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Delayed-released dimethyl fumarate (DMF) is an oral disease-modifying therapy (DMT) approved for treating patients with multiple sclerosis (MS). This post-marketing study aimed at collecting real-world data on the safety, effectiveness, and tolerability of DMF in patients with relapsing remitting multiple sclerosis (RRMS).
1-year post-marketing survey of patients prescribed DMF followed-up quarterly in hospital setting and private neurological practices in Switzerland from January 2015 to January 2018. Data on relapses, Expanded disability status scale (EDSS) score change, safety, tolerability, treatment adherence as judged by the treating neurologist and satisfaction were collected. Patients could refer to a patient support program.
Of the 158 patients, 67 (42.4%) were treatment naïve, 91 (57.6%) switched from a prior MS DMT to DMF, 131 (82.9%) were treatment adherent, 108 (68.4%) used the support program, and 45 (28.5%) discontinued the therapy. Insufficient tolerability and insufficient effectiveness were the main reasons for discontinuation. 134 (84.8%) patients remained relapse free, 97 (61.4%) had stable or decreased EDSS score after 12 months. 74 (46.8%) patients reported adverse events; of these, 28 (17.7%) discontinued DMF treatment. Physicians and patients rated treatment satisfaction similarly (median score 8.0 of 10).
The results obtained from this real-world observation are consistent with the efficacy and safety findings reported in pivotal and larger observational trials evaluating DMF treatment. Most side effects were experienced early after therapy initiation reflecting the timing of therapy discontinuation.
The results obtained from this real-world observation are consistent with the efficacy and safety findings reported in pivotal and larger observational trials evaluating DMF treatment. Most side effects were experienced early after therapy initiation reflecting the timing of therapy discontinuation.A disintegrin and metalloprotease 17 (ADAM17) catalyzes the cleavage and release of the ectodomains of its substrates at the cell surface in a process termed ectodomain shedding. However, not all ADAM17 substrates have been identified. Here, we used cell surface protein-specific labeling and proteomic approaches to detect and identify ADAM17 substrates. HeLa cell surface proteins were labeled with a fluorescent dye and cultured with or without TAPI-2, an ADAM17 inhibitor. Labeled proteins released into the culture medium were detected by 2-dimensional gel electrophoresis (2DE). Protein spots showing decreased intensity in response to TAPI-2 were selected as substrates of ADAM17 or their binding proteins, and identified by mass spectrometry. ADAM17 knockdown was preformed to examine the behavior of identified proteins. Of 347 proteins detected by 2DE, 49 showed lower intensity in TAPI-2 (+) than in TAPI-2 (-) samples (p 50% decreased intensity identified clusterin as a novel ADAM17 substrate, in addition to known substrates such as desmoglein-2. Western blot analysis showed that ADAM17 knockdown decreased the levels of clusterin fragments cleaved and released from the cell surface. The results identified clusterin as a novel ADAM17 substrate. The method used to identify clusterin could be used to identify the substrates of other sheddases involved in ectodomain shedding.The study assessed the levels of organochlorine pesticides (OCPs) in eight brands (A-H) of regularly consumed maize-based complementary/breakfast foods in Nigeria. We also evaluated the dietary exposure of infants and young children to the detected OCPs. The OCP residues were quantified using GC-ECD. A total of 10 OCPs residues (β-HCH, δ- HCH, heptachlor, endosulfan sulfate, aldrin, endrin, dieldrin, p,p'-DDE, p,p'-DDT and methoxychlor) were detected. Total OCPs burden was highest in brands F, D, and G with mean concentrations of 45.98 mg kg-1, 28.54 mg kg-1 and 21.87 mg kg-1, respectively and the lowest burdens in brands H (1.72 mg kg-1) and A (6.61 mg kg-1). Hazard index (HI) for all the age categories were >1 and all the 6 carcinogens (β-HCH, heptachlor, aldrin, dieldrin, p,p'-DDE, and p,p'-DDT) identified had cancer risk index range of 5.43 × 10-4 to 2.05 × 10-6 which were above acceptable risk. These results indicated the possibility of both systemic and cancer risks to infants and children consumers of the foods. Food brands manufacturers need to carry out regular pesticide residues analysis of raw materials especially maize prior to the production in order to ensure food safety and quality.Food thickeners are widely used to aid the oral administration of medications to patients with dysphagia. Powder-type food thickeners are used to modulate the viscosity of therapeutic solutions depending on the swallowing capacity of patients. Food thickeners inhibit or delay the disintegration of some medications, resulting in reduced pharmaceutical effects of the medications and/or their excretion in the stool. A short immersion time (within 1 min) is important to overcome these problems. Although thickened drinks are commercially available, their use as vehicles for medications is not well understood. In this study, we evaluated the effects of thickened drinks on the disintegration time of therapeutic tablets. Furthermore, we compared the thickened drinks with powder-type xanthan gum-based food thickeners. Forty tablets were used, including naked tablets, film-coated tablets, orally disintegrating tablets, enteric-coated tablets, and sugar-coated tablets. For the disintegration test, the tablets were immersed in thickened drinks or food thickeners for 1 min. The changes in the disintegration time of the 40 tablets immersed in the thickened drinks were comparable with those in food thickeners. The disintegration time of several tablets was shorter or unchanged after immersion in the thickened drinks. The disintegration time of rapidly disintegrating tablets tended to increase when immersed in thickened drinks, but it was less than 2 min for the majority of the tablets. These results demonstrate that thickened drinks, similar to food thickeners, could help administer medications to patients. MDL-800 price Overall, our study provides valuable information for pharmacists and clinicians to decide the most suitable way to deliver medications to patients with dysphagia.
Website: https://www.selleckchem.com/products/mdl-800.html
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