Foger K.,TU Munich |
Gora-Stahlberg G.,TU Munich |
Sejvar J.,Centers for Disease Control and Prevention |
Ovuga E.,Gulu University |
And 5 more authors.
PLoS Neglected Tropical Diseases | Year: 2017
Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder. © 2017 Public Library of Science. All Rights Reserved.
Barthel D.,Asklepios Klinik Sankt Augustin |
Ganser G.,St. Josef Stift Sendenhorst |
Kuester R.-M.,Asklepios Rheumazentrum Hamburg |
Onken N.,Pediatric Practice |
And 2 more authors.
Journal of Rheumatology | Year: 2015
Objective. Evolving inflammatory bowel disease (IBD) is a matter of interest in patients with juvenile idiopathic arthritis (JIA) and might be associated with JIA therapy. Methods. Data from the German biologics registry (Biologika in der Kinderrheumatologie; BiKeR) from 2001 to 2013 were analyzed. Results. There were 3071 patients with 8389 patient-years (PY) of observation followed. IBD was diagnosed in 11 patients, 8 with Crohn disease and 3 with ulcerative colitis. IBD incidence in patients with JIA was 1.31/1000 PY and higher than published IBD incidences in pediatric populations. Compared with the total BiKeR cohort, patients with IBD more commonly had enthesitis-related arthritis, extended oligoarthritis, psoriatic arthritis, and also rheumatoid factor (RF)-negative polyarthritis. No IBD occurred in patients with systemic JIA or RF-positive polyarthritis. In patients treated with methotrexate (MTX), the IBD incidence was significantly lower compared with patients not treated with MTX. Etanercept (ETN) monotherapy, but not the combination of ETN and MTX, was associated with an increased incidence of IBD. Conclusion. Incidence of IBD in patients with JIA is higher than in the population. MTX turned out to be protective, even in combination with ETN. The Journal of Rheumatology Copyright © 2015. All rights reserved.
PubMed | Westkustenklinikum Heide, MVZ Human Genetics, University of Würzburg, University of Cologne and 9 more.
Type: Journal Article | Journal: Brain & development | Year: 2016
Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year.To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly.Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers.All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients.Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital.
News Article | February 15, 2017
NDA Partners Chairman Carl Peck, MD, announced today that Deborah Wenkert, MD a former Clinical Research Medical Director at Amgen and pediatrics, rheumatology, and bone disease expert has joined the company as an Expert Consultant. Following an immunology postdoc at Harvard University, Dr. Wenkert was an instructor at Washington University School of Medicine and then, for eleven years, an Adjunct Assistant/Associate Clinical Professor at St Louis University School of Medicine in the division of rheumatology. Concurrent with her position at St. Louis University, Dr. Wenkert conducted research in adult and pediatric metabolic bone and genetic disorders and provided care to affected children as the Associate Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospital for Children, St Louis. “Dr. Deborah Wenkert’s knowledge and expertise in adult and pediatric metabolic bone and genetic disorders, in addition to, her extensive experience in pediatric rheumatology and pediatric clinical trials will provide an excellent resource to our clients and to our growing Pediatric Practice,” said Dr. Peck. “We are very pleased to welcome her to NDA Partners.” Dr. Wenkert earned her MD from the University of Texas Medical Branch (Galveston, Texas), attended graduate school at Baylor College of Medicine Graduate School, and obtained a BA in Biochemistry from Rice University. She is board certified in pediatrics and pediatric rheumatology, a member of the American Society for Bone and Mineral Research, and a Fellow of the American Academy of Pediatrics and American College of Rheumatology. About NDA Partners NDA Partners is a strategy consulting firm specializing in expert product development and regulatory advice to the medical products industry and associated service industries such as law firms, investment funds and government research agencies. The highly experienced Principals and Premier Experts of NDA Partners include three former FDA Center Directors; the former Chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK; an international team of more than 100 former pharmaceutical industry and regulatory agency senior executives; and an extensive roster of highly proficient experts in specialized areas including nonclinical development, toxicology, pharmacokinetics, CMC, medical device design control and quality systems, clinical development, regulatory submissions, and development program management. Services include product development and regulatory strategy, expert consulting, high-impact project teams, and virtual product development teams.
PubMed | Pediatric Practice, Protestant Hospital, Pediatric Diabetes Practice, Heinrich Heine University Düsseldorf and 4 more.
