Incidence of new fractures in older patients with osteoporosis receiving biosimilar teriparatide or reference products: A retrospective cohort study.

AIMS: Biosimilar products have clinical characteristics similar to those of brand-name products and can reduce medical costs. However, the use of biosimilar products for osteoporosis treatments remains limited due to concerns regarding its safety and efficacy. We aimed to clarify the effectiveness and safety of the biosimilar teriparatide compared with those of the reference product using the incidence of new fractures and osteosarcoma as outcomes in osteoporosis patients. METHODS: This study used the DeSC database, which contains medical claims data for various insurers in Japan. We included patients with osteoporosis aged ≥65 years who newly received either biosimilar teriparatide or the reference products between April 2019 and November 2022. Competing risk analyses were performed with adjustments for patient characteristics. The primary and secondary outcomes were the occurrence of new fractures and osteosarcoma, respectively. RESULTS: Among 45 861 included patients, 3613 and 42 248 were in the biosimilar and reference product groups, respectively. The median follow-up duration was 439 days. New fractures occurred in 6.7% of patients. Cumulative incidence function curves showed similar risks of new fractures over time in both groups. The cause-specific hazard ratio for new fractures was 0.95 (95% confidence interval: 0.82-1.11) for the biosimilar group compared with that of the reference product group. The incidence of osteosarcoma did not differ significantly between the groups (P = .559). CONCLUSIONS: The biosimilar teriparatide showed effectiveness and safety comparable with those of the reference products in treating osteoporosis patients. Our results suggest that clinicians need not hesitate to prescribe biosimilar teriparatide for osteoporosis patients.

Cilostazol versus Aspirin or Clopidogrel for Reducing Post-Stroke Aspiration Pneumonia: A Nationwide Retrospective Cohort Study.

INTRODUCTION: The association between the use of cilostazol as a post-stroke antiplatelet medication and a reduction in post-stroke pneumonia has been suggested. However, whether cilostazol has a greater preventive effect against post-stroke aspiration pneumonia (AP) than other antiplatelet medications remains unclear. Thus, this study aimed to evaluate whether cilostazol has a greater preventive effect against post-stroke AP than aspirin or clopidogrel. METHODS: Through the Japanese Diagnosis Procedure Combination database, we identified patients who were hospitalized for ischemic stroke between April 2012 and September 2019. We performed 1:1 propensity score matching between patients who received cilostazol alone at discharge and those who received aspirin or clopidogrel alone at discharge. The primary outcome was the 90-day readmission for post-stroke AP. The occurrence of recurrent ischemic stroke within 90 days was also evaluated. RESULTS: Among the 305,543 eligible patients with ischemic stroke, 65,141 (21%), 104,157 (34%), and 136,245 (45%) received cilostazol, aspirin, and clopidogrel, respectively. Propensity score matching generated 65,125 pairs. The cilostazol group had a higher proportion of 90-day post-stroke readmissions with AP than the aspirin or clopidogrel groups (1.5% vs. 1.2%, p < 0.001). The proportion of patients with recurrent ischemic stroke within 90 days was also higher in the cilostazol group (2.4% vs. 2.2%, p = 0.017). CONCLUSION: The present study suggests that cilostazol may not have a greater effect on preventing post-stroke AP within 90 days than other antiplatelet medications. Nevertheless, further randomized controlled trials with longer follow-up periods are warranted.

Do Orally Disintegrating Tablets Facilitate Medical Adherence and Clinical Outcomes in Patients with Post-stroke Dysphagia?

Orally disintegrating tablets (ODTs) dissolve rapidly in contact with saliva and have been reported to facilitate oral administration of medications in swallowing difficulties. However, their clinical benefits remain unclear because no previous studies have examined whether ODTs facilitate medication adherence and clinical outcomes in patients with post-stroke dysphagia. This study evaluated the association between ODT prescriptions and clinical benefits using high-dimensional propensity score (hd-PS) matching to adjust for confounding factors. Using a large Japanese commercial medical and dental claims database, we identified patients aged ≥ 65 years with post-stroke dysphagia between April 2014 and March 2021. To compare 1-year outcomes of medication adherence, cardiovascular events, and aspiration pneumonia between patients taking ODTs and non-ODTs, we performed hd-PS matching. We identified 11,813 patients without ODTs and 3178 patients with ODTs. After hd-PS matching, 2246 pairs were generated. Medication adherence for 1 year, based on the proportion of days covered, was not significantly different between the non-ODT and ODT groups before (0.887 vs. 0.900, P = 0.999) and after hd-PS matching (0.889 vs. 0.902, P = 0.977). The proportion of cardiovascular events (0.898 vs. 0.893, P = 0.591) and aspiration pneumonia (0.380 vs. 0.372, P = 0.558) were also not significantly different between the groups. This study found no significant differences in medication adherence, cardiovascular diseases, or aspiration pneumonia between the non-ODT and ODT groups in patients with post-stroke dysphagia. Both groups achieved a proportion of days covered exceeding 80%. Clinicians may consider prescribing ODTs or non-ODTs based on patient preferences rather than solely on post-stroke conditions.

