Santen (Japan)

PurposePharmacodynamic biomarkers of sirolimus were investigated using omics analysis of tear fluids from Japanese patients with meibomian gland dysfunction (MGD).MethodsIn a Phase 2a trial, sirolimus or vehicle eyedrops were administered twice daily for 12 weeks. Tear samples from 29 patients (15 sirolimus, 14 vehicle) were collected pre- and post-treatment. LC-MS/MS-based proteomics and lipidomics were performed. Within-group changes were analyzed, followed by differential expression and pathway analysis. Key candidates were evaluated using estimation plots (Registration ID: UMIN000049186).ResultsOver 3000 proteins and 55 lipids were quantified. mTOR signaling components (ATP6V1D, RRAGC, DEPTOR) were significantly modulated. ATP6V1D showed a significant decrease in the sirolimus group (p = 0.0024), but not in the vehicle group (p = 0.528). Lipids 12-HETE and 13-HpODE significantly increased post-treatment in the sirolimus group.ConclusionResults suggested that sirolimus inhibited the mTOR pathway. ATP6V1D, 12-HETE, and 13-HpODE were suggested to be pharmacodynamic biomarkers for sirolimus. These findings may facilitate pharmacodynamic monitoring of mTOR-targeted therapies for ocular surface disorders.

BackgroundMyopia progression through childhood to early adulthood can cause serious visual complications and impose a significant economic impact due to its high prevalence and associated management costs. This systematic literature review evaluates the economic impact, health care resource utilisation (HCRU), and cost-effectiveness of current myopia interventions.MethodsThe systematic literature review was performed via the OVID SP® platform (software version 04.07.00, Mumbai, India) covering literature from 2009–2024, with no geographic restriction. Economic evaluation studies used the Markov model and the risk-of-bias was assessed using the Drummond and Jefferson checklist. s and full texts were screened independently by two reviewers; uncertainties and disagreements were resolved through reconciliation or arbitration by a third independent reviewer.ResultsA total of 20 studies were included: 12 cost-effectiveness, four HCRU, and eight for health care costs across different age groups, with a predominance of studies from East Asia (China, Hong Kong, Singapore). Among the paediatric population, the most cost-effective interventions included digital strategies for early prevention and screening, low-dose atropine (0.05%) with an incremental cost-effectiveness ratio of 234 USD/Spherical Equivalent Refraction reduction, and non-pharmacological defocus incorporated multiple segment lenses (7074 USD/quality-adjusted life year (QALY) gained). In adults, ranibizumab was cost-effective (35 288 USD/QALY gained) for pathologic myopia, while small incision lenticule extraction surgery yielded long-term savings (15 USD/QALY gained). Economic burden was largely driven by vision correction procedures and specialist visits, with notable regional and socioeconomic disparities in Spain and China. In adults, HCRU (frequent treatment, monitoring, hospitalisation, and emergency visits) was higher for myopic choroidal neovascularisation compared to paediatric population, and direct costs exceeded indirect costs.Conclusions Myopia presents a substantial economic burden, highlighting the need for optimising cost-effective interventions to reduce severity, prevent long-term vision loss, and lessen the financial burden. However, limited data, geographical bias, methodological inconsistencies, and heterogeneity in outcomes emphasise the need for more standardised, comprehensive evaluations to ensure broader applicability.

To evaluate parameters measured using the tear film imager (TFI) prototype, a new technology that enables to quantify the tear film thickness of lipid and mucoaqueous layers. In this cross-sectional study, patients with dry eye, meibomian gland dysfunction (MGD), and non-dry eye/MGD from February 2020 to January 2021 were analyzed. Quantified TFI outputs included lipid layer thickness (LLT), mucoaqueous layer thickness (MALT), MALT rate of change (MALTR), and lipid breakup time. Two other interferometry devices, LipiView2 and DR-1α, were used for comparison. TFI outputs and other clinical parameters were analyzed using correlation coefficients. Each patient underwent one or several study visits. Baseline values of three device outputs, other clinical parameters, and their changes were examined. This study involved 28 patients (8 patients with dry eyes, 13 with MGD, and 7 with non-dry eye/MGD). Baseline TFI, LipiView2, and DR-1α values were associated with various clinical parameters. The LLT values estimated using TFI had a correlation with the plugging score in the upper eyelid (r=-0.42). Several TFI values have correlated better than LipiView2 and DR-1α, particularly with questionnaire scores. MALTR by TFI revealed a correlation between standardized patient evaluation on eye dryness (SPEED) and dry eye-related quality of life score (DEQS) scores (r=0.59, 0.43), respectively. TFI enabled to quantify the LLT and MALT separately over time and shows the moderate correlations between TFI measurements and clinical parameters, which yields the potential for TFI to serve as a complementary tool for assessing dry eye and MGD.

