Olanzapine Plus Samidorphan in Subjects with Schizophrenia and Comorbid Alcohol Use Disorder: Rationale and Design for a Phase II, Double-blind, Randomized Study.

Background: Alcohol use disorder (AUD) is a common comorbidity in patients with schizophrenia. Although pharmacological options for the management of each disease exist separately, there is no agent approved for both. Moreover, studies conducted in this patient population, who face practical and social challenges as a consequence of being diagnosed with schizophrenia and comorbid AUD, are limited. Methods: We describe the design of a Phase II, double-blind, randomized trial to evaluate adult outpatients with schizophrenia and comorbid AUD receiving a combination of olanzapine plus samidorphan (OLZ+SAM; ALKS 3831), a novel entity currently under development for the treatment of schizophrenia. The combination drug formulation of OLZ+SAM is intended to provide the antipsychotic efficacy of OLZ while mitigating the weight gain and concomitant metabolic abnormalities commonly associated with OLZ alone. In considering this patient population, the novel primary efficacy endpoint is the time from randomization to the first event of exacerbation of disease symptoms (EEDS) based on the occurrence of any of eight prespecified events related to worsening of disease symptoms and/or AUD, as confirmed by a blinded independent adjudication committee. The rate and number of EEDS, improvement in drinking level, and the safety and tolerability of OLZ in combination with SAM will also be assessed. Discussion: A limited number of studies have been conducted in patients with schizophrenia and AUD, and the need for further research in this difficult-to-study population is well documented. This study is, to our knowledge, the largest and longest trial with a randomized, double-blind, active-controlled design. In addition to providing evidence for the development of OLZ+SAM (ALKS 3831) as a therapeutic option, the study aims to provide insights into the clinical management of subjects with schizophrenia and comorbid AUD. Trial registration: Clinical trials NCT02161718, registered May 2014; EudraCT Number: 2014-001211-39.

Parental perceptions of clinical research in the pediatric emergency department.

BACKGROUND: There is a paucity of information about parental perceptions of clinical research in children, particularly in the emergency department (ED) setting. METHODS: Parents accompanying their child to the ED completed a self-administered survey gauging perceptions of research and willingness to enroll a child in a clinical research study. Factor analysis was used to correlate survey responses into domains representing parents' feeling about participation in a research study. Logistic regression was used to assess the predictors of caregivers' amenability to research participation for their child. RESULTS: Three hundred eighty-eight parents were enrolled. Most subjects were willing to enroll their child in a study involving follow-up after ED care (87%) and collection of a urine or saliva sample (79% and 81%, respectively) and extant blood (69%). Fewer were amenable to studies that involve an investigational medication (26%) or additional phlebotomy (27%). Overall, more than 90% of parents felt that research was needed to help other children and was conducted in a way that is morally right, and 25% felt that research may compromise their child's confidentiality. Factor analyses yielded 3 factors that accounted for the variance across the survey questions. Patient and parent demographics, including the patient's triage acuity level, were not associated with willingness to participate in research. CONCLUSIONS: Most parents are amenable to having their child participate in a research study in the ED setting. Most parents share a sense of altruism that research is needed to help children, and this belief is predictive of willingness to participate in a research study.

Core temperature influences on the relationship between exercise-induced leukocytosis and cortisol or TNF-alpha.

INTRODUCTION: The extent to which exercise in the heat modifies leukocytosis and the relationship between the leukocytosis and tumor necrosis factor-alpha (TNF-alpha) or cortisol is not well understood. Thus, this study attempted to determine the combined effect of exercise and differing elevations in core temperature on exercise-induced leukocytosis and to examine associations between any leukocytosis and cortisol orTNF-alpha. METHODS: Eight male subjects completed two 40-min trials while immersed in 25 and 38.5 degrees C water. Leukocytes, TNF-alpha, and cortisol were determined at baseline, immediately post-, and 2 h post-exercise. RESULTS: Both trials resulted in significant 13-33% increases in total leukocytes, mostly driven by a 24-30% increase in neutrophils. A significant relationship was found between the change in core temperature (T(re)) during exercise and the increase in total leukocytes (r = 0.561). Similarly, the change in T(re) was related to the change in cortisol (r = 0.557) and TNF-alpha (r = 0.483). Yet the exercise-induced change in cortisol was not significantly correlated to any changes in leukocytes. There was a trend for the relationships between the exercise-induced change in TNF-alpha and the changes in total leukocytes (r = 0.491) and neutrophils (r = 0.479). DISCUSSION: These results suggest that although neither cortisol nor TNF-alpha are strong predictors of the leukocyte response during exercise or recovery, each factor may be one of many potential modifiers of the total leukocyte response.