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pediatric therapeutics

Jimmy W Huh, Ramesh Raghupathi
Pediatric traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality in children. Experimental and clinical studies demonstrate that the developmental age, the type of injury (diffuse vs. focal) and sex may play important roles in the response of the developing brain to a traumatic injury. Advancements in acute neurosurgical interventions and neurocritical care have improved and led to a decrease in mortality rates over the past decades. However, survivors are left with life-long behavioral deficits underscoring the need to better define the cellular mechanisms underlying these functional changes...
June 19, 2018: Neuropharmacology
Saeed Majidi, Abdolrahman Parna, Majid Zamani, Kourosh Akhbari
Background: Painful diagnostic and therapeutic procedures performed for children are routine actions. Opioids and nonsteroidal anti-inflammatory drugs such as acetaminophens are among medications that can be used for this purpose. This study aimed to compare the onset and duration of action of intrabuccal (IB, submucosal) space and intramuscular (IM) injection of ketamine in pediatrics. Materials and Methods: This clinical trial study was carried out on 126 children of 1-15 years old referred to the emergency room of Al-Zahra and Kashani Hospitals in Isfahan and divided into two 63 populated groups of IM and IB...
2018: Advanced Biomedical Research
Paola Bettinsoli, Giulia Ferrari-Toninelli, Sara Anna Bonini, Michela Guarienti, Davide Cangelosi, Luigi Varesio, Maurizio Memo
Neuroblastoma is a pediatric tumor of the sympatoadrenal lineage of the neural crest characterized by high molecular and clinical heterogeneity, which are the main causes of the poor response to standard multimodal therapy. The identification of new and selective biomarkers is important to improve our knowledge on the mechanisms of neuroblastoma progression and to find the targets for innovative cancer therapies. This study identifies a positive correlation among tropomodulins (TMODs) proteins expression and neuroblastoma progression...
June 5, 2018: Oncotarget
Kim R Kampen, Sergey O Sulima, Benno Verbelen, Tiziana Girardi, Stijn Vereecke, Gianmarco Rinaldi, Jelle Verbeeck, Joyce Op de Beeck, Anne Uyttebroeck, Jules P P Meijerink, Anthony V Moorman, Christine J Harrison, Pieter Spincemaille, Jan Cools, David Cassiman, Sarah-Maria Fendt, Pieter Vermeersch, Kim De Keersmaecker
The R98S mutation in ribosomal protein L10 (RPL10 R98S) affects 8% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) cases, and was previously described to impair cellular proliferation. The current study reveals that RPL10 R98S cells accumulate reactive oxygen species which promotes mitochondrial dysfunction and reduced ATP levels, causing the proliferation defect. RPL10 R98S mutant leukemia cells can survive high oxidative stress levels via a specific increase of IRES-mediated translation of the anti-apoptotic factor B-cell lymphoma 2 (BCL-2), mediating BCL-2 protein overexpression...
June 21, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Bongjin Lee, Soo Jung Kim, June Dong Park, Jiun Park, Ae Hee Jung, Sun Hoi Jung, Yu Hyeon Choi, Hee Gyung Kang, Il Soo Ha, Hae Il Cheong
Vancomycin is known to be unintentionally eliminated by continuous renal replacement therapy, and the protein bound fraction of vancomycin is also known to be different in adults and children. However, there are only a few studies investigating the relationship between the dose of continuous venovenous hemodiafiltration (CVVHDF) parameters and serum concentration of vancomycin in pediatric patients. The aim of this study was to determine clinical and demographic parameters that significantly affect serum vancomycin concentrations...
2018: PloS One
Brady S Moffett, Mindl M Weingarten, Lindsay R Schmees, Marianne Galati, Jennifer Erklauer, James J Riviello
OBJECTIVE: The purpose of this study is to describe the pharmacokinetics of phenytoin in pediatric patients receiving fosphenytoin. DESIGN: Retrospective, population pharmacokinetic analysis. SETTING: Emergency department or PICU of a large tertiary care children's hospital. PATIENTS: Patients less than 19 years old who received fosphenytoin in the PICU or emergency center for treatment of seizures from January 2011 to June 2017 were included...
June 20, 2018: Pediatric Critical Care Medicine
Andrew M Donson, Vladimir Amani, Elliot A Warner, Andrea M Griesinger, Davis A Witt, Jean M Mulcahy Levy, Lindsey M Hoffman, Todd C Hankinson, Michael H Handler, Rajeev Vibhakar, Kathleen Dorris, Nicholas K Foreman
Children with ependymoma are cured in less than 50% of cases, with little improvement in outcome over the last several decades. Chemotherapy has not impacted survival in ependymoma, due in part to a lack of preclinical models that has precluded comprehensive drug testing. We recently developed two human ependymoma cell lines harboring high-risk phenotypes which provided us with an opportunity to execute translational studies. ependymoma and other pediatric brain tumor cell lines were subject to a large-scale comparative drug screen of ependymoma -approved oncology drugs for rapid clinical application...
