1) The central venous catheterization (CVC) training program for 2 trainees involves an instructor, a CVC insertion simulator (Kyoto Kagaku Co., Ltd), and a simulated patient.
2) The questionnaire filled out by trainees after the program showed favorable opinions, particularly the method of learning after the practice.
3) It is important that effective simulation programs for trainees are designed to develop practical procedures and professional attitudes as a physician using both a simulator and a simulated patient.

Introduction: The link between the hydration state and the functional effects of formulations and natural systems is been demonstrated by several studies. Measurement of skin hydration has been used to assess barrier function integrity in vivo and stratum corneum (SC), hydration may increase after the topical application of natural or formulate systems. Thermal muds have great hydration properties thanking at its high water contain due to presence of clays minerals1). Our work was focused on the evaluation of skin’s hydration potentialities of Japanese Biofango®. Objectives: Mudtherapy increase the hydration state of skin and modify its selective permeability favouring the permeation of therapeutic substances product by maturation process. Our goal was the development of a tensiometric model for assessment and optimisation of Japanese Biofango mudtherapy protocol by the evaluation of skin hydration measuring water contact angles on skin surface2). Our work was performed at Sanraku-en spas centre (Tonami-Japan). Materials and Methods: Biofango was constituted by Kunigel, Kaolinite, and WakuraDiatomite contains montmorillonite. BFM mixture was prepared and collected from Sanraku-en maturation plant. Samples were stored at -25°C. Skin’s hydration state analysis were performed before and after treatment by contact angle method (CA) using DSA 2-Kruss Dynamic Tenskinmeter3) water as liquid test and accordingly to traditional Sanraku-en/Biofango protocol. Four subjects with differents age, sex and weights (KS, YS, MO, and KM) were considered as test. Sanraku-en mudtherapy protocol’s steps were (a) first blood pressure measurement, (b) water’s CA measurements on left and right arm before treatment, (c) thermal bath (8’), (d) water’s CA measurements, (e) BFM mudtherapy (20’), (f) water’s CA measurements on polish skin, (g) shower (3’), (h) water’s CA measurements, and (i) final blood pressure measurement. Results: CA of water on subject KS skin showed elevated levels before (CAt0>89.5 deg) and after (CAtf>89.5 deg) treatment. YS subject showed increases of skin hydration after treatment (CAt0>89.5 deg, CAtf=40.27 deg), MO showed more increase of skin hydration than YS (CAt0>89.5 deg, CAtf=20.12 deg), and KM (CAt0>89.5 deg, CAtf=41.30 deg) showed an hydration state similar to YS. Regarding YS subject, we optimized its mudtherapy by the inversion of bath (CAt0>89.5 deg, CAtf>89.5 deg) with mudtherapy phases. As results a major increase of hydration state respect normal protocol (CAt0>89.5 deg, CAtf =30.4 deg) reflecting on skin moisturize after bath phase also (CAt0>89.5 deg, CAtf=87.43 deg). Conclusions: Analyses of hydration state of skin by measurement of water’s contact angles consented to evaluate the capability of Biofango BFM to modify the selective permeability of stratum corneum. Thanking to the method developed was possible to optimise and personalize Sanraku-en protocol.

Introduction: Sanraku-en spa started to purpose the “Shogawa biofangotherapy” using hot spring water and different kind of clays of natural origin (called Biofango) matured for three weeks during which bacterial flora develop with production of constitutive elements having therapeutic properties [4]. In collaboration with Ascendant Co. Ltd was ideated and developed the production of the first japanese Biofango supported by Toho University, University of Science and Technology of Hokuriku, and University of Hishigawa opening at new perspective in mudtherapy for therapeutic use in Japan (Biofango project). Objectives: The goal was the assessing the surface energy of Biofango by TVS modelling and TVS mud index 1, 2). Tensiometric analyses of Biofango mixtures were performed at Sanraku-en spas centre (Tonami-Japan) and its quality control has been carried out in the Permanent Thermal Observatory (OTP) of University of Padova. Organic compounds analysis (TOC) were performed in the Department of Pharmaceutical and Pharmacological Sciences of University of Padova (Italy). Materials and Methods: Biofango was prepared using KomatsuClay, MotoyamaClay, WakuraDiatomite and KasaokaBentonite. Pre-test mixtures were K01 (Bentonite 1.75, KomatsuClay 0.5, Diatomite 0.25) and M01 (Bentonite 1.75 MotoyamaClay 0.5 Diatomite 0.25). After were prepared K02 (Bentonite 1.25, Kaolinite 1.5, Diatomite 0.25) and A01 (KasaokaBentonite 1.25, Kaolinite 0.5, Diatomite 0.25) mixtures. Final Biofangos were BFM+0%Dolomite, MAT1+10%Dolomite, MAT2+18%Dolomite, and MAT3+35%Dolomite were analysed by XRF/XRD. TOC analyses were performed on a Perkin-Elmer-2400 analyser with Perkin-Elmer-AD-4 autobalance and tensiometric investigations were performed by DSA 10 (Krüss) tensiometer employing (a) PFPE, Fomblin HC/OH-1000, diiodomethane, glycerine as liquid tests and (b) Owens-Wendt3) mathematical model to convert contact angles in surface enery parameters. Results: XRD analyses of Biofango demonstrating presence of Kaolinite-Quartz-Feldspar in Komatsu Clay, Kaolinite-Quartz-Feldspar-Carbon in MotoyamaClay, Quartz-Montmorillonite-Feldspar-Grauconite in WakuraDiatomite, and Montmorillonite-Quartz-Feldspar-Christoballite in KasaokaBentonite while XRF showed presence of SiO2 (KomatsuClay 53.38%, MotoyamaClay 48.86%, WakuraDiatomite 78.20%, KasaokaBentonite 66.01%) and Al2O3 (KomatsuClay 53.38%, MotoyamaClay 48.86%, WakuraDiatomite 78.20%, KasaokaBentonite 66.01%) as principal elements. TOC analyses demonstrated an increase of C% with production of CO2 in relation to the amount of Dolomite in Biofango mixtures (MAT1=1.26%, MAT2=2.36%, MAT3=3.29%). Tensiometric investigations showed a correlation between C% and dispersed components (DC) measured on Biofango mixtures (MAT1=3.0 mN/m, MAT2=2.1 mN/m, MAT3=2.0 mN/m) and between C% and TVS mud index levels (MAT1=68.7 mN/m eq., MAT2=74.06 mN/m eq., MAT3=75.9 mN/m eq.). Conclusions: Tensiometric investigations of Biofango consented to determine the correlations between chemico-mineralogical data and surface energy parameters. Thanking to the high sensitivity of TVS mud index used as integrated tensiometric marker was possible to determine directly and in a non invasive way the quality of Biofango mixtures opening at new perspective in their monitoring and control before their employment in mudtherapy in Japanese spas after their maturation process.

Objective: The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. Methods: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens.The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). Results: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration.Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). Conclusion The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib.

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. Conclusion Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. Methods: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms “thrombocytopenia” and “platelet count decreased”) occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Results: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56–1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6–26.7) months. Conclusion Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. Methods: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms “thrombocytopenia” and “platelet count decreased”) occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Results: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56–1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6–26.7) months. Conclusion Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.