A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2. PATIENTS AND METHODS: This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics. RESULTS: Thirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib). CONCLUSION: The toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.

Audiovisual speech from emotionally expressive and lateralized faces.

Emotional expression and how it is lateralized across the two sides of the face may influence how we detect audiovisual speech. To investigate how these components interact we conducted experiments comparing the perception of sentences expressed with happy, sad, and neutral emotions. In addition we isolated the facial asymmetries for affective and speech processing by independently testing the two sides of a talker's face. These asymmetrical differences were exaggerated using dynamic facial chimeras in which left- or right-face halves were paired with their mirror image during speech production. Results suggest that there are facial asymmetries in audiovisual speech such that the right side of the face and right-facial chimeras supported better speech perception than their left-face counterparts. Affective information was also found to be critical in that happy expressions tended to improve speech performance on both sides of the face relative to all other emotions, whereas sad emotions generally inhibited visual speech information, particularly from the left side of the face. The results suggest that approach information may facilitate visual and auditory speech detection.

Evaluation of a group-based substance abuse treatment program for adolescents.

The effectiveness of adolescent substance abuse treatment has been repeatedly demonstrated, but specific treatment approaches have rarely been sufficiently documented to permit replication. This study evaluated the effectiveness of a manual-guided, outpatient, group-based treatment program for adolescents (N = 194) who were mild-to-moderate substance abusers. In addition to evaluating the group-based treatment model, the study was designed to compare the effectiveness of two approaches to preparing youth to engage in treatment, whereby adolescents received one of two types of treatment induction, either motivational interviewing or counseling overview. Self-reported pretreatment substance use and criminal behaviors were compared with these behaviors 6 and 12 months following treatment entry using a General Linear Mixed Model analytic approach that controlled for the effects of potential confounding variables and examined individual and program factors that might explain treatment response. Participants significantly reduced marijuana use at 6 months, and these reductions were largely sustained at 12 months. No changes in alcohol use or criminal involvement were obtained. Further examination of marijuana use indicated differential treatment response based on participants' emotional abuse history, family satisfaction, school adjustment, and pretreatment substance use frequency. This treatment approach appears promising for marijuana-abusing youth.

Predicting retention of adolescents in substance abuse treatment.

Because retention of adolescents in substance abuse treatment is critical to treatment effectiveness, factors that predict length of time in treatment were examined among youth (N=173) admitted to five outpatient clinics. At admission, youth received a comprehensive psychosocial assessment. Relevant predictors of length of treatment were determined using Poisson regression analyses. Factors positively associated with treatment duration included use of drugs in addition to alcohol and marijuana, having less deviant peers, absence of substance-caused emotional problems, and viewing counselor's skills more positively. In contrast, pressure to enter treatment was unrelated to treatment duration. Results suggest that the counselor-client relationship and peer influences be explicitly considered in treatment.

Bedside cardiology skills training for the osteopathic internist using simulation technology.

Medical practice changes that limit patient availability, instructor time, and advances in technology have led to a greater use of simulators and multimedia computers in medical education. These systems address the problem of inadequate bedside skills training and poor proficiency among all health care providers. While studies have shown their effectiveness among medical students, residents, and practicing physicians, none has focused on the osteopathic internist population--one that is becoming more responsible for conducting initial and follow-up physical examinations. This report describes the use of "Harvey," the cardiology patient simulator, and the UMedic Multimedia Computer System at a workshop conducted at the American College of Osteopathic Internists' 61st Annual Convention and Scientific Sessions. Participants in this study significantly improved their ability to identify common cardiac auscultatory events, as indicated by pretest-to-posttest scores. Workshop participants were nearly unanimous in their belief that they would like to use these tools for learning and assessment.

Response of bone mineral density to once-weekly administration of risedronate.

OBJECTIVE: To evaluate the changes in bone mineral density (BMD) and the tolerability associated with treatment with risedronate, 30 mg once weekly. METHODS: Risedronate, 30 mg, was administered once weekly before breakfast to patients with osteoporosis or osteopenia. All patients were also treated with calcium, 1,500 mg daily, and supplemental vitamin D. Patients receiving treatment with other antiresorptive agents were not excluded. BMD was assessed with dual-energy x-ray absorptiometry (DEXA) at baseline and 1 year. RESULTS: After a mean of 11.6 +/- 0.4 months, mean BMD had increased at the lumbar spine and total hip, respectively, by 5.7% (P<0.001) and 2.9% (P<0.001) among all patients, by 4.8% (P<0.001) and 2.2% (P<0.04) among 23 treated with risedronate alone, and by 6.7% (P<0.003) and 3.6% (P<0.004) among 21 receiving risedronate and other antiresorptive agents. Linear regression analysis of the relationship between baseline T-score and BMD increment at the lumbar spine and femoral neck showed a statistically significant negative correlation, an indication of an enhanced response to treatment in patients with lower baseline T-scores. Adverse events possibly associated with risedronate therapy were recorded in 3 of the 70 enrolled patients (dyspepsia in 2 and urticaria in 1). Of 44 patients with follow-up DEXA scans, 12 (27%) had not tolerated alendronate (10 mg daily) previously, but they tolerated once-weekly risedronate therapy without difficulty. CONCLUSION: A once-weekly 30-mg regimen of risedronate increases BMD when administered alone or with other antiresorptive agents. Few adverse events possibly associated with risedronate therapy were noted.