Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

β-globin haplotypes in normal and hemoglobinopathic individuals from Reconcavo Baiano, State of Bahia, Brazil

Five restriction site polymorphisms in the β-globin gene cluster (HincII-5‘ ε, HindIII-G γ, HindIII-A γ, HincII- ψβ1 and HincII-3‘ ψβ1) were analyzed in three populations (n = 114) from Reconcavo Baiano, State of Bahia, Brazil. The groups included two urban populations from the towns of Cachoeira and Maragojipe and one rural Afro-descendant population, known as the “quilombo community”, from Cachoeira municipality. The number of haplotypes found in the populations ranged from 10 to 13, which indicated higher diversity than in the parental populations. The haplotypes 2 (+ - - - -), 3 (- - - - +), 4 (- + - - +) and 6 (- + + - +) on the βA chromosomes were the most common, and two haplotypes, 9 (- + + + +) and 14 (+ + - - +), were found exclusively in the Maragojipe population. The other haplotypes (1, 5, 9, 11, 12, 13, 14 and 16) had lower frequencies. Restriction site analysis and the derived haplotypes indicated homogeneity among the populations. Thirty-two individuals with hemoglobinopathies (17 sickle cell disease, 12 HbSC disease and 3 HbCC disease) were also analyzed. The haplotype frequencies of these patients differed significantly from those of the general population. In the sickle cell disease subgroup, the predominant haplotypes were BEN (Benin) and CAR (Central African Republic), with frequencies of 52.9% and 32.4%, respectively. The high frequency of the BEN haplotype agreed with the historical origin of the afro-descendant population in the state of Bahia. However, this frequency differed from that of Salvador, the state capital, where the CAR and BEN haplotypes have similar frequencies, probably as a consequence of domestic slave trade and subsequent internal migrations to other regions of Brazil

Nestedness of Ectoparasite-Vertebrate Host Networks

Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks—including three derived from molecular bloodmeal analysis of mosquito feeding patterns—using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same “generalized” hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations) can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Biological associations of color variation in the Indo-Pacific swimming crab Charybdis hellerii

A marine biological invasion is a natural process accelerated by human activities, and the crab Charybdis hellerii is an example of a globally widespread invasive species. This study evaluated color variation in C. hellerii and its relationship to the sex, size and sexual maturity of these crabs, and compared the efficiency of a freeware digital image-editing program with a commercially available program. The color of the individuals was analyzed using standardized digital images. The color pattern varied significantly with size; smaller and immature individuals were darker than larger and mature ones. The female abdomen changed in morphology and color with sexual maturity, becoming wider and orange-colored. There was no statistical difference in the color values between males and females and immature males did not show morphological or color differences in their abdomen. This study highlights the possible relationships of the color and physiological state of the reproductive system, which could help in future studies of behavior, avoiding the need to dissect and/or remove individuals from nature for assessment of sexual maturity. The freeware program showed the same efficiency in digital image analysis as a widely known commercial program.Invasões biológicas marinhas são processos naturais acelerados pelas atividades humanas e o siri Charybdis hellerii é um exemplo de espécies invasoras distribuídas pelo mundo. Este estudo avaliou a variação de cor em C. hellerii e sua relação com o sexo, tamanho e maturidade sexual desses indivíduos, e comparou a eficiência de um programa de edição de imagem de licença livre com um programa disponível comercialmente. A cor dos indivíduos foi analisada usando imagem digital padronizada. O padrão de cor variou significantemente com o tamanho; indivíduos pequenos e imaturos são mais escuros que indivíduos maiores e maduros. Os abdomens das fêmeas mudaram morfologicamente e na cor de acordo com a maturidade sexual, tornando-se mais largos e de cor alaranjada. Não houve diferença estatística nos valores de cor entre machos e fêmeas, e machos imaturos não mostraram diferenças morfológicas e de cor em seus abdomens. Este estudo ressalta as possíveis relações da cor e estado fisiológico do sistema reprodutivo o que pode ajudar futuramente em estudos comportamentais, evitando a necessidade de dissecar e/ou remover indivíduos da natureza para avaliar a maturidade sexual. O programa livre obteve a mesma eficiência na análise de imagem digital em relação ao programa comercial amplamente conhecido.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal do Amazonas (UFAM), Programa de Pós-Graduação em Ciência e Tecnologia para Recursos Amazônicos (PPGCTRA), Instituto de Ciências Exatas e Tecnologia (ICET), Rua Nossa Senhora do Rosário, 3863, 69103-128 Itacoatiara, AM, BrasilUniversidade Estadual Paulista (UNESP), Faculdade de Ciências Agrárias e Veterinárias, Centro de Aquicultura, Instituto de Estudos Avançados do Mar, Departamento de Biologia Aplicada, Laboratório de Morfologia de Invertebrados, Campus de Jaboticabal, Via de Acesso Prof. Paulo Donato Castellane, s/n, 14884-900 Jaboticabal, SP, BrasilUniversidade de São Paulo (USP), Instituto Oceanográfico (IOUSP), Departamento de Oceanografia Biológica (DOB), Praça do Oceanográfico, 191, 05508-120 São Paulo, SP, BrasilUniversidade Estadual Paulista (UNESP), Faculdade de Ciências Agrárias e Veterinárias, Centro de Aquicultura, Instituto de Estudos Avançados do Mar, Departamento de Biologia Aplicada, Laboratório de Morfologia de Invertebrados, Campus de Jaboticabal, Via de Acesso Prof. Paulo Donato Castellane, s/n, 14884-900 Jaboticabal, SP, BrasilCNPq: 301240/2006-0CNPq: 308215/2010-9FAPESP: 2005/04707-5FAPESP: 2010/50188-