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pediatric clinical pharmacology

Constanze Hantel, Igor Shapiro, Giada Poli, Costanza Chiapponi, Martin Bidlingmaier, Martin Reincke, Michaela Luconi, Sara Jung, Felix Beuschlein
In recent years it has been recognized that clinical translation of novel therapeutic strategies for patients with adrenocortical carcinoma (ACC) often fails. These disappointing results indicate that the currently utilized tumor models only poorly reflect relevant pathophysiology and, thereby, do not predict clinical applicability of novel pharmacological approaches. However, also the development of new preclinical ACC models has remained a challenge with only one human cell line (NCI-H295R) and one recently established human pediatric xenograft model (SJ-ACC3) being available for this highly heterogeneous malignancy...
October 15, 2016: Oncotarget
Eda Cengiz, Peiyao Cheng, Katrina J Ruedy, Craig Kollman, William V Tamborlane, Georgeanna J Klingensmith, Robin L Gal, Janet Silverstein, Joyce Lee, Maria J Redondo, Roy W Beck
OBJECTIVE: Current data are limited on the course of type 1 diabetes (T1D) in children and adolescents through the first few years of diabetes. The Pediatric Diabetes Consortium T1D new onset (NeOn) Study was undertaken to prospectively assess natural history and clinical outcomes in children treated at 7 US diabetes centers from the time of diagnosis. This paper describes clinical outcomes in the T1D NeOn cohort during the first 3 years postdiagnosis. RESULTS: A total of 1048 participants (mean age 9...
October 19, 2016: Pediatric Diabetes
Kayi Eliacik, Nurullah Bolat, Cemil Koçyiğit, Ali Kanik, Ellen Selkie, Huseyin Yilmaz, Gonul Catli, Nihal Olgac Dundar, Bumin Nuri Dundar
BACKGROUND: The rapid rise in the global prevalence of obesity suggests that environmental factors may be responsible. The increased use of technology is associated with increased rates of obesity due to declines in physical activity and significant sedentary life style. Internet addiction is also a growing health issue associated with diminished physical activity and poor sleep quality as well as various health problems. The purpose of this study was to determine associations between Internet addiction and adolescent obesity-related problems...
October 18, 2016: Eating and Weight Disorders: EWD
Maxime Luu, Marc Bardou, Philippe Bonniaud, Françoise Goirand
Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered: This drug evaluation summarizes published data on pharmacokinetic and pharmacodynamic properties of omalizumab, on clinical efficacy and safety, including real-world evidence, and provides a medico-economic evaluation of the drug...
October 17, 2016: Expert Opinion on Drug Metabolism & Toxicology
M Lambert, V Niehaus, C Correll
This review aims to describe the importance of i) detecting individuals at clinical high-risk for psychosis (schizophrenia) or bipolar disorder, especially in children and adolescents, in order to enable early intervention, and ii) evaluating different intervention strategies, especially pharmacotherapy, during the subsyndromal or "prodromal" stages of these severe and often debilitating disorders. The different approaches regarding the psychotic and bipolar clinical high-risk state are discussed, including reasons and evidence for early (pharmacological) intervention and risks of treatment vs...
October 13, 2016: Pharmacopsychiatry
(no author information available yet)
Howard Jacob is best known for pioneering genomic sequencing of a patient to solve a mysterious pediatric case in 2010. With roots in pharmacology and cardiovascular disease, however, his career has largely been dedicated to dissecting the physiology and genetics of the rat to help understand complex human diseases. Howard was Director of the Human and Molecular Genetics Center at the Medical College of Wisconsin for 16 years, during which time he applied a combination of approaches, including quantitative genetics, integrative physiology and next-generation sequencing, in rat models to shed light on cardiovascular, metabolic and renal disorders...
October 1, 2016: Disease Models & Mechanisms
Maria Claudia Rodríguez, Perla Villamor, Tatiana Castillo
INTRODUCTION: Pain is a disease by itself and it's a public health concern of major implication in children, not just because of the emotional component of the child and his family, but also due to the potential morbidity and mortality involving it. A proper assessment of pain it's a challenge in the pediatric population, due to their lack of understanding and verbalization of hurt. Additionally, a satisfactory treatment of pediatric pain can be arduous due to a lack of clinical knowledge, insufficient pediatric research, and the fear to opioid side effects and addiction...
November 2016: International Journal of Pediatric Otorhinolaryngology
Maria Grazia Clemente, Claudia Mandato, Marco Poeta, Pietro Vajro
Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]...
September 28, 2016: World Journal of Gastroenterology: WJG
Farah S Hussain, Eric T Dobson, Jeffrey R Strawn
The last decade has seen considerable advances in the treatment of anxiety disorders in children and adolescents and a considerable expansion of the evidence base for psychopharmacologic in this population. The extant data suggest that, for fear-based anxiety disorders (e.g., generalized anxiety disorder, social phobia/social anxiety disorder, and separation anxiety disorder), selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SSNRIs) are well tolerated and offer considerable benefit...
June 2016: Current Treatment Options in Psychiatry
Joseph D Tobias, Thomas P Green, Charles J Coté
Codeine has been prescribed to pediatric patients for many decades as both an analgesic and an antitussive agent. Codeine is a prodrug with little inherent pharmacologic activity and must be metabolized in the liver into morphine, which is responsible for codeine's analgesic effects. However, there is substantial genetic variability in the activity of the responsible hepatic enzyme, CYP2D6, and, as a consequence, individual patient response to codeine varies from no effect to high sensitivity. Drug surveillance has documented the occurrence of unanticipated respiratory depression and death after receiving codeine in children, many of whom have been shown to be ultrarapid metabolizers...
