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IMPORTANCE: Cochlear implants are an effective technique for enhancing speech perception abilities in quiet environments for people with severe to profound deafness. Nevertheless, complex sound signals perception, such as music perception, remains challenging for cochlear implant users. OBJECTIVE: To assess the benefit of a tonotopic map on music perception in new cochlear implant users. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, double-blind, 2-period crossover study including 26 new cochlear implant users was performed over a 6-month period (June 2021 to November 2021). An anatomical tonotopic map was created using postoperative flat-panel computed tomography and a reconstruction software based on Greenwood function. New cochlear implant users older than 18 years with bilateral severe to profound sensorineural hearing loss or complete hearing loss for less than 5 years were selected in the University Hospital Centre of Rennes in France. The trial was conducted from June to November 2021 (inclusion) and to February 2022 (end of the assessment procedure at 12 weeks postactivation), and the analysis itself was completed in December 2022. INTERVENTION: Each participant was randomized to receive a conventional map followed by a tonotopic map or vice versa. MAIN OUTCOMES AND MEASURES: Participants performed pitch-scaling tasks (multidimensional qualitative assessment, melodic contour identification, melodic recognition test) after 6 weeks of each setting. RESULTS: Thirteen participants were randomized to each sequence. Two of the 26 participants recruited (1 in each sequence) had to be excluded due to the COVID-19 pandemic. The multidimensional qualitative assessment (Gabrielsson test), melodic contour identification, and melodic recognition scores were significantly higher with the tonotopic setting than the conventional one (mean effect [ME], 7.8; 95% CI, 5.0-10.5; ME, 12.1%; 95% CI, 5.7%-18.4%; ME, 14.4%, 95% CI, 8.5%-20.2%; and ME, 2.1, 95% CI, 1.7-2.5, respectively). Among the different dimensions evaluated by the Gabrielsson test, the mean scores for clarity, spaciousness, fullness, nearness, and total impression were significantly higher with tonotopic fitting. Ninety-two percent of the participants kept the tonotopy-based map after the study period. CONCLUSIONS: In this randomized clinical trial of patients with new cochlear implants, a tonotopic-based fitting was associated with better results in perception of complex sound signals such as music listening experience. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04922619

A differential stimulated I.R. detection scheme is presented in order to obtain a better contrast in crack detection on real samples whose surface exhibits topographical and optical irregularities. A finite element simulation confirms the magnitude and shape of the signals for vertical and slanted cracks.

Objectives: The objective of this study was to compare the pharmacokinetics of the low-molecular-weight heparin enoxaparin in obese and nonobese volunteers, by means of two administration regimens.Methods: Enoxaparin was administered subcutaneously (1.5 mg/kg once daily for 4 days) and in a single 6-hour infusion (1.5 mg/kg) to 24 obese volunteers and 24 age-, sex-, and height-matched nonobese volunteers in a randomized, open-label, 2-way crossover design. Blood plasma was assessed for anti-Xa and anti-IIa activity and activated partial thromboplastin time.Results: After subcutaneous administration, steady-state exposure was achieved after the second dose in nonobese volunteers and after the third dose in obese volunteers. Time to maximum anti-Xa activity was 1 hour longer in obese volunteers, but maximum anti-Xa activity was similar in both groups. For anti-Xa activity, exposure at steady-state was 16% higher in obese volunteers than in nonobese volunteers (90% confidence interval, 108%-125%). After intravenous infusion, total body clearance and volume of distribution at steady state were higher in obese volunteers than in nonobese volunteers, but when adjusted for weight, these values were about 10% lower in obese volunteers. Anti-IIa activity after subcutaneous administration did not differ significantly between obese and nonobese volunteers. Pharmacodynamic analysis of activated partial thromboplastin time showed similar results in obese and nonobese volunteers after both intravenous and subcutaneous administration. No deaths or serious adverse events occurred during the study.Conclusions: Enoxaparin was well tolerated when administered subcutaneously or intravenously, and there appears to be no need to modify the currently recommended dose for obese volunteers.

Objective.The primary objective of this study was to assess the kinetics of ketoprofen in synovial fluid and intra-articular tissues in relation to plasma. The secondary objective was to study whether intra-articular tissues act as reservoirs.Methods.The ketoprofen concentration was analysed in plasma, synovial fluid and intra-articular tissues after single application of a 30 mg plaster (n=40), multiple applications for 5 days (n=30) or oral intake of 50 mg (n=30) in patients undergoing knee arthroscopy.Results.Median CMax values after topical application were 12.8 ng/ml in synovial fluid, 56.7 ng/g in synovial tissue, 349.3 ng/g in mensicus and 568.9 ng/g in cartilage.Conclusion.Topical applications of ketoprofen allow the attainment of high intra-articular tissue concentrations.Keywords:Knee joint, Absorption, Ketoprofen, Synovial tissue.

The indirect effect of diet on the single-and multiple-dose pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice-resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was given in the first period and a high-calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after drug intake. Ketoprofen plasma concentrations were measured over 24 h after the first dose on day 1 and over 36 h after the final dose on day 5 of each period.

The tolerance and pharmacokinetic behaviour of a new injectable streptogramin antibiotic, RP 59500 were evaluated on 26 healthy male volunteers in a double-blind, placebo-controlled, phase I study. The doses used were 1·4, 2·8, 4·6, 7·0, 9·8, 12·6, 16·8, 22·4 and 29·4 mg/kg; each dose was administered as a 1 h infusion to eight subjects, two of them receiving placebo. Blood levels of RP 59500 were measured by both microbiological and HPLC assays. At the end of the infusion, Cm for RP 59500 ranged from 0·95±0·22 to 24·20±8·82 mg/L. The apparent elimination half-life of the compound ranged from 1·27 to 1·53 h. RP 59500 did not significantly affect any of the laboratory or clinical assessments (blood pressure, pulse rate, ECG, peak expiratory flow rate). Reported adverse effects were of mild intensity; the most frequent event was mild pain or burning at the infusion site with doses of 7 mg/kg or higher. These results support further studies of RP 59500 in phase II clinical trials.