TY - JOUR A1 - Ziegler, Mirjam A1 - Kaiser, Anna A1 - Igel, Christine A1 - Geissler, Julia A1 - Mechler, Konstantin A1 - Holz, Nathalie E. A1 - Becker, Katja A1 - Döpfner, Manfred A1 - Romanos, Marcel A1 - Brandeis, Daniel A1 - Hohmann, Sarah A1 - Millenet, Sabina A1 - Banaschewski, Tobias T1 - Actigraphy-derived sleep profiles of children with and without attention-deficit/hyperactivity disorder (ADHD) over two weeks — comparison, precursor symptoms, and the chronotype JF - Brain Sciences N2 - Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6–12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms. KW - sleep KW - actigraphy KW - attention-deficit/hyperactivity disorder (ADHD) KW - intra-individual variability (IIV) KW - chronotype KW - children KW - continuous performance task (CPT) KW - precursor symptoms KW - ESCAlife Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250084 SN - 2076-3425 VL - 11 IS - 12 ER - TY - JOUR A1 - Wiegering, V. A1 - Schlegel, P. G. A1 - Winkler, B. A1 - Lazarus, M. A1 - Wirth, C. A1 - Ernestus, K. A1 - Walles, T. A1 - Liese, J. T1 - Persisting Cough as the Single Presenting Symptom of an Intrathoracic Tumor in a Nine-Month-Old Child with Adenovirus Airway Infection JF - Journal of Case Reports and Studies N2 - We report on a nine-month-old girl who presented with persisting cough, and diminished ventilation of the left hemithorax. Viral pneumonia was suspected after Adenovirus detection by PCR, but chest X-rays showed a persistent shadowing of the left hemithorax and persistent coughing despite clinical improvement. Because of the discrepancy between clinical and radiological signs further investigations by ultrasound and CT scan were performed, which visualized an intrathroracic tumor. Histopathology confirmed diagnosis of a teratoma. This case highlights the need for careful evaluation by the treating physicians. If the chest X-ray provides a discrepancy to the clinical findings or persistent pathologies exist, differential diagnosis should be discussed and further diagnostics be performed. KW - tumor KW - children Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125536 VL - 3 IS - 2 ER - TY - JOUR A1 - Wannagat, Wienke A1 - Waizenegger, Gesine A1 - Niedling, Gerhild T1 - Coherence formation during narrative text processing: a comparison between auditory and audiovisual text presentation in 9- to 12-year-old children JF - Cognitive Processing N2 - In an experiment with 114 children aged 9–12 years, we compared the ability to establish local and global coherence of narrative texts between auditory and audiovisual (auditory text and pictures) presentation. The participants listened to a series of short narrative texts, in each of which a protagonist pursued a goal. Following each text, we collected the response time to a query word that was either associated with a near or a distant causal antecedent of the final sentence. Analysis of these response times indicated that audiovisual presentation has advantages over auditory presentation for accessing information relevant for establishing both local and global coherence, but there are indications that this effect may be slightly more pronounced for global coherence. KW - text comprehension KW - multimodal narratives KW - coherence KW - children Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235744 SN - 1612-4782 VL - 22 ER - TY - JOUR A1 - Walter, Maggie C. A1 - Reilich, Peter A1 - Thiele, Simone A1 - Schessl, Joachim A1 - Schreiber, Herbert A1 - Reiners, Karlheinz A1 - Kress, Wolfram A1 - Müller-Reible, Clemens A1 - Vorgerd, Matthias A1 - Urban, Peter A1 - Schrank, Bertold A1 - Deschauer, Marcus A1 - Schlotter-Weigel, Beate A1 - Kohnen, Ralf A1 - Lochmüller, Hans T1 - Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial JF - Orphanet Journal of Rare Diseases N2 - Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results: During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion: Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis. KW - Deflazacort KW - muscle strength KW - gridle muscular-dystrophy KW - Duchenne dystrphy KW - Miyoshi myopathy KW - mutation KW - prednisone KW - gene KW - 2B KW - children KW - design KW - steroids KW - therapy KW - dysferlinopathy