Publications by authors named "Nobuyuki Oshima"

7 Publications

  • Page 1 of 1

Investigations into the Potential of Using Open Source CFD to Analyze the Differences in Hemodynamic Parameters for Aortic Dissections (Healthy versus Stanford Type A and B).

Ann Vasc Surg 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan.

Background: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters.

Methods: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated.

Results: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow.

Conclusions: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.
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October 2021

A randomized, placebo-controlled study to evaluate the efficacy and safety of adding omarigliptin to insulin therapy in Japanese patients with type 2 diabetes and inadequate glycaemic control.

Diabetes Obes Metab 2021 06 17;23(6):1242-1251. Epub 2021 Feb 17.

Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.

Aim: To evaluate the efficacy and safety of adding the once-weekly oral dipeptidyl peptidase-4 inhibitor omarigliptin to treatment of Japanese patients with type 2 diabetes and inadequate glycaemic control on insulin monotherapy.

Materials And Methods: In a 52-week clinical trial, Japanese patients on insulin monotherapy were randomized to once-weekly omarigliptin 25 mg (N = 123) or placebo (N = 61) for a 16-week, double-blind, placebo-controlled period. After Week 16, patients continued or switched to omarigliptin for a 36-week open-label period.

Results: From a mean baseline of approximately 8.8%, the Week 16 least squares mean changes in HbA1c were -0.61% (omarigliptin) and 0.29% (placebo); the between-group difference was -0.90% (p < .001). At Week 52, the mean change from baseline in HbA1c was -0.57% in both the group on omarigliptin for 52 weeks and the group on omarigliptin for 36 weeks (switched from placebo at Week 16). During the first 16 weeks of treatment, the incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuation from trial medication because of an AE were similar in both groups. A slight increase in incidence of symptomatic hypoglycaemia was observed in the omarigliptin group (n = 13 [10.6%]) compared with placebo (n = 4 [6.6%]). No severe hypoglycaemia was reported during the study. No new safety signals emerged with treatment beyond Week 16 through Week 52.

Conclusion: The addition of once-weekly omarigliptin to insulin therapy for up to 52 weeks was generally well tolerated and provided clinically meaningful improvement in glycaemic control throughout the trial period. NCT02906709.
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June 2021

Switch rates, time-to-switch, and switch patterns of antiretroviral therapy in people living with human immunodeficiency virus in Japan, in a hospital-claim database.

BMC Infect Dis 2019 Jun 10;19(1):505. Epub 2019 Jun 10.

Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: Regardless of chronic treatment with antiretroviral therapy (ART), the switching rate for ART regarding anchor drugs has not been articulated in real-world clinical-settings in Japan. We assessed switch rates and time-to-switch of ART regimens according to anchor drug classes (integrase strand transfer inhibitors (INSTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)) and common switching patterns of anchor drug classes in people living with human immunodeficiency virus (HIV) (PLWH) from 2008 to 2016.

Methods: This retrospective, observational study used data of 1694 PLWH drawn from a large-scale medical claims database. The median time-to-switch and switch rates of anchor drug class were estimated by Kaplan-Meier analysis. To estimate 95% confidence intervals for switch rates and median days, the Brookmeyer and Crowley method and Greenwood method were used respectively. The switching patterns were summarized based on the time of switching. The switch rates were compared between two anchor drug classes for each year using log-rank tests.

Results: We focused our results on 2011-2016 (n = 1613), during which most ART prescriptions were observed. A total of 268 patients switched anchor drug class from the first to a second regimen. The switch rate constantly increased over four years for NNRTIs (17.8-45.2%) and PIs (16.2-47.6%), with median time-to-switch of 1507 and 1567 days, respectively, while INSTI maintained a low switch rate (2.3-7.6%), precluding median-days calculation. The majority originally treated with NNRTI and PI switched to INSTI regardless of the switching timing after starting the first regimen (< 1 year: 91.7 and 97.5%, respectively, and ≥ 1 year: 100.0 and 97.5%, respectively). The risk of switching anchor drug classes was lower for INSTI than for other anchor drug classes in the first regimen even after adjusting for potential confounding factors.

