Objective: We investigated the health-related quality of life (HRQoL) of patients with chronic diseases in community pharmacies in Japan and examined its relationship to patient attributes, an area that has not been previously studied.Method: We surveyed 1,500 participants with chronic diseases and 1,500 from the general population without chronic diseases (Free-GP) using the EuroQol (5-dimension, 5-level) questionnaire. Patient attributes included the number of drugs used, duration of medication, number of chronic conditions, perceived disease severity, and perceived treatment importance. Logistic regression analyses assessed how these attributes influenced the likelihood of reporting “full health” (no problems on all HRQoL questions) among patients with chronic disease. An exploratory decision tree analysis was performed to identify patient attributes that might decrease HRQoL.Result: The HRQoL score of patients (0.856) was lower than that of Free-GP (0.942). The HRQoL of patients tended to increase with aging. Among patients, the mean HRQoL score was 0.781 for polypharmacy, which decreased with the addition of disease severity perception (even lower for those in their 20s-40). Even in the absence of polypharmacy, the average HRQoL score decreased when patients were in their 20s with multimorbidity. The HRQoL scores of non-polypharmacy patients in their 30s or older were higher than the mean scores of patients with chronic disease.Conclusion: To provide extensive care for patients with reduced HRQoL in community pharmacies, it is necessary to focus on polypharmacy. Reduced HRQoL should be considered in younger patients with multimorbidity, even in the absence of polypharmacy.

In recent years, the relationship between healthy life expectancy and exercise has been shown, and the same is also reported for the disabilities. However, we have not yet found any reports on the effects of exercise in children with lower extremity amputations. In this study, we had followed a seven-year-old boy who had undergone right knee rotationplasty for the Ewing's sarcoma, and studied the changes in his athletic abilities, bone density, and body composition with the use of a running-specific prosthesis (RSP). After becoming independent on walking with a daily-use prosthesis, he started using the RSP during exercise such as running. We measured the above parameters before the introduction of RSP, then again after one year use of the RSP. The results showed positive changes in all measurements: increased motor strength around hip, longer time on one leg standing test, increased one leg jump, faster walking speed, wider stride, improved bone density, and improved body compositions. The use of RSP's along with daily-use prostheses for children in their growth period may have favorable effects on their athletic abilities, bone densities, and body compositions.

In recent years, the relationship between healthy life expectancy and exercise has been shown, and the same is also reported for the disabilities. However, we have not yet found any reports on the effects of exercise in children with lower extremity amputations. In this study, we had followed a seven-year-old boy who had undergone right knee rotationplasty for the Ewing's sarcoma, and studied the changes in his athletic abilities, bone density, and body composition with the use of a running-specific prosthesis (RSP). After becoming independent on walking with a daily-use prosthesis, he started using the RSP during exercise such as running. We measured the above parameters before the introduction of RSP, then again after one year use of the RSP. The results showed positive changes in all measurements: increased motor strength around hip, longer time on one leg standing test, increased one leg jump, faster walking speed, wider stride, improved bone density, and improved body compositions. The use of RSP's along with daily-use prostheses for children in their growth period may have favorable effects on their athletic abilities, bone densities, and body compositions.

The COVID-19 pandemic has substantially transformed the healthcare sector. While telemedicine has rapidly advanced, the essential roles of medical professionals, such as doctors and nurses, have been reaffirmed. Even prior to the pandemic, we had been evaluating pharmacists’ interpersonal roles from both patient and pharmacist perspectives using role theory. Accordingly, we investigated whether perceptions of pharmacists’ roles changed among patients and pharmacists through comparable surveys conducted before and during the pandemic. A nationwide online survey was conducted twice (April 30-May 7, 2021, and April 22-25, 2022), targeting 1,000 patients who used community pharmacies and 600-800 pharmacists employed at those pharmacies across Japan. The questionnaire comprised 12 items： 11 concerning pharmacists’ interpersonal roles, including communication, comprehending medication effects, and serving as a family pharmacist or drug expert, and one additional item addressing expectations during the pandemic. A five-point Likert scale was used. Compared with pre-pandemic results, patient evaluations revealed no statistically significant changes in either 2021 or 2022. However, pharmacists’ self-evaluations declined in response to the question, “Are pharmacists more expert in medicine than doctors?” The newly introduced question regarding pharmacists’ contributions to the community received higher ratings from patients than from pharmacists, indicating considerable patient expectations. Overall, only pharmacists’ perceptions changed, demonstrating decreased confidence and self-evaluation. Conversely, patient perceptions remained stable, suggesting that pharmacists are more sensitive to social changes than patients themselves.

