Comparative Effectiveness of Biologics Across Subgroups of Patients with Moderate-to-Severe Plaque Psoriasis: Results at Week 12 from the PSoHO Study in a Real-World Setting

Introduction: In routine clinical care, important treatment outcomes among patients with moderate-to-severe plaque psoriasis (PsO) have been shown to vary according to patient demographics and disease characteristics. This study aimed to provide direct comparative effectiveness data at week 12 between anti-interleukin (IL)-17A biologics relative to other approved biologics for the treatment of PsO across seven clinically relevant patient subgroups in the real-world setting. Methods: From the international, non-interventional Psoriasis Study of Health Outcomes (PSoHO), 1981 patients with moderate-to-severe PsO were grouped a priori according to seven clinically relevant demographic and disease variables with binary categories, which were sex (male or female), age ( 30 kg/m2), race (White or Asian), PsO disease duration (< 15 or ≥ 15 years), psoriatic arthritis (PsA) comorbidity (present or absent), and prior biologic use (never or ≥ 1). Across these subgroups, effectiveness was compared between the anti-IL-17A cohort (ixekizumab, secukinumab) versus all other approved biologics and ixekizumab versus five individual biologics. The proportion of patients in each subgroup who achieved 90% improvement in Psoriasis Area and Severity Index (PASI90) and/or static Physician Global Assessment (sPGA) 0/1, PASI100, or PASI90 at week 12 were assessed. Comparative analyses were conducted using frequentist model averaging (FMA). Missing data were imputed using non-responder imputation. Results: Patients in each of the seven subgroups achieved similar response rates to those of the overall treatment cohort, apart from patients with PsA treated with other biologics who had 7-10% lower response rates. Consequently, patients with comorbid PsA had significantly higher odds of achieving skin clearance at week 12 with anti-IL-17A biologics compared to other biologics. Patients in all subgroups had significantly higher odds of achieving PASI90 and/or sPGA (0,1), PASI100, and PASI90 in the anti-IL-17A cohort relative to the other biologics cohort, except for the Asian subgroup. No sex- or age-specific differences in treatment effectiveness after 12 weeks were identified, neither between the treatment cohorts nor between the individual treatment comparisons. Conclusions: Despite relative consistency of comparative treatment effectiveness across subgroups, the presence of comorbid PsA may affect a patient's clinical response to some treatments. Keywords: Biologic; Comorbidity; Demographic; Effectiveness; Psoriasis; Real-world; Subgroup; Treatment

Agenten organisieren ein Intranet: Ein agentenbasierter Ansatz der Implementierung von Organisation auf Intranets

Zusammenfassung: 'Das Papier präsentiert ein Konzept für die Modellierung von Organisationen als System von kommunizierenden Agenten, eine Referenzarchitektur für agentenbasierte Modellierung von betrieblichen Anwendungen und ein ganzheitliches Konzept für die gemeinsame Entwicklung von Organisationen und Kommunikationskanälen

Concept of the Munich/Augsburg Consortium Precision in Mental Health for the German Center of Mental Health

The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventing chronicity.” PriMe bundles interdisciplinary research from the Ludwig-Maximilians-University (LMU), Technical University of Munich (TUM), University of Augsburg (UniA), Helmholtz Center Munich (HMGU), and Max Planck Institute of Psychiatry (MPIP) and has a focus on schizophrenia (SZ), bipolar disorder (BPD), and major depressive disorder (MDD). PriMe takes a longitudinal perspective on these three disorders from the at-risk stage to the first-episode, relapsing, and chronic stages. These disorders pose a major health burden because in up to 50% of patients they cause untreatable residual symptoms, which lead to early social and vocational disability, comorbidities, and excess mortality. PriMe aims at reducing mortality on different levels, e.g., reducing death by psychiatric and somatic comorbidities, and will approach this goal by addressing interdisciplinary and cross-sector approaches across the lifespan. PriMe aims to add a precision medicine framework to the DZPG that will propel deeper understanding, more accurate prediction, and personalized prevention to prevent disease chronicity and mortality across mental illnesses. This framework is structured along the translational chain and will be used by PriMe to innovate the preventive and therapeutic management of SZ, BPD, and MDD from rural to urban areas and from patients in early disease stages to patients with long-term disease courses. Research will build on platforms that include one on model systems, one on the identification and validation of predictive markers, one on the development of novel multimodal treatments, one on the regulation and strengthening of the uptake and dissemination of personalized treatments, and finally one on testing of the clinical effectiveness, utility, and scalability of such personalized treatments. In accordance with the translational chain, PriMe’s expertise includes the ability to integrate understanding of bio-behavioral processes based on innovative models, to translate this knowledge into clinical practice and to promote user participation in mental health research and care

Learning outcomes physiotherapy in neurology – a structured consensus finding of the Austrian University Network Physiotherapy in Neurology (ÖHPN)

Gesundhei

α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good