Descriptive analysis of adverse drug reaction reports in children and adolescents from Germany: frequently reported reactions and suspected drugs

Abstract Background Adverse drug reactions (ADRs) in the pediatric population may differ in types and frequencies compared to other populations. Respective studies analyzing ADR reports referring to children have already been performed for certain countries. However, differences in drug prescriptions, among others, complicate the transferability of the results from other countries to Germany or were rarely considered. Hence, the first aim of our study was to analyze the drugs and ADRs reported most frequently in ADR reports from Germany referring to children contained in the European ADR database (EudraVigilance). The second aim was to set the number of ADR reports in relation to the number of drug prescriptions. These were provided by the Research Institute for Ambulatory Health Care in Germany. Methods For patients aged 0–17 years 20,854 spontaneous ADR reports were received between 01/01/2000–28/2/2019. The drugs and ADRs reported most frequently were identified. Stratified analyses with regard to age, sex and drugs used “off-label” were performed. Reporting rates (number of ADR reports/number of drug prescriptions) were calculated. Results Methylphenidate (5.5%), ibuprofen (2.3%), and palivizumab (2.0%) were most frequently reported as suspected. If related to the number of drug prescriptions, the ranking changed (palivizumab, methylphenidate, ibuprofen). Irrespective of the applied drugs, vomiting (5.4%), urticaria (4.6%) and dyspnea (4.2%) were the ADRs reported most frequently. For children aged 0–1 year, drugs for the treatment of nervous system disorders and foetal exposure during pregnancy were most commonly reported. In contrast, methylphenidate ranked first in children older than 6 years and referred 3.5 times more often to males compared to females. If age- and sex-specific exposure was considered, more ADR reports for methylphenidate referred to children 4–6 years and females 13–17 years. Drugs for the treatment of nervous system disorders ranked first among “off-label” ADR reports. Conclusions Our analysis underlines the importance of putting the number of ADR reports of a drug in context with its prescriptions. Additionally, differences in age- and sex-stratified analysis were observed which may be associated with age- and sex-specific diseases and, thus, drug exposure. The drugs most frequently included in “off-label” ADR reports differed from those most often used according to literature.

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A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children

Pharmaceutics ◽

10.3390/pharmaceutics13020204 ◽

2021 ◽

Vol 13 (2) ◽

pp. 204

Author(s):

Erik Sjögren ◽

Joel Tarning ◽

Karen I. Barnes ◽

E. Niclas Jonsson

Keyword(s):

Body Composition ◽

Drug Exposure ◽

Drug Disposition ◽

Pediatric Population ◽

Model Performance ◽

Vulnerable Population ◽

Pbpk Modeling ◽

Malnourished Children ◽

Physiologically Based Pharmacokinetic ◽

Physiologically Based

Malnutrition in children is a global health problem, particularly in developing countries. The effects of an insufficient supply of nutrients on body composition and physiological functions may have implications for drug disposition and ultimately affect the clinical outcome in this vulnerable population. Physiologically-based pharmacokinetic (PBPK) modeling can be used to predict the effect of malnutrition as it links physiological changes to pharmacokinetic (PK) consequences. However, the absence of detailed information on body composition and the limited availability of controlled clinical trials in malnourished children complicates the establishment and evaluation of a generic PBPK model in this population. In this manuscript we describe the creation of physiologically-based bridge to a malnourished pediatric population, by combining information on (a) the differences in body composition between healthy and malnourished adults and (b) the differences in physiology between healthy adults and children. Model performance was confirmed using clinical reference data. This study presents a physiologically-based translational framework for prediction of drug disposition in malnourished children. The model is readily applicable for dose recommendation strategies to address the urgent medicinal needs of this vulnerable population.

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EPID-26. CLINICAL AND HISTOLOGICAL CHARACTERIZATION OF PRIMARY CENTRAL NERVOUS SYSTEM SARCOMA IN PEDIATRICS. A SINGLE INSTITUTION EXPERIENCE IN A MIDDLE-INCOME COUNTRY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.344 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii84-ii84

Author(s):

Edgar Cabrera ◽

Nelson Aponte ◽

Johnny Garcia ◽

Fredy Salazar ◽

Eric Bouffet ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Pediatric Population ◽

