Therapies In Japan Research Articles

Beyond Psyche: Aesthetic Attunement and Alternative Psychological Care Through the Heart

Putting aside the idea of psyche as the universal basis of personhood in Euro-American psychology, this special issue charts new ground, engaging hybrid and alternative therapies in Japan and China that center the indigenous notion of the heart— xin in Chinese and kokoro in Japanese —as the basis for developing a novel, alternative template for psychological care. Xin is both body and mind, the ground for cognition, emotion, virtue, and bodily sensation. It is less concerned with being than with living and life, and thereby troubling ontological debates. Since xin is the means by which people experience culture, a xin-based approach to mental health care brings a new vision of inclusion. It is key to the aesthetic order associated with Confucianism. Aesthetic order requires people to tune in, artfully, to yin-yang dynamism in themselves, society, and the cosmos. Optimally, this aesthetic attunement brings about a fuller, holistic relationality. Yet, cultivating aesthetic attunement at all levels of individual and social life can become a source of distress for the heart. Heart-related distress of varying intensities eludes psychiatric diagnostic categories. Contributors to this special issue explore the possibility of establishing an embodied, felt (affective), and artful (aesthetic) template of psychological care anchored in the heart.

Review Mechanisms for Advanced Medical Therapies in Japan and Thailand: A Proposal for the Use of Expert Clinical Benefit Assessments at Designated Institutions

AbstractAdvanced new therapies, such as stem cell and gene therapies and xenotransplantation, represent challenges for regulatory and ethical review. Major drug agencies, such as in the U.S., India, and Europe, have asserted regulatory authority and require ethics review by local ethics review committees, using the same strict requirements as those for standard drug approvals. In spite of this, unapproved and undocumented stem cell clinics flourish in all of these places, suggesting that current approaches do not offer patients sufficient protection. Japan has attempted another approach, requiring approvals at local levels for all regenerative medical procedures, and a faster approval of promising new interventions. The Japanese approach has, however, also been criticized as not striking a proper balance between early access and a proper assessment of safety and effectiveness. For smaller and less-resourced countries, such as Thailand, one major challenge is limited expertise to conduct the evaluation of these advanced new therapies. This article provides an overview of the issues facing regulators and proposes that countries should restrict the early adoption of advanced new therapies to specialized clinics with appropriate scientific and ethical expertise for review. Review in these institutions should focus on expert clinical benefit assessments for individual patients being offered such interventions, independently of whether they are offered as research or therapy.

Assessing the economics of biologic and small molecule therapies for the treatment of moderate to severe ulcerative colitis in Japan: a cost per responder analysis of upadacitinib

Aim Patients with moderately to severely active ulcerative colitis have an increasing number of advanced therapy options including several biologics and Janus kinase inhibitors. Though data on efficacy and safety of these advanced therapies are available, less is known about the potential economic implications of their utilization in Japan. We evaluated the relative value of these advanced therapies in Japan using a locally developed cost per responder model. Methods A model was developed using relevant clinical endpoints and treatment costs to calculate cost per responder of all advanced therapies used for moderately to severely active ulcerative colitis treatment in Japan. Cost per responder was assessed in biologic-naïve and biologic-exposed populations, respectively. The model incorporated induction and maintenance therapy pathways as patients progressed through based on efficacy rates (clinical response, clinical remission and endoscopic improvement). Total costs for induction and maintenance included: drug acquisition, drug administration and serious adverse event management (as necessary) for responders, with additional rescue treatment cost only for non-responders. Results Upadacitinib showed lower cost per clinical response and cost per clinical remission across both biologic-naïve and biologic-exposed populations with only one exemption in cost per clinical remission in biologic-naïve population. In addition, upadacitinib demonstrated lower cost per endoscopic improvement in both populations. Janus kinase inhibitors outperformed with lower cost per responder than other mediations across all outcomes and patient populations with the exception of tofacitinib for clinical remission in biologic-exposed UC population. Limitations Comparative data used in this analysis have been derived from network meta-analysis, not from direct comparison. Conclusions The results of this cost per responder analysis suggest upadacitinib is a cost-effective option for the first- and second-line treatment of moderately to severely active ulcerative colitis in Japan.

Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer EGFR Exon 20 insertion mutations after platinum-based chemotherapy

Background In the single-arm CHRYSALIS trial, advanced non-small cell lung cancer patients harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon 20ins) showed durable responses to amivantamab, an EGFR-MET bispecific antibody targeting tumors with EGFR Exon 20ins. This study compared the effectiveness of amivantamab to real-world systemic anti-cancer therapies in Japan. Patients and methods External control patients were selected by applying CHRYSALIS eligibility to Japanese patients from LC-SCRUM-Asia. External control patients were included for every qualifying line of therapy after platinum-based chemotherapy. Propensity score weighting was applied to external control patients to adjust for differences in baseline characteristics. Outcomes were compared between external control patients, and all and Asian-only CHRYSALIS patients using weighted Cox proportional hazards regression models for progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS), and generalized estimating equations with repeated measurements for overall response rate (ORR). Results One hundred fifteen CHRYSALIS and 94 external control patients were identified. Compared to external control patients, amivantamab-treated patients had significantly longer OS (median OS 19.88 vs 14.09 months, HR [95% CI] 0.59 [0.40–0.88]), PFS (median PFS 6.74 vs 4.73 months, HR 0.59 [0.45–0.78]), TTNT (median TTNT 12.16 vs 5.09 months, HR 0.39 [0.29–0.53]), and significantly higher ORR (41.7% vs 14.1%). Analyses of amivantamab-treated Asian patients (n = 61) showed similar clinical benefits. Conclusion In the absence of clinical evidence from randomized clinical trials, this study reflects the benefit of amivantamab after platinum-based chemotherapy for advanced non-small cell lung cancer patients harboring EGFR Exon 20ins, compared to current real-world therapies.

Current regenerative medicine-based approaches for skin regeneration: A review of literature and a report on clinical applications in Japan.

Current trends indicate a growing interest among healthcare specialists and the public in the use of regenerative medicine-based approaches for skin regeneration. The approaches are categorised in either cell-based or cell-free therapies and are reportedly safe and effective. Cell-based therapies include mesenchymal stem cells (MSCs), tissue induced pluripotent stem cells (iPSCs), fibroblast-based products, and blood-derived therapies, such as those employing platelet-rich plasma (PRP) products. Cell-free therapies primarily involve the use of MSC-derived extracellular vesicles/exosomes. MSCs are isolated from various tissues, such as fat, bone marrow, umbilical cord, menstrual blood, and foetal skin, and expanded ex vivo before transplantation. In cell-free therapies, MSC exosomes, MSC-derived cultured media, and MSC-derived extracellular vesicles are collected from MSC-conditioned media or supernatant. In this review, a literature search of the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus was conducted using several combinations of terms, such as ‘stem’, ‘cell’, ‘aging’, ‘wrinkles’, ‘nasolabial folds’, ‘therapy’, ‘mesenchymal stem cells’, and ‘skin’, to identify relevant articles providing a comprehensive update on the different regenerative medicine-based therapies and their application to skin regeneration. In addition, the regulatory perspectives on the clinical application of some of these therapies in Japan are highlighted.

