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PurposeThe purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans.MethodsStudy 1: SFPP tape-type patch (2–60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics.Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch.ResultsStudy 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4–72.2 %. Cmax and AUC0-∞ were dose-proportional.Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch.ConclusionsSustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1960-6) contains supplementary material, which is available to authorized users.

The size of the tree in TDT is suggested to reflect characteristics of depression in elderly people, such as introversion, reserve, antisocial attitude, a feeling of inferiority, weakness of ego, and lack of vigour. Furthermore, the numbers of occupied areas were found to be relatively useful in detecting depression in elderly people.

BackgroundWe present a case involving conservative treatment of placenta accreta, with a subsequent diagnosis of Asherman’s syndrome.Case presentationA 41-year-old Japanese woman (G2P0A2) delivered a healthy male infant via cesarean section due to preeclampsia. The placenta did not spontaneously separate and was manually removed. Adhesion was tight and placenta accreta was diagnosed. During the procedure, no uterine inversion or perforation, and no uterine cavity adhesion, were observed. Four months postoperatively, hysteroscopy was performed. Adhesion was detected at the fundus of her uterus where the placenta had adhered to the uterus. Asherman’s syndrome was diagnosed.ConclusionsAsherman’s syndrome might occur after conservative management of placenta accreta, which may be a direct cause of placenta accreta recurrence. When Asherman’s syndrome is diagnosed, the site of the placenta and adhesion should be monitored during subsequent pregnancies.

Key Clinical messageEculizumab in pregnancy has been reported to be effective in improving outcomes in patients with paroxysmal nocturnal hemoglobinuria. However, a cesarean section may result in surgery‐triggered hemolysis. An additional dose of eculizumab just prior to delivery is an appropriate choice to prevent postoperative hemolysis.