Search

Background: Digital therapeutics (DTx), the provision of treatment through mobile devices such as smartphones, have attracted great interest as a new medical modality. However, the number of authorized therapeutic applications in the US and Japan is low. Understanding the obstacles in obtaining regulatory authorizations will be the key in promoting timely development of therapeutic applications. Thus, we conducted a comprehensive analysis of the clinical study designs of therapeutic applications authorized in the US and Japan., Methods: Data on authorized therapeutic applications and the regulations involved were collated from the databases of the Food and Drug Administration (USA), Ministry of Health, Labour and Welfare (Japan), and Pharmaceuticals and Medical Devices Agency (Japan)., Results: Most therapeutic applications authorized targeted neuropsychiatric disorders and used cognitive behavioral therapy (CBT)-based treatments. All the involved clinical trials were randomized-controlled studies. Various types of controls-such as standard care, sham application, digital control, and therapies delivered by healthcare providers-were used. Both subjective and objective indices were acceptable as the primary endpoints. Long-term efficacy was evaluated, and all adverse events were assessed comprehensively. The setting up of controls and the need to study long-term efficacy depend heavily on the applications functionality and the target disease characteristics., Conclusions: This study reveals the points to be considered in planning clinical studies and regulatory strategies for authorizing therapeutic applications. Therapeutic applications can provide new therapy and have potential to solve unmet clinical needs. Our findings shed a light on efficient development and rapid commercialization of therapeutic applications., (© 2022. The Author(s).)

Background: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients., Methods: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO 2 ], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation., Results: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO 2 , 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively)., Conclusions: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The number of heart transplantation in Japan has gradually increased since the revised organ transplantation act became effective in July 2010. The long-term survival after heart transplantation is superior, compared to the survival in Europe and United States of America( USA). However, the number of patients on a waiting list is rapidly increasing due to an extreme donor shortage. Because of stagnating heart transplantation, there is a need for an optimal solution to an insufficient donor organ supply. We have experienced 125 adult heart transplantations with acceptable survival rate of over 90% at five years. On the other hand, an expected waiting period is lengthening to far longer than five years. Here, based on our experience, we describe the "real world" outcomes and mention the future aspect of the patients on the waiting list on ventricular assist device (VAD). Our suggestions are 1) to promote VAD weaning in patients with myocardial recovery, 2) to aggressively utilize marginal donors, and 3) to expand the indication to destination therapy.

Increased variety and use of chemicals and the number of chemical disasters have changed chemical management. Europe and the United States have adopted self-regulation in chemical management; furthermore, countries worldwide must comply with the relevant United Nations recommendations and international standards for chemical management. Japan has experienced numerous pollution incidents and occupational disasters, resulting in the development of laws and regulations on chemical management; however, these policies are inconsistent with international trends. In particular, the shift from a compliance approach to self-regulation and measures for small businesses remain as challenges. This paper discusses the current situation and issues in chemical management in Japan, focusing on international trends.

The aim of the study was to investigate the incidence of and risk factors for de novo malignancy after heart transplantation (HTx) in a single center. We assessed 102 consecutive patients who received HTx and were followed-up in our center regularly for > 1 year from June 2006 to May 2018. We investigated the incidence of and risk factors for de novo malignancy. The cumulative incidence of each malignancy type during the follow-up period was one (0.98%) for skin cancer, four (3.92%) for nonskin solid organ cancer, and six (5.88%) for posttransplant lymphoproliferative disorder (PTLD). The percentage of patients with more than one infectious event ≤ 1 year after HTx was higher in the malignancy group than in the non-malignancy group. Furthermore, Kaplan-Meier analysis revealed that the incidence rate of infectious events was higher in patients with malignancies than in those without (log-rank P < 0.001). After dividing malignancies into a PTLD group and a solid organ malignancy group, we found that negative Epstein-Barr virus serostatus, cytomegalovirus-positive antigenemia, and the occurrence of any viral or gastrointestinal infectious event at ≤ 1 year were more frequent in patients with PTLD than in patients without it. The survival rate was significantly lower for patients with solid organ malignancy than for patients without malignancy. In conclusion, there was a correlation between infectious events and de novo malignancy, particularly in patients with PTLD. We should confirm this finding by conducting a larger cohort study.