MCL-041: Outcomes for Recurrent Mantle Cell Lymphoma Post-BTK Inhibitor Therapy in Japan: An Administrative Database Study

<h3>Objective</h3> No standard drug therapies are currently available after covalent BTK inhibitor (BTKi; ibrutinib) treatment of patients with mantle cell lymphoma (MCL). We investigated real-world treatment patterns and outcomes for MCL patients following BTKi treatment in Japan. <h3>Design</h3> Real-world data (Apr. 2008 – Sep. 2020), provided by Medical Data Vision Co. Ltd., was from a Japanese hospital-sourced administrative database. First-line (1L) therapy was the first identified use of an anti-tumor drug. Follow-up was from the initiation of 1L until the end of available data. <h3>Setting</h3> Hospital <h3>Patients</h3> Adult patients (aged ≥20 years) treated for recurrent MCL between Dec. 2010 –Sep. 2019 and who had received prior BTKi therapy. Patients not excluded: any level of existing disability. <h3>Interventions</h3> Available BTKi and other MCL therapies in Japan during the study period. <h3>Main Outcome Measures</h3> Treatment patterns, outcomes, and demographics. <h3>Results</h3> 1,203 patients (mean age 71, male 74%) received at least 1L and were included in the study population. Of these, 270 (22%) patients received BTKi (ibrutinib) at any line of therapy, with the majority receiving it as second-line (41%) or third-line therapy (21%). Of the 270 BTKi-treated patients, 183 (68%) patients discontinued this agent, and 108 (40%) subsequently received post-BTKi therapy. These 108 patients received 60 unique anti-tumor drug combinations; 27% bendamustine-based, 19% bortezomib-based, and 13% cytarabine-based. The median (95% CI) time to treatment discontinuation of post-BTKi treatments was 1.5 (1.1–2.0) months. The median (95% CI) overall survival for post-BTKi therapies was 5.5 (3.9–9.4) months. Numerically higher patient rates received blood transfusion (39% <i>vs</i> 15%), concomitant radiotherapy (8% <i>vs</i> 4%), and anti-infectives (52% <i>vs</i> 32%) and experienced febrile neutropenia requiring GCSF treatment (13% <i>vs</i> 1%) for post-BTKi vs BTKi treatments, respectively. Atrial fibrillation/flutter (5% <i>vs</i> 10%) rates were lower for post-BTKi than BTKi (ibrutinib) treatment. <h3>Conclusions</h3> Patients with MCL who have been previously treated with BTKi subsequently experience extremely poor outcomes with currently available therapy options. The development of safe and effective targeted therapy after BTKi is needed to improve the otherwise dismal outcomes of these patients.

Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan

The chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009–2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

A multicenter prospective cohort study on the effect of smoking cessation on periodontal therapies in Japan.

Few prospective studies have reported the effects of periodontal therapy on patients who attempted to quit smoking. This study aimed to assess how smoking cessation affects periodontal therapy. Twenty-five smokers with periodontitis were investigated by dividing them into two groups, a smoking cessation support group and a continued smoking group. Those in the support group received counseling and nicotine replacement therapy, followed by periodontal treatment conducted by dentists who had completed an e-learning course on smoking cessation. Clinical parameters were measured at baseline, 3, and 6 months. Most clinical parameters improved for those in the smoking cessation support group. There were no significant improvements in bleeding on probing (BOP) or the number of severe periodontal disease sites in the continued smoking group. Probing pocket depth (PPD) and clinical attachment levels (CAL) at sites that received scaling and root planing (SRP) significantly improved in all subjects. BOP did not improve at reevaluation in the smoking relapse subgroup. Patients in the smoking cessation support program led by dental professionals showed more improvement in BOP than those in the continued smoking group.

The first national survey of anesthesia techniques for fetal therapies in Japan.

