Search

Purpose: Rett syndrome is a severe neurodevelopmental disorder that affects about 1 in 10,000 females. Clinical trials of disease modifying therapies are on the rise, but there are few psychometrically sound caregiver-reported outcome measures available to assess treatment benefit. We report on a new caregiver-reported outcome measure, the Rett Caregiver Assessment of Symptom Severity (RCASS). Methods: Using data from the Rett Natural History Study (n=649), we examined the factor structure, using both exploratory and confirmatory factor analysis, and the reliability and validity of the RCASS. Results: The four-factor model had the best overall fit, which covered movement, communication, behavior, and Rett-specific symptoms. The RCASS had moderate internal consistency. Strong face validity was found with age and mutation type, and criterion validity was established with other similar measures, including the Revised Motor-Behavior Assessment Scale, Clinical Severity Scale, Clinical Global Impression Scale, and the Child Health Questionnaire. Conclusion: These data provide initial evidence that the RCASS is a viable caregiver-outcome measure for use in clinical trials in Rett syndrome. Future work to assess sensitivity to change and other measures of reliability, such as test-retest and inter-rater agreement, are needed.

Objectives: Efficacy and safety results from the EMERGE (NCT02484547) and ENGAGE (NCT02477800) phase 3 studies of aducanumab in early Alzheimer’s disease (AD) have been published. In EMERGE, but not in ENGAGE, high-dose aducanumab demonstrated significant treatment effects across primary and secondary endpoints. Low-dose aducanumab results were consistent across studies with non-significant differences versus placebo that were intermediate to the highdose arm in EMERGE. The present investigation examined data from EMERGE and ENGAGE through post-hoc analyses to determine factors that contributed to discordant results between the high-dose arms of the two studies. Design: EMERGE and ENGAGE were 2 phase 3, randomized, double-blind, placebo-controlled, parallel-group studies. Setting: EMERGE and ENGAGE were 2 global multicenter studies involving 348 sites in 20 countries. Participants: Participants in EMERGE and ENGAGE were aged 50 to 85 years and had mild cognitive impairment or mild AD dementia with confirmed amyloid pathology. The randomized and dosed population (all randomized patients who received at least one dose of study treatment) included 1638 patients in EMERGE and 1647 in ENGAGE. Intervention: In EMERGE and ENGAGE, participants were randomized to receive low- or high-dose aducanumab or placebo (1:1:1) once every 4 weeks. Measurements: In this paper, 4 areas were investigated through post-hoc analyses to understand the discordance in the high-dose arms of the EMERGE and ENGAGE studies: baseline characteristics, amyloid-related imaging abnormalities, non-normality of the data, and dosing/exposure to aducanumab. Results: Post-hoc analyses showed that outcomes in the ENGAGE high-dose group were affected by an imbalance in a small number of patients with extremely rapid progression and by lower exposure to the target dose of 10 mg/kg. These factors were confounded and present in early enrolled patients but were not present in later-enrolled patients who were randomized to the target dosing regimen of 10 mg/kg after titration. Neither baseline characteristics nor amyloid-related imaging abnormalities contributed to the difference in results between the high-dose arms. Conclusions: Results were consistent across studies in later enrolled patients in which the incidence of rapidly progressing patients was balanced across treatment arms.

Achtsamkeit wurde aus dem „Oko-Regal“ geholt und hat sich zum gesellschaftlichen Trend entwickelt. Viele Unternehmen und Organisationen in Deutschland und sogar mehr als die Halfte aller mittelstandischen und grosen Unternehmen in den USA bieten bereits achtsamkeitsbasierte Weiterbildungen an. [1] Achtsamkeit wird dabei einerseits zur Starkung der Gesundheit im betrieblichen Gesundheitsmanagement eingesetzt. Sie kommt aber immer haufiger auch zur Verbesserung der Zusammenarbeit und des Fuhrungsstils im Training von Fuhrungskraften und Teams zur Anwendung. Doch was ist Achtsamkeit eigentlich? Und bleibt dafur uberhaupt ausreichend Zeit in unserer schnelllebigen Arbeitswelt, die uns gerade jetzt wahrend der Corona-Pandemie vor immer neue Herausforderungen stellt? Eine der grosten aktuellen Untersuchungen zu Achtsamkeit in Unternehmen erforscht die Effekte von Achtsamkeit am Arbeitsplatz. Das bisherige Ergebnis zum Ende der ersten Studienreihe mit mehr als 340 Teilnehmenden belegt, dass gerade in der Krise Achtsamkeit als wirksames Mittel gilt — sowohl fur die individuelle Gesundheit als auch fur den Fuhrungsstil und die Zusammenarbeit.