KW - Limb girdle muscular dystrophy (LGMD) Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125663 SN - 1750-1172 VL - 8 IS - 26 ER - TY - JOUR A1 - von Lukowicz, Hannah A1 - Schlegel, Paul-Gerhardt A1 - Härtel, Christoph A1 - Morbach, Henner A1 - Haubitz, Imme A1 - Wiegering, Verena T1 - ESPED survey on newly diagnosed immune thrombocytopenia in childhood: how much treatment do we give? JF - Molecular and Cellular Pediatrics N2 - Background Immune thrombocytopenia (ITP) is an autoimmune disease associated with isolated thrombocytopenia, which is caused by an imbalance between platelet production and platelet destruction. Petechial and mucous membrane hemorrhages are characteristic of ITP, but life-threatening bleeding rarely occurs. Depending on the bleeding symptoms, ITP can be treated with glucocorticoids (GC), intravenous immunoglobulins (IVIG), or in severe cases, platelet transfusions. Mild bleeding does not necessarily require therapy. Using the German Surveillance Unit for rare Pediatric Diseases (ESPED) we conducted a prospective survey on ITP patients in all German Children's Hospitals between September 2018 and August 2019. We collected data on ITP, including the clinical course, therapy implementation recommendations (according to the Association of German Scientific Medical Societies guidelines), outcome, and influence of treatment regimens depending on the treating physician´s experience with ITP patients. Results Of the 287 recorded cases of children with ITP, 268 questionnaires were sent to the authors. Two hundred seventeen of the questionnaires fulfilled the inclusion criteria. ITP affected boys and girls similarly, and the median age of manifestation was 3.5 years. The main reasons for hospitalization were thrombocytopenia, bleeding signs, hematomas, and/or petechiae. Bleeding scores were ≤ 3 in 96% of children, which corresponded to a low-to-moderately low risk of bleeding. No life-threatening bleeding was documented. The most common therapies were IVIG (n = 59), GC (n = 33), or a combination of these (n = 17). Blood products (i.e., red blood cells, platelet concentrate, and fresh frozen plasma) were given to 13 patients. Compared to the established guidelines, 67 patients were over-treated, and 2 patients were under-treated. Conclusions Adherence to German ITP treatment guidelines is currently limited. To improve patient safety and medical care, better medical training and dissemination of the guidelines are required in line with targeted analyses of patients with serious bleeding events to identify potential risk constellations. KW - pediatric immune thrombocytopenia KW - acute ITP KW - newly diagnosed ITP KW - ESPED KW - autoimmunity KW - treatment guidelines KW - intravenous immunoglobulins KW - bleeding score KW - children Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261832 VL - 8 ER - TY - JOUR A1 - Tecle, Nyat-Eyob A1 - Hackenberg, Stephan A1 - Scheich, Matthias A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Gehrke, Thomas T1 - Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases JF - European Journal of Pediatrics N2 - Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1–18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved. Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient’s outcome. What is Known: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery. What is New: • The focus identification has no impact on patient’s outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved. KW - lateral neck abscesses KW - children KW - focus of infection KW - surgery Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324179 VL - 182 IS - 1 ER - TY - JOUR A1 - Taurines, R. A1 - Fekete, S. A1 - Preuss-Wiedenhoff, A. A1 - Warnke, A. A1 - Wewetzer, C. A1 - Plener, P. A1 - Burger, R. A1 - Gerlach, M. A1 - Romanos, M. A1 - Egberts, K. M. T1 - Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone JF - Journal of Neural Transmission N2 - Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions. KW - risperidone KW - children KW - serum concentration KW - schizophrenia KW - therapeutic drug monitoring KW - pharmacovigilance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324833 VL - 129 IS - 5-6 ER - TY - JOUR A1 - Streng, Andrea A1 - Prifert, Christiane A1 - Weissbrich, Benedikt A1 - Sauerbrei, Andreas A1 - Krumbholz, Andi A1 - Schmid-Ott, Ruprecht A1 - Liese, Johannes G. T1 - Similar severity of influenza primary and re-infections in pre-school children requiring outpatient treatment due to febrile acute respiratory illness: prospective, multicentre surveillance study (2013-2015) JF - BMC Infectious Diseases N2 - Background Influenza virus infections in immunologically naïve children (primary infection) may be more severe than in children with re-infections who are already immunologically primed. We compared frequency and severity of influenza virus primary and re-infections in pre-school children requiring outpatient treatment. Methods Influenza-unvaccinated children 1–5 years of age presenting at pediatric practices with febrile acute respiratory infection < 48 h after symptom onset were enrolled in a prospective, cross-sectional, multicenter surveillance study (2013–2015). Influenza types/subtypes were PCR-confirmed from oropharyngeal swabs. Influenza type/subtype-specific IgG antibodies serving as surrogate markers for immunological priming were determined using ELISA/hemagglutination inhibition assays. The acute influenza disease was defined as primary infection/re-infection by the absence/presence of influenza type-specific immunoglobulin G (IgG) and, in a second approach, by the absence/presence of subtype-specific IgG. Socio-demographic and clinical data were also recorded. Results Of 217 influenza infections, 178 were due to influenza A (87 [49%] primary infections, 91 [51%] re-infections) and 39 were due to influenza B (38 [97%] primary infections, one [3%] re-infection). Children with “influenza A primary infections” showed fever with respiratory symptoms for a shorter period than children with “influenza A re-infections” (median 3 vs. 4 days; age-adjusted p = 0.03); other disease characteristics were similar. If primary infections and re-infections were defined based on influenza A subtypes, 122 (87%) primary infections (78 “A(H3N2) primary infections”, 44 “A(H1N1)pdm09 primary infections”) and 18 (13%) re-infections could be classified (14 “A(H3N2) re-infections” and 4 “A(H1N1)pdm09 re-infections”). Per subtype, primary infections and re-infections were of similar disease severity. Children with re-infections defined on the subtype level usually had non-protective IgG titers against the subtype of their acute infection (16 of 18; 89%). Some patients infected by one of the influenza A subtypes showed protective IgG titers (≥ 1:40) against the other influenza A subtype (32/140; 23%). Conclusions Pre-school children with acute influenza A primary infections and re-infections presented with similar frequency in pediatric practices. Contrary to expectation, severity of acute “influenza A primary infections” and “influenza A re-infections” were similar. Most “influenza A re-infections” defined on the type level turned out to be primary infections when defined based on the subtype. On the subtype level, re-infections were rare and of similar disease severity as primary infections of the same subtype. Subtype level re-infections were usually associated with low IgG levels for the specific subtype of the acute infection, suggesting only short-time humoral immunity induced by previous infection by this subtype. Overall, the results indicated recurring influenza virus infections in this age group and no or only limited heterosubtypic antibody-mediated cross-protection. KW - influenza KW - children KW - disease severity KW - IgG KW - immunology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265841 VL - 22 ER - TY - JOUR A1 - Streng, Andrea A1 - Prifert, Christiane A1 - Weissbrich, Benedikt A1 - Liese, Johannes G. T1 - Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11–2012/13 JF - BMC Infectious Diseases N2 - Background Previous influenza surveillance at paediatric intensive care units (PICUs) in Germany indicated increased incidence of PICU admissions for the pandemic influenza subtype A(H1N1)pdm09. We investigated incidence and clinical characteristics of influenza in children admitted to PICUs during the first three post-pandemic influenza seasons, using active screening. Methods We conducted a prospective surveillance study in 24 PICUs in Bavaria (Germany) from October 2010 to September 2013. Influenza cases among children between 1 month and 16 years of age admitted to these PICUs with acute respiratory infection were confirmed by PCR analysis of respiratory secretions. Results A total of 24/7/20 influenza-associated PICU admissions were recorded in the post-pandemic seasons 1/2/3; incidence estimates per 100,000 children were 1.72/0.76/1.80, respectively. Of all 51 patients, 80 % had influenza A, including 65 % with A(H1N1)pdm09. Influenza A(H1N1)pdm09 was almost absent in season 2 (incidence 0.11), but dominated PICU admissions in seasons 1 (incidence 1.35) and 3 (incidence 1.17). Clinical data was available for 47 influenza patients; median age was 4.8 years (IQR 1.6–11.0). The most frequent diagnoses were influenza-associated pneumonia (62 %), bronchitis/bronchiolitis (32 %), secondary bacterial pneumonia (26 %), and ARDS (21 %). Thirty-six patients (77 %) had underlying medical conditions. Median duration of PICU stay was 3 days (IQR 1–11). Forty-seven per cent of patients received mechanical ventilation, and one patient (2 %) extracorporeal membrane oxygenation; 19 % were treated with oseltamivir. Five children (11 %) had pulmonary sequelae. Five children (11 %) died; all had underlying chronic conditions and were infected with A(H1N1)pdm09. In season 3, patients with A(H1N1)pdm09 were younger than in season 1 (p = 0.020), were diagnosed more often with bronchitis/bronchiolitis (p = 0.004), and were admitted to a PICU later after the onset of influenza symptoms (p = 0.041). Conclusions Active screening showed a continued high incidence of A(H1N1)pdm09-associated PICU admissions in the post-pandemic seasons 1 and 3, and indicated possible underestimation of incidence in previous German studies. The age shift of severe A(H1N1)pdm09 towards younger children may be explained by increasing immunity in the older paediatric population. The high proportion of patients with underlying chronic conditions indicates the importance of consistent implementation of the current influenza vaccination recommendations for risk groups in Germany. KW - post-pandemic KW - intensive care KW - children KW - influenza Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125280 VL - 15 IS - 573 ER - TY - JOUR A1 - Sonnenschein-van der Voort, Agnes M. M. A1 - Arends, Lidia R. A1 - de Jongste, Johan C. A1 - Annesi-Maesano, Isabella A1 - Arshad, S. Hasan A1 - Barros, Henrique A1 - Basterrechea, Mikel A1 - Bisgaard, Hans A1 - Chatzi, Leda A1 - Corpeleijn, Eva A1 - Correia, Sofia A1 - Craig, Leone C. A1 - Devereux, Graham A1 - Dogaru, Cristian A1 - Dostal, Miroslav A1 - Duchen, Karel A1 - Eggesbø, Merete A1 - van der Ent, C. Kors A1 - Fantini, Maria P. A1 - Forastiere, Francesco A1 - Frey, Urs A1 - Gehring, Ulrike A1 - Gori, Davide A1 - van der Gugten, Anne C. A1 - Hanke, Wojciech A1 - Henderson, A. John A1 - Heude, Barbara A1 - Iñiguez, Carmen A1 - Inskip, Hazel M. A1 - Keil, Thomas A1 - Kelleher, Cecily C. A1 - Kogevinas, Manolis A1 - Kreiner-Møller, Eskil A1 - Kuehni, Claudia E. A1 - Küpers, Leanne K. A1 - Lancz, Kinga A1 - Larsen, Pernille S. A1 - Lau, Susanne A1 - Ludvigsson, Johnny A1 - Mommers, Monique A1 - Andersen, Anne-Marie Nybo A1 - Palkovicova, Lubica A1 - Pike, Katherine C. A1 - Pizzi, Constanza A1 - Polanska, Kinga A1 - Porta, Daniela A1 - Richiardi, Lorenzo A1 - Roberts, Graham A1 - Schmidt, Anne A1 - Sram, Radim J. A1 - Sunyer, Jordi A1 - Thijs, Carel A1 - Torrent, Maties A1 - Viljoen, Karien A1 - Wijga, Alet H. A1 - Vrijheid, Martine A1 - Jaddoe, Vincent W. V. A1 - Duijts, Liesbeth T1 - Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children JF - The Journal of Allergy and Clinical Immunology N2 - Background Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. Results Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). Conclusion Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth." KW - gestational age KW - low birth weight KW - infant growth KW - wheezing KW - asthma KW - epidemiology KW - cohort studies KW - children Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120714 VL - 133 IS - 5 ER -