Type: Journal Article | Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association | Year: 2016
Data on regional differences in the quality of medical care in Germany are scarce. This study aimed to compare outcome quality and medical treatment of pediatric patients with type 1 diabetes between the federal states of Germany.24,928 patients (<18 years of age) with type 1 diabetes and German residence were selected from the Diabetes-Patienten-Verlaufsdokumentation database. Indicators of outcome quality were HbA1C, overweight prevalence, and rate of severe hypoglycemia. To reflect medical treatment, use of insulin pumps and use of rapid-acting or long-acting insulin analogues were analyzed. Logistic regression models were created for binary variables with federal state as independent predictor. Linear regression was applied for HbA1C and Poisson regression for rate of severe hypoglycemia. Confounders: Sex, age, diabetes duration, migratory background.Disparity was observed for indicators of outcome quality between the 16 federal states of Germany (all p<0.05). After adjustment, HbA1C varied between 55.8mmol/mol and 67.3mmol/mol, overweight prevalence between 10.0 and 15.3%, severe hypoglycemia ranged from 0.06 events/PY to 0.21 events/PY. Overall, the best outcome quality appeared to be present in Saxony. Medical treatment also differed. The percentage of pediatrics on insulin pumps varied between 26.3 and 51.8%. The use of rapid-acting analogues ranged from 56.6 to 96.2% and the use of long-acting analogues varied between 41.9 and 96.9% (all p<0.0001).Medical treatment and outcome quality in pediatrics with type 1 diabetes differed within Germany. Disparities in individual socioeconomic status, regional deprivation, or differences in medical reimbursement decisions might have contributed to the patterns observed.
Cochard M.,Pediatric Rheumatology |
Clet J.,Pediatric Rheumatology |
Le L.,Pediatric Rheumatology |
Pillet P.,Pediatric Rheumatology |
And 4 more authors.
Rheumatology | Year: 2010
Objectives: To determine whether PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) patients have a positive family history (FH) for recurrent fever syndromes. Method: For all patients with PFAPA seen in two paediatric rheumatology centres (Romandy, Switzerland and Bordeaux, France), parents were interviewed to record the FH for periodic fever. As controls, we interviewed a group of children without history of recurrent fever. Results: We recruited 84 patients with PFAPA and 47 healthy children. The FH for recurrent fever (without an infectious cause and recurring for at least half a year) was positive in 38/84 (45%), and was positive for PFAPA (diagnosis confirmed by a physician) in 10/84 (12%) of the PFAPA patients. For 29 of the 38 patients with positive FH, the affected person was a sibling or a parent. None of the healthy children had a positive FH for recurrent fever or PFAPA. A positive FH for rheumatological diseases was seen in both groups of children. Conclusion: These data show that a significant percentage of PFAPA patients present a positive FH of recurrent fever and PFAPA. This familial susceptibility suggests a potential genetic origin for this syndrome. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Behre U.,Pediatric Practice |
Bleckmann G.,Kinder und Jugendarzt |
Crasta P.D.,Glaxosmithkline |
Leyssen M.,Glaxosmithkline |
And 3 more authors.
Human Vaccines and Immunotherapeutics | Year: 2012
This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5-87.5) and 78.3% (95% CI: 73.1-83.0) of subjects aged 7-8 y and 12-13 y, respectively 5-10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9-99.4) and 93.7% (95% CI: 90.2-96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥100 mIU/ml. Overall, 99.6% (95% CI: 98-100) and 97.2% (95% CI: 94.5-98.8) of subjects aged 7-8 y and 12-13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7-8 y and adolescents aged 12-13 y received three doses of a monovalent pediatric HBV vaccine (10 μg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels. © 2012 Landes Bioscience.