June 20, 2018: Molecular Cancer Therapeutics
Schirin Akhbari Ziegler, Tineke Dirks, Heleen A Reinders-Messelink, André Meichtry, Mijna Hadders-Algra
PURPOSE: To monitor changes in time spent on pediatric physical therapy actions during a COPing With and CAring for Infants With Special Needs (COPCA) course. METHODS: Data were collected before (T0), during, and after (T3) the course, which was attended by 15 Swiss physical therapists. Four treatment sessions of each therapist were video recorded and analyzed with the Groningen Observation Protocol 2.0, allowing for quantification of relative duration of therapeutic actions...
July 2018: Pediatric Physical Therapy
Marco Solmi, Cristiano A Köhler, Brendon Stubbs, Ai Koyanagi, Beatrice Bortolato, Francesco Monaco, Davy Vancampfort, Myrela O Machado, Michael Maes, Ioanna Tzoulaki, Joseph Firth, John P A Ioannidis, André F Carvalho
BACKGROUND: Multiple environmental factors have been implicated in obesity and multiple interventions, besides drugs and surgery, have been assessed in obese patients. Results are scattered across many studies and meta-analyses and they often mix obese and overweight individuals. MATERIALS AND METHODS: PubMed and Cochrane Database of Systematic Reviews were searched through January 21st , 2017 for meta-analyses of cohort studies assessing environmental risk factors for obesity, and randomized controlled trials investigating non-pharmacological, non-surgical therapeutic interventions for obesity...
June 20, 2018: European Journal of Clinical Investigation
Elizabeth Spencer, Evan Norris, Chadwick Williams, Marla C Dubinsky
Background: Thiopurine metabolite monitoring to proactively dose optimize to achieve therapeutic levels has not been used consistently, and it is unclear if this would lead to better outcomes. We aimed to compare 6-month outcomes between standard and optimized dosing strategies and define long-term predictors of thiopurine durability. Methods: Two hundred sixteen pediatric IBD patients with at least 2 6-thioguanine nucleotide (6-TGN) levels were grouped for analysis by start dose: >2...
June 16, 2018: Inflammatory Bowel Diseases
Justin Taylor, Dean Pavlick, Akihide Yoshimi, Christina Marcelus, Stephen S Chung, Jaclyn F Hechtman, Ryma Benayed, Emiliano Cocco, Benjamin H Durham, Lillian Bitner, Daichi Inoue, Young Rock Chung, Kerry Mullaney, Justin M Watts, Eli L Diamond, Lee A Albacker, Tariq I Mughal, Kevin Ebata, Brian B Tuch, Nora Ku, Maurizio Scaltriti, Mikhail Roshal, Maria Arcila, Siraj Ali, David M Hyman, Jae H Park, Omar Abdel-Wahab
Rearrangements involving the neurotrophic receptor kinase genes (NTRK1, NTRK2, and NTRK3; hereafter referred to as TRK) produce oncogenic fusions in a wide variety of cancers in adults and children. Although TRK fusions occur in <1% of all solid tumors, inhibition of TRK results in profound therapeutic responses resulting in breakthrough FDA-approval of the TRK inhibitor larotrectinib for adult and pediatric solid tumor patients regardless of histology. In contrast to solid tumors, the frequency of TRK fusions and clinical effects of targeting TRK in hematologic malignancies is unknown...
June 19, 2018: Journal of Clinical Investigation
Samuel Clifton Willimon, Michael T Busch, Crystal A Perkins
BACKGROUND: Pigmented villonodular synovitis (PVNS) is a benign proliferative synovial disorder most commonly described in adults. The purpose of this study is to describe the presentation and management of a large single-center series of pediatric patients with PVNS of the knee. METHODS: A retrospective review was performed of consecutive pediatric patients treated for PVNS at a single institution from 2001 to 2016. Inclusion criteria were patients below 20 years of age with surgical treatment of histologically proven PVNS of the knee...
June 18, 2018: Journal of Pediatric Orthopedics
Loreto Castellon, Daniel Jerez, Jaime Mayorga, Alejandra Gallego, Carlos Fuenzalida, German Laissle
: Mandibular reconstruction in pediatric patients is controversial. The scant pediatric experience and the infrequent occurrence of this type of pathology in children complicate therapeutic decisions. The literature contains different treatment protocols and describes the bone graft alternatives to be used. MATERIALS AND METHOD: This is a retrospective review of patients under the age of 15 who were subjected to resection and reconstruction. RESULTS: A total of 18 patients were included in the study: 8 women and 10 men...
