Effect of action-based cognitive remediation on cognition and neural activity in bipolar disorder:Study protocol for a randomized controlled trial

Abstract Background Cognitive impairment is present in bipolar disorder (BD) during the acute and remitted phases and hampers functional recovery. However, there is currently no clinically available treatment with direct and lasting effects on cognitive impairment in BD. We will examine the effect of a novel form of cognitive remediation, action-based cognitive remediation (ABCR), on cognitive impairment in patients with BD, and explore the neural substrates of potential treatment efficacy on cognition. Methods/design The trial has a randomized, controlled, parallel-group design. In total, 58 patients with BD in full or partial remission aged 18–55 years with objective cognitive impairment will be recruited. Participants are randomized to 10 weeks of ABCR or a control group. Assessments encompassing neuropsychological testing and mood ratings, and questionnaires on subjective cognitive complaints, psychosocial functioning, and quality of life are carried out at baseline, after 2 weeks of treatment, after the end of treatment, and at a six-month-follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and 2 weeks into treatment. The primary outcome is a cognitive composite score spanning verbal memory, attention, and executive function. Two complete data sets for 52 patients will provide a power of 80% to detect a clinically relevant between-group difference on the primary outcome. Behavioral data will be analyzed using mixed models in SPSS while MRI data will be analyzed with the FMRIB Expert Analysis Tool (FEAT). Early treatment-related changes in neural activity from baseline to week 2 will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest and with an exploratory whole-brain analysis. Discussion The results will provide insight into whether ABCR has beneficial effects on cognition and functioning in remitted patients with BD. The results will also provide insight into early changes in neural activity associated with improvement of cognition, which can aid future treatment development. Trial registration Clinicaltrials.gov, NCT03295305. Registered on 26 September 2017

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Lernräume erfahren - gemeinsam "praktisch" erleben

Das Angebot der an der Goethe-Universität Frankfurt angesiedelten Hochschullernwerkstatt Arbeitsstelle für Diversität und Unterrichtsentwicklung - Didaktische Werkstatt zielt auf eine phasen- und institutionsübergreifende Professionalisierung (angehender) Lehrkräfte im Kontext diversitätssensibler Praktiken. Dabei setzt sie insbesondere auf offene Angebote für alle drei Phasen der Lehrkräftebildung, Forschendes Lernen sowie gezielte Theorie-Praxis-Begegnungen mit Blick auf Inklusion und Diversität im Unterricht. Als Kooperationsprojekt mit dem Hessischen Kultusministerium stellt die Didaktische Werkstatt selbst eine Schnittstelle zwischen Forschung, Lehre und Praxis dar und verbindet in einem multiprofessionellen Netzwerk verschiedenste Akteure. Dies spiegelt sich in den vielfältigen Arbeitsbereichen der Didaktischen Werkstatt wider, wie bspw. Praxisprojekten, Fortbildungen, universitäre Lehre, Forschung sowie die Arbeit der European Agency for Special Needs and Inclusive Education. Darüber hinaus findet sich in der Werkstatt eine Präsenzbibliothek als physischer Lern- und Kommunikationsort, der Raum für Begegnung mit Material und Austausch mit anderen (angehenden) Lehrkräften und Bildungsforschenden bietet. Bereits vor der Covid 19-Pandemie wurden erste Unternehmungen zur Ergänzung und Unterstützung des physischen Raums der Didaktischen Werkstatt durch digitale Elemente getroffen, bspw. durch digitale Wegweiser in der Präsenzbibliothek oder durch die Erstellung von Infopaketen zu pädagogisch relevanten Inhalten. Auf die anfänglichen Bestrebungen zur Digitalisierung wirkte die Pandemie wie ein Katalysator: Die bereits vorhandenen digitalen Elemente wurden für (Ersatz-) Angebote der Didaktischen Werkstatt weiterentwickelt und auf neue Arbeitsbereiche erweitert. Das Resultat sind innovative Angebote, die das Potential von analogen und digitalen Formaten verknüpfen, wobei letztere zur Orientierung und Auseinandersetzung in Bezug auf die Räumlichkeiten und Materialien der Didaktischen Werkstatt beitragen. Eines dieser Angebote ist das nachfolgend dargestellte hybride Lehr-Lernformat in Form eines Parcours, das im Rahmen eines multiprofessionellen Klausurtags der Didaktischen Werkstatt erarbeitet wurde. Neben der methodischen Ausgestaltung des Parcours, wurde am Klausurtag auch die inhaltliche Rahmung des Lehr-Lernformats mit Fokus auf Fallarbeit entwickelt. Um dem Anspruch der Didaktischen Werkstatt nach Professionalisierung im Kontext diversitätssensibler Praktiken gerecht zu werden, beziehen sich die eingesetzten Fälle auf Situationen, die ein diversitätssensibles Handeln erforderlich machen. Zentrales Anliegen ist dabei die Anregung zu mehrperspektivischen Betrachtungsweisen solcher Situationen und das Aufbrechen eventueller Kategorisierungstendenzen. (DIPF/Orig.

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

A Q-methodology study of flare help-seeking behaviours and different experiences of daily life in rheumatoid arthritis

© 2014 Lin et al.; licensee BioMed Central Ltd. Background: Previous studies have not addressed rheumatoid arthritis (RA) patients' help-seeking behaviours for RA flares, and only one small qualitative study has addressed how patients experience daily life on current treatment regimes. Thus, this study aims to identify clusters of opinion related to RA patients' experiences of daily life on current treatments, and their help-seeking behaviours for RA flares. Methods: Using Q-methodology (a methodology using qualitative and quantitative methods to sort people according to subjective experience), two separate studies were conducted with the same sample of RA patients (mean age 55, 73% female). Thirty participants sorted 39 statements about daily life (Q-study 1) and 29 participants separately sorted 23 statements about flare help-seeking (Q-study 2). Data were examined using Q-factor analysis. Results: Daily life with RA (Q-study 1): Three factors relating to the experience of living with RA were extracted and explained. Patients belonging to Factor A (mean age 62, 86% female) use effective self-management techniques to control the daily impact of RA. Those in Factor B (mean age 55, 75% male) struggle to self-manage and cope. Whilst patients in Factor C (mean age 42, 100% female) prioritise life responsibilities over their RA, reporting less impact. Flare help-seeking (Q-study 2): Two factors explaining the experience of flare help-seeking (unrelated to the factors from Q-study 1) were extracted and explained. Factor X (68.8% on biologics) reported seeking help quickly, believing the medical team is there to help. Factor Y (0% on biologics) delay help-seeking, concerned about wasting the rheumatologist's time, believing they should manage alone. All participants agreed they sought help due to intense pain and persistent, unmanageable symptoms. Conclusions: Patients with different characteristics appear to manage RA life in different ways and men may struggle more than women. Whilst all patients are prompted to seek help by persistent, unmanageable symptoms, some delay help-seeking. Further research is needed to quantify the severity of daily symptoms, the level of symptoms needed for patients to define themselves as in flare and to understand the support needs of RA men

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron