Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil.

Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). However, amino acid substitutions associated with resistance (RAS) have been extensively described and can contribute to treatment failure, and diagnosis of RAS requires considerable infrastructure, not always locally available. Dried serum spots (DSS) sampling is an alternative specimen collection method, which embeds drops of serum onto filter paper to be transported by posting to a centralized laboratory. Here, we assessed feasibility of genotypic analysis of HCV from DSS in a cohort of 80 patients from São Paulo state Brazil. HCV RNA was detected on DSS specimens in 83 % of samples of HCV infected patients. HCV genotypes 1a, 1b, 2a, 2c and 3a were determined using the sequence of the palm domain of NS5B region, and RAS C316N/Y, Q309R and V321I were identified in HCV 1b samples. Concerning therapy outcome, 75 % of the patients who used INF +RBV as a previous protocol of treatment did not respond to DAAs, and 25 % were end-of-treatment responders. It suggests that therapy with INF plus RBV may contribute for non-response to a second therapeutic protocol with DAAs. One patient that presented RAS (V321I) was classified as non-responder, and combination of RAS C316N and Q309R does not necessarily imply in resistance to treatment in this cohort of patients. Data presented herein highlights the relevance of studying circulating variants for a better understanding of HCV variability and resistance to the therapy. Furthermore, the feasibility of carrying out genotyping and RAS phenotyping analysis by using DSS card for the potential of informing future treatment interventions could be relevant to overcome the limitations of processing samples in several location worldwide, especially in LMICs.

Otimização hemodinâmica em trauma grave: uma revisão sistemática e metanálise / Hemodynamic optimization in severe trauma: a systematic review and meta-analysis

Objetivo: O trauma grave pode associar-se a ocorrência de importante choque hemorrágico e ao comprometimento da perfusão dos órgãos. Formulamos a hipótese de que o tratamento direcionado por objetivo conferiria benefícios em termos de morbidade e mortalidade, em casos graves de trauma. Métodos: Realizamos uma busca sistemática nas bases de dados MedLine, Embase e Cochrane Controlled Clinical Trials Register com relação a pacientes vítimas de trauma grave. A mortalidade foi o desfecho primário dessa revisão. Os desfechos secundários incluíram taxas de complicações, duração da permanência no hospital e na unidade de terapia intensiva, e o volume de fluidos administrados. A metanálise foi realizada utilizando o programa de computador RevMan, e os dados apresentados são as odds ratios (OR) para desfechos dicotomizados e as diferenças médias e diferenças médias padrão para desfechos contínuos. Resultados: Foram analisados quatro estudos clínicos randomizados e controlados, que incluíram 419 pacientes. O risco de mortalidade foi significantemente reduzido nos pacientes com tratamento direcionado por objetivo, em comparação ao grupo controle (OR=0,56; IC95%: 0,34-0,92). A duração da permanência na unidade de terapia intensiva (DM: 3,7 dias; IC95%: 1,06-6,5) e no hospital (DM: 3,5 dias; IC95%: 2,75-4,25) foi significantemente mais curta ...

Objective: Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. Methods: The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized, controlled trials of goal-directed therapy in severe trauma patients. Mortality was the primary outcome of this review. Secondary outcomes included complication rates, length of hospital and intensive care unit stay, and the volume of fluid and blood administered. Meta-analysis was performed using RevMan software, and the data presented are as odds ratios for dichotomous outcomes and as mean differences (MDs) and standard MDs for continuous outcomes. Results: Four randomized, controlled trials including 419 patients were analyzed. Mortality risk was significantly reduced in goal-directed therapy-treated patients, compared to the control group (OR=0.56, 95%CI: 0.34-0.92). Intensive care (MD: 3.7 days 95%CI: 1.06-6.5) and hospital length of stay (MD: 3.5 days, 95%CI: 2.75-4.25) were significantly shorter in the protocol group patients. There were no differences in reported total fluid volume or blood transfusions administered. Heterogeneity in reporting among the studies prevented quantitative analysis of complications. Conclusion: Following severe trauma, early goal-directed therapy was associated with lower ...

Hemodynamic optimization in severe trauma: a systematic review and meta-analysis.

OBJECTIVE: Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. METHODS: The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized, controlled trials of goal-directed therapy in severe trauma patients. Mortality was the primary outcome of this review. Secondary outcomes included complication rates, length of hospital and intensive care unit stay, and the volume of fluid and blood administered. Meta-analysis was performed using RevMan software, and the data presented are as odds ratios for dichotomous outcomes and as mean differences (MDs) and standard MDs for continuous outcomes. RESULTS: Four randomized, controlled trials including 419 patients were analyzed. Mortality risk was significantly reduced in goal-directed therapy-treated patients, compared to the control group(OR=0.56, 95%CI: 0.34-0.92). Intensive care (MD: 3.7 days 95%CI: 1.06-6.5)and hospital length of stay (MD: 3.5 days,95%CI: 2.75-4.25) were significantly shorter in the protocol group patients.There were no differences in reported total fluid volume or blood transfusions administered. Heterogeneity in reporting among the studies prevented quantitative analysis of complications. CONCLUSION: Following severe trauma, early goal-directed therapy was associated with lower mortality and shorter durations of intensive care unit and hospital stays. The findings of this analysis should be interpreted with caution due to the presence of significant heterogeneity and the small number of the