Van Der Meeren O.,Glaxosmithkline |
Behre U.,Pediatric Practice |
Vaccine | Year: 2016
Objective: Vaccination of infants against hepatitis B virus (HBV) using hepatitis B vaccine is effective in preventing the infection during early childhood and there is a growing evidence of long-term protection. So far, no need for a booster dose has been identified in healthy subjects; however further follow-up continues to determine the exact duration of protection. We evaluated antibody persistence and immune response to a hepatitis B vaccine challenge dose in children aged 15-16 years, previously vaccinated with 3-doses of the same vaccine in infancy (third dose received before 18 months of age). Methods: A single hepatitis B vaccine challenge dose containing 10. μg hepatitis B surface (HBs) antigen was administered to adolescents aged 15-16 years. Blood samples were taken before and one month after the challenge dose to measure anti-HBs antibodies using a chemiluminescence immunoassay. Solicited local and general symptoms, as well as unsolicited and serious adverse events were recorded after the challenge dose. Results: 303 subjects were enrolled, of whom 302 and 293 subjects formed the total vaccinated and according-to-protocol cohorts, respectively. Pre-challenge, 65.4% (95% CI: 59.6-70.9) subjects were seroprotected (anti-HBs antibody concentration ≥10. mIU/mL). One month post-challenge, 97.9% (95% CI: 95.6-99.2) were seroprotected, while 90.8% (95% CI: 86.8-93.8) had anti-HBs antibody concentrations ≥100. mIU/mL. The post-challenge geometric mean concentration (GMC; 4134.9 [95% CI: 3114.2-5490.1]) was 150-fold higher than the pre-challenge GMC. Overall, 96.9% (95% CI: 94.2-98.6) subjects mounted an anamnestic response. The safety and reactogenicity profile of the hepatitis B vaccine challenge dose was consistent with previous experience. Conclusions: Immunity to hepatitis B persists in 15-16 year old adolescents following primary vaccination in infancy. Trial registration: http://www.clinicaltrials.gov NCT01847430. © 2016.
Bulow L.,Johannes Gutenberg University Mainz |
Lissewski C.,University Hospital |
Bressel R.,Pediatric Practice |
Rauch A.,University of Zürich |
And 3 more authors.
American Journal of Medical Genetics, Part A | Year: 2015
Fetal hydrops, fetal pleural effusions, hydrothorax, and chylothorax, may be associated with various genetic disorders, in particular with the Noonan, cardio-facio-cutaneous and Costello syndromes. These syndromes, collectively called RASopathies, are caused by mutations in the RAS/MAPK pathway, which is known to play a major role in lymphangiogenesis. Recently, germline mutations in the Casitas B-cell lymphoma (CBL) gene were reported in 25 patients and of these, 20 had juvenile myelomonocytic leukemia (JMML). The disorder was named "CBL syndrome" or "Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia" (NSLL). To date, prenatal abnormalities have not been reported and it is still debated whether the CBL syndrome falls into the category of a RASopathy, or represents a different entity. Here we report on three unrelated patients with CBL mutations manifesting with hydrops fetalis, fetal pleural effusions and/or congenital hydro-/chylothorax. Our findings further connect the CBL syndrome with the RASopathies. © 2014 Wiley Periodicals, Inc.
PubMed | Pediatric Practice and Glaxosmithkline
Type: Journal Article | Journal: Vaccine | Year: 2016
Vaccination of infants against hepatitis B virus (HBV) using hepatitis B vaccine is effective in preventing the infection during early childhood and there is a growing evidence of long-term protection. So far, no need for a booster dose has been identified in healthy subjects; however further follow-up continues to determine the exact duration of protection. We evaluated antibody persistence and immune response to a hepatitis B vaccine challenge dose in children aged 15-16 years, previously vaccinated with 3-doses of the same vaccine in infancy (third dose received before 18 months of age).A single hepatitis B vaccine challenge dose containing 10g hepatitis B surface (HBs) antigen was administered to adolescents aged 15-16 years. Blood samples were taken before and one month after the challenge dose to measure anti-HBs antibodies using a chemiluminescence immunoassay. Solicited local and general symptoms, as well as unsolicited and serious adverse events were recorded after the challenge dose.303 subjects were enrolled, of whom 302 and 293 subjects formed the total vaccinated and according-to-protocol cohorts, respectively. Pre-challenge, 65.4% (95% CI: 59.6-70.9) subjects were seroprotected (anti-HBs antibody concentration 10mIU/mL). One month post-challenge, 97.9% (95% CI: 95.6-99.2) were seroprotected, while 90.8% (95% CI: 86.8-93.8) had anti-HBs antibody concentrations 100mIU/mL. The post-challenge geometric mean concentration (GMC; 4134.9 [95% CI: 3114.2-5490.1]) was 150-fold higher than the pre-challenge GMC. Overall, 96.9% (95% CI: 94.2-98.6) subjects mounted an anamnestic response. The safety and reactogenicity profile of the hepatitis B vaccine challenge dose was consistent with previous experience.Immunity to hepatitis B persists in 15-16 year old adolescents following primary vaccination in infancy.http://www.clinicaltrials.govNCT01847430.