An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine

BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron(R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, polio, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. METHODS: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6--8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. RESULTS: In the intent-to-treat population, paracetamol reduced the incidence of fever >=38[degree sign]C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39[degree sign]C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39[degree sign]C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. CONCLUSIONS: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.Trial registration: NCT00294294

Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination

Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA+ mature oligodendrocytes and Olig2+ oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA+ and Olig2+ cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA+, but not Olig2+ cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS

Quality assurance of investigator initiated clinical trials in oncology:from protocol development to publication

Diese Dissertation befasst sich mit den erforderlichen Veraenderungen in der Durchfuehrung wissenschaftlich initiierter klinischer Studien der Gesellschaft fuer Paediatrische Onkologie und Haematologie (GPOH) in Kooperation mit internationalen Gruppen anderer europaeischer Laender nach der Implementierung der Richtlinie 2001/20/EC, um die Qualitaetssicherung von der Protokollentwicklung bis zur Publikation optimal zu gewaehrleisten. Besondere Schwerpunkte liegen dabei auf Aspekten der Pharmakovigilanz und der Harmonisierung der Sicherheitsevaluation bei onkologischen Studien mit der Darstellung von Mustern fuer Protokoll, Meldeformulare und Standardarbeitsanweisungen. Als Beispiel fuer die Dokumentation von Sicherheitsdaten ist eine detaillierte Analyse zum Sicherheits- und Toxizitaetsprofil einer Induktionschemotherapie mit Vincristin, Ifosfamid, Doxorubicin und Etoposid (VIDE) bei Ewing-Sarkom-Patienten der Studie EURO-E.W.I.N.G. 99 angefuehrt. This dissertation deals with the essential changes, which were required in academic investigator initiated oncology clinical trials organised by the German Society of Paediatric Oncology and Haematology (GPOH) in cooperation with oncology research groups from other European countries, following implementation of the Directive 2001/20/EC to ensure optimal quality assurance from development of the protocol through to publication. Emphasis was placed on particular aspects of pharmacovigilance in particular the harmonisation of safety evaluation in oncology clinical trials with examples given for protocol development, reporting forms and standard operating procedures. As an example of the documentation of safety data is a detailed analysis of the safety and toxicity profile of induction chemotherapy with vincristine, ifosfamide, doxorubicin und etoposide in patients with Ewing's sarcoma in the EURO-E.W.I.N.G. 99 clinical trial presented

Age and Gender Representation on German TV: A Longitudinal Computational Analysis

Television offers an enticing glimpse into the world, but its perspective is often skewed. When societal groups are systematically excluded from appearing on the screen, they lose the chance to represent their characteristics and interests. Recipients may then form distorted perceptions and attitudes towards those groups. Empirical research on the prevalence of such biases - especially across stations, time, and genre - has been limited by the effort of manual content analyses. We develop and validate a deep-learning based method for measuring age and gender of faces in video material. An analysis of approximately 16 million faces from six years of German mainstream TV across six stations is fused with existing program metadata indicating timing and genre of broadcasts, including advertisements. Multilevel regression models show a consistent and temporally stable discrimination against women and elderly people, along with a double discrimination of elderly women. A significant amount of variation across genres and systematic differences between public and private broadcasters furthermore indicate previously undocumented heterogeneity in the representation of societal groups on TV. We discuss potential implications of a genre-specific differentiation against the backdrop of societal trends

Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination

Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA(+) mature oligodendrocytes and Olig2(+) oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA(+) and Olig2(+) cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA(+), but not Olig2(+) cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS

Fitnesssport vor Ballsport – Neuere Erkenntnisse zur Entwicklung des Sportengagements von Mädchen im Jugendalter mit und ohne Migrationshintergrund

Gehrmann S, Kraus C-I, Fast N, Kleindienst-Cachay C, Kastrup V. Fitnesssport vor Ballsport – Neuere Erkenntnisse zur Entwicklung des Sportengagements von Mädchen im Jugendalter mit und ohne Migrationshintergrund. In: Golenia M, Jürgens M, Kohake K, Neuber N, eds. Wissenstransfer – ein zentrales Thema für die Sportpädagogik? 35. Jahrestagung der dvs-Sektion Sportpädagogik vom 16.-18. Juni 2022 in Münster. Münster; 2022