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