake of cancer patients and its relation with clinical and demographic characteristics, and to assess the contribution of dietary intake, appetite/symptoms and clinical and demographic characteristics to their quality of life. Methods The consumption of energy and macronutrients of patients was estimated. The relation between dietary intake and clinical and demographic characteristics was evaluated by analysis of variance. The intake of energy and macronutrient of the patients was compared to the nutritional recommendations using 95% confidence interval. The Cancer Appetite and Symptom Questionnaire (CASQ) and the European Organization for Research and Treatment of Cancer (EORTC QLQ C-30) were used to assess appetite/symptoms and quality of life, respectively. The psychometric properties of the instruments were estimated. A structural equation model was prepared. Results In this study, 772 cancer patients (63.1% women) participated. There was a significant relation between dietary intake and work activity, economic class, specialty field of cancer, type of treatment and nutritional status. Patients' energy and macronutrients intake was below recommended values. Both CASQ and EORTC QLQ C-30 were refined to fit the data. In the structural model, impaired appetite, more symptoms, presence of metastasis, being female and of higher economic classes were characteristics that significantly contributed to interfering in patients' quality of life. Conclusion The dietary intake of oncology patients did not reach the recommended values. Different characteristics impacted on quality of life of patients and should be considered in clinical and epidemiological protocols.

RESUMO Objetivo Estimar a ingestão dietética de pacientes com câncer e sua relação com características clínicas e demográficas, além de verificar a contribuição da ingestão dietética, apetite/sintomas e características clínicas e demográficas para a qualidade de vida deles. Métodos Foi estimado o consumo de energia e de macronutrientes. A relação entre ingestão dietética e características clínicas e demográficas foi avaliada pela análise de variância. A ingestão de energia e macronutrientes dos pacientes foi comparada com a necessidade nutricional, utilizando intervalo de confiança de 95%. O Cancer Appetite and Symptom Questionnaire (CASQ) e o European Organization for Research and Treatment of Cancer (EORTC QLQ C-30) foram utilizados para avaliar apetite/sintomas e qualidade de vida, respectivamente. As propriedades psicométricas dos instrumentos foram estimadas. Elaborou-se modelo de equações estruturais. Resultados Participaram do estudo 772 pacientes oncológicos (63,1% mulheres). Observou-se relação significativa entre ingestão dietética e atividade laboral, classe econômica, especialidade do diagnóstico, tipo de tratamento e estado nutricional. O consumo de energia e macronutrientes dos pacientes esteve abaixo do recomendado. Tanto o CASQ quando o EORTC QLQ C-30 foram refinados para bom ajustamento aos dados. No modelo estrutural, comprometimento do apetite, maior acometimento por sintomas, presença de metástase, ser mulher e pertencer às classes econômicas mais altas foram características que contribuíram significativamente para o comprometimento da qualidade de vida dos pacientes oncológicos. Conclusão A ingestão dietética dos pacientes oncológicos não atingiu os níveis recomendados. Diferentes características impactaram na qualidade de vida dos pacientes e devem ser consideradas em protocolos clínicos e epidemiológicos.

What are the personal and professional characteristics that distinguish the researchers who publish in high- and low-impact journals? A multi-national web-based survey.

PURPOSE: This study identifies the personal and professional profiles of researchers with a greater potential to publish high-impact academic articles. METHOD: The study involved conducting an international survey of journal authors using a web-based questionnaire. The survey examined personal characteristics, funding, and the perceived barriers of research quality, work-life balance, and satisfaction and motivation in relation to career. The processes of manuscript writing and journal publication were measured using an online questionnaire that was developed for this study. The responses were compared between the two groups of researchers using logistic regression models. RESULTS: A total of 269 questionnaires were analysed. The researchers shared some common perceptions; both groups reported that they were seeking recognition (or to be leaders in their areas) rather than financial remuneration. Furthermore, both groups identified time and funding constraints as the main obstacles to their scientific activities. The amount of time that was spent on research activities, having >5 graduate students under supervision, never using text editing services prior to the publication of articles, and living in a developed and English-speaking country were the independent variables that were associated with their article getting a greater chance of publishing in a high-impact journal. In contrast, using one's own resources to perform studies decreased the chance of publishing in high-impact journals. CONCLUSIONS: The researchers who publish in high-impact journals have distinct profiles compared with the researchers who publish in low-impact journals. English language abilities and the actual amount of time that is dedicated to research and scientific writing, as well as aspects that relate to the availability of financial resources are the factors that are associated with a successful researcher's profile.

Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross-Cultural Adaptation and Validation Study.

BACKGROUND: Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. METHODS: This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2/df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach's alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). RESULTS: Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2/df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). The model exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2: λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2: λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2: λ: p = .058; i: p < .001; Res: p < .001). CONCLUSION: The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatments.

Psychometric characteristics of the Functional Assessment of Cancer Therapy-General when applied to Brazilian cancer patients: a cross-cultural adaptation and validation.

BACKGROUND: The psychometric properties of an instrument should be evaluated routinely when using different samples. This study evaluated the psychometric properties of the Functional Assessment of Cancer Therapy-General (FACT-G) when applied to a sample of Brazilian cancer patients. METHODS: The face, content, and construct (factorial, convergent, and discriminant) validities of the FACT-G were estimated. Confirmatory factor analysis (CFA) was conducted the ratio chi-square by degrees of freedom (χ (2)/df), the comparative fit index (CFI), the Tucker-Lewis index (TLI), and the root mean square error of approximation (RMSEA) as indices. The invariance of the best model was assessed with multi-group analysis using the difference of chi-squares method (Δχ(2)). Convergent validity was assessed using Average Variance Extracted (AVE) and discriminant validity was determined via correlational analysis. Internal consistency was assessed using the Cronbach's alpha (α) coefficient, and the Composite Reliability (CR) was estimated. RESULTS: A total of 975 cancer patients participated in the study, with a mean age of 53.3 (SD = 13.0) years. Of these participants, 61.5 % were women. In CFA, five correlations between errors were included to fit the FACT-G to the sample (χ (2)/df = 8.611, CFI = .913, TLI = .902, RMSEA = .088). The model did not indicate invariant independent samples (Δχ(2): µ: p < .001, i: p < .958, Cov: p < .001, Res: p < .001). While there was adequate convergent validity for the physical well-being (AVE = .54) and social and family Well-being factors (AVE = .55), there was low convergent validity for the other factors. Reliability was adequate (CR = .76-.89 and α = .71-.82). Functional well-being, emotional well-being, and physical well-being were the factors that demonstrated a strong contribution to patients' health-related quality of life (ß = -.99, .88, and .64, respectively). CONCLUSION: The FACT-G was found to be a valid and reliable assessment of health-related quality of life in a Brazilian sample of patients with cancer.

Eticidade do uso de placebo em pesquisa clínica: proposta de algoritmos decisórios / Ethics of the use of placebos in clinical research: a proposal for decision-making algorithms

O uso de placebo em pesquisa clínica tem sido motivo de debate nos últimos anos, sobretudo após a Associação Médica Mundial publicar, em 2002, nota de esclarecimento do parágrafo 29 da Declaração de Helsinki. O Brasil tem se destacado por sua posição firme e contrária ao uso flexível de placebo. Tanto o Conselho Federal de Medicina quanto o Conselho Nacional de Saúde editaram resoluções que normatizam seu uso no Brasil, de forma a não admiti-lo em caso da existência de um método terapêutico melhor. O presente artigo reforça essa posição e tem por objetivo descrever as diversas aplicações de placebo em pesquisa clínica, bem como trazer à luz a complexa decisão sobre a eticidade de seu uso. Além disso, os autores propõem uma reflexão acerca da utilização de placebo no âmbito da pesquisa, por meio de algoritmos decisórios baseados nas normativas éticas brasileiras...