Usability of the Japanese Late-Stage Elderly Questionnaire for screening major depression.

BACKGROUND: Older adults with major depression are at risk of frailty and long-term care needs. Consequently, screening for major depression is imperative to prevent such risks. In Japan, the Late-Stage Elderly Questionnaire was developed to evaluate older adults' holistic health, including mental well-being. It comprises one specific question to gauge life satisfaction, but the effectiveness of this question to screen for major depression remains unclear. Therefore, we aimed to assess the usability of this question to screen for major depression. METHODS: This retrospective cohort study used a large, commercially available claims database in Japan. Participants were older adults aged ≥75 years who completed the Late-Stage Elderly Questionnaire and were classified with and without new major depression within 1 year. We evaluated the questionnaire's ability to screen for major depression using C-statistics, developing three models to assess the cut-off value based on responses to the life satisfaction question ('Satisfied', 'Somewhat satisfied', 'Somewhat unsatisfied', or 'Unsatisfied'), estimating the sensitivity and specificity of each model. RESULTS: Among 11 117 older adults, 77 newly experienced major depression within 1 year. The C-statistic for screening major depression was 0.587. The model setting the cut-off between 'Somewhat unsatisfied' and 'Unsatisfied' the demonstrated lowest sensitivity and highest specificity, while the model setting the cut-off between 'Satisfied' and 'Somewhat satisfied' demonstrated highest sensitivity and lowest specificity. CONCLUSIONS: Our results suggest that due to its poor screening ability and high rate of false negatives, the question assessing life satisfaction in the Late-Stage Elderly Questionnaire may not be useful for screening major depression in older adults and may require modification.

Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue.

Although povidone-iodine (PVP-I) has been used as a gargle since 1956, its effectiveness and material safety have been remained controversial. The aim of this study was to investigate the toxicity of PVP-I to epithelial cells in a concentration range significantly lower than that used clinically. Study design was in vitro laboratory investigations and in vivo histological and immunologic analysis. We examined the effects of PVP-I at concentrations of 1 × 10(-2) to 1 × 10(3) µM and 1 × 10(-4) to 1 × 10 µM on HeLa cells as a model of epithelial cells and rat oral mucosa, respectively, after 1 or 2 days of exposure. Annexin V/FLUOS was used to distinguish live, apoptotic and necrotic cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was also used to observe whether apoptotic epithelial cells exist in rat oral mucosa after 1 day of exposure of PVP-I. HeLa cells developed concentration-dependent cytotoxicity, and epithelium of rat oral mucosa was thinned in a concentration-dependent manner. HeLa cell apoptosis increased after 1 × 10(0) µM of PVP-I exposure for 2 days. In the TUNEL method, many apoptotic epithelial cells were observed in the rat oral mucosa after 1 day of exposure to diluted 1 × 10(-2) µM of PVP-I, but minimal apoptotic epithelial cells were observed using 1 × 10(-3) µM of PVP-I. Our findings suggest that exposure to PVP-I, of which concentrations are even lower than those used clinically, causes toxicity in epithelial cells. This knowledge would help us better understand the risk of the use of PVP-I against mucosa.

Retraction notice to Cost-effectiveness of the Recombinant Zoster Vaccine among People Living with Human Immunodeficiency Virus in Japan: [VHRI Volume 44, November 2024, 101025].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the authors due to an error in the study discovered after the paper was published. In this study, the cost-effectiveness of the recombinant zoster vaccine (RZV) (Shingrix®) for people living with HIV (PLWHIV) aged ≥50 years was analyzed, comparing a 2-dose RZV strategy to no RZV strategy. The initial model indicated that the no RZV strategy was more cost-effective than the 2-dose RZV strategy (Erratum to Table 2). However, an error occurred in the model, where the cost parameter for the 2-dose RZV strategy was mistakenly applied as if PLWHIV individuals received the 2-dose vaccine in every cycle, significantly inflating the cost of this strategy. Upon correcting the model to reflect that the 2-dose RZV is administered only at cycle 0, the revised results indicate that the 2-dose RZV strategy is dominant over the no RZV strategy (Erratum to Table 2). Given that this error leads to a completely reversed conclusion, this paper has been retracted.

