Biosimilars: a systematic review of published and ongoing clinical trials of antipsoriatics in chronic inflammatory diseases

Biosimilars for psoriasis treatment are currently being developed. Comparison of their efficacy and safety is a challenge. For approval, the European Medicines Agency (EMA) considers indirect evidence from other indications (for example, rheumatoid arthritis) as sufficient. Systematic review of biosimilars for psoriasis and other indications, review of ongoing trials in trial registers. Systematic search for randomized controlled trials (RCT) on biosimilars to adalimumab, etanercept, infliximab, and ustekinumab compared to their reference medication: (1) Publications in Medline, Medline In‐Process, Embase, Cochrane Library (efficacy, safety, immunogenicity) and (2) ongoing studies in clinical trial registers. No trials on biosimilars in psoriasis patients were identified. As to the infliximab biosimilar, there is data on patients with ankylosing spondylitis and rheumatoid arthritis, indicating no clinically relevant differences regarding efficacy and safety. Currently, there are two registered studies of an adalimumab biosimilar and one study of an etanercept biosimilar in psoriasis patients. Further ongoing studies on biosimilars to adalimumab, etanercept, and infliximab – all in rheumatoid arthritis patients – were identified. There is currently only limited data regarding RCTs with biosimilars. Provision of further clinical data and inclusion of patients in patient registers will be crucial.     

Physostigmine Restores Impaired Autophagy in the Rat Hippocampus after Surgery Stress and LPS Treatment

Tissue damage and pathogen invasion during surgical trauma have been identified as contributing factors leading to neuroinflammation in the hippocampus, which can be protected by stimulation of the cholinergic anti-inflammatory pathway using the acetylcholinesterase inhibitor physostigmine. Macroautophagy, an intracellular degradation pathway used to recycle and eliminate damaged proteins and organelles by lysosomal digestion, seems to be important for cell survival under stress conditions. This study aimed to examine the role of autophagy in physostigmine-mediated hippocampal cell protection in a rat model of surgery stress. In the presence or absence of physostigmine, adult Wistar rats underwent surgery in combination with lipopolysaccharide (LPS). Activated microglia, apoptosis-, autophagy-, and anti-inflammatory-related genes and -proteins in the hippocampus were determined by Real-Time PCR, Western blot and fluorescence microscopy after 1 h, 24 h and 3 d. Surgery combined with LPS-treatment led to microglia activation after 1 h and 24 h which was accompanied by apoptotic cell death after 24 h in the hippocampus. Furthermore, it led to a decreased expression of ATG-3 after 24 h and an increased expression of p62/ SQSTM1 after 1 h and 24 h. Administration of physostigmine significantly increased autophagy related markers and restored the autophagic flux after surgery stress, detected by increased degradation of p62/ SQSTM1 in the hippocampus after 1 h and 24 h. Furthermore, physostigmine reduced activated microglia and apoptosis relevant proteins and elevated the increased expression of TGF-beta1 and MFG-E8 after surgery stress. In conclusion, activation of autophagy may be essential in physostigmine-induced neuroprotection against surgery stress.     

Multisubject Decomposition of Event-related Positivities in Cognitive Control: Tackling Age-related Changes in Reactive Control

Age-related neurocognitive effects have been observed at different levels ranging from reduced amplitudes of even-related potentials and brain oscillations, to topography changes of brain activity. However, their association remains incompletely understood. We investigated time-frequency and time-course effects in functional networks underlying the P300 and their involvement in reactive control. Electroencephalographic (EEG) data of three different age groups (30 young: 18–26 years, 30 mid-aged: 49–58 years, 30 elderly: 65–75 years) was measured while they performed a cued colour/thickness switching task. Neural data was analysed concerning the targets. To consider restart, mixing, and switching processes, the targets´ position after a cue (first or third target) as well as their context in the single-task (distractor cue) or the mixed-task block (switch- or repeat cue) was analysed. P300 EEG data was decomposed by means of group-independent component and time-frequency analyses focusing on theta and beta oscillations. RTs generally slowed down with age (main effect group), and effects were specifically strong in targets after a switching cue (larger Cohens d). Peaking at around 300 ms, we detected five functionally independent networks reflecting the multicomponent process underlying task-switching. These networks differed in terms of their topography (parietal and frontal), their involvement in task processes (switch-specific, mixing-, restart-, and single-task processes) and in terms of frequency effects. All were affected by age, as indicated by amplitude changes of the target-P300 and power reductions most consistently shown in beta oscillations. Most extensive age-related changes were observed in one parietal network sensitive to mixing and restart processes. Changes included a topography shift, P300 and beta amplitudes, and were ongoing in the elderly group.     

Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study

Journal of Neuro-Oncology - The ideal delivery of radiation to the surgical cavity of brain metastases (BMs) remains the subject of debate. Risks of local failure (LF) and radiation necrosis (RN)...     

Hawks,Doves and Rasch decisions: Understanding the influence of different cycles of an OSCE on students’ scores using Many Facet Rasch Modeling

Introduction: OSCEs are commonly conducted in multiple cycles (different circuits, times, and locations), yet the potential for students’ allocation to different OSCE cycles is rarely considered as a source of variance—perhaps in part because conventional psychometrics provide limited insight.

Methods: We used Many Facet Rasch Modeling (MFRM) to estimate the influence of “examiner cohorts” (the combined influence of the examiners in the cycle to which each student was allocated) on students’ scores within a fully nested multi-cycle OSCE.

Results: Observed average scores for examiners cycles varied by 8.6%, but model-adjusted estimates showed a smaller range of 4.4%. Most students’ scores were only slightly altered by the model; the greatest score increase was 5.3%, and greatest score decrease was ?3.6%, with 2 students passing who would have failed.

Discussion: Despite using 16 examiners per cycle, examiner variability did not completely counter-balance, resulting in an influence of OSCE cycles on students’ scores. Assumptions were required for the MFRM analysis; innovative procedures to overcome these limitations and strengthen OSCEs are discussed.

Conclusions: OSCE cycle allocation has the potential to exert a small but unfair influence on students’ OSCE scores; these little-considered influences should challenge our assumptions and design of OSCEs.