The aim of this study was to survey the frequency of various anesthetic techniques used in the anesthetic management of both the mother and fetus during fetal therapies in Japan. We sent a postal survey to the institutions with physicians who held membershipof the Japan Society of Fetal Therapy to describe maternal and fetal anesthetic management during fetal therapies performed from January 2016 to March 2017. The therapies included were thoracoamniotic shunting (TAS), intrauterine transfusion (IUT), radiofrequency ablation (RFA), fetoscopic laser photocoagulation (FLP), fetoscopic endotracheal occlusion (FETO), and ex utero intrapartum treatment (EXIT). Survey respondents were asked to specify the standard anesthetic technique used in each of these procedures done during the study period. The most common anesthetic techniques used in each therapy were sedation/analgesia with local anesthesia in TAS (31%), local anesthesia alone in IUT (47%), neuraxial anesthesia in RFA (50%), FLP (66%) and FETO (100%), and general endotracheal anesthesia in EXIT. Fetal analgesia was utilized in 61% of TAS, 33% of IUT, 10% of RFA, 22% of FLP, 100% of FETO, and 50% of EXIT. In all fetal therapies, the most common route of administration for fetal anesthesia was maternal administration. In this first published description of the frequency of various anesthetic techniques used during fetal therapies in Japan, we found that anesthetic techniques varied depending on the degree of invasiveness to the mother and fetus. Fetal anesthesia was not always performed, and the most common route for fetal anesthesia was maternal administration.

1481O - Clinical development of molecular-targeted therapies for non-small cell lung cancer through nationwide genome screening in Japan (LC-SCRUM-Japan)

1481O - Clinical development of molecular-targeted therapies for non-small cell lung cancer through nationwide genome screening in Japan (LC-SCRUM-Japan)

Abstract 2721: Establishment of a catalog of somatic genetic alterations of Japanese cancer patients across multiple tumor types at Shizuoka Cancer Center

Abstract Background: Recent progression of systematic tumor-molecular profiling study centered on genome sequencing have elucidated molecular signature underlying each tumor type. Tumor molecular profiling enables efficient identification of somatic genetic alterations as potential therapeutic targets. In January 2014, the Shizuoka Cancer Center of Japan launched Project HOPE, which is the first prospective molecular profiling study centered on genome sequencing across multiple tumor types in Japan. Herein, we describe the distributions of the tumor mutation burden (TMB; number of mutations/Mb), genetic alterations frequency, mutational signature across tumor types, and their associations with tissue of origin, histological type, carcinogenic factors, and ethnicity. Methods: Between January 2014 and January 2017, 3,163 tumor samples from 3,011 patients who underwent surgery at the Shizuoka Cancer Center were collected with informed consent and subjected to whole-exome sequencing (WES) with an Ion Proton system. Corresponding peripheral blood samples were also subjected to WES for identification of tumor-specific genetic alterations. Oncogenic fusions were detected by targeted RNA sequencing. Among them, data of 2,126 primary tumor samples obtained from 2,091 patients without neoadjuvant chemotherapy and/or radiation therapy were selected for this study. Results: The principal tumor types of ≥40 primary tumors were as follows (N, TMB): colon adenocarcinoma (COAD; 459, 3.6), rectal adenocarcinoma (READ; 366, 3.1), lung adenocarcinoma (LUAD; 290, 1.7), stomach adenocarcinoma (STAD; 221, 3.0), hepatocellular carcinoma (HCC; 112, 3.6), head and neck squamous cell carcinoma (HNSC; 112, 2.8), breast invasive ductal carcinoma (IDC; 82, 1.1), lung squamous cell carcinoma (LUSC; 81, 5.9). Approximately 8.9% of the samples (154 / 1,723) showed a high mutation burden above the threshold defined by the TMB distribution in each principal tumor type, and the mutation signature was related to a defect of DNA repair and exposure to environmental mutagens. In comparison of distribution of TMB in each tumor type between TCGA and this study, some differences in TMB distribution were observed, including LUAD, LUSC, and IDC. In gene mutations based on OncoKB site (October 2018), level 1 or 2 of somatic gene mutation was frequently observed in glioma (84.6%), gastrointestinal stromal tumor (77.4%), melanoma (40.0%), and LUAD (40.0%). Conclusions: This established catalog of somatic genetic alterations across multiple tumor types in Japanese cancer patients can contribute as benchmark to clinical-trial design with the aim of expanding the number of patients suitable for molecular-targeted therapies in Japan. Based on these data, we are planning clinical trials of molecular-targeted therapies for patients with solid tumor harboring gene alterations. Citation Format: Hirotsugu Kenmotsu, Masakuni Serizawa, Takeshi Nagashima, Keiichi Ohshima, Keiichi Hatakeyama, Yuji Shimoda, Shumpei Ohnami, Koji Maruyama, Tohru Mochizuki, Yasuto Akiyama, Takashi Sugino, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi. Establishment of a catalog of somatic genetic alterations of Japanese cancer patients across multiple tumor types at Shizuoka Cancer Center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2721.