Background: Alzheimer’s disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. Objectives: We evaluated the efficacy and safety of aducanumab in early Alzheimer’s disease. Design: EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer’s disease. Setting: These studies involved 348 sites in 20 countries. Participants: Participants included 1638 (EMERGE) and 1647 (ENGAGE) patients (aged 50–85 years, confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia, of which 1812 (55.2%) completed the study. Intervention: Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (10 mg/kg target dose), or placebo via IV infusion once every 4 weeks over 76 weeks. Measurements: The primary outcome measure was change from baseline to week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; and biomarker endpoints. Results: EMERGE and ENGAGE were halted based on futility analysis of data pooled from the first approximately 50% of enrolled patients; subsequent efficacy analyses included data from a larger data set collected up to futility declaration and followed prespecified statistical analyses. The primary endpoint was met in EMERGE (difference of -0.39 for high-dose aducanumab vs placebo [95% CI, -0.69 to -0.09; P=.012; 22% decrease]) but not in ENGAGE (difference of 0.03, [95% CI, -0.26 to 0.33; P=.833; 2% increase]). Results of biomarker substudies confirmed target engagement and dose-dependent reduction in markers of Alzheimer's disease pathophysiology. The most common adverse event was amyloid-related imaging abnormalities-edema. Conclusions: Data from EMERGE demonstrated a statistically significant change across all four primary and secondary clinical endpoints. ENGAGE did not meet its primary or secondary endpoints. A dose-and time-dependent reduction in pathophysiological markers of Alzheimer’s disease was observed in both trials.

Amyloid beta (Aβ) plaque is a defining pathologic feature of Alzheimer disease (AD). Aducanumab, a monoclonal IgG1 that selectively binds aggregated species of Aβ, has been shown by amyloid positron emission tomography (Amyloid PET) to reduce Aβ plaques in patients with prodromal and mild AD. This is the first autopsy report of the AD neuropathology in a patient previously treated with aducanumab. The patient was an 84-year-old woman who was randomized to the placebo arm of the PRIME Phase 1b study (221AD103). The patient progressed to moderate dementia (MMSE = 14/30), beyond the targeted early AD treatment stage, before receiving aducanumab in the long-term extension (LTE). The patient then received 32 monthly doses of aducanumab, titrated up to 6 mg/kg, for a cumulative dose of 186 mg/kg. In the LTE, Amyloid PET scans demonstrated robust Aβ plaque reduction, from a composite standard uptake value ratio (SUVR) of 1.5 at screening to

Das vorliegende Kapitel 2 ist Teil eines Baukastens mit konkreten, pragmatisch anwendbaren Werkzeugen fur einen Kulturwandel. Kulturwandel bezeichnet hier den sog. uberfachlichen Teil von Change-Prozessen, d. h. eine nachhaltige Veranderung von Verhalten und Einstellungen der Menschen innerhalb einer Organisation. Dieses Kapitel stellt den zweiten Teil der Grundlagen dar. Es fuhrt in die zwei grundlegenden Modelle und die Designprinzipien zum Veranderungsprozess in Organisationen ein. Zu den Modellen gehoren das 4-Phasen-Modell des Kulturwandels fur eine systematische Planung und Durchfuhrung. Das AkKo-Modell beschreibt die vier Determinanten, die fur Verhaltensveranderungen eines Individuums unabdingbar sind. Die funf Designprinzipien zeigen, wie die Aktivitaten gestaltet werden sollten, um das Verhalten einer ganzen Organisation zu verandern. Die beiden Modelle und Prinzipien basieren auf aktuellen Forschungsergebnissen aus der Verhaltensforschung, der Psychologie und den Neurowissenschaften und sind in der jahrzehntelangen praktischen Erfahrung der Autoren insbesondere fur den nachhaltigen Erfolg von Kulturwandel relevant.

Das vorliegende Kapitel 5 ist Teil eines Baukastens mit konkreten, pragmatisch anwendbaren Werkzeugen fur einen Kulturwandel. Kulturwandel bezeichnet hier den sog. uberfachlichen Teil von Change-Prozessen, d. h. eine nachhaltige Veranderung von Verhalten und Einstellungen der Menschen innerhalb einer Organisation. Dieses Kapitel beschreibt die dritte von vier Phasen eines systematisch begleiteten Kulturwandels, die Umsetzung. Es zeigt auf, wie bei der Umsetzung eines Kulturwandelprojektes eine integrierte Philosophie genutzt werden kann, die sowohl beharrlich und stringent die Richtung vorgibt als auch fur Einbindung der breiten Mitarbeiterbasis sorgt. Dazu helfen drei Ansatze: „Huckepackansatz“, der Veranderungsprogramme – wo moglich – in bereits bestehende Initiativen integriert, die Umsetzung von Prototypen zur Erreichung rascher Erfolgsbeispiele und Lernerfahrungen, bevor Veranderungen grosflachig ausgerollt werden, und die Entwicklung symbolischer Aktionen, deren Sichtbarkeit allen Stakeholdern zeigt, dass die Veranderung bereits begonnen hat. Zudem legt das Kapitel einen Fokus auf die Kommunikation in Wandlungsprozessen mithilfe eines Kommunikationsplans und einer breiten Auswahl an Kommunikationsinstrumenten. Die Durchfuhrung von Workshops in unterschiedlichen Facetten, deren Inhalte und Prozesse aktiv den Kulturwandel antreiben, ist ebenfalls Teil des Kapitels.

