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

Effect of hydro-alcoholic extract of Proveskia abrotanoides on blood glucose and liver enzymes level in streptozotocin-induced diabetic rats

Background and Objective: Diabetes mellitus is a metabolic disorder that is characterized by hyperglycemia resulting from defects in insulin secretion and action, or even both of them. Proveskia abrotanoides has anti-bacterial, anti-parasitic, antioxidant, anti-inflammatory, and analgesic effects. This study was done to evaluate the effect of hydro-alcoholic extract of Proveskia abrotanoides on blood glucose and liver enzymes level in streptozotocin-induced diabetic rats. Methods: In this experimental study, 60 male Wistar rats were randomly allocated into including healthy control, healthy received Glibenclamide, healthy -treated with 150, 300 and 600 mg/kg/bw of Proveskia abrotanoides extract, diabetic control, diabetic treated with 150, 300 and 600 mg/kg/bw of extract, positive control (diabetic treated with the Glibenclamide). After the treatments, the blood samples were taken from the animals and the level of blood glucose and liver enzymes including ALT, AST, and ALP were measured. Finally, the effect of hydro-alcoholic extract of Proveskia abrotanoides was compared with Glibenclamide as a conventional drug. Results: The results showed a significant increase in liver enzymes (ALT, AST, ALP) in hyperglycemic rats compared to the healthy controls (P<0.05). The mean of AST, ALT and ALP enzymes in hyperglycmia group were 286.83±7.46, 172.16±5.74, 526.17±8017, respectively while in healthy control it was 239±12.16, 100±2.42 and 196.33±6.82, respectively. In hyperglycemic rats treatment with doses of 150, 300, and 600 significantly reduced liver enzymes levels in compare to hyperglycemic contol group (P<0.05). In group treated with 150 mg/kg/bw, the average of ALP, AST, and ALT enzymes was 160.67±6.29, 127.33±5.23 and 260.33±7.18, respectively. The mean of ALP, AST, and ALT enzymes in group treated with 300 mg/ kg/bw was 197.5±6.71, 144.33±8.82 and 201.67±9.60, respectively. In group treated with 600 mg/kg/bw, the mean of ALP, AST, and ALT enzymes was 192.23±8.23, 111.17±6.13 and 329±7.43, respectively. The hydro-alcoholic extract of Proveskia abrotanoides significantly reduced serum glucose and liver enzymes in comparison with Glibenclamide group (P<0.05). Conclusion: The hydro-alcoholic extract of Proveskia abrotanoides reduces liver enzymes and blood glucose level in streptozotocin-induced diabetic rats

The Effect of Ultrasonic Waves on Sugar Extraction and Mechanical Properties of Sugar Beet

Sugar, which can be extracted from sugar cane and sugar beet, is one of the most important ingredients of food. Conducting more research to increase the extraction efficiency of sugar is necessary due to high production of sugar beet and its numerous processing units in northern Khorasan province. In this research, the effect of temperature, time and the frequency of ultrasonic waves on mechanical properties of sugar beet and its extraction rate of sugar in moisture content of 75% were studied. In this regard, an ultrasonic bath in laboratory scale was used. The studied parameters and their levels were frequency in three levels (zero, 25 and 45 KHz), temperature in three levels (25, 50 and 70 ° C) and the imposed time of ultrasonic waves in three levels (10, 20 and 30 min). Samples were prepared using planned experiments and the results were compared with control sugar beet samples. A Saccharimeter was used to measure the concenteration of sugar in samples. Two different types of probe including semi-spherical end and the other one with sharpened edges were used to measure mechanical properties. The studied parameters of frequency, temperature and time showed significant effect on sugar extraction and their resulted effect in optimized levels revealed up to 56% increase in sugar extraction compared with control samples. The obtained values of elastic modulus and shear modulus showed a decreasing trend. The obtained values of total energy of rupture, the total energy of shear, the maximum force of rupture, and the yield point of rupture showed an increasing trend. The frequency had no significant effect on the yield point of rupture and shear force