Background : Left ventricular assist device (LVAD) therapy has improved the clinical outcomes in advanced heart failure patients, however, this may differ between countries. We aimed to compare outcomes between Japanese and US LVAD cohorts. Methods : For 416 consecutive LVAD patients who received HeartMate II LVAD implantation and completed a one-year follow-up, age-matched Japanese patients (the Japanese registry for mechanically assisted circulatory support (J-MACS) group) and the US patients were compared for their clinical outcomes. Results : 154 J-MACS patients and 77 US patients were compared. Survival, free from hemocompatibility-related adverse events (HRAEs) in the J-MACS was statistically comparable with the US (75% vs. 63%, p = 0.79). J-MACS had more disabling strokes than the US (0.221 vs. 0.052/patient-year, p = 0.005), whereas there was less nonsurgical bleeding (0.045 vs. 0.117/patient-year, p = 0.024). The net hemocompatibility score was statistically comparable between the groups (1.54 vs. 1.19 points/patient, p = 0.99). Post-LVAD prothrombin time with international normalized ratio (INR) <1.5 (odds ratio 4.07) was a risk factor for HRAEs in J-MACS, whereas INR >3.0 (odds ratio 5.71) was a risk factor in the US ( p < 0.05 for both). Conclusion : In the age-matched cohorts, the J-MACS group experienced more strokes, while the US group had more bleedings. "Tailor-made" therapeutic strategy might be required for each country, given the unique variation of HRAE incidence among each country., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support., Methods: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined., Results: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1-733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181-730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08-0.63; P=0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke)., Conclusions: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.

Until 2010, Japan had been using the Toyobo (Nipro, Osaka, Japan) extracorporeal left ventricular assist device (VAD) developed 30 years ago as a 2-3 year bridge to transplantation (BTT). In contrast, western nations started to use implantable VADs in the 1980s that allow in-home care as destination therapy (DT) as well as BTT. Designated in 2007 as "medical devices in high demand," the 5 major implantable mechanical hearts are smoothly undergoing clinical testing. The HeartMate XVE (Thoratec Corp., Pleasanton, CA, USA) gained approval from the Ministry of Health in November of 2009, the DuraHeart (TerumoHeart, Ann Arbor, MI, USA) and EVAHEART (Sun Medical, Nagano, Japan) in December 2010, and obtained formal insurance reimbursement in April 2011. The Jarvik 2000 (Jarvik Heart Inc., New York, NY, USA) and HeartMate II (Thoratec) VADs are pending approval. On the other hand, the organ transplantation law allowing explantation of donor organs from brain-dead patients finally passed in July 2009 and was realized in July 2010. This law paved the way to pediatric heart transplants as well as a dramatic increase in overall organ transplantation cases. Because many juvenile patients awaiting donor organs need a VAD as a long-term bridge, development and clinical introduction of pediatric VADs capable of implantation is an exigency. Although expectations for transplants are high, the donor numbers are low. Therefore, the demand for implantable VADs capable of long-term home treatment is extremely high in Japan., (Copyright © 2012. Published by Elsevier Ltd.)

Japan has witnessed the rise of STDs, and the increase in the number of HIV cases infected through sexual contact in the last decade. Background of these trends will be the exceptionally high prevalence of paid sex in Japan among developed countries and the diversified unprotected sexual behaviors that have prevailed among general population since 1990s. STDs are also increasing and HIV infection through sexual contact has resumed to increase among other developed countries in the same period of time. Coordinated research among developed countries is becoming increasingly important to clarify the specific and general causes of such phenomena and thus to explore the possibility of coordinated responses toward these global challenges.