Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavior disorders, and subaverage IQ

OBJECTIVE: The aim of this study was to examine the safety and efficacy of risperidone, with or without concomitant psychostimulant use, in the treatment of children with conduct disorder (CD) or other disruptive behavior disorders [oppositional defiant disorder (ODD), disruptive behavior disorder-not otherwise specified (DBD-NOS)], and comorbid attention-deficit hyperactivity disorder (ADHD). METHODS: Data from two 6-week placebo-controlled trials assessing risperidone therapy in children with subaverage IQs and CD, ODD, DBD-NOS were combined, and patients with comorbid ADHD were selected for this post hoc analysis. Patients were grouped according to randomized drug therapy (risperidone or placebo), and then subgrouped according to their use of a concomitant psychostimulant. Safety outcomes included adverse events and weight change, while efficacy outcomes included changes in scores on disruptive behavior and hyperactivity-based subscales of two behavior-rating instruments (Nisonger Child Behavior Rating Form and the Aberrant Behavior Checklist). RESULTS: The analysis included 155 of 208 originally tested children divided into four sub-groups (35-43 patients each). There was no significant difference in the frequency of adverse events in patients who received risperidone alone and those who received risperidone plus a stimulant. The most common adverse events in risperidone-treated patients were somnolence, headache, dyspepsia, rhinitis, and vomiting. Within each randomized treatment group, actual weight gain was comparable, regardless of concomitant stimulant use. Risperidone-treated patients had clinically and statistically significant reductions in both disruptive behavior and hyperactivity subscale scores, compared to placebo, regardless of concomitant stimulant use. The addition of risperidone to a psychostimulant resulted in significantly better control of hyperactivity (p < 0.001) than was achieved with stimulant treatment alone, without causing an increase in adverse events. CONCLUSION: Risperidone was a safe and effective treatment, with or without a combined psychostimulant, for both disruptive behavior disorders and comorbid ADHD in children.     

Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses

Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses.     

3He MR imaging of porcine paranasal sinuses

RATIONALE AND OBJECTIVES: The aim of this study was to test the effectiveness of laser-hyperpolarized helium 3 (3He) as a contrast agent for magnetic resonance (MR) imaging of porcine paranasal sinuses. MATERIALS AND METHODS: Imaging experiments were conducted on the heads of four 50-kg Yorkshire pigs after open sinus surgery was performed. Paranasal sinus MR images were obtained with laser-polarized 3He gas produced through the spin-exchange method. The gas was delivered into the sinuses through two 14-gauge plastic catheters inserted in the nostrils. The 3He MR images were then compared with spatially correlated proton MR images. RESULTS: The porcine paranasal sinuses were adequately depicted by MR imaging with hyperpolarized 3He. The signal intensity of the paranasal sinuses on the 3He MR images was related to the size of the opening joining the sinuses to the nasal cavity and was clearly time dependent. CONCLUSION: Hyperpolarized 3He MR imaging may be particularly useful for identifying the anatomic configuration of the paranasal sinuses, as well as for assessing sinus aeration. Further study of the time-dependence of 3He signal intensity may help increase understanding of gas exchange in the sinuses.     

Breast cancer in men

Most men with breast cancer present with a mass in the breast, the evaluation of which should include a tissue diagnosis. If the presence of invasive cancer is established, adequate local therapy includes total removal of the breast. Most tumors are hormone-receptor positive. In high-risk patients, the use of endocrine adjuvant therapy and/or combined endocrine and chemotherapy should be considered. Patients with estrogen-receptor (ER)-negative disease should be offered chemotherapy. In patients with metastatic disease and ER-positive tumors, initial treatment should be endocrine therapy; systemic chemotherapy should be used in patients who are either hormone-receptor negative or resistant to available endocrine therapies.     

Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials

OBJECTIVE: A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales. METHOD: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data. RESULTS: The most common symptoms identified by parents were tantrums, aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom category, largest for self-injury (2.11) and tantrums (1.95). CONCLUSIONS: Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior. Rating individualized participant-chosen target symptoms seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect and might have clinical application.     

Exploring the Manifestations of Anxiety in Children with Autism Spectrum Disorders

This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.     

International consensus statement on attention-deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBDs): clinical implications and treatment practice suggestions.

Researchers and clinicians worldwide share concerns that many youngsters with attention-deficit/hyperactivity disorder (ADHD) and/or disruptive behaviour disorders (DBDs) do not receive appropriate treatment despite availability of effective therapies. At the request of Johnson and Johnson (sponsor), 11 international experts in child and adolescent psychiatry were selected by Professor Stan Kutcher (chair) to address these concerns. This paper describes the experts' consensus conclusions, including treatment practice suggestions for physicians involved in the early treatment of youngsters with ADHD (or hyperkinetic disorder, in countries preferring this classification) and/or DBDs internationally: suggested first-line treatment for ADHD without comorbidity is psychostimulant medication aided by psychosocial intervention. For ADHD with comorbid conduct disorder (CD), psychosocial intervention combined with pharmacotherapy is suggested. For primary CD, suggested first-line treatment is psychosocial intervention, with pharmacotherapy considered as an 'add-on' when aggression/impulsivity is marked and persistent. Pharmacotherapy requires careful titration; full-day coverage is the suggested goal. Regular long-term follow-up is recommended.     

Experience with similar biologic rituximab in 77 patients of granulomatosis with polyangiitis—a real-life experience

Clinical Rheumatology - To present single centre experience on the efficacy and safety of similar biologic of rituximab in patients with granulomatosis with polyangiitis (GPA). This was a...