Jain R.,R D Clinical Research Inc |
Jain R.,Texas Tech University |
Segal S.,Institute for Clinical Research |
Kollins S.H.,Duke University |
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2011
Objective This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method This 8-week, placebo-controlled, fixed-dose trial, including 3 weeks of dose escalation, of patients 6 to 17 years old with ADHD evaluated the efficacy and safety of CLON-XR 0.2 mg/day or CLON-XR 0.4 mg/day versus placebo in three separate treatment arms. Primary endpoint was mean change in ADHD Rating ScaleIV (ADHD-RS-IV) total score from baseline to week 5 versus placebo using a last observation carried forward method. Secondary endpoints were improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales, Conners Parent Rating ScaleRevised: Long Form, Clinical Global Impression of Severity, Clinical Global Impression of Improvement, and Parent Global Assessment from baseline to week 5. Results Patients (N = 236) were randomized to receive placebo (n = 78), CLON-XR 0.2 mg/day (n = 78), or CLON-XR 0.4 mg/day (n = 80). Improvement from baseline in ADHD-RS-IV total score was significantly greater in both CLON-XR groups versus placebo at week 5. A significant improvement in ADHD-RS-IV total score occurred between groups as soon as week 2 and was maintained throughout the treatment period. In addition, improvement in ADHD-RS-IV inattention and hyperactivity/impulsivity subscales, Conners Parent Rating ScaleRevised: Long Form, Clinical Global Impression of Improvement, Clinical Global Impression of Severity, and Parent Global Assessment, occurred in both treatment groups versus placebo. The most common treatment-emergent adverse event was mild-to-moderate somnolence. Changes on electrocardiogram were minor and reflected the known pharmacology of clonidine. Conclusions Clonidine hydrochloride extended-release tablets were generally well tolerated by patients in the study and significantly improved ADHD symptoms in this pediatric population. Clinical trials registry informationStudy Evaluating the Safety and Efficacy of Clonicel to Treat Children and Adolescents with Attention Deficit Hyperactivity Disorder (ADHD), URL: http://www.clinicaltrials.gov, unique identifier: NCT00556959. © 2011 American Academy of Child and Adolescent Psychiatry.
Takebayashi M.,Institute for Clinical Research
Journal of ECT | Year: 2010
The history of the practice and the guidelines of electroconvulsive therapy (ECT) in Japan is reviewed in this paper. Although the practice of ECT began in Japan at the same time as the discovery of ECT in the world, the diffusion and buildup of ECT practice did not progress in comparison with this treatment modality worldwide for a long time. Recently, the establishment of the Japanese ECT guidelines, which emphasize the administration of a modified ECT using a brief pulse device, has been underway. In 2009, the first ECT network meeting was held in Tokyo, which helped to stimulate the development of ECT practice and improve the guidelines for its use in Japan. Copyright © 2010 by Lippincott Williams & Wilkins.
Kondo M.,University of Tsukuba |
Hoshi S.-L.,University of Tsukuba |
Yamanaka T.,Institute for Clinical Research |
Ishiguro H.,Kyoto University |
Toi M.,Kyoto University
Breast Cancer Research and Treatment | Year: 2011
The 21-gene signature is validated as a good predictor of recurrence for lymph node-negative/positive, hormone receptor-positive, early-stage breast cancer in Japanese patient population. This study evaluates the cost-effectiveness of two scenarios designed to include the assay into Japan's social health insurance benefit package: one for LN-, ER+, ESBC and another for LN-/+, ER+, ESBC. An economic decision tree and Markov model under Japan's health system from the societal perspective is constructed with new evidence from the Japanese validation study. Incremental cost-effectiveness ratios are estimated as ¥384,828 (US$3,848) per QALY for the indication for LN- scenario and ¥568,533 (US$5,685) per QALY for the indication for LN-/+ scenario. Both are not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, ¥5,000,000/QALY (US$50,000/QALY). Sensitivity analyses show that this result is plausibly robust, since ICERs do not exceed the threshold by various changes of assumptions made and values employed. In conclusion, the inclusion of the assay in Japan's social health insurance benefit package for not only LN- diseases but also LN+ diseases is cost-effective. Such a decision can be justifiable as an efficient use of finite resources for health care. © 2010 Springer Science+Business Media, LLC.
Kiba T.,Institute for Clinical Research
Neuroscience Letters | Year: 2015
It was recently reported that ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets. This study has examined how gene families involved in metabolism are regulated in rat pancreatic islets after VMH lesions formation. Total pancreatic islets RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. The VMH lesions regulated the genes that are involved in functions related to metabolism in the pancreas islets. Real-time polymerase chain reaction also confirmed that gene expressions of arachidonate 15-lipoxygenase (. Alox15) was up-regulated and pancreatic lipase (. Pnlip) was downregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of multiple metabolism genes in rat pancreatic islets. © 2015 Elsevier Ireland Ltd.
Fujinaka H.,Institute for Clinical Research
Nephrology (Carlton, Vic.) | Year: 2010
Insulin-like growth factor I (IGF-I) acts on target cells in an endocrine and/or local manner through the IGF-I receptor (IGF-IR), and its actions are modulated by multiple IGF binding proteins (IGFBP). To elucidate the roles of local IGFBP in kidney glomeruli, the expression and localization of their genes were examined and compared with normal and proteinuric kidney glomeruli. A cDNA microarray database (MAd-761) was constructed using human kidney glomeruli and cortices. The gene expression levels of IGF-I, IGF-1R and IGFBP (1-10) were examined in glomeruli and cortices by polymerase chain reaction (PCR) and in situ hybridization (ISH), and the expression levels of IGFBP that were abundantly found in the glomerulus were compared between normal and proteinuric kidneys in rats and humans. IGFBP-2, -7 and -8 were demonstrated to be abundantly and preferentially expressed in the glomerulus. In PCR, the expression levels of the IGFBP-2, -7, -8 and -10 genes in glomeruli were shown to have more than doubled compared with their levels in the cortices. In ISH, the IGFBP-2, -7, -8 and -10 genes were found to be localized in glomerular cells including podocytes, and their increased expression was observed in inflammatory glomeruli. IGF-I gene expression was localized in glomerular podocytes, whereas the IGF-IR gene was expressed in glomerular podocytes and cortical tubular cells. In nephrotic rats, the expression of the IGFBP-10 gene was increased in glomerular podocytes; however, the expression levels of IGFBP-2, -7 and -8 did not change. IGFBP-2, -7, -8 and -10 are produced by normal and injured glomerular podocytes and may regulate local IGF-I actions in podocytes and/or cortical tubular cells in the kidney. © 2010 The Authors. Nephrology © 2010 Asian Pacific Society of Nephrology.