RESUMO
This open-label randomized trial compared isoniazid (9 months) to rifampin (4 months) on toxicity and completion in a jailed population with latent tuberculosis infection. Rifampin resulted in fewer elevated liver function tests (risk ratio [RR] 0.39, 95% confidence interval [CI] [0.18, 0.86]) and less toxicity requiring medication withdrawal (RR 0.51, 95% CI [0.13, 2.01]), although one participant receiving rifampin experienced an allergic reaction. Completion was achieved for 33% receiving rifampin compared to 26% receiving isoniazid (p = .10). With careful monitoring rifampin is a safe and less toxic regimen and appears to be a reasonable alternative because of its shorter duration, allowing more people to complete treatment behind bars. Therapy completion in released inmates is unacceptably low and ensuring follow-up after discharge must be part of a decision to treat.
Assuntos
Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Prisões , Rifampina/uso terapêutico , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Terapia Diretamente Observada , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Testes de Função Hepática , Masculino , Adesão à Medicação , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Fatores SocioeconômicosRESUMO
CONTEXT: A polymerase chain reaction-based companion diagnostic (cobas 4800 BRAF V600 Mutation Test) was recently approved by the US Food and Drug Administration to select patients with BRAF-mutant metastatic melanoma for treatment with the BRAF inhibitor vemurafenib. OBJECTIVES: (1) To compare the analytic performance of the cobas test to Sanger sequencing by using screening specimens from phase II and phase III trials of vemurafenib, and (2) to assess the reproducibility of the cobas test at different testing sites. DESIGN: Specimens from 477 patients were used to determine positive and negative percent agreements between the cobas test and Sanger sequencing for detecting V600E (1799T>A) mutations. Specimens were evaluated with a massively parallel pyrosequencing method (454) to resolve discordances between polymerase chain reaction and Sanger results. Reproducibility of the cobas test was assessed at 3 sites by using 3 reagent lots and an 8-member panel of melanoma samples. RESULTS: A valid cobas result was obtained for all eligible patients. Sanger sequencing had a failure rate of 9.2% (44 of 477). For the remaining 433 specimens, positive percent agreement was 96.4% (215 of 223) and negative percent agreement, 80% (168 of 210). Among 42 cobas mutation-positive/Sanger V600E-negative specimens, 17 were V600E positive and 24 were V600K positive by 454. The cobas test detected 70% of V600K mutations. In the reproducibility study, a correct interpretation was made for 100% of wild-type specimens and specimens with greater than 5% mutant alleles; V600E mutations were detected in 90% of specimens with less than 5% mutant alleles. CONCLUSIONS: The cobas test (1) had a lower assay failure rate than that of Sanger, (2) was more sensitive in detecting V600E mutations, (3) detected most V600K mutations, and (4) was highly reproducible.