June 18, 2018: Journal of Craniofacial Surgery
Aliesha Griffin, Kyla R Hamling, SoonGweon Hong, Mana Anvar, Luke P Lee, Scott C Baraban
Epilepsy is a common chronic neurological disease affecting almost 3 million people in the United States and 50 million people worldwide. Despite availability of more than two dozen FDA-approved anti-epileptic drugs (AEDs), one-third of patients fail to receive adequate seizure control. Specifically, pediatric genetic epilepsies are often the most severe, debilitating and pharmaco-resistant forms of epilepsy. Epileptic syndromes share a common symptom of unprovoked seizures. While some epilepsies/forms of epilepsy are the result of acquired insults such as head trauma, febrile seizure, or viral infection, others have a genetic basis...
2018: Frontiers in Pharmacology
Claudia Balsamo, Carlotta Biagi, Margherita Mancini, Ilaria Corsini, Rosalba Bergamaschi, Marcello Lanari
BACKGROUND: Acute mastoiditis is the main suppurative complication of acute otitis media. Its incidence ranges from 1.2 to 4.2/100.000 children/year and a rise has been reported in the last years. There are controversial data regarding risk factors for mastoiditis and its complications. AIM OF THE STUDY: to evaluate demographics and clinical characteristics of children with acute mastoiditis and to identify possible risk factors for complications. METHODS: We retrospectively reviewed medical charts of all the children aged 1 month-14 years admitted to our Paediatric Emergency Department from January 2002 to December 2016...
June 18, 2018: Italian Journal of Pediatrics
Edoardo Bruno Vicenzi, Simone Cesaro
INTRODUCTION: Posaconazole is a broad-spectrum triazole widely used to prevent and treat invasive mycoses in adults. Since it received marketing authorization more than a decade ago, many authors have reported on its off-label use in pediatric patients, despite the fact that the pharmacokinetics, safety and efficacy in children have not been extensively investigated. AREAS COVERED: We reviewed pediatric studies published between 2010 and 2017 describing the prophylactic and therapeutic use of posaconazole, with special attention to the correlation between oral dose, plasma levels, safety, and effectiveness...
June 18, 2018: Expert Review of Anti-infective Therapy
Leena Choi, Robert J Carroll, Cole Beck, Jonathan D Mosley, Dan M Roden, Joshua C Denny, Sara L Van Driest
Motivation: Phenome-wide association studies (PheWAS) have been used to discover many genotype-phenotype relationships and have the potential to identify therapeutic and adverse drug outcomes using longitudinal data within electronic health records (EHRs). However, the statistical methods for PheWAS applied to longitudinal EHR medication data have not been established. Results: In this study, we developed methods to address two challenges faced with reuse of EHR for this purpose: confounding by indication, and low exposure and event rates...
April 18, 2018: Bioinformatics
M Carolina Rivacoba, M Luisa Ceballos, Paulina Coria
Peritoneal dialysis-related infections are the main complication in pediatric patients undergoing this renal replacement therapy, associating a high rate of morbidity, generating also a decreasing survival of the peritoneal membrane and worsening the patient outcome. We describe the recommended diagnostic and therapeutic modalities to treat dialysis-related in children.
April 2018: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Henning Willers, Antino Allen, David Grosshans, Stephen J McMahon, Cläre von Neubeck, Claudia Wiese, Bhadrasain Vikram
In the clinic, proton beam therapy (PBT) is based on the use of a generic relative biological effectiveness (RBE) of 1.1 compared to photons in human cancers and normal tissues. However, the experimental basis for this RBE lacks any significant number of representative tumor models and clinically relevant endpoints for dose-limiting organs at risk. It is now increasingly appreciated that much of the variations of treatment responses in cancers are due to inter-tumoral genomic heterogeneity. Indeed, recently it has been shown that defects in certain DNA repair pathways, which are found in subsets of many cancers, are associated with a RBE increase in vitro...
June 14, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Richard T Wang, Florian Barthelemy, Ann S Martin, Emilie D Douine, Ascia Eskin, Ann Lucas, Jenifer Lavigne, Holly Peay, Negar Khanlou, Lee Sweeney, Rita M Cantor, M Carrie Miceli, Stanley F Nelson
Antisense oligonucleotide (AON) mediated exon skipping is an emerging therapeutic for individuals with Duchenne muscular dystrophy (DMD). Skipping of exons adjacent to common exon deletions in DMD using AONs can produce in-frame transcripts and functional protein. Targeted skipping of DMD exons 8, 44, 45, 50, 51, 52, 53, and 55 are predicted to benefit 47% of affected individuals. We observed a correlation between mutation subgroups and age at loss of ambulation in DuchenneConnect, a large database of phenotypic and genetic data for DMD (N = 765)...
June 16, 2018: Human Mutation
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