本邦における認知療法, 認知行動療法, 生活技能訓練および社会技能訓練の動向

本邦における認知療法, 認知行動療法, 生活技能訓練および社会技能訓練の動向

Diagnosis of sepsis-induced disseminated intravascular coagulation and coagulopathy.

Disseminated intravascular coagulation (DIC) is a frequent complication in sepsis. Once patients develop DIC, the mortality rate increases significantly. Moreover, recent studies have suggested that coagulation disorder plays a significant role in the development of organ dysfunction in sepsis. Thus, the early detection of DIC is vital in sepsis care, and the Japanese Association for Acute Medicine established a set of original diagnostic criteria in 2006 (JAAM DIC). Since then, the usefulness of the JAAM DIC has been repeatedly reported, and these criteria have been widely adopted in emergency and critical care settings in Japan. Different criteria have also been released by the International Society on Thrombosis and Haemostasis (ISTH overt‐DIC), and the latter criteria are presently considered to be the international standard. Compared with the JAAM DIC, the ISTH overt‐DIC criteria are stricter and the timing of diagnosis is later. This discrepancy is because of conceptual differences. As many physicians think sepsis‐associated DIC is the target of anticoagulant therapies in Japan, the JAAM DIC criteria were designed to allow the early initiation of treatment. As other countries do not provide DIC‐specific treatments, early diagnosis is not necessary, and this situation has led to a significant gap. However, as overt‐DIC is a late‐phase coagulation disorder, a need for early detection has been advocated, and members of the ISTH have recently proposed the category of sepsis‐induced coagulopathy. In this review, we introduce the strengths and weaknesses of the major criteria including JAAM‐DIC, ISTH overt‐DIC, sepsis‐induced coagulopathy, and Japanese Society on Thrombosis and Haemostasis‐DIC.

Treatment patterns and adherence to antihypertensive combination therapies in Japan using a claims database

Fixed-dose combinations (FDCs) for blood pressure control can simplify prescribing, improve medication adherence, and be cost-effective. In Japan, real-world data about the class effects of antihypertensive drugs on medication adherence are limited. Using the nationwide database of medical health claims from Diagnosis Procedure Combination hospitals, treatment patterns and adherence were analyzed for 47,891 patients prescribed antihypertensive medication between April 2014 and March 2015. Adherence was assessed by the proportion of days covered (expressed as % PDC). Patients were prescribed a mean of 2.0 ± 1.0 antihypertensive drugs and 2.4 ± 1.7 pills for their index prescription. Mean adherence overall was 91.5% PDC and was inversely correlated with the number of antihypertensive drugs or pills prescribed on the index date. Mean % PDC was significantly higher (all P < 0.0001) for CCB + ARB versus ARB + thiazide diuretic combinations and for CCB + ARB + β-blocker versus CCB + ARB + thiazide diuretic combinations. Adherence was significantly higher (P < 0.0001) for FDC (CCB + ARB) versus corresponding single-drug combinations, but not for other comparisons of FDCs versus single-drug combinations. On the other hand, FDCs were not always used effectively; specifically, FDCs were frequently used concomitantly with a single agent(s) from the same drug class(es) as the FDC. From the results of our study, no clear differences were observed in medication adherence according to the presence or absence of FDC formulations, and there were cases in which FDCs were not being utilized effectively to simplify prescribing.