Association between self-reported difficulty in chewing or swallowing and frailty in older adults: A retrospective cohort study.

Oral frailty can contribute to physical and mental health disorders. Previous research has shown an association between frailty and self-reported difficulty in chewing or swallowing. However, their combined assessment has obscured their specific impact on frailty-related outcomes. To investigate the independent associations between difficulty in chewing or swallowing and 1-year frailty outcomes, while also examining their interactions. This retrospective cohort study utilized the DeSC database to identify older adults aged ≥ 75 years who underwent health checkups between April 2014 and November 2022. Multivariate Cox regression analyses were conducted to assess the association between self-reported difficulty in chewing or swallowing and outcomes, including hospitalization due to aspiration pneumonia, all-cause hospitalization, and all-cause mortality within 1 year. Interactions between chewing and swallowing difficulties were also evaluated. Among 359,111 older adults, 39.0% reported oral function difficulties. Swallowing difficulty alone lacked significant outcome association. However, chewing difficulty alone was significantly associated with higher risks of hospitalization due to aspiration pneumonia (hazard ratio (HR), 1.35; 95% confidence interval (CI), 1.15-1.58; P < 0.001), all-cause hospitalization (HR, 1.08; 95% CI, 1.05-1.11; P < 0.001), and all-cause mortality (HR, 1.28; 95% CI, 1.14-1.44; P < 0.001) compared with no self-reported difficulty. A significant positive interaction between self-reported difficulty in chewing and swallowing was observed for all-cause mortality (P = 0.009). Self-reported difficulty in chewing was significantly associated with higher risks of hospitalization due to aspiration pneumonia, all-cause hospitalization, and all-cause mortality among older adults. Chewing and swallowing difficulties showed a synergistic effect, significantly increasing all-cause mortality risk.

Changes in the mumps vaccine coverage and incidence of mumps before and after the public subsidization program: A descriptive study using a population-based database in Japan.

BACKGROUND: Continuous mumps vaccine coverage is essential for eradicating mumps. However, due to safety concerns, Japan's mumps vaccination program transitioned from routine to voluntary. To improve coverage, some municipalities introduced subsidization programs, but the effects on vaccination rates and mumps incidence remain unclear. METHODS: In April 2018, a city in Japan launched a subsidization program for the mumps vaccine for children aged 1-6 years. Using vaccination records and healthcare claims from July 2016 to December 2019, we analyzed changes in vaccination coverage and mumps incidence before and after the program's initiation. RESULTS: At the program's start, mumps vaccination coverage among eligible children was 3.3%, increasing by approximately 1.5% monthly to 38.4% after 21 months. Among 308,976 individuals, 145 mumps cases were identified: 92 cases (0.27 per 1,000 person-years) occurred before, and 53 (0.15 per 1,000 person-years) occurred after the program's start. CONCLUSIONS: Although the mumps vaccination coverage rate increased following the program's initiation, it remained below the level required for eradication.

Association between subjective physical function and occurrence of new fractures in older adults: A retrospective cohort study.

BACKGROUND: The Late-Stage Elderly Questionnaire has been incorporated into health assessments for older adults in Japan, encompassing three self-administered questions on subjective physical function: subjective gait speed decline, recent fall history, and exercise habits. Nevertheless, its efficacy in predicting new fracture occurrences remains uncertain. METHODS: This retrospective cohort study utilized Japan's DeSC database, a large commercially available claims database. Participants were older adults aged ≥75 years and provided complete responses to the Late-Stage Elderly Questionnaire at health check-ups. We performed two Cox regression analyses for new fractures based on the responses to the three questions (Model 1) and on age, sex, and responses to the three questions (Model 2). The predictive abilities of the 1-year occurrence of new fractures were compared between the two models. RESULTS: Of 11 683 eligible older adults, 927 (7.93%) experienced new fractures. Model 1 revealed significant associations between new fractures and subjective gait speed decline (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.40-1.89), recent fall history (HR, 2.03; 95% CI, 1.77-2.33), and absence of exercise habits (HR, 1.29; 95% CI, 1.13-1.47). Model 2 demonstrated superior predictive ability (area under the curve, 0.677; 95% CI, 0.659-0.695) compared with Model 1 (area under the curve, 0.633; 95% CI, 0.614-0.652), with a net reclassification improvement of 0.383 (95% CI, 0.317-0.449). CONCLUSION: Three subjective physical well-being factors were significantly associated with new fracture development in older adults. These results suggest that the three-question assessment may be a valuable screening tool for identifying new fractures. Geriatr Gerontol Int 2024; 24: 337-343.

