TY - JOUR A1 - Kühn, Heike A1 - Schön, Franz A1 - Edelmann, Karola A1 - Brill, Stefan A1 - Müller, Joachim T1 - The Development of Lateralization Abilities in Children with Bilateral Cochlear Implants JF - ORL N2 - Objectives: The purpose of this study was to investigate the development of lateralization skills in children who received bilateral cochlear implants (CIs) in sequential operations. Methods: The lateralization skills of 9 children with a mean age of 4.1 years at the first surgery and 5.5 years at the second surgery were assessed at 3 time intervals. Children were assessed with a 3-loudspeaker setup (front, left and right) at 0.9 years (interval I) and 1.6 years (interval II) after the second implantation, and after 5.3 years of bilateral implant use (interval III) with a 9-loudspeaker setup in the frontal horizontal plane between -90° and 90° azimuth. Results: With bilateral implants, a significant decrease in lateralization error was noted between test interval I (45.0°) and II (23.3°), with a subsequent significant decrease at test interval III (4.7°). Unilateral performance with the CI did not improve significantly between the first 2 intervals; however, there was a bias of responses towards the unilateral side by test interval III. Conclusions: The lateralization abilities of children with bilateral CIs develop in a relatively short period of time (1-2 years) after the second implant. Children appear to be able to acquire binaural skills after bilateral cochlear implantation. KW - localization KW - bilateral cochlear implant KW - children KW - MED-EL cochlear implant KW - lateralization Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196375 SN - 0301-1569 SN - 1423-0275 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 75 IS - 2 ER - TY - JOUR A1 - Kuhn, Joachim A1 - Gripp, Tatjana A1 - Flieder, Tobias A1 - Dittrich, Marcus A1 - Hendig, Doris A1 - Busse, Jessica A1 - Knabbe, Cornelius A1 - Birschmann, Ingvild T1 - UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays JF - PLOS ONE N2 - Introduction The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery. Methods Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM) mode (UPLC-MRM MS). Internal standards (ISs) were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion. Results The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 mu g/L (r > 0.99). Limits of detection (LOD) in the plasma matrix were 0.21 mu g/L for dabigatran and 0.34 mu g/L for rivaroxaban, and lower limits of quantification (LLOQ) in the plasma matrix were 0.46 mu g/L for dabigatran and 0.54 mu g/L for rivaroxaban. The intraassay coefficients of variation (CVs) for dabigatran and rivaroxaban were < 4% and 6%; respectively, the interassay CVs were < 6% for dabigatran and < 9% for rivaroxaban. Inaccuracy was < 5% for both substances. The mean recovery was 104.5% (range 83.8-113.0%) for dabigatran and 87.0%(range 73.6-105.4%) for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20 degrees C, 4 degrees C and even at RT for at least one week. A method comparison between our UPLC-MRM MS method, the commercially available automated Direct Thrombin Inhibitor assay (DTI assay) for dabigatran measurement from CoaChrom Diagnostica, as well as the automated anti-Xa assay for rivaroxaban measurement from Chromogenix both performed by ACL-TOP showed a high degree of correlation. However, UPLC-MRM MS measurement of dabigatran and rivaroxaban has a much better selectivity than classical functional assays measuring activities of various coagulation factors which are susceptible to interference by other coagulant drugs. Conclusions Overall, we developed and validated a sensitive and specific UPLC-MRM MS assay for the quick and specific measurement of dabigatran and rivaroxaban in human plasma. KW - LC-MS/MS KW - validation KW - serum KW - quantification KW - apixaban KW - diagnostic accuracy KW - performance liquid chromatography KW - factor XA inhibitor KW - direct oral anticoagulants KW - direct thrombin inhibitor Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136023 VL - 10 IS - 12 ER - TY - JOUR A1 - Lindhoff-Last, Edelgard A1 - Birschmann, Ingvild A1 - Bidenharn, Antonia J. A1 - Kuhn, Joachim A1 - Lindau, Simone A1 - Konstantinides, Stavros A1 - Grottke, Oliver A1 - Nowak-Göttl, Ulrike A1 - Lucks, Jessica A1 - Zydek, Barbara A1 - Heymann, Christian von A1 - Sümnig, Ariane A1 - Beyer-Westendorf, Jan A1 - Schellong, Sebastian A1 - Meybohm, Patrick A1 - Greinacher, Andreas A1 - Herrmann, Eva T1 - Pharmacokinetics of phenprocoumon in emergency situations – results of the prospective observational RADOA-registry (reversal agent use in patients treated with direct oral anticoagulants or vitamin K antagonists registry) JF - Pharmaceuticals N2 - Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days. KW - phenprocoumon KW - pharmacokinetics KW - emergency KW - major bleeding KW - urgent surgery KW - INR rebound Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297226 SN - 1424-8247 VL - 15 IS - 11 ER -