The use of placebos in clinical research has been a matter of considerable debate in recent years, notably when the World Medical Association published, in 2002, a note of clarification for paragraph 29 of the Helsinki Declaration. Brazil is known for its strong opposition to the flexible use of placebos. Both the Federal Council of Medicine and the National Health Council have published resolutions regulating the use of placebos in Brazil, preventing their use if there is a more effective therapeutic method already in place. The present study reinforces that position and aims to describe the various uses of placebos in clinical research, as well as examining the complex decisions relating to the ethics of their use. Additionally, the authors propose a reflection on the use of placebos through decision-making algorithms based on Brazilian ethical standards...

El uso del placebo en la investigación clínica ha sido un tema de debate en los últimos años, sobre todo después de que la Asociación Médica Mundial publicara, en 2002, una nota aclaratoria del párrafo 29 de la Declaración de Helsinki. Brasil se ha destacado por su firme posición en contra de la utilización flexible del placebo. Tanto el Consejo Federal de Medicina como el Consejo Nacional de Salud editaron resoluciones que regulan el uso del placebo en Brasil, no admitiéndose su uso cuando existe un mejor método terapéutico. El presente artículo refuerza esa posición y tiene como objetivo describir diferentes usos del placebo en la investigación clínica, así como contribuir en la discusión sobre la ética de su uso. Además, los autores proponen una reflexión sobre el uso del placebo en la investigación a través de algoritmos para la toma de decisiones, los cuales se basan en las normativas éticas de Brasil...

Surgical site infection: an observer-blind, randomized trial comparing electrocautery and conventional scalpel.

AIM: To evaluate the incidence of surgical site infection (SSI) based on the type of scalpel used for incisions in the skin and in subcutaneous tissues. METHODS: Observer-blind, randomized equivalence clinical trial with two arms (electrocautery versus conventional scalpel) which evaluated 133 women undergoing elective abdominal gynecologic oncology surgery. A simple randomization stratified by body mass index (BMI: 30 kg/m(2)) was carried out. Women were evaluated at 14 and 30 days following the operation. A multivariate analysis was performed in order to check whether the type of scalpel would be a risk factor for SSI. RESULTS: Group arms were balanced for all variables, excepted for surgical time, which was significantly higher in the electrocautery group (mean: 161.1 versus 203.5 min, P = 0.029). The rates of SSI were 7.4% and 9.7%, respectively, for the conventional scalpel and electrocautery groups (P = 0.756). The exploratory multivariate model identified body mass index ≥30 kg/m(2) (OR = 24.2, 95% CI: 2.8-212.1) and transverse surgical incision (OR = 8.1, 95% CI: 1.5-42.6) as independent risk factors for SSI. The type of scalpel used in surgery, when adjusted for these variables and the surgery time, was not a risk factor for SSI. CONCLUSION: This study showed that the SSI rates for conventional scalpel and electrocautery were not significantly different. These results were consistent with others reported in the literature and would not allow a surgeon to justify scalpel choice based on SSI. TRIAL NUMBER: NCT01410175 (Clinical Trials - NIH).

Absence of TGF-ßRII predicts bone and lung metastasis and is associated with poor prognosis in stage III breast tumors.

In the case of operated breast cancer (BC), prognostic markers help to determine if the patient needs additional treatment and predictive markers help the clinician to decide which treatment to use. Thus, a better knowledge of known predictive and prognostic markers and the identification of new markers, may improve the treatment of BC patients. The transforming growth factor-beta type II receptor (TGF-ßRII), a main receptor of transforming growth factor beta pathway, is a potential new prognostic marker. The aims of the present study were to investigate both the predictive and prognostic impact of TGF-ßRII in BC samples. TGF-ßRII protein expression was evaluated using immunohistochemistry on a tissue microarray containing 110 TNM stage III BC samples obtained prior to doxorubicin-based neoadjuvant chemotherapy (NAC). Our results demonstrate that TGF-ßRII did not predict the response to NAC. On the other hand, an association between TGF-ßRII-negative tumor and higher risk of metastasis to lungs and bones was verified. TGF-ßRII negativity was an independent prognostic factor for decreased disease-free and overall survival.

[The evaluation of an instrument for pediatric oncology patient classification]. / Avaliação de um instrumento para classificação de pacientes pediátricos oncológicos.

The objectives of this study were to assess the interrater reproducibility of the instrument to classify pediatric patients with cancer; verify the adequacy of the patient classification instrument for pediatric patients with cancer; and make a proposal for changing the instrument, thus allowing for the necessary adjustments for pediatric oncology patients. A total of 34 pediatric inpatients of a Cancer Hospital were evaluated by the teams of physicians, nurses and nursing technicians. The Kappa coefficient was used to rate the agreement between the scores, which revealed a moderate to high value in the objective classifications, and a low value in the subjective. In conclusion, the instrument is reliable and reproducible, however, it is suggested that to classify pediatric oncology patients, some items should be complemented in order to reach an outcome that is more compatible with the reality of this specific population.

Avaliação de um instrumento para classificação de pacientes pediátricos oncológicos / The evaluation of an instrument for pediatric oncology patient classification / Evaluación de un instrumento para clasificación de pacientes pediátricos oncológicos

Este estudo teve como objetivos avaliar a reprodutibilidade interavaliadores do instrumento para a classificação de pacientes pediátricos portadores de câncer; verificar se o instrumento de classificação de pacientes é adequado a pacientes pediátricos portadores de câncer e elaborar uma proposta de modificação do instrumento, permitindo a adaptação para pacientes pediátricos oncológicos. Foram avaliados, na unidade de internação pediátrica de um Hospital de câncer, 34 pacientes pelas equipes de médicos, enfermeiros e técnicos de enfermagem. Para a avaliação do grau de concordância entre os escores obtidos pelos avaliadores foi utilizado o coeficiente Kappa, que revelou um valor intermediário/alto nas classificações objetivas, e um valor baixo nas subjetivas. Conclui-se que o instrumento é confiável e reprodutível, porém, para classificação do paciente pediátrico oncológico, sugere-se a complementação de itens para atingir um resultado mais compatível com a realidade dessa população.

The objectives of this study were to assess the interrater reproducibility of the instrument to classify pediatric patients with cancer; verify the adequacy of the patient classification instrument for pediatric patients with cancer; and make a proposal for changing the instrument, thus allowing for the necessary adjustments for pediatric oncology patients. A total of 34 pediatric inpatients of a Cancer Hospital were evaluated by the teams of physicians, nurses and nursing technicians. The Kappa coefficient was used to rate the agreement between the scores, which revealed a moderate to high value in the objective classifications, and a low value in the subjective. In conclusion, the instrument is reliable and reproducible, however, it is suggested that to classify pediatric oncology patients, some items should be complemented in order to reach an outcome that is more compatible with the reality of this specific population.

Estudio que objetivó estimar la reproductibilidad inter-evaluadores del instrumento para la clasificación de pacientes pediátricos portadores de cáncer; verificar si el instrumento de clasificación de pacientes es adecuado para pacientes pediátricos portadores de cáncer y elaborar una propuesta de modificación del instrumento, permitiendo su adaptación para pacientes pediátricos oncológicos. Fueron evaluados 34 pacientes en la unidad de internación pediátrica de un Hospital oncológico por parte de los equipos de médicos, enfermeros y técnicos de enfermería. Para estimar el grado de concordancia entre los puntajes obtenidos por los evaluadores, se utilizó el coeficiente Kappa, que expresó un valor entre intermedio y alto en las clasificaciones objetivas, y un valor bajo en las subjetivas. Se concluye en que el instrumento es confiable y reproducible, aunque para la clasificación del paciente pediátrico oncológico se sugiere la implementación de ítems para alcanzar un resultado más compatible con la realidad de éste población.