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

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

Assessment of resistances to multiple pathogens in experimental sweet pepper hybrids

The aim of this study was to assess resistance to some of the major sweet pepper pathogens [Phytophthora capsici, Pepper yellow mosaic virus (PepYMV) and Meloidogyne incognita] in a group of experimental hybrids and their respective parental lines, and to identify hybrids possibly resistant to all three pathogens. Ten parental breeding lines, thirty experimental hybrids and seven commercial controls (Konan-R, Magali-R, Martha-R, Stephany, Mallorca, Magnata Super and Criollo de Morelos-334) were used. Each experiment was set up in a randomized complete block design with three replications and plots consisting of 16 plants. For assessment of resistance to P. capsici and PepYMV, the percent of asymptomatic plants was considered. In evaluating reactions to M. incognita, both the nematode reproduction index and the nematode reproduction factor were calculated. Five hybrids were found with resistance to all three pathogens. For all three pathogens, there was evidence that hybrids with two resistant parental lines showed slightly higher levels of pathogen resistance than those with only one resistant parental line. © 2017, Sociedade de Olericultura do Brasil. All rights reserved

Morphoagronomic characteristics display high genetic diversity in Murupi chili pepper landraces

Murupi chili pepper is a hot Amazonian pepper that has been used as flavoring in the region, yet its diversity is unknown. This paper aims to assess the diversity in 20 landraces from Peruvian, Colombian, and Brazilian Amazon. The experiment was installed in Manaus-AM, using a randomized complete block design with three replicates and five plants per plot. Analyses of variance showed significant differences for all nine descriptors. Fruit yield showed, in average, to be 208.08 fruits per plant, tantamount to 381.44 g per plant. Given 50% of relative distances estimated by generalized Mahalanobis distances and, nearest neighbor clustering, they displayed six groups. Cluster I comprised 50% of the landraces. Clusters IV, V and VI were represented by ‘8’ (Putumayo, Colombia), ‘27’ (Yurimaguas, Peru) and ‘24’ (Jutaí-AM, Brazil), respectively. The highest yielding landrace showed to be ‘17’ (Manicoré-AM, Brazil), bearing 685.5 fruits and 1.92 kg per plant. Our findings suggest Murupi pepper may possibly be improved by selection and/ or hybridization. © 2018, Sociedade de Olericultura do Brasil. All rights reserved

Combining ability in sweet pepper for resistance to powdery mildew Capacidade de combinação em pimentão para resistência a oídio

With the increase of the production of pepper in protected environment, pathogens began to cause serious damages to producers such as Leveillula taurica (Lév.) Arn., fungus that causes powdery mildew. The systemic fungicides have not shown very satisfactory results. Thus, considering that protected cropping of pepper in Brazil is significant and growing, the incorporation of genes that confer resistance to powdery mildew is important for the maintenance of this cropping system. In this research, carried out in 2007 in Campinas, São Paulo State, Brazil, the agronomic performance and resistance to powdery mildew was determined by triple hybrids of sweet pepper through general and specific combining ability of their parents. For agronomic performance of the triple hybrid, it was evaluated the weight length and width average of the fruit, length and width ratio of the fruit and wall thickness. For severity of powdery mildew a scale of scores from 1 to 5 was used. For statistical and genetic analysis, it was adopted Griffing's method two, model I, adapted for partial diallel. The experimental design was completely randomized blocks, with 17 treatments, including ten experimental hybrids and seven parents, eight replications and four plants per plot. The additive effects were greater than the non-additive effects for all agronomic characters; 'P36-R' and 'Platero' were highlighted as good combiners; 'Quantum-R x HV-12', 'Rubia x HV-12' and 'P36-R x HV-12' presented the best specific combining ability; the mean square of the specific combining ability for the severity of the disease was significant indicating the importance of genes with dominant and epistatic effect; triple hybrids obtained by crosses with 'Quantum-R' and 'Rubia-R' had negative general combining ability and the best reactions to powdery mildew.<br>Com o aumento do cultivo protegido de pimentão, patógenos como Leveillula taurica (Lév.) Arn., fungo causador do oídio, passaram a causar sérios prejuízos aos produtores. Os fungicidas sistêmicos não têm apresentado resultados muito satisfatórios. Assim, levando-se em conta que o cultivo protegido de pimentão no Brasil é importante e crescente, a incorporação de genes que conferem resistência ao oídio é relevante para a manutenção desse sistema de cultivo. Nesse trabalho, realizado em 2007 em Campinas-SP, determinou-se o potencial agronômico e de resistência a oídio de híbridos triplos de pimentão por meio da capacidade geral e específica de combinação dos genitores. Para determinar o desempenho agronômico dos híbridos triplos, avaliaram-se o peso, comprimento e largura média do fruto, relação entre comprimento e largura do fruto e espessura da polpa. Para a avaliação da severidade da doença utilizou-se escala de notas de 1 a 5. Para as análises estatístico-genéticas, adotou-se o método dois, modelo I de Griffing, adaptado para dialelo parcial. O delineamento experimental utilizado foi o de blocos ao acaso, com 17 tratamentos, incluindo dez híbridos experimentais e sete genitores, oito repetições e quatro plantas por parcela. Os efeitos aditivos foram superiores aos efeitos nãoaditivos para todos os componentes agronômicos avaliados; 'P36-R' e 'Platero' destacaram-se como bons combinadores para os caracteres agronômicos avaliados; 'Quantum-R x HV-12', 'Rubia-R x HV-12' e 'P36-R x HV-12' apresentaram os maiores efeitos da capacidade específica de combinação para a maioria dos caracteres avaliados; o quadrado médio da capacidade específica de combinação significativo para a severidade da doença indicou a importância de genes com efeito de dominância e epistasia; híbridos triplos obtidos do cruzamento com 'Quantum-R' e 'Rubia-R' apresentaram capacidade geral de combinação negativa e as melhores reações de resistência ao oídio