September 19, 2016: Pediatrics
Swantje Völler, Georg Hempel, Gudrun Würthwein, Alan V Boddy, Miriam Krischke, Nicolas André, Maurizio D'Incalci, Gianni Bisogno, Joachim Boos
Following the publication of our paper regarding a population-based model of doxorubicin pharmacokinetics in children in Clinical Pharmacokinetics last year (Voller et al. 54:1139-1149, 2015), we have received many inquiries on the practical clinical consequences of this model; however, a population-based model is only one of the aspects to be taken into account when developing dosing algorithms. In addition, any new method of dose calculation would need clinical validation and, subsequently, a new clinical trial...
September 19, 2016: Clinical Pharmacokinetics
S Ahmed, S Tabassum, S M Rahman, S Akhter, M M Rahman, F Bayes, S Roy
Recurrent headache is common in children. Among them migraine is the most common disabling cause of primary headache. It causes serious disability in child's life and family. It causes negative impact on their quality of life. Clinical characteristic of migraine in children differ from adult. It may be shorter in duration and bifrontal or bitemporal in location in contrast to adult which is longer in duration and usually unilateral. It is less common before 3 years of age. Males are more affected before puberty...
July 2016: Mymensingh Medical Journal: MMJ
Marco Pozzi, Valentino Conti, Federica Locatelli, Sara Galbiati, Sonia Radice, Emilio Clementi, Sandra Strazzer
OBJECTIVE: Information on course and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation and in pediatric patients is lacking. To increase knowledge on the course and treatment of PSH in pediatric patients during rehabilitation, we retrospectively analyzed 23 pediatric patients with PSH, describing the course of PSH and administered drugs, and explored the association of PSH remission with drug doses. SETTING: Neurorehabilitation unit of IRCCS Eugenio Medea, Bosisio Parini (LC), Italy...
September 6, 2016: Journal of Head Trauma Rehabilitation
Nilay Thakkar, Sara Salerno, Christoph P Hornik, Daniel Gonzalez
Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e...
September 1, 2016: Pharmaceutical Research
Tal Burt, Christy S John, Jon L Ruckle, Le T Vuong
INTRODUCTION: Phase-0 studies, including microdosing, also called Exploratory Investigational New Drug (eIND) or exploratory clinical trials, are a regulatory framework for first-in-human (FIH) trials. Common to these approaches is the use and implied safety of limited exposures to test articles. Use of sub-pharmacological doses in phase-0/microdose studies requires sensitive analytic tools such as accelerator mass spectrometer (AMS), Positron Emission Tomography (PET), and Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to determine drug disposition...
August 26, 2016: Expert Opinion on Drug Delivery
Ayşe Kacar Bayram, Hüseyin Per, Sevda Ismailoğullari, Mehmet Canpolat, Hakan Gumus, Murat Aksu
Objective Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic and/or hypnopompic hallucinations, and sleep paralysis. It is one of the most important causes of excessive daytime sleepiness in the pediatric population. The aim of this study is to present the clinical and laboratory findings, and treatment results of pediatric patients with narcolepsy. Materials and Methods We studied five unrelated consecutive children with narcolepsy, focusing on clinical and laboratory features, the therapy and outcome over the 33-month follow-up period...
August 26, 2016: Neuropediatrics
S M MacLeod, Mje Greff, D C Knoppert, S Ito, M J Rieder
The world's 1.89 billion children (0-14) too frequently receive treatments that have not been validated through clinical pharmacology research, especially in low and middle income countries. Initial findings from an international asset map of professionals and clinician scientists available to address the needs for education, research and treatment support suggest a critical shortage of clinical pharmacologists, clinical pharmacists and other professionals with advanced training in the evaluation of therapies for childhood conditions and illnesses...
August 24, 2016: Clinical Pharmacology and Therapeutics
Basanagoud Mudigoudar, Sarah Weatherspoon, James W Wheless
The medical management of the epilepsy syndromes of early childhood (eg, infantile spasms, Dravet syndrome, and Lennox-Gastaut syndrome) is challenging; and requires careful evaluation, classification, and treatment. Pharmacologic therapy continues to be the mainstay of management for these children, and as such it is important for the clinician to be familiar with the role of new antiepileptic drugs. This article reports the clinical trial data and personal experience in treating the severe epilepsies of childhood with the recently Food and Drug Administration-approved new antiepileptic drugs (vigabatrin, rufinamide, perampanel, and clobazam) and those in clinical trials (cannabidiol, stiripentol, and fenfluramine)...
May 2016: Seminars in Pediatric Neurology
Katherine Taylor, Wooheon Thomas Kim, Malak Maharramova, Victor Figueroa, Smruthi Ramesh, Armando Lorenzo
INTRODUCTION: Smaller children are presenting for renal transplantation as the treatment of choice for end-stage renal disease. Adult donor organs are more successful than pediatric deceased donor organs. An adult kidney may sequester ~75% of the circulating volume of a 5 year-old child and requires significantly increased cardiac output to maintain renal perfusion. Treatment includes volume, inotropic or vasopressor agents, or central neuroaxial blockade for sympatholysis. We describe the perioperative anesthestic management as a guide to clinical outcomes...
October 2016: Paediatric Anaesthesia
Elin T G Kersten, Gerard H Koppelman, Bernard J Thio
Beta2-adrenoreceptor agonists (β2-agonists) are extensively used in the treatment of childhood asthma. However, there have been concerns regarding their adverse effects and safety. In 2005, the FDA commissioned a "Black Box Warning" communicating the potential for an increased risk for serious asthma exacerbations or asthma related deaths, with the regular use of LABAs. In a meta-analysis of controlled clinical trials, the incidence of severe adverse events appeared to be highest in the 4-11 year age group...
June 16, 2016: Paediatric Respiratory Reviews
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