Degarelix therapy for prostate cancer in a real-world setting: experience from the German IQUO (Association for Uro-Oncological Quality Assurance) Firmagon® registry.

BACKGROUND: We investigated the use of the gonadotropin-releasing hormone (GnRH) antagonist degarelix in everyday clinical practice using registry data from uro-oncology practices in Germany. METHODS: Data were analysed retrospectively from the IQUO (Association for uro-oncological quality assurance) patient registry. Data were prospectively collected from all consecutive PCa patients treated with degarelix (n = 1010) in 138 uro-oncology practices in Germany between May 2009 and December 2013. RESULTS: Median overall survival had not yet been reached in the all-patient group or in subgroups who had or had not received prior hormonal therapy (HT). Cox regression analysis showed that patients who had received prior HT (n = 542) had a 58 % increased mortality risk (hazard ratio 1.58, 95 % CI 1.20-2.09) versus patients who had not (n = 468) (p = 0.001). Also, in patients who had received prior luteinizing hormone-releasing hormone (LHRH) analogue therapy (LHRH agonists or GnRH antagonists), median time to PSA progression was shorter (209 weeks) than in those who had not received prior LHRH analogues (n = 555; median PSA progression-free survival not yet reached). Degarelix was generally well tolerated. CONCLUSIONS: Degarelix was effective and well tolerated in everyday clinical practice, confirming observations from clinical studies. Patients who received prior HT appeared to have a significantly higher mortality risk.

A kinetic model for simultaneous saccharification and fermentation of Avicel with Saccharomyces cerevisiae.

This work describes a numerical model for predicting simultaneous saccharification and fermentation of Avicel, an insoluble crystalline cellulose polymer. Separate anoxic cultivations of 40 g/L glucose and 100 g/L Avicel were conducted to verify model predictions and obtain parameters to describe the reaction kinetics. Saccharification of Avicel was achieved with Trichoderma reesei cellulases from the enzyme preparation Spezyme CP with an enzyme loading of 10 FPU/g cellulose. Cultivations were supplemented with 50 IU/g cellulose of ß-glucosidase from Novozym 188 to prevent product inhibition by cellobiose. Saccharomyces cerevisiae MH-1000 is a robust industrial strain and was used to ferment glucose to ethanol, glycerol, and carbon dioxide. The numerical model presented in this paper differs from previous models by separating the endoglucanase and exoglucanase enzyme kinetics and allowing for inhibitive site competition. Assuming all enzymes remain active and that each enzyme complex has a corresponding constant specific activity, the model is capable of predicting adsorbed enzyme concentrations with reasonable accuracy. Comparison of predicted values to experimental measurements indicated that the numerical model was capable of capturing the significant elements involved with cellulose conversion to ethanol.

Structured desmopressin withdrawal improves response and treatment outcome for monosymptomatic enuretic children.

PURPOSE: In this national, multicenter, retrospective survey we tested whether structured withdrawal of desmopressin, in which dose frequency rather than dose quantity was gradually decreased, would improve outcome. MATERIAL AND METHODS: Enrolled in the study were 487 monosymptomatic enuretic patients from a total of 181 centers (The Enuresis Algorithm of Marschall Survey Group). At study outset 41% of patients had 7 wet nights per week, 45% had 3 to 6 and 14% had fewer than 3. All patients were treated with desmopressin, which was abruptly terminated or tapered with analogue by a structured scheme. Response rates were compared in the groups according to International Children's Continence Society guidelines. RESULTS: The 173 children with abrupt termination had a 51% response rate, including a full and partial response in 44.1% and 27%, respectively, and no response in 22%. The 314 children with tapering had a 72% response rate, including a full and partial response in 66.8% and 24%, and no response in 4% (p <0.0001). Enuresis frequency with abrupt termination decreased from 21 wet nights per month before treatment to 6. The tapering group had 21 wet nights per months before and 2 after treatment (p <0.0001). Followup at 1 month showed fewer than 2 wet nights per month in 57% of cases with abrupt termination and in 80% with tapering (p <0.0001). Pretreatment had no influence. No severe side effects occurred. CONCLUSIONS: This national, multicenter, retrospective analysis proves that antidiuretic treatment followed by a structured withdrawal program is superior to regular treatment with abrupt termination in enuretic children. Hence, desmopressin followed by structured withdrawal should be the standard. It is also superior to published outcomes of alarm treatment.