Transarterial radioembolization vs transarterial chemoembolization with drug-eluting beads for treating hepatocellular carcinoma: a cost-effectiveness analysis in Japanese healthcare system.

PURPOSE: Transarterial radioembolization (TARE) is effective for unresectable hepatocellular carcinoma; however, it awaits approval in Japan. This study aimed to simulate the cost-effectiveness of TARE over chemoembolization when TARE is approved in Japan and identify the requirements for cost-effectiveness. MATERIALS AND METHODS: A Markov model was constructed to analyze the costs and effectiveness associated with TARE and transarterial chemoembolization with drug-eluting beads (DEB-TACE) for 2-month cycles over 5 years. In the primary analysis, the intention-to-treat survival data were used to calculate transition probabilities, whereas the ancillary analysis assessed the per-protocol survival data. DEB-TACE costs were calculated using the Japanese nationwide claims Diagnosis Procedure Combination database between April 2018 and March 2022, whereas TARE costs were estimated using database and international sources. The incremental cost-effectiveness ratio (ICER) was determined based on the payer's perspective and compared with the Japanese willingness-to-pay threshold of 5 million Japanese yen (JPY) (31,250 USD) per quality-adjusted life years (QALY). RESULTS: From the claims database, 6,986 patients with hepatocellular carcinoma who received DEB-TACE were identified. In the primary analysis, the ICER was 5,173,591 JPY (32,334 USD)/QALY, surpassing the Japanese willingness-to-pay threshold. However, the ancillary analysis showed a lower ICER of 4,156,533 JPY (25,978 USD)/QALY, falling below the threshold. The one-way deterministic sensitivity analysis identified progression-free survival associated with TARE and DEB-TACE, DEB-TACE costs, and radioactive microsphere reimbursement price as key ICER influencers. The primary analysis suggested that setting the reimbursement price of radioactive microspheres below 1.399 million JPY (8,744 USD), approximately 2.8% lower than the price in the United Kingdom, would place the ICER below the Japanese willingness-to-pay threshold. CONCLUSIONS: Under specific conditions, TARE can be a more cost-effective treatment than DEB-TACE. If the reimbursement price of radioactive microspheres is set approximately 2.8% lower than that in the United Kingdom, TARE could be cost-effective compared with DEB-TACE.

A Review of Studies Using Japanese Nationwide Administrative Claims Databases.

BACKGROUND: Administrative claims databases are increasingly being used worldwide for research purposes. We reviewed original published articles that used one of the four nationwide administrative claims databases in Japan: the National Database of Health Insurance Claims and Specific Health Checkups (NDB), NDB Open Data, the JMDC Claims Database, and the Diagnosis Procedure Combination (DPC) database. METHODS: Studies published from January 2010 to July 2022 using the JMDC and DPC databases, and from January 2013 to July 2022 using the NDB and NDB Open Data were identified using PubMed. The number of original articles was divided into 19 fields. The annual growth rate of the number of studies was calculated using the four databases. RESULTS: Overall, 1047 studies were included (95 for the NDB, 31 for the NDB Open Data, 222 for the JMDC database, and 699 for the DPC databases). Studies using one of these four databases increased from around 2010, and the average annual growth rate was approximately 41% from 2010 to 2021. DPC database studies had a higher proportion of articles on surgery (19.2%), urology (3.0%), neurosurgery (6.2%), anesthesiology (1.9%), and emergency medicine (14.0%), whereas the NDB and JMDC data had higher proportions of those regarding internal medicine. CONCLUSIONS: Since 2010, these four databases have increasingly attracted attention, and the number of studies using them has grown rapidly. Our review suggests that each has unique features, and researchers should understand the database characteristics to operate their studies.

Amelioration of the progression of an atopic dermatitis-like skin lesion by silk peptide and identification of functional peptides.

The efficacy of silk peptide in treatment of atopic dermatitis was examined in a picryl chloride-induced atopic dermatitis model in NC/Nga mice. Silk peptide ameliorated the development of atopic dermatitis by lowering the serum IgE concentration. Treatment of cultured spleen cells with silk peptide reduced IgE production by enhancing the production of IFN-γ and reducing the level of IL-4. The functional peptides in the silk peptide were identified as mixture of GAGA sequences containing peptides by mass spectrometry and in vitro assay. Our findings indicate that silk peptide exerts an effect on atopic dermatitis by modulating the Th1/Th2 balance.