Das vorliegende Kapitel 1 ist Teil eines Baukastens mit konkreten, pragmatisch anwendbaren Werkzeugen fur einen Kulturwandel. Kulturwandel bezeichnet hier den sog. uberfachlichen Teil von Change-Prozessen, d. h. eine nachhaltige Veranderung von Verhalten und Einstellungen der Menschen innerhalb einer Organisation. Dieses Kapitel stellt den ersten Teil der Grundlagen dar: Es erlautert den Begriff „Organisationskultur“ mit seinen bestimmenden Faktoren und Kulturwandel. Zudem veranschaulicht dieses Kapitel die Bedeutung von Kultur fur Organisationen; Studien zeigen u. a., dass Veranderungsprozesse haufig scheitern, weil das Thema Kulturwandel nicht berucksichtigt wird. Veranderung gelingt, wenn sich nicht nur Prozesse und Systeme, sondern auch Verhalten und Einstellungen von Mitarbeitern andern. Das Kapitel bietet zudem Einblick in die Entwicklung von Organisationstheorien bis hin zum aktuellen Verstandnis von Kulturwandel und beleuchtet den Wandel von einer ehemals bestehenden Skepsis uber psychologische Themen in Fuhrungsetagen zu einem verbreiteten Selbstverstandnis der Bedeutung von Kulturthemen fur den Geschaftserfolg.

Das vorliegende Kapitel 3 ist Teil eines Baukastens mit konkreten, pragmatisch anwendbaren Werkzeugen fur einen Kulturwandel. Kulturwandel bezeichnet hier den sog. uberfachlichen Teil von Change-Prozessen, d. h. eine nachhaltige Veranderung von Verhalten und Einstellungen der Menschen innerhalb einer Organisation. Dieses Kapitel beschreibt die erste von vier Phasen eines systematisch begleiteten Kulturwandels, die Ausrichtung. In diesem Kapitel werden praktische Werkzeuge fur diese Phase verstandlich dargestellt. Es zeigt, wie mithilfe einer Aktionsdiagnose ein faktenbasiertes Verstandnis uber die Richtung des Veranderungsprogramms erreicht werden kann. Auserdem zeigt es, wie systematisch Stakeholder eingeordnet werden konnen, z. B. mit dem Stakeholder-Priorisierungs-Raster (SPR), und anschliesend, wie Hypothesen uber die gewunschten Verhaltens - und Einstellungsanderungen von einzelnen Zielgruppen mit sog. „Ist-Soll“-Paaren definiert werden. Letztlich beschreibt es den Prozess, den das Top-Team der Veranderung durchlauft, um mit einem gemeinsamen Verstandnis hinter der Veranderung zu stehen und so die Veranderung auch bei moglichen Krisen als Team geschlossen vorantreiben zu konnen.

BackgroundRett syndrome (RTT) is a severe neurodevelopmental disorder with complex medical comorbidities extending beyond the nervous system requiring the attention of health professionals. There is no peer-reviewed, consensus-based therapeutic guidance to care in RTT. The objective was to provide consensus on guidance of best practice for addressing these concerns.MethodsInformed by the literature and using a modified Delphi approach, a consensus process was used to develop guidance for care in RTT by health professionals.ResultsTypical RTT presents early in childhood in a clinically recognisable fashion. Multisystem comorbidities evolve throughout the lifespan requiring coordination of care between primary care and often multiple subspecialty providers. To assist health professionals and families in seeking best practice, a checklist and detailed references for guidance were developed by consensus.ConclusionsThe overall multisystem issues of RTT require primary care providers and other health professionals to manage complex medical comorbidities within the context of the whole individual and family. Given the median life expectancy well into the sixth decade, guidance is provided to health professionals to achieve current best possible outcomes for these special-needs individuals.

