Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70–75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.This study was supported by FCT (“Portuguese Foundation for Science and Technology”) through a PhD grant to RB (SFRH/ BD/111321/2015). Further funding was obtained from the project “Advancing cancer research: from basic knowledge to application” NORTE-01-0145-FEDER-000029: “Projetos Estruturados de I & D & I,” funded by Norte 2020—Programa Operacional Regional do Norte. This article is a result of the project PTDC/MED-ONC/31438/2017 (The Other Faces of Telomerase: Looking beyond Tumor Immortalization), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI) and by Portuguese funds through FCT. Further funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalisation— COMPETE 2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390:CANCEL STEM

O discurso médico e a Educação Física nas escolas (Brasil, século XIX)

Para os médicos, a reforma da sociedade não residia apenas nas ruas, nas avenidas, nas construções, enfim, em uma urbanização com base em preceitos da saúde. Era impreterível incutir uma reforma dos corpos, que ocorria primeiro no núcleo familiar através da educação higiênica na infância. É neste campo específico da Higiene que os exercícios físicos tornaram-se foco de interesse dos médicos. O objetivo deste estudo é descrever o contexto de escolarização da Educação Física mediante o discurso médico do século XIX. Para isto, realizou-se uma pesquisa histórica e documental que teve como fontes: as teses para a obtenção do título de doutor da Faculdade de Medicina do Rio de Janeiro e Bahia. Conclui-se que a mentalidade higienista colaborou para a lenta difusão dos exercícios físicos no contexto educacional do século XIX. Contudo a relevância da ginástica era secundária no projeto higienista

Avaliação da estrutura organizacional da assistência ambulatorial em HIV/Aids no Brasil Evaluation of the organizational structure of HIV/AIDS outpatient care in Brazil

OBJETIVO: No contexto de acesso universal à terapia antiretroviral, os resultados do Programa de Aids dependem da qualidade do cuidado prestado. O objetivo do estudo foi avaliar a qualidade do cuidado dos serviços ambulatoriais que assistem pacientes de Aids. MÉTODOS: Estudo realizado em sete Estados brasileiros, em 2001 e 2002. Foi avaliada a qualidade do atendimento a pacientes com Aids quanto à disponibilidade de recursos e a organização do trabalho de assistência. Um questionário com 112 questões estruturadas abordando esses aspectos, foi enviado a 336 serviços. RESULTADOS: A taxa de resposta foi de 95,8% (322). Os indicadores de disponibilidade de recursos mostram uma adequação maior do que os indicadores de organização do trabalho. Não faltam antiretrovirais em 95,5% dos serviços, os exames de CD4 e Carga Viral estão disponíveis em quantidade adequada em 59 e 41% dos serviços, respectivamente. Em 90,4% dos serviços há pelo menos um profissional não médico (psicólogo, enfermeiro ou assistente social). Quanto à organização, 80% não agendavam consulta médica com hora marcada; 40,4% agendavam mais que 10 consultas médicas por período; 17% não possuíam gerentes exclusivos na assistência e 68,6% não realizavam reuniões sistemáticas de trabalho com a equipe. CONCLUSÕES: Os resultados apontam que além de garantir a distribuição mais homogênea de recursos, o programa precisa investir no treinamento e disseminação do manejo do cuidado, conforme evidenciado nos resultados da organização de trabalho.<br>OBJECTIVE: In the context of universal access to antiretroviral treatment, the results of the Brazilian AIDS Program will depend on the quality of the care provided. The aim of the present study was to evaluate the healthcare provided by outpatient services for the treatment of AIDS patients. METHODS: The present study was carried out in seven Brazilian States between 2001 and 2002. We evaluated the quality of the care provided to AIDS patients from the standpoint of resource availability and care process organization. A questionnaire comprising 112 structured questions addressing these aspects was sent to 336 services. RESULTS: Response rate was 95.8% (322). Greater adequacy is seen for indicators of resource availability than for those of work organization. The supply of antiretroviral medication is sufficient in 95.5% of services. CD4 and viral load tests are available at adequate amounts in 59 and 41% of services, respectively. In 90.4% of services there is at least one non-medical professional (psychologist, nurse, or social worker). As to work organization, 80% scheduled the date but not the time of medical appointments; 40.4% scheduled more than 10 appointments per period; 17% did not have exclusive managers; and 68.6% did not hold systematic staff meetings. CONCLUSIONS: The results indicate that, in addition to ensuring the more homogeneous distribution of resources, the program must invest in the training and dissemination of care management skills, as confirmed by the results of care process organization