Package insert revisions for three therapies in Japan

Package insert revisions for three therapies in Japan

PHP90 - Health Economics of Orphan Drugs in Japan

To understand the impact of policy on orphan drug pricing and health economics in Japan as compared to in the EU5. The study employed a pragmatic literature, industry, and policy review to determine nuanced pricing and reimbursement dynamics for orphan gene, stem cell, and PD-1/L1 therapies in Japan. While innovative and orphan drug pricing and access in the EU5 often relies on cost-effectiveness analyses and budget impact, pricing in Japan strictly follows either the cost-calculation or the comparison pricing pathway, as the country places a larger emphasis on innovation and unmet therapeutic need. Japan’s HTA allows new drugs to use innovation (first-in-class) premiums (70-120%) and marketability (orphan indication) premiums (5-20%). An additional 15-20% premium is available to drugs with Sakigake designation, given to domestically-developed therapies expected to have outstanding efficacy. Orphan gene therapy with no comparator, SPINRAZA, was quickly priced in Japan at ¥9,320,424 (€70,785). In Europe, SPINRAZA is only approved in Germany, which cited major improvement of therapeutic benefit to price the therapy at €89,600; other more cost-effectiveness-conscious countries have not yet chosen to reimburse the therapy. Although historically more lenient on budget impact than EU5 countries, since 2016, Japan has also necessitated re-pricing of “huge sellers,” or products with annual sales of ¥100-150 billion ($0.97-1.45 billion), such as SOVALDI, which received a 31.7% Japanese price-cut to the therapy. Still not as important an influence on reimbursement decisions in Japan as in Europe, budget impact of orphan and novel therapies is on Japan’s radar. Japan rewards drugs for innovation and unmet need fulfillment, as long as budget impact is not excessive; European HTA policies look at cost-effectiveness and therapeutic benefit to gauge pricing. Domestic manufacturers launching therapies in Japan are poised preferentially, and global manufacturers should emphasize the novel/orphan nature of products as opposed to their cost-effectiveness.

Design characteristics of the Corrona Japan rheumatoid arthritis registry

Objectives: The primary objective is to prospectively study the comparative safety and effectiveness of older and newer classes of nonbiologic DMARDs (Disease-modifying antirheumatic drugs), biologic DMARDs and targeted synthetic therapies approved for rheumatoid arthritis (RA) in a real-world patient population in Japan.Methods: Prospective, multicenter, noninterventional, observational study across geographic distribution of both private and public institutions for patients with RA who are newly prescribed one of the following medications: (1) methotrexate; (2) anti-TNF biologic DMARDs; (3) non-TNF biologic DMARDs; and (4) approved JAK inhibitors at the time of enrollment into the registry. Target enrollment is currently 2000 subjects. Baseline and follow-up data on patient demographics, medical history, disease activity, laboratory results, comorbidities, hospitalizations, and targeted safety events are obtained via Physician and Patient Questionnaires.Results: Fifty sites are anticipated to participate with 40 sites ethics committee (EC) approved at the time of submission consisting of 23% clinics, 21% private academic hospitals, 29% private mid-sized to large hospitals, 15% national academic hospitals, and 12% national hospitals.Conclusion: The Corrona Japan RA Registry will provide real-world evidence from both private and public institutions on the comparative effectiveness and safety of recently approved RA therapies in Japan.