Intake of oral supplements with the aim of a cutaneous antiaging effect are increasingly common. Hyaluronic acid (HA) is a promising candidate, as it is the key factor for preserving tissue hydration. In our practice study, we evaluated the effect of an oral HA preparation diluted in a cascade-fermented organic whole food concentrate supplemented with biotin, vitamin C, copper, and zinc (Regulatpro Hyaluron) on skin moisture content, elasticity, skin roughness, and wrinkle depths. Twenty female subjects with healthy skin in the age group of 45 to 60 years took the product once daily for 40 days. Different skin parameters were objectively assessed before the first intake, after 20 and after 40 days. Intake of the HA solution led to a significant increase in skin elasticity, skin hydration, and to a significant decrease in skin roughness and wrinkle depths. The supplement was well tolerated; no side effects were noted throughout the study.

Background The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS). Patients and methods In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded. Results Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p = .46). Conclusion Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in prospective randomized clinical trials. We compared the effect of more than six cycles of TMZ in comparison with exactly six cycles on overall survival (OS) and progression-free survival (PFS) by multivariate analysis and found a benefit in PFS but not OS. Thus, our data do not suggest prolonging TMZ maintenance therapy beyond six cycles, which should be considered in neurooncological practice.

Tooth colour determination is an essential component in the preservative and prosthetic workflow during production of tooth-coloured restorations. The aim of the study was to compare the clinical suitability of conventional, visual tooth colour determination and digital methods. Tooth colour of vital, natural central incisors among a total of 107 subjects was determined visually by a dentist (VD) and dental technician (VDT) using VITA Toothguide 3D-MASTER®, digitally by the spectrophotometer VITA Easyshade Advance 4.0 (reference instrument) and Trios®Color intra-oral scanner (test subject). Reliability was examined by repeating the digital measurements of 20 teeth three times. The analysis was based on the recorded 3D-MASTER values and L*a*b/L*C*h parameters. The measuring accuracy was 43.9% with the Trios®Color scanner, 35.5% for VD and 34.6% for VDT. In 25.5% of cases, the scanner’s results corresponded with VD and in 33.6% with VDT. The visual methods corresponded with 45.8%. All mean values of the recorded colour differences fell within the clinically acceptable range of ΔE ≤ 6.8. The intra-oral scanner attained repeatability of 78.3% and the VITA Easyshade system of 76.6%. The Trios®Color intra-oral scanner appears to be a good alternative to the current standard of visual tooth colour determination. The new module attains better results than the visual method and is comparable to the reference instrument. Dentistry becomes increasingly digitalized and tooth colour determination devices have generally to be improved. Therefore, the investigation of a new digital device is important for future developments.

Introduction L’aducanumab est un AC monoclonal humain ciblant les formes agregees d’Aβ (oligomeres solubles et fibrilles insolubles). EMERGE et ENGAGE sont 2 etudes de phase III mondiales, randomisees, en double insu, controlees vs placebo, de 18 mois. Objectifs Ces etudes, aux methodologies identiques, ont evalue l’efficacite et la securite d’emploi de l’aducanumab chez des patients de 50 a 85 ans avec une maladie d’Alzheimer (MA) debutante (troubles cognitifs legers dus a la MA ou demence legere liee a la MA). Patients et methodes Les criteres d’inclusion comprenaient une TEP-amyloide positive, un MMSE de 24 a 30, un score CDR Global de 0,5, et un score RBANS-DMI ≤ 85. Pendant la periode controlee vs placebo de 18 mois, les patients ont ete randomises 1/1/1 pour recevoir l’aducanumab a dose faible, l’aducanumab a dose elevee ou un placebo, administre en IV toutes les 4 semaines. Le critere de jugement principal etait la variation du score CDR-SB a la sem 78. Les criteres secondaires etaient la variation des scores MMSE, ADAS-Cog13 et ADCS-ADL-MCI. Resultats Apres l’analyse de futilite planifiee, une analyse realisee suite au gel de base final a montre que EMERGE avait satisfait son critere de jugement principal, conformement au plan d’analyse statistique prespecifie. Les patients traites par aducanumab a dose elevee ont presente une reduction significative du declin clinique mesure par les CDR-SB a la semaine 78 (22 % vs placebo, p = 0,01). Discussion ENGAGE n’a pas satisfait son critere de jugement principal. Cependant, les donnees des patients de l’etude ENGAGE qui avaient atteint une exposition suffisante a l’aducanumab a dose elevee ont corrobore les resultats d’EMERGE. Le profil de securite d’emploi et de tolerance de l’aducanumab dans les etudes EMERGE et ENGAGE concordait avec celui observe dans les etudes precedentes. Conclusion EMERGE a satisfait a son critere de jugement principal, conformement au plan d’analyse statistique prespecifie. Les donnees d’un sous-groupe de patients d’ENGAGE corroborent les resultats d’EMERGE.