Progression Free Survival ◽

Molecular Data ◽

Middle Income ◽

Patient Demographics ◽

Time Period ◽

Cell Architecture ◽

Intracranial Lesions

Abstract INTRODUCTION Primary central nervous system (CNS) sarcomas are rare mesenchymal non-meningothelial tumors accounting for less than 0.2% of intracranial lesions. Diagnosis and management are challenging due to the current lack of substantive clinical, histological and molecular data. METHODS We retrospectively identified all patients with diagnosis of primary CNS sarcoma at the Hospital Fundación Pediatrico la Misericordia (HOMI) in Bogota, Colombia. We collected patient demographics, disease characteristics, and outcomes for analysis. RESULTS Between 2008 and 2020, twenty-four consecutive patients were diagnosed at the HOMI representing 6% of all CNS tumors diagnosed over the same time period. The median age at presentation was 9.48 years (range:1.6–13.4). The median time of symptoms prior to diagnosis was 2 weeks (0.1–24). The most common presentation was headache (21/24- 89%) and vomiting (19/24- 79%). The frontal lobe was involved in 63% of patients (15/24) and only one patient presented with a cerebellar lesion. Histologically, these tumors were characterized by a pleomorphic spindle cell architecture and high mitotic activity. All samples lacked immunoreactivity to GFAP, CD34, EMA, and S100 and all samples had strong nuclear immunopositivity for TLE-1; BCL-2 was reactive in eighteen cases. Gross total resection was attained in fifteen patients, most patients received focal radiation therapy and ICE chemotherapy. Progression-free survival at 12 and 24 months was 57% and 31% respectively. Overall survival was 77% at 12 months and 39% at 24 months. Thirteen patients relapsed, 11 presented with local failures, and 2 with intracranial recurrences outside of the radiation field. CONCLUSION Our study identifies TLE-1 as a diagnostic marker of primary CNS sarcoma, a highly malignant supratentorial tumor of childhood. Further molecular studies are urgently needed to elucidate the biology of this disease and the unusually high incidence observed in the Colombian pediatric population.

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Imaging and clinical features of neurocutaneous melanosis in the pediatric population.

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405617666210527091109 ◽

2021 ◽

Vol 17 ◽

Author(s):

Mormina Enricomaria ◽

Granata Francesca ◽

Vinci Sergio Lucio ◽

Coglitore Alessandra ◽

Caragliano Antonio Armando ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Features ◽

Pediatric Population ◽

Cord Compression ◽

Imaging Method ◽

Imaging Features ◽

Multisystem Disease ◽

Neurocutaneous Melanosis ◽

Pubmed Database

Background: Neurocutaneous melanosis (NCM) is a rare nonfamilial phakomatosis characterized by the presence of congenital melanocytic nevi and abnormal melanocytes infiltration of the leptomeninges. Objective & Methods: This paper shows the importance of early diagnosis and the most important imaging features of the disease on CT and MR scans. PubMed database was searched from January 1972 to September 2020. Papers including imaging findings of NCM, clinical, follow-up, and treatment features were collected, selecting only 89 studies. Discussion: NCM is a term used for the first time by van Bogaert in 1948. It refers to a condition caused by an error during morphogenesis and migration leading to leptomeningeal melanocytic accumulation. Although histological findings are the gold standard for diagnosis confirmation, neuroimaging and clinical features strongly support the suspect of NCM. Localization and extension of the lesions are predictive of neurological manifestations related to increased intracranial pressure, mass lesions, or spinal cord compression. CT demonstrates sites of increased density in the anterior temporal lobe - mainly the amygdala - thalami, cerebellum, and frontal lobes base. However, MRI is the best imaging method to diagnose central nervous system lesions, often appearing as T1-short signal areas of the cerebral parenchyma, indicative of central nervous system melanosis. MRI can also reveal associated intracranial and intraspinal abnormalities. Conclusion: Early imaging, when available, is helpful if NCM suspect is raised and may be of guidance in comparing later studies. NCM requires a multidisciplinary approach since it is a multisystem disease with a genetic component.

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Supratentorial Tanycytic Ependymoma in an Adult Male: Case Report and Review of Literature

Case Reports in Oncology ◽

10.1159/000380906 ◽

2015 ◽

Vol 8 (1) ◽

pp. 159-163 ◽

Cited By ~ 1

Author(s):

Giselle Lopez ◽

Roger E. McLendon ◽

Katherine B. Peters

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Case Report ◽

Adult Male ◽

Clear Cell ◽

Pediatric Population ◽

Ependymal Cells ◽

Review Of Literature ◽

Tanycytic Ependymoma ◽

Central Nervous System Neoplasm

Ependymomas, tumors of the ependymal cells, are very rare and usually present in the pediatric population. Furthermore, there are even rarer variants of ependymomas that can include cellular, papillary, clear cell, and tanycytic subtypes. We present a case of a supratentorial tanycytic ependymoma in an adult male and review the literature in regard to this rare primary central nervous system neoplasm.

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Uptake Pattern of HIV Counseling and Testing Services: A 4-Year Review in Plateau State, Nigeria

Journal of BioMedical Research and Clinical Practice ◽

10.46912/jbrcp.63 ◽

2018 ◽

Vol 1 (2) ◽

pp. 183-187

Author(s):

F A Magaji ◽

A N Ocheke ◽

V C Pam ◽

T Afolaramin ◽

J Musa ◽

...

