Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Factors affecting speech perception in children cochlear 22-channel cochlear prosthesis [Abstract]

Since the implantation of the first children with the Nucleus 22-channel cochlear prosthesis in Melbourne in 1985, there have been rapid expansion world-wide in the number of children using this implant system. Longer-term experience with implanted children has led to improvements in paediatric assessment and management. Speech processing strategies have also been improved, resulting in a series of increases in speech perception benefits.3-5 Apri

Speech perception for children with different levels of residual hearing using the cochlear 22-channel cochlear prosthesis [Abstract[

Paper presented at the 12th National Conference of the Audiological Society of Australia. Brisbane, 29 April - 2 May 1996.This is a publisher’s version of an article published in Australian Journal of Audiology 1996. This version is reproduced with permission from the publisher, Australian Academic Press. http://www.australianacademicpress.com.au/Over the past 10 years, since the implantation of the first children with the Nucleus 22-channel cochlear prosthesis in Melbourne, the number of profoundly deaf children using this implant system has rapidly expanded. Longer-term experience with implanted children has led to improvements in paediatric assessment and management. Speech processing strategies have also been improved, resulting in a series of increases in speech perception benefits. Results of comparative studies of Speak and Multipeak speech processing strategies have shown that open-set word and sentence scores for a group of thirteen children evaluated over a two year period showed an advantage with the Speak speech processing strategy. The increases were noted particularly in speech perception in poor signal-to-noise conditions. Analysis has shown that consonant perception was significantly increased, due to an improved place perception. Given current speech perception scores for implanted children, it has been suggested that severely-to-profoundly deaf children currently using hearing aids could in fact benefit more from a cochlear implant. Preliminary investigation of results for children in the Melbourne and Sydney cochlear implant programs has shown that children with higher levels of preoperative residual hearing as a group do score significantly on open-set word and sentence perception tests using the implant alone. In children with lower levels of residual hearing, results were variable across the group

Oxidative and nonoxidative benzodiazepines and the risk of femur fracture

Benzodiazepine use is a well-identified risk factor for falls and the resulting femur fractures in elderly adults. Benzodiazepines not requiring hepatic biotransformation may be safer than agents undergoing oxidation because oxidative activity has been shown to decline with age. The association between the use of either oxidative or nonoxidative benzodiazepines and the risk of femur fracture among elderly adults living in nursing homes was studied. A nested case-control study was conducted using the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database; the records of 9,752 patients hospitalized for incident femur fracture during the period 1992 to 1996 were extracted, matching by age, gender, state, and index date to the records of 38,564 control patients. Conditional logistic regression models were conducted to estimate the odds ratios (ORs) for femur fracture with adjustment for potential confounders. The adjusted OR for the overall use of benzodiazepines was 1.10 (95% confidence interval [CI], 0.98-1.20); the risk seemed of only slightly greater magnitude for exposure to nonoxidative agents (1.18; 95% CI, 1.03- 1.36) than to oxidative benzodiazepines (1.08; 95% CI, 0.95-1.23). Among the latter, the effect was mainly accounted for by the use of agents with a long elimination half-life. A dose relationship was observed exclusively among users of long half-life oxidative benzodiazepines. The risk associated with the use of nonoxidative benzodiazepines showed no relationship to the age of the patients. In contrast, patients aged 85 years or older receiving oxidative benzodiazepines at high dosages or as needed had a two- to three- fold increased risk of femur fracture than did patients in the younger age group. Among older individuals, the use of benzodiazepines slightly increased the risk of femur fracture, mainly irrespective of the metabolic fate of the drug. Our results suggest that the use of nonoxidative benzodiazepines does not carry a lower risk for femur fracture than does the use of oxidative benzodiazepines. However, the latter agents may be associated with a somewhat higher risk of side effects among the oldest old, especially at higher dosages