A Patients' Perspective Towards the Injection Devices for Humira® and Imraldi® in a Nationwide Switching Program.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObjective: Due to a tender process in Iceland, all patients on Humira® were switched nationwide to its biosimilar Imraldi® in March 2019. The study aimed to explore the patient's perspective of the Humira® and Imraldi® injection devices. Methods: A standard telephone interview was carried out among patients with inflammatory arthritis, inflammatory bowel disease and psoriasis, who underwent this nationwide switching program a few months earlier. Results: The response rate was 84.5% (n = 198). The average age was 50.8 years, and 53.5% were female. The patients self-administered the drugs in 96% of the cases. The majority (90.5%) stated that they received individualized instruction on using the Humira® pen, compared to 18.2% who accepted instruction in the case of the Imraldi® pen. Almost half (46.6%) of the patients found it more difficult to use the Imraldi® pen than the Humira® pen, while only 12.5% found the Imraldi® pen easier to use. Firstly, these differences were due to more painful insertion of the needle (62.2%) and secondly, due to the experience, the injection process was different (63.0%). Conclusion: Patients with inflammatory disorders who have been treated regularly with adalimumab preferred the Humira® injection device over the Imraldi® device, according to our results. After all, these injection devices' structure and content are not the same, although both contain the same active ingredient, i.e. adalimumab. Our results highlight the importance of thorough information, not only with an information letter but also with the possibilities for individualized introduction in planning switching to biosimilars. Keywords: Humira; Imraldi; adalimumab; injection devices; medicine administration at home

PHAEOCHROMOCYTOMA

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72570/1/j.1445-2197.1988.tb01080.x.pd

Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021–April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations

The Non-Canonical CTD of RNAP-II Is Essential for Productive RNA Synthesis in Trypanosoma brucei

The carboxy-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II (RNAP-II) is essential for gene expression in metazoa and yeast. The canonical CTD is characterized by heptapeptide repeats. Differential phosphorylation of canonical CTD orchestrates transcriptional and co-transcriptional maturation of mRNA and snRNA. Many organisms, including trypanosomes, lack a canonical CTD. In these organisms, the CTD is called a non-canonical CTD or pseudo-CTD (ΨCTD. In the African trypanosome, Trypanosoma brucei, the ΨCTD is ∼285 amino acids long, rich in serines and prolines, and phosphorylated. We report that T. brucei RNAP-II lacking the entire ΨCTD or containing only a 95-amino-acid-long ΨCTD failed to support cell viability. In contrast, RNAP-II with a 186-amino-acid-long ΨCTD maintained cellular growth. RNAP-II with ΨCTD truncations resulted in abortive initiation of transcription. These data establish that non-canonical CTDs play an important role in gene expression

Catalytic Intermolecular Hetero-Dehydro-Diels–Alder Cycloadditions: Regio- and Diasteroselective Synthesis of 5,6-Dihydropyridin-2-ones

A novel catalyzed intermolecular heterodehydro-Diels–Alder reaction between push–pull 1,3-dien-5-ynes and aldimines or silylaldimines is reported. The sequence is promoted both by gold(I) or silver(I) catalysts and leads to the diastereo- and regioselective formation of 5,6-dihydropyridin-2-onesMICINN (Spain) (grants CTQ2009-09949, CTQ2010-16790, PTA2008-1524-P contract to J.M.F.-G. and Ramon y Cajal postdoctoral contract to M.A.F.-R.) and FICYT (project IB08-088)This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/page/policy/articlesonrequest/index.htm

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.Swedish Research Council Knut and Alice Wallenberg Foundation AFA Foundation Swedish Brain Foundatio

Purinergic modulation of microglial cell activation

Microglial cells are resident macrophages in the brain and their activation is an important part of the brain immune response and the pathology of the major CNS diseases. Microglial activation is triggered by pathological signals and is characterized by morphological changes, proliferation, phagocytosis and the secretion of various cytokines and inflammatory mediators, which could be both destructive and protective for the nervous tissue. Purines are one of the most important mediators which regulate different aspects of microglial function. They could be released to the extracellular space from neurons, astrocytes and from the microglia itself, upon physiological neuronal activity and in response to pathological stimuli and cellular damage. Microglial activation is regulated by various subtypes of nucleotide (P2X, P2Y) and adenosine (A1, A2A and A3) receptors, which control ionic conductances, membrane potential, gene transcription, the production of inflammatory mediators and cell survival. Among them, the role of P2X7 receptors is especially well delineated, but P2X4, various P2Y, A1, A2A and A3 receptors also powerfully participate in the microglial response. The pathological role of microglial purine receptors has also been demonstrated in disease models; e.g., in ischemia, sclerosis multiplex and neuropathic pain. Due to their upregulation and selective activation under pathological conditions, they provide new avenues in the treatment of neurodegenerative and neuroinflammatory illnesses

Organocatalytic asymmetric domino Michael–Henry reaction for the synthesis of substituted bicyclo[3.2.1]octan-2-ones

This paper was submitted for publication in the journal "Chemical Communications" and the definitive version can be found at: http://dx.doi.org/10.1039/c3cc39165eThe first organocatalytic asymmetric reaction between 1,4-cyclohexanedione and nitroalkenes have been studied, affording bicyclo[3.2.1]octane derivatives containing four continuous stereogenic centres. The products were obtained through a domino Michael-Henry process as a single diastereoisomer with excellent enantioselectivities