Keyword(s):

General Population ◽

Descriptive Analysis ◽

Information Management System ◽

Male Population ◽

Female Population ◽

Hiv Counseling And Testing ◽

Hiv Counseling ◽

Counseling And Testing ◽

Plateau State ◽

Age And Sex

Plateau state is one of the HIV high-burden states in Nigeria with few people knowing their HIV status as a result of challenges with access to HIV Counseling and Testing (HCT) services. This study was aimed at determining the HCT uptake among the general population as well as the pattern by age and sex in Plateau state. The study was a 4-year descriptive analysis of HCT services in the general population of Plateau state, Nigeria based on data generated between January 2012 and December 2015. The data on HCT services were managed through the electronic Nigerian National HIV/AIDS Response Information Management System (eNNRIMS) which was web-based software. The data was disaggregated by year, age and sex in the software and analysis was done using excel to obtained the proportions and trend of HCT uptake in the general population and by year, age and sex. Out of a total of 495,718 tested for HIV, 400,699 people received their test results giving an 80.8% HCT uptake in Plateau state. The highest (99.7%) HCT uptake was in 2014 and the least (67.7%) was in 2012. The age group 25 – 49 years accounted for nearly two-thirds of HCT uptake. The female population had higher percentages of between 7.2% and 17.6% HCT uptake across the years compared to their male counterparts. The HCT uptake was relatively high, and it was even higher among the female population compared to the HCT uptake among male population in Plateau state Nigeria.

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DI-090 Off-label drug prescriptions in hospital

European Journal of Hospital Pharmacy ◽

10.1136/ejhpharm-2013-000436.261 ◽

2014 ◽

Vol 21 (Suppl 1) ◽

pp. A106.2-A106

Author(s):

I Sánchez Martínez ◽

N Manresa Ramón ◽

I De Gorostiza Frias ◽

MA Moregó Soler ◽

B Arribas Díaz ◽

...

Keyword(s):

Drug Prescriptions ◽

Off Label

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Evaluation of Psychotropic Drug Use in Adolescents Accessing a General Emergency Medical Department for Mental Disorders

Adolescents ◽

10.3390/adolescents1010001 ◽

2020 ◽

Vol 1 (1) ◽

pp. 1-9

Author(s):

Martina Buttera ◽

Antonio Clavenna ◽

Lucia Tansini ◽

Erica Maselli ◽

Alessandro Albizzati ◽

...

Keyword(s):

Drug Use ◽

Mental Disorders ◽

Mental Disorder ◽

Psychotropic Drug ◽

Pediatric Population ◽

Drug Prescription ◽

University Hospital ◽

Medical Department ◽

Off Label ◽

Psychotropic Drug Use

Background: Given the paucity of data concerning the care of adolescents attending an emergency department (ED) for mental disorders, we performed an observational study with the aim to describe psychotropic drug use in an Italian ED. Methods: A retrospective chart review of adolescents (13–17 years) visited in the ED of the San Paolo University Hospital in Milan for mental disorders between January and June 2018 was conducted. Information concerning age, gender, type of disorder, psychotropic drug use in the ED and outcome of the visit were analyzed, using an anonymous patient code. Results: A total of 1298 adolescents, 13–17 years old, were visited in the ED, 56 (4%) of whom had a diagnosis of mental disorder (34 females and 22 males). The most common disorder was anxiety (21 patients), followed by predominant psychomotor disorder (13 patients). In all, 30 adolescents received a psychotropic drug. Benzodiazepines were the most commonly used drugs (73% of the subjects), and delorazepam was administered/prescribed to 17 adolescents, despite the fact that evidence on its safety, efficacy, and its off-label use in the pediatric population is lacking. Conclusions: One out of two adolescents attending the ED for an acute episode of mental disorder received a psychotropic drug prescription, mainly in an off-label manner. More evidence is needed to guide the pharmacological management of acute episodes of mental disorders.

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Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)

Journal of International Medical Research ◽

10.1177/0300060519855575 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3151-3159 ◽

Cited By ~ 2

Author(s):

Changjin Liu ◽

Jing Wen ◽

Jialin Xiang ◽

Xuhong Ouyang ◽

Yan Yang ◽

...

Keyword(s):

Cystatin C ◽

Pediatric Population ◽

Age Groups ◽

Serum Markers ◽

Reference Intervals ◽

Specific Reference ◽

Healthy Children ◽

Serum Samples ◽

Serum Cystatin C ◽

Age And Sex

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.