Conclusions: Patients with an ART regimen including INSTI as an anchor drug class maintained a low switch rate for long durations. The major switching strategies of anchor drug class for secondary treatment were from NNRTI or PI to INSTI. These results suggest that INSTI may be a durable anchor drug class for PLWH on ART although there are limitations inherent to the database.
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June 2019

Evaluation of Montelukast for the Treatment of Children With Japanese Cedar Pollinosis Using an Artificial Exposure Chamber (OHIO Chamber).

Allergy Rhinol (Providence) 2018 Jan-Dec;9:2152656718783599. Epub 2018 Jul 13.

Merck & Co., Inc., Kenilworth, New Jersey, USA.

Background: This study evaluated the efficacy of montelukast in reducing seasonal allergic rhinitis symptoms in Japanese children with Japanese cedar (JC) pollinosis induced in an artificial exposure chamber (OHIO Chamber).

Methods: Pediatric patients aged 10 to 15 years sensitive to JC pollen entered a randomized, double-blind, single-site, crossover study. After confirmation of an allergic response to a JC pollen exposure for 3 hours in the OHIO Chamber during the screening period, subjects received either montelukast 5 mg chewable tablets or placebo for a 7-day treatment period, followed by a 3-hour pollen exposure in the chamber. After a 7-day washout period, subjects crossed over to the other treatment. Subjects were instructed to self-assess their nasal symptoms using 5-point scale for every 30 minutes. The primary end point was the change from baseline (just before entering the exposure chamber for each exposure) in total nasal symptom score (TNSS; the sum of nasal congestion, nasal discharge, and sneezing scores) over 3 hours of pollen exposure. Adverse events (AEs) were evaluated throughout the study.

Results: A total of 220 subjects (median age, 12 years) received treatment. For TNSS, the between-group difference in the change (95% confidence interval) was -0.01 (-0.11 to 0.10); the change between placebo and montelukast 5 mg was not significant. TNSS in the screening and treatment periods after receiving placebo for 7 days was 1.58 and 1.31, respectively, suggesting a placebo response. On account of high placebo response, a post hoc analysis was conducted. The analysis in a subgroup of subjects who did not show placebo response demonstrated a difference in the efficacy between montelukast and placebo (nominal  < .037). The most common AE was positive urine protein (4.6% with montelukast vs 7.8% with placebo).

Conclusions: Although montelukast was well tolerated, this study did not demonstrate a treatment difference between active drug and placebo in Japanese children exposed to JC pollen in the OHIO Chamber.:, NCT01852812.
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July 2018

Montelukast in the treatment of perennial allergic rhinitis in paediatric Japanese patients; an open-label clinical trial.

J Drug Assess 2016 19;5(1):6-14. Epub 2016 Sep 19.

Merck & Co. Inc. , Kenilworth , NJ , USA.

: This study was conducted to evaluate the safety and tolerability, and population pharmacokinetics (PPK) of montelukast as well as efficacy in the treatment of perennial allergic rhinitis (PAR) in paediatric Japanese patients aged between 1 and 15 years. : In this multi-centre, open-label trial, 87 paediatric Japanese patients with PAR received montelukast 4 mg oral granules (OG) for 4 weeks (1-5-year-olds,  = 15), 4 mg OG for 12 weeks (1-5-year-olds,  = 36), 5 mg chewable tablets (CT) for 12 weeks (6-9-year-olds,  = 18), or 5 mg CT for12 weeks (10-15-year-olds,  = 18). Clinical exams and laboratory assessments were conducted at study visits, and adverse events (AE) were monitored throughout the study up to 14 days after the last visit. Population pharmacokinetic approach was used to estimate AUC, C, T and apparent elimination half-life in each age group. Efficacy was assessed based on global evaluations by the subject's caregiver. : There were no serious AEs and one discontinuation due to an AE. The most common AEs in any of the treatment groups were nasopharyngitis, pharyngitis, and acute sinusitis. Montelukast exposure (AUC) was similar in the 1-5-year-old group and the 6-9-year-old group, but 19% lower in the 10-15-year-old group. Among all patients, the total proportion of patients whose global evaluation was "very much better" was 5.7% (week 2), 11.5% (week 4), and 16.9% (week 12) reflecting improvement in symptoms over time. : Montelukast was generally well tolerated in Japanese children with PAR. AUCwas similar in 1-5 and 6-9-year-olds, while a lower exposure was observed in the 10-15-year-old group likely due to differences in bodyweight. The exposure in Japanese paediatric patients was generally consistent with that in non-Japanese paediatric and adult patients. As assessed by the patients' caregivers, montelukast also demonstrated symptomatic improvement based on global evaluations of PAR.
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September 2016

