Learnings from Regional Market Dynamics of Originator and Biosimilar Infliximab and Etanercept in Germany.

Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on: (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010-2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers' and insurers' views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variations across the 17 German Regional Associations of Statutory Health Insurance Accredited Physicians (PA regions). Quantitative analyses indicated that biosimilar market shares for infliximab and etanercept were significantly lower in former East Germany when compared to former West Germany regions. Through qualitative interview analyses, this study showed that the use of infliximab and etanercept biosimilars across Germany is primarily influenced by (1) the regional-level implementation of biosimilar quotas and the presence of monitoring/sanctioning mechanisms to ensure adherence to these quotas, (2) the different insurer-manufacturer discount contracts, and (3) gainsharing arrangements established at the insurer-prescriber level

Linear dichroism and circular dichroism in photosynthesis research

The efficiency of photosynthetic light energy conversion depends largely on the molecular architecture of the photosynthetic membranes. Linear- and circular-dichroism (LD and CD) studies have contributed significantly to our knowledge of the molecular organization of pigment systems at different levels of complexity, in pigment–protein complexes, supercomplexes, and their macroassemblies, as well as in entire membranes and membrane systems. Many examples show that LD and CD data are in good agreement with structural data; hence, these spectroscopic tools serve as the basis for linking the structure of photosynthetic pigment–protein complexes to steady-state and time-resolved spectroscopy. They are also indispensable for identifying conformations and interactions in native environments, and for monitoring reorganizations during photosynthetic functions, and are important in characterizing reconstituted and artificially constructed systems. This educational review explains, in simple terms, the basic physical principles, and theory and practice of LD and CD spectroscopies and of some related quantities in the areas of differential polarization spectroscopy and microscopy

Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones

ACKNOWLEDGMENTS This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003).Peer reviewedPublisher PD

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities.

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities

Biosimilars: Good for the patient and the care budget. Distrust against generic biotech agents is unfounded

status: publishe

Bioavailability of pivampicillin and ampicillin trihydrate administered as an oral paste in horses

Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses, Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only, The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg, Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin, Ampicillin concentrations in plasma were determined up to 24 hours after administration, After administration of pivampicillin to starved and fed horses the mean areas under the plasma concentration-time curve (AUCs) were 23.0 and 19.3 mu g.h.ml(-1), respectively, After administration of ampicillintrihydrate to fed horses the mean AUC was 0.7 mu g.h.ml(-1). The peak plasma concentrations were 4.8, 6.7, and 0.1 mu g/ml, after administration of pivampicillin to starved and fed horses and of ampicillin trihydrate to fed horses, respectively, There was no statistically significant difference in peak plasma concentration or AUC between pivampicillin administered to starved or fed horses, It is concluded that pivampicillin administered as an oral paste at a dose of 19.9 mg/kg gives satisfactory plasma concentrations in both starved and fed horses, whereas ampicillin trihydrate produces negligible plasma concentrations, Pivampicillin binds to feedstuffs at the pH found in the horse's stomach and small intestine. After incubation for 6h at pH 6, approximately 15% remains in solution, and after incubation for 3h at pH 1.9, approximately 40% remains in solution, Ampicillin, which binds to feedstuffs to a lesser extent, has a lower bioavailability than pivampicillin, Therefore, binding to feedstuffs does not seem to be a critical factor in the absorption of aminopenicillins

Knowledge and perception of biosimilars in ambulatory care

Background: With the approval of biosimilars for subcutaneously administered products, such as adalimumab, etanercept and insulin, biosimilars become increasingly available in ambulatory care. Little is known about the knowledge and attitudes of healthcare providers who are in charge of dispensing and prescribing biosimilars in this context. This study aims to assess the knowledge and perception about biosimilars among community pharmacists and physicians. Methods: Belgian community pharmacists (n = 177) and physicians (n = 30) were surveyed on their knowledge, experience with dispensing/prescribing biologicals including biosimilars, perception regarding int

Non-adherence to inhaled corticosteroids and the risk of asthma exacerbations in children

Erwin C Vasbinder,1 Svetlana V Belitser,2 Patrick C Souverein,2 Liset van Dijk,3 Arnold G Vulto,1 Patricia MLA van den Bemt1 1Erasmus University Medical Center, Department of Hospital Pharmacy, Rotterdam, 2Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3NIVEL, Utrecht, the Netherlands Background: Non-adherence to inhaled corticosteroids (ICSs) is a major risk factor for poor asthma control in children. However, little is known about the effect of adherence to ICS on the incidence of asthma exacerbations. The objective of this study was to examine the effect of poor adherence to ICS on the risk of exacerbations in children with asthma. Methods: In this nested case–control study using data from the Dutch PHARMO Record Linkage System, children aged 5–12 years who had an asthma exacerbation needing oral corticosteroids or hospital admission were matched to patients without exacerbations. Refill adherence was calculated as medication possession ratio from ICS-dispensing records. Data were analyzed using a multivariable multiplicative intensity regression model. Results: A total of 646 children were included, of whom 36 had one or more asthma exacerbations. The medication possession ratio was 67.9% (standard deviation [SD] 30.2%) in children with an exacerbation versus 54.2% (SD 35.6%) in the control group. In children using long-acting beta-agonist, good adherence to ICS was associated with a higher risk of asthma exacerbations: relative risk 4.34 (95% confidence interval: 1.20–15.64). Conclusion: In children with persistent asthma needing long-acting beta-agonist, good adherence to ICS was associated with an increased risk of asthma exacerbations. Possible explanations include better motivation for adherence to ICS in children with more severe asthma, and reduced susceptibility to the consequences of non-adherence to ICS due to overprescription of ICS to children who are in clinical remission. Further study into the background of the complex interaction between asthma and medication adherence is needed. Keywords: asthma exacerbation, children, database, inhaled corticosteroids, refill adherence pharmacoepidemiology, observational study, the Netherlands&nbsp