| 1. |
- Hagell, Peter, et al.
(författare)
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Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
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Ingår i: Journal of Neurology. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
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Tidskriftsartikel (refereegranskat)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
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| 2. |
- Athanassiou, N., et al.
(författare)
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Simulation of thermal and mechanical performance of laser cladded disc brake rotors
- 2022
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Ingår i: Proceedings of the Institution of mechanical engineers. Part J, journal of engineering tribology. - London : SAGE Publications Ltd. - 1350-6501 .- 2041-305X. ; 236:1, s. 3-14
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Tidskriftsartikel (refereegranskat)abstract
- Disc brakes wear during braking events and release airborne particulates. These particle emissions are currently one of the highest contributors to non-exhaust particle emissions and introduce health hazards as well as environmental contamination. To reduce this problem, wear and corrosion-resistant disc coatings have been implemented on grey cast iron brake disc rotors by using various deposition techniques such as thermal spraying and overlay welding. High thermal gradients during braking introduce risks of flaking off and cracking of thermally sprayed coatings with adhesive bonding to the substrate. Overlay welding by laser cladding offers metallurgical bonding of the coating to the substrate and other benefits that motivate laser cladding as a candidate for the coating of the grey cast iron brake discs. This study aims to investigate the effect of laser cladding on the thermal and thermo-structural performance of the coated grey cast iron brake discs. Therefore, thermal and thermo-stress analysis with COMSOL Multiphysics 5.6 software is performed on braking events of grey cast iron brake discs as non-coated – reference and laser cladding coated with stainless steel welding consumables. The Results demonstrated that surface temperatures were more localised, overall higher in the laser cladded coating with over three times the stresses attained of reference grey cast iron discs. The output of the simulations has been compared by tests found in the literature. Laser cladding presented higher reliability and braking performance, nonetheless requiring the evaluation of its thermal impact on other system components.
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| 3. |
- Bergquist, Filip, 1970, et al.
(författare)
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Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:10
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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