Efficacy and safety of asenapine in Asian patients with an acute exacerbation of schizophrenia: a multicentre, randomized, double-blind, 6-week, placebo-controlled study.

Psychopharmacology (Berl) 2016 Jul 8;233(14):2663-74. Epub 2016 Jun 8.

MSD K.K., Tokyo, Japan.

Rationale: Asenapine is a second generation anti-psychotic approved in the USA in 2009 for the treatment of schizophrenia, but its efficacy has not been proven in Asian patients.

Objectives: The objectives of this study are to evaluate the efficacy and tolerability of asenapine in Asian patients experiencing an acute exacerbation of schizophrenia.

Methods: In this prospective, double-blind study, patients in Japan, Korea, and Taiwan were randomized (1:1:1) to asenapine 5 mg twice daily (bid), 10 mg bid or placebo for 6 weeks after a 3- to 7-day washout/screening period. The primary endpoint was the mean change in the positive and negative syndrome scale (PANSS) total score from baseline to day 42/treatment end.

Results: Of the 532 participants randomized, 530 received treatment. The primary endpoint was significantly greater with asenapine 5 and 10 mg bid than with placebo (-12.24 and -14.17 vs. -0.95; p < 0.0001). The results of secondary endpoints including PANSS negative subscale scores and PANSS responders at the end of treatment supported the results of the primary endpoint. There were no significant differences in the incidence of treatment-emergent adverse events reported with asenapine 5 and 10 mg bid and placebo (84.6, 80.7, and 81.6 %). There was a mean (± standard deviation) change in weight of -1.76 ± 2.45 kg for placebo, +0.42 ± 2.65 kg for asenapine 5 mg bid, and +0.81 ± 2.89 kg for asenapine 10 mg bid group.

Conclusions: Asenapine was effective and generally well tolerated when used for the treatment of acute exacerbations of schizophrenia in Asian patients.
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July 2016

A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.

Lipids Health Dis 2015 May 1;14:40. Epub 2015 May 1.

Merck & Co., Inc, Kenilworth, NJ, USA.

Background: Recent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial. Adults with type 2 diabetes and hypercholesterolemia whose LDL-C measured <140 mg/dl (subjects receiving lipid-lowering drugs) or <160 mg/dl (subjects not receiving lipid-lowering drugs) at the start of the screening phase, were randomized after a 5-week wash-out period to ezetimibe 10 mg or placebo (1:1) for 24 weeks. Changes in HbA1c, glycoalbumin and fasting plasma glucose from baseline to week 24 were evaluated. The non-inferiority margin was set at 0.5% for HbA1c.

Results: Overall, 152 subjects were randomized (75 to ezetimibe and 77 to placebo). From baseline to 24 weeks, HbA1c significantly increased in both the ezetimibe and placebo groups (between-treatment difference 0.08 [95% CI: -0.07 to 0.23]). Ezetimibe was statistically non-inferior to placebo. At 24 weeks, the mean change from baseline in glycoalbumin levels (between-treatment differences 0.00 [95% CI: -0.47, 0.47]) and fasting plasma glucose (between-treatment differences -4.8 [95% CI: -12.1, 2.1]) were similar in both treatment groups.

Conclusions: These results suggest that ezetimibe 10 mg does not result in dysregulation of glucose metabolism in Japanese patients with type 2 diabetes and hypercholesterolemia over 24 weeks of treatment.

Trial Registration: identifier NCT01611883 .
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May 2015