Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Incontri, scontri, confronti Appunti sulla ricezione della xilografia nordica in Italia tra XV e XX secolo

Germany, France, Italy: the attribution of the first woodcut images has long been debated between several countries, to gain the technological primacy of the invention of reproductive printmaking, before Gutenberg’s movable type printing. Today we know how difficult it is, if not impossible, to establish a place and a date of origin of image printing in Europe. Impossible and probably unimportant. Printing was a European phenomenon in the 15th century, and we may ask ourselves whether a northern woodcut beyond the Italian borders was intended as something different than an Italian one. The contrast between northern and southern prints, which has been claimed by art historians from Vasari until the half of the 20th century, seems to be denied by early modern Italian sources. For example, a German woodcut from the first decades of the 15th century and a Florentine painting from the end of the 14th century can coexist as models for the illumination of the same manuscript. This unpublished case study of two Florentine 15th-century illuminations shows how a European cultural horizon was more common than we think today, and how much woodcut has been a fundamental tool for this broadening of horizons, since its very beginning

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Stable and metastable solubility diagrams for the system CaCO3 — MgCO3 — H2O at ordinary temperature

The aqueous solubility of a binary carbonate system is governed by the total solubility product, which is the sum ∑∏ of the partial solubility products of the two end members. ∑∏ plotted as a function of the mole fraction in the solid phase and that in the aqueous solution yields traces which are similar to phase diagrams depicting vapour pressures of liquid mixtures. The stable diagram CaCO₃ — MgCO₃ — H₂O is characterized by two stable eutectic points, i.e. the diagram is of the dystectic type, due to the existence of dolomite as an intermediate phase. The solubility of magnesian calcites involves metastable states, because several limits of solid immiscibility may be exceeded.La solubilité dans l'eau d'un système binaire de carbonates est régie par le produit total de solubilité, qui est la somme ∑∏ des produits partiels de solubilité des deux pôles. ∑∏, tracé en fonction du titre molaire de la phase solide et de celui dans la solution aqueuse, donne des courbes semblables aux diagrammes de phase pour la tension de vapeur de mélanges liquides. Le diagramme stable CaCO₃ — MgCO₃ — H₂O comprend deux points eutectiques stables à cause de l'intervention de la dolomite comme phase intermédiaire. La solubilité des calcites magnésiennes est caractérisée par des états métastables qui se produisent par suite de transgressions de plusieurs limites de miscibilité solide.Lippmann Friedrich. Stable and metastable solubility diagrams for the system CaCO3 — MgCO3 — H2O at ordinary temperature. In: Bulletin de Minéralogie, volume 105, 3, 1982. pp. 273-279