Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Spatially structured genetic diversity of the Amerindian yam (Dioscorea trifida L.) assessed by SSR and ISSR markers in Southern Brazil

Dioscorea trifida L. (Dioscoreaceae) is among the economically most important cultivated Amerindian yam species, whose origin and domestication are still unresolved issues. in order to estimate the genetic diversity maintained by traditional farmers in Brazil, 53 accessions of D. trifida from 11 municipalities in the states of São Paulo, Santa Catarina, Mato Grosso and Amazonas were characterized on the basis of eight Simple Sequence Repeats (SSR) and 16 Inter Simple Sequence Repeats (ISSR) markers. the level of polymorphism among the accessions was high, 95 % for SSR and 75.8 % for ISSR. the SSR marker showed higher discrimination power among accessions compared to ISSR, with D parameter values of 0.79 and 0.44, respectively. Although SSR and ISSR markers led to dendrograms with different topologies, both separated the accessions into three main groups: I-Ubatuba-SP; II-Iguape-SP and Santa Catarina; and III-Mato Grosso. the accessions from Amazonas State were classified in group II with SSR and in a separate group with ISSR. Bayesian and principal coordinate analyzes conducted with both molecular markers corroborated the classification into three main groups. Higher variation was found within groups in the AMOVA analysis for both markers (66.5 and 60.6 % for ISSR and SSR, respectively), and higher Shannon diversity index was found for group II with SSR. Significant but low correlations were found between genetic and geographic distances (r = 0.08; p = 0.0007 for SSR and r = 0.16; p = 0.0002 for ISSR). Therefore, results from both markers showed a slight spatially structured genetic diversity in D. trifida accessions maintained by small traditional farmers in Brazil.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Luiz de Queiroz Coll Agr, Dept Genet, BR-13400970 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, BR-09972270 São Paulo, BrazilUniv Calif Davis, Dept Plant Sci MS1, Sect Crop & Ecosyst Sci, Davis, CA 95616 USAUniversidade Federal de São Paulo, Dept Biol Sci, BR-09972270 São Paulo, BrazilFAPESP: 2007/04805-2Web of Scienc

Agravos clínicos atendidos pelo Serviço de Atendimento Móvel de Urgência (SAMU) de Porto Alegre - RS Agravios clínicos atendidos por el Servicio de Atención Móvil de Urgencia (SAMU) de Porto Alegre - RS Conditions treated in the Mobile Medical Emergency Services in Porto Alegre - RS

OBJETIVO: Caracterizar os agravos clínicos atendidos pelo Serviço de Atendimento Móvel de Urgência (SAMU), de Porto Alegre, no período de janeiro a junho de 2008. MÉTODOS: Estudo transversal, descritivo, exploratório. Utilizaram-se dados do sistema de informações do SAMU que foram transportados para o Programa Excel. O tratamento e análise dos dados foram descritivos. RESULTADOS: Os agravos neurológicos, cardiovasculares, respiratórios, digestivos e metabólicos foram os mais prevalentes, e a maioria ocorreu na faixa etária de 41-60 anos. Os hospitais públicos e unidades de pronto-atendimento foram as principais portas de entrada dos pacientes atendidos pelo SAMU. CONCLUSÃO: Os resultados podem contribuir para uma melhor organização do serviço e apontam necessidades de qualificação do atendimento de enfermagem que tem participação decisiva no cuidado ao paciente.<br>OBJETIVO: Caracterizar los agravios clínicos atendidos por el Servicio de Atención Móvil de Urgencia (SAMU), de Porto Alegre, en el período de enero a junio del 2008. MÉTODOS: Estudo transversal, descriptivo, exploratorio. Se utilizaron datos del sistema de informaciones del SAMU que fueron pasados al Programa Excel. El tratamiento y análisis de los datos fueron descriptivos. RESULTADOS: Los agravios neurológicos, cardiovasculares, respiratorios, digestivos y metabólicos fueron los más prevalentes, y la mayoría ocurrió en el grupo etáreo de 41-60 años. Los hospitales públicos y unidades de pronta-atención fueron las principales puertas de entrada de los pacientes atendidos por el SAMU. CONCLUSION: Los resultados pueden contribuir para una mejor organización del servicio y señalan necesidades de calificación de la atención de enfermería que tiene participación decisiva en el cuidado al paciente.<br>OBJECTIVE: To characterize the conditions treated in the Mobile Medical Emergency Services (SAMU) in Porto Alegre, from January to June 2008. METHODS: A cross- sectional, descriptive and exploratory study was performed. Data from the information system of the SAMU were used, which were dowloaded into the Microsoft Excel program. Descriptive data analysis was performed. RESULTS: Neurologic, cardiovascular, respiratory, digestive and metabolic disorders were most prevalent; most of these occurred in the age group ranging between 41-60 years. Public hospitals and emergency care units were the main ports of entry for patients treated at SAMU. CONCLUSION: These results may contribute to better organization and point of service qualification requirements for the nursing staff that has substantial involvement in patient care

Percepção de saúde na etnia Guarani Mbyá e a atenção à saúde Perception of health among the Guarany Mbyá ethnic group and health care

O artigo resulta de pesquisa qualitativa sobre a percepção de saúde da etnia Guarani Mbyá, realizada em três aldeias no Rio Grande do Sul e uma em Santa Catarina. As características culturais da etnia foram pesquisadas na literatura, observadas no trabalho de campo e confirmadas nas vinte entrevistas abertas realizadas com membros das comunidades e profissionais de saúde da Fundação Nacional de Saúde (Funasa) que responde pela assistência básica às aldeias. Os resultados mostram que os Mbyá consideram o choque cultural com a sociedade envolvente o principal fator de adoecimento, enfatizando a importância de preservar e valorizar seu modo de vida tradicional para a manutenção da saúde de indivíduos e coletividades. Os dados permitem associar suas representações sobre saúde aos problemas fundiários e de justiça social vivenciados pelos grupos. Apontam a importância de aprimorar a formação dos quadros técnicos de saúde, especificamente no que diz respeito à compreensão das diferenças interétnicas entre a cultura Mbyá e ocidental para garantir a efetividade de tratamentos e programas. A análise ressalta ainda aspectos positivos e negativos na operacionalização da assistência à saúde nas aldeias e, nas considerações finais, são apresentadas sugestões para seu aprimoramento.<br>The article results from a qualitative research on the perception of health of the Guarany Mbyá ethnic group held in 3 villages in the South of Brazil. The cultural characteristics of the group were surveyed in the literature, observed in fieldwork and confirmed in the 20 open interviews conducted with community members and health professionals from the National Health Foundation (FUNASA), responsible for the basic assistance to the villages. The results show that the Mbyá consider the cultural shock with the surrounding society the main factor of illness, emphasizing the importance of preserving and enhancing their traditional way of living for maintaining the health of individuals and communities. The data allow to associate their health representations to the land and social justice problems experienced by the groups. They point to the importance of improving the training of the technical health staff, specifically related to the understanding of the inter-ethnic differences between the Mbyá and Western culture to ensure the effectiveness of treatments and programs. The analyses also highlights positive and negative aspects of the operationalization of health care in the villages and in the final considerations are given suggestions aiming its improvement