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Off-label drug prescriptions in French general practice: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2018-026076 ◽

2019 ◽

Vol 9 (4) ◽

pp. e026076 ◽

Cited By ~ 1

Author(s):

François Drogou ◽

Allison Netboute ◽

Joris Giai ◽

Xavier Dode ◽

David Darmon ◽

...

Keyword(s):

General Practice ◽

Drug Prescription ◽

Low Frequency ◽

Cross Sectional Study ◽

Drug Prescriptions ◽

Off Label Use ◽

Sectional Study ◽

Cross Sectional ◽

Off Label ◽

Label Use

ObjectivesOff-label drug prescribing is a public health and economic issue. The aim of this study was to describe off-label prescription in general practice in France, in terms of frequency and nature, and to identify its main determining factors.DesignMulticentre cross-sectional studySettingTwenty-three training general practice officesParticipantsAll the voluntary patients coming for a medical consultation or visited at home over a cumulative period of 5 days per office between November 2015 and January 2016.MethodsEleven interns, acting as observers, collected data. Two reviewers analysed the drugs prescribed by the trainers, in order to identify those prescribed off-label in terms of their indication or the age of the patient. We used a univariate, then a multivariate model, based on hierarchical mixed-effects logistic regression.ResultsAmong the 4932 drug prescriptions registered, 911 (18.5%[95% CI17.4% to 19.6%]) were off-label, of which 865 (17.6%) due to the indication of the drug and 58 (1.2%) due to the age of the patient. The prescription never mentioned the off-label use, neither was the patient informed of it, as required by the French law. With the multivariate analysis, variables contributing to off-label prescription were the number of drugs (OR=1.05 for each additional drug), the initiation of new drug therapy (OR=1.26) and the non-specific goal of the prescription (OR=1.43); the age of the patient ≤14 years (OR=1.42); the rural location of the physician’s practice (OR=1.38) and the low frequency of the visits of national health insurance representatives (OR=0.93).ConclusionAlmost one out of five drugs prescribed in French general practice was off-label. It seems necessary to better train physicians in clinical pharmacology, to provide them with more effective drug prescription software, to reinforce postmarketing surveillance and to clearly define off-label use by consensus.

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Disseminated inflammation of the central nervous system associated with acute hepatitis E: a case report

BMC Neurology ◽

10.1186/s12883-020-01952-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jan Rahmig ◽

Arne Grey ◽

Marco Berning ◽

Jochen Schaefer ◽

Martin Lesser ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Acute Hepatitis ◽

Liver Enzymes ◽

Hepatitis E ◽

Neurological Deficits ◽

Off Label ◽

The Central Nervous System ◽

Acute Hepatitis E

Abstract Background Hepatitis E infection affects over 20 million people worldwide. Reports of neurological manifestations are largely limited to the peripheral nervous system. We report a middle-aged genotype 3c male patient with acute hepatitis E virus (HEV) infection and severe neurological deficits with evidence of multiple disseminated inflammatory lesions of the central nervous system. Case presentation A 42-year-old male patient presented to our emergency department with musculoskeletal weakness, bladder and bowel retention, blurred vision and ascending hypoesthesia up to the level of T8. Serology showed elevated liver enzymes and positive IgM-titers of hepatitis E. Analysis of cerebrospinal fluid (CSF) showed mild pleocytosis and normal levels of glucose, lactate and protein. HEV-RNA-copies were detected in the CSF and stool. Within 3 days after admission the patient became paraplegic, had complete visual loss and absent pupillary reflexes. MRI showed inflammatory demyelination of the optic nerve sheaths, multiple subcortical brain regions and the spinal cord. Electrophysiology revealed axonal damage of the peroneal nerve on both sides with absent F-waves. Treatment was performed with methylprednisolone, two cycles of plasma exchange (PLEX), one cycle of intravenous immunoglobulins (IVIG) and ribavirin which was used off-label. Liver enzymes normalized after 1 week and serology was negative for HEV-RNA after 3 weeks. Follow-up MRI showed progressive demyelination and new leptomeningeal enhancement at the thoracic spine and cauda equina 4 weeks after admission. Four months later, after rehabilitation was completed, repeated MRI showed gliotic transformation of the spinal cord without signs of an active inflammation. Treatment with rituximab was initiated. The patient remained paraplegic and hypoesthesia had ascended up to T5. Nevertheless, he regained full vision. Conclusions Our case indicates a possible association of acute HEV infection with widespread disseminated central nervous system inflammation. Up to now, no specific drugs have been approved for the treatment of acute HEV infection. We treated our patient off-label with ribavirin and escalated immunomodulatory therapy considering clinical progression and the possibility of an autoimmune response targeting nerve cell structures. While response to treatment was rather limited in our case, detection of HEV in patients with acute neurological deficits might help optimize individual treatment strategies.

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