Background/Aims: The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. Methods: SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Results: Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). Conclusions These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

Purpose: Although patients with late-onset hypogonadism (LOH) often experience lower urinary tract symptoms (LUTS), LUTS are not generally included in LOH symptoms. No study has examined the direct relation of the Aging Males Symptoms rating scale (AMS) and the International Prostate Symptom Score (IPSS) with the quality of life (QOL) index. We analyzed the relation between the IPSS and QOL index and various factors including the AMS in patients with LOH syndromes. Materials and Methods: This study comprised 1,688 men with LOH symptoms who visited our hospital or affiliated clinic. Factors associated with the IPSS were assessed in terms of age, scores of several questionnaires including the AMS, endocrinological variables, and serum concentration of PSA. Among these same factors, those associated with the QOL index were also evaluated. Finally, the same analyses were repeated in 187 patients with low serum testosterone concentration (<3.0 ng/ mL). Results: In a multivariate analysis using the significant items from the univariate analysis, AMS, age, and Erection Hardness Score correlated significantly with the IPSS. A trend analysis using items other than the AMS as adjustment factors also confirmed the relationship between an increase in QOL index and an increase in AMS. Similar results were obtained in the analysis of patients with low serum testosterone concentration. Conclusions We revealed that the relation of IPSS with the QOL index for LUTS is closely associated with the AMS for LOH, regardless of testosterone level. When patients complain of LOH symptoms, a careful, detailed inquiry into LUTS is required.

Objective: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. Methods: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. Results: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Conclusion The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

Objective: The practices pertaining to hereditary breast and ovarian cancer (HBOC) in Japan have been rapidly changing owing to the clinical development of poly(ADP-ribose) polymerase inhibitors, the increasing availability of companion diagnostics, and the broadened insurance coverage of HBOC management from April 2020. A questionnaire of gynecologic oncologists was conducted to understand the current status and to promote the widespread standardization of future HBOC management. Methods: A Google Form questionnaire was administered to the members of the Japan Society of Gynecologic Oncology. The survey consisted of 25 questions in 4 categories: respondent demographics, HBOC management experience, insurance coverage of HBOC management, and educational opportunities related to HBOC. Results: A total of 666 valid responses were received. Regarding the prevalence of HBOC practice, the majority of physicians responded in the negative and required human resources, information sharing and educational opportunities, and expanded insurance coverage to adopt and improve HBOC practice. Most physicians were not satisfied with the educational opportunities provided so far, and further expansion was desired. They remarked on the psychological burdens of many HBOC managements. Physicians reported these burdens could be alleviated by securing sufficient time to engage in HBOC management, creating easy-to-understand explanatory material for patients, collaboration with specialists in genetic medicine, and educational opportunities. Conclusion Gynecologic oncologists in Japan are struggling to deal with psychological burdens in HBOC practice. To promote the clinical practice of HBOC management, there is an urgent need to strengthen human resources and improve educational opportunities, and expand insurance coverage for HBOC management.

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

OBJECTIVE: The present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception. METHODS: We retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation. RESULTS: Of the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m² and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m² had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively. CONCLUSIONS: MPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m².
Body Mass Index ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Fertility Preservation ; Fertilization ; Follow-Up Studies ; Humans ; Insulin Resistance ; Live Birth ; Medroxyprogesterone Acetate ; Metformin ; Pregnancy ; Prognosis ; Recurrence ; Retrospective Studies