BackgroundRheumatoid arthritis (RA) is a global health concern with increasing prevalence. Despite recommendations for regular disease activity assessments, their implementation in routine clinical practice remains challenging. The Medical Support System for Rheumatoid Arthritis (MiRAi) is an offline, semi-automated system that calculates disease activity indices by integrating patient and clinician inputs from electronic health records (EHRs).ObjectiveThis study evaluated the association between MiRAi implementation and the frequency of disease activity assessments in patients with RA.MethodsWe conducted a retrospective cohort study of patients with RA treated at a tertiary hospital in Japan between April 2022 and March 2023. We included all adult outpatients (aged ≥18 years) with RA diagnosed according to the 2010 ACR/EULAR [American College of Rheumatology/European Alliance of Associations for Rheumatology] classification criteria. The hospital introduced MiRAi in June 2022 and achieved full deployment by October 2022. MiRAi calculated the clinical disease activity index (CDAI) and the modified health assessment questionnaire (mHAQ) through automated extraction of joint counts, patient global assessment, and functional status from structured EHR fields. Primary outcomes included the frequency of CDAI and mHAQ assessments. We administered a structured post-implementation survey to assess rheumatologists’ perceptions of MiRAi.ResultsPhysicians used MiRAi for 236/884 (26.7%) patients with RA. Patients with documented CDAI and mHAQ scores increased from 29 (5.9%) in June 2022 to 81 (19.0%) in November 2022, representing a 3.2-fold increase. Among surveyed rheumatologists (n=10), 5 (50%) reported the regular use of MiRAi. Physicians who regularly used MiRAi (n=5) cited improved accuracy in disease assessment and enhanced treatment decision-making. Non-users and occasional users (n=5) identified three primary barriers: limited familiarity with MiRAi, time constraints, and discrepancies between clinical judgment and MiRAi-generated outputs. Despite MiRAi’s availability, only 168 (19%) patients underwent quantitative disease activity assessment by the study end. Among 15 patients with high disease activity (CDAI >22), physicians recorded 3 treatment modifications and 2 intra-articular steroid injections.ConclusionsMiRAi implementation increased disease activity assessment frequency by 3.2-fold over 6 months; however, physician adoption remained at 26.7%, below the 80% target for routine care. Future implementation strategies should address identified barriers through system integration, structured user training, and workflow optimization to achieve guideline-concordant care for patients with RA.

To evaluate the impact of disc hemorrhages (DHs) at different locations on clustered visual field (VF) progression in patients with primary open-angle glaucoma (POAG) over a 3-year prospective study. A prospective multicenter cohort study. Patients diagnosed with POAG and intraocular pressure (IOP) ≤18 mmHg undergoing prostaglandin analog monotherapy. Visual field testing, IOP measurements, fundus photography, and OCT scans were conducted quarterly over a 3-year period. Disc hemorrhage locations were categorized into superior, inferior, temporal, and nasal quadrants. The VF was subdivided into superior, inferior, and central regions, with the central VF further divided into superior central and inferior central zones. A multivariable linear mixed-effects model with random intercepts and slopes was employed to analyze the relationship between DH history at specific locations and progressive changes in clustered total deviation (TD). Association between DH location and the rate of clustered VF progression. Among 186 eyes from 109 patients, DH occurred in 61 eyes (32.8%). Superior, inferior, temporal, and nasal DH were observed in 19, 31, 21, and 2 eyes, respectively. A faster superior TD slope was significantly associated with inferior DH (P = 0.032), but not with superior or temporal DH. A faster inferior TD slope was significantly associated with a worse inferior baseline TD value (P = 0.009) and marginally associated with superior DH (P = 0.053) but not with inferior or temporal DH. A faster central TD slope was significantly associated with temporal DH (P < 0.001) and inferior DH (P = 0.034) but not with superior DH. Detailed analysis revealed that inferior DH was significantly associated with the superior central TD slope (P = 0.010) but not with the inferior central TD slope. Although DH recurrence was observed in 37 eyes, the number of DH events did not show an additive effect on corresponding clustered VF progression. The location of DH was strongly associated with corresponding clustered VF progression in patients with POAG. Both temporal and inferior DH represent risk factors for central VF progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;With the popularity of electric vehicles, the application development of heat pump type automobile air conditioning system has been focused. Meanwhile, the traditional R134a needs to be replaced by more environmentally-friendly refrigerants under the Kigali Amendment. In this paper, a novel direct expansion heat pump air conditioning system with three circuit switching (DXACS) was proposed, and three low GWP refrigerants R1234yf, R1234ze(E) and R290 were carried out to evaluate the system performance. The results show that the winter range attenuation ratio of DXACS is 26.9%, significantly lower than the prototype EV360 (57.5%); the DXACS with R290 shows the best heating performance, &lt;i&gt;COP&lt;/i&gt;&lt;sub&gt;h&lt;/sub&gt; and &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;cv&lt;/sub&gt; are 2.3% and 57.3% higher than R134a in extremely cold conditions, respectively. This study provides valuable insights for the development of efficient and green thermal management technology of new energy vehicles.&lt;/div&gt;&lt;/div&gt;

ObjectiveEvidence-based medicine (EBM) competency is crucial for healthcare professionals; however, validated tools to assess EBM skills in Japanese are scarce. This study aimed to develop and validate a Japanese version of the Assessing Competency in EBM (ACE) tool.MethodsWe translated the ACE tool into Japanese, following international standards, and distributed it online to 99 healthcare professionals and students. The participants completed demographic questions and the Japanese version of the ACE tool. A subset also completed the retest and Fresno test. Internal consistency was assessed using Cronbach's alpha, test-retest reliability using the intraclass correlation coefficient (ICC), and construct validity using a confirmatory factor analysis and correlation with the Fresno test.ResultsThe Japanese version of the ACE tool showed a low internal consistency (Cronbach's alpha =0.31, 95% CI: 0.09-0.49), but an acceptable test-retest reliability (ICC =0.64, 95% CI: 0.40-0.81). A confirmatory factor analysis provided moderate support for the structure of the tool (SRMR =0.092, RMSEA =0.048, CFI =0.852). The tool demonstrated a moderate correlation with the Fresno test (r =0.35). The median completion time was 847 s (IQR, 577-1,249 s).ConclusionAlthough the Japanese version of the ACE tool showed some promising aspects, including a quick administration and partial validity, its low internal consistency suggests that refinement is needed before it can be confidently used in Japanese medical education settings. Future studies should focus on improving the tool's reliability, potentially through in-person administration, to develop a robust EBM assessment tool in the Japanese healthcare context.