Abstract Objective To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. Materials and methods The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. Results Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. Conclusion The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases. MEDLINE LILACS Library databases records investigators analysis infections teratogenicity Longterm Long term longterm long 3 g discontinuation 1 41 41% bias i.e., ie i e (i.e. g, , g) intake anticoagulants disease cases 4 i.e. (i.e i.e

CONTEXTO E OBJETIVOS: A quantificação dos sinais do exame clínico como a presença de descoramento sugerindo anemia é um passo fundamental para o diagnóstico clínico. Avaliar dois métodos para o diagnóstico de anemia realizados por meio do exame físico-método de cruzes (+,++,+++,++++) e método de estimativa do valor de hemoglobina feito pelo médico ou estudante de medicina. Verificar se a acurácia desses métodos se relaciona com a experiência clínica. TIPO DE ESTUDO E LOCAL: 44 médicos assistentes, residentes e estudantes de medicina selecionados de forma aleatória completaram o exame clínico de cinco pacientes com anemia leve a grave. MÉTODOS: Os examinadores utilizaram o método das cruzes em quatro níveis e, também estimaram o nível da hemoglobina. Ambos os métodos foram comparados com a hemoglobina medida (padrão-ouro). RESULTADOS: O valor estimado da hemoglobina se correlacionou melhor com a hemoglobina aferida por método automático do que a avaliação realizada pelo método das cruzes para as comparações realizadas entre médicos assistentes, residentes e alunos (coeficiente de correlação de Spearman respectivamente de 1,0, 1,0 e 0,9 para hemoglobina estimada e - 0,8, - 0,8 e - 0,7 para o método das cruzes). Não houve nenhuma diferença no valor estimado de hemoglobina entre os médicos assistentes, os residentes e os alunos. Entretanto, a correlação entre o valor estimado da hemoglobina e o método das cruzes somente foi positiva para os médicos assistentes, sugerindo algum tipo de melhora na avaliação da presença de anemia com a experiência clínica (p = 0,04). CONCLUSÕES: Este estudo mostrou que a estimativa do valor da hemoglobina pelo exame físico apresenta maior acurácia do que a avaliação pelo método de cruzes, considerando-se a medida automática de hemoglobina como padrão-ouro. A experiência clínica não melhora o diagnóstico de anemia.

CONTEXT AND OBJECTIVES: Quantification of clinical signs such as the presence or absence of pallor at clinical examination is a key step for making diagnoses. The aim was, firstly, to evaluate two methods for anemia diagnosis by physical examination: four-level evaluation (crosses method: +/++/+++/++++) and estimated hemoglobin values, both performed by medical students and staff physicians; and secondly, to investigate whether there was any improvement in assessment accuracy according to the number of years in clinical practice. DESIGN AND SETTING: Forty-four randomly selected physicians and medical students in a tertiary care teaching hospital completed a physical examination on five patients with mild to severe anemia. METHODS: The observers used four-level evaluation and also predicted the hemoglobin level. Both methods were compared with the real hemoglobin value as the gold standard. RESULTS: The mean estimated hemoglobin value correlated better with the real hemoglobin values than did the four-level evaluation method, for attending physicians, residents and students (Spearman's correlation coefficients, respectively: 1.0, 1.0 and 0.9 for guessed hemoglobin and -0.8, -0.8 and -0.7 for the four-level evaluation method). There were no differences in the mean "guessed" hemoglobin values from attending physicians, residents and students. However, the correlation between guessed hemoglobin value and the four-level method was positive for attending physicians, thus suggesting some kind of improvement with time (p = 0.04). CONCLUSIONS: This study showed that estimated hemoglobin was more accurate than evaluation by the four-level method. The number of years in clinical practice did not improve the accuracy of clinical examination for anemia.