Microarray Analysis of the Effects of Amelogenin on U937 Monocytic Cells

Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults. These bacteria which invade periodontal tissue are phagocytosed mainly by monocytes and macrophages in this immune response, and will be presented to lymphocytes. Recently, therapies for regenerating periodontal tissues have been used extensively to treat periodontal disease, and in particular, enamel matrix derivative (EMD) is commonly used for such therapies in Japan. Amelogenin is a type of the extracellular matrix protein that accounts for 90% of the constituents of EMD. In this study, we carried out a detailed microarray analysis in order to evaluate a gene group involved in amelogenin stimuli in the human monocytic cell line U-937. Microarray analysis revealed that statistically significant changes were apparent in 273 genes (163 up-regulated and 110 down-regulated) subsequent to 4 h of amelogenin stimulation. The most highly enriched categories included “cell cycle”, “DNA replication”, and “DNA repair” in up-regulated annotation terms. On the other hand, “type I diabetes mellitus”, “allograft rejection”, and “graft versus host disease” were observed in down-regulated annotation terms. Specifically, the gene expression of major to compatibility complex (MHC) class I/II and CD80/86 was impaired in U937 cells after stimulation with amelogenin. In addition, the results of heat-map showed that the gene expression of inflammatory cytokine such as tumor necrosis factor (TFN), interleukin-18 (IL-18), and CXCL16 was markedly decreased after stimulation of monocytes with amelogenin. In conclusion, the findings of our study showed that by inducing monocyte growth through the suppression of the antigen-presenting ability of U937 cells, amelogenin may affect the immune responses of periodontal tissues originating from monocytes. Examining the effects of amelogenin on the transformation of macrophages differentiating from monocytes may establish a molecular basis for the anti-inflammatory effect of amelogenin in periodontal tissues.

13 - Accelerated Pathways for Cell Therapies in Japan: An Experiment in Ethics and Regulation

13 - Accelerated Pathways for Cell Therapies in Japan: An Experiment in Ethics and Regulation

Evaluating the Quality of Website Information of Private-Practice Clinics Offering Cell Therapies in Japan.

BackgroundAlthough the safety and effectiveness of stem cell therapies are yet to be proven, recent studies show that such therapies are being advertised with some questionable marketing techniques to effect positive portrayal of the therapies on the webpages of private-practice clinics to sell their therapies worldwide. In such context, those clinics communicate directly with consumers (patients and their family members) via the clinics’ websites. Meanwhile, the Health Science Council at the Ministry of Health, Labour, and Welfare (MHLW) in Japan has pointed out noncompliance of some local clinics with the provisions concerning medical advertising in the Medical Care Act in the past. However, locally little is known about the current status of those clinics including the quality of their webpage information disseminated.ObjectiveTo evaluate the quality of website information of private-practice clinics offering cell therapies in Japan.MethodsTwenty-four websites with 77 treatments from the Google search were identified for evaluation. The following three exploratory analyses were performed: first in order to ascertain web-based portrayal of private-practice clinics offering cell therapies, a descriptive analysis was conducted using a coding frame; second we evaluated the quality of the target website information from the viewpoint of the level of consideration taken for patients and their family members, using 10 quality criteria (“the Minimum Standard”) from the e-Health Code of Ethics 2.0; third we counted and coded expressions that matched set categories for “name-dropping” and “personalized medicine” in the information posted on these websites.ResultsAnalysis on the treatments (N=77) revealed 126 indications (multiple response): the top three indications were “cancer,” “skin-rejuvenation/antiaging/anti–skin aging,” and “breast augmentation/buttock augmentation.” As for the portrayal of treatment risks and benefits, 78% (60/77) of treatments were mentioned with “benefits,” whereas 77% (59/77) of treatments were mentioned with “risks.” As for the source(s) cited for the discussions of treatment risks and benefits, no treatment quoted an expert’s opinion for the risks, whereas 7% (6/77) treatments quoted external sources for the benefits. As for the results with e-Health Code of Ethics 2.0, not a single clinic fulfilled all the 10 criteria; 63% (15/24) of the clinics was found exercising “name-dropping,” and 21% (5/24) of the clinics mentioned expressions related to “personalized medicine” on their websites.ConclusionsOur website content analyses confirmed the following: (1) the clinics mentioned the risks or benefits of the treatments with hardly any scientific citations, (2) the way the website information was disseminated was inappropriate for patients and their families, and (3) many websites seemed to be using marketing techniques in order to draw patients’ interests or attentions. It is important that more similar studies are undertaken globally to enable an orchestrated regulatory approach toward private-practice clinics.