Search

Objectives: There is limited evidence on methods to allocate budgets to healthcare providers under capitation schemes. The objective of this study was to construct and test models that predict outpatient visits and expenditure for each healthcare facility using subscriber data from the preceding year. Study design: We used the database of the Universal Coverage Scheme in Bangkok, Thailand that stores subscriber information and healthcare service utilization data. One-percent and ten-percent random samples of subscribers were selected as training and testing groups, respectively. Methods: Using data of the training group, we constructed a model using a random forest algorithm to predict outpatient visits and expenditure in 2017 from the 2016 data. The model was applied to the testing group and facility-level predicted number of visits and expenditure were compared with actual data. Results: The identically-structured training and testing groups consisted of 37,259 and 371,650 subscribers, respectively. Approximately 25% of subscribers utilized outpatient services. The R2 for models predicting facility-level utilization rate (visits/subscribers) and expenditure per subscriber in 2017 were 0.85 and 0.75, respectively. Conclusions: The model to predict outpatient visits and expenditure performed well. Such a prediction model may be useful for allocating budgets to healthcare facilities under capitation systems.

Objective: To examine the age in months at which infants visited outpatient clinics or emergency rooms for the first time for nonfatal injuries and to identify risk factors for the occurrence of these injuries. Study design: Retrospective cohort study. Methods: We used a health insurance claims database in Japan. Infants born between April 2012 and December 2014 were identified and followed until 12 months of age. We identified their first visit to outpatient clinics or emergency rooms because of nonfatal injuries (wounds/fractures, foreign bodies, and burns). Cox regression analysis was used to examine the association of nonfatal injuries with infants’ sex, birth order, and parental age. Results: We identified 46,431 eligible infants. Of these, 7606 (16.4%) were brought to an outpatient clinic or emergency room for nonfatal injuries within 12 months of birth. Of the 7,606, 21.7% were aged ≤4 months and 44.7% ​≤ ​7 months. First-born infants were more likely to have wounds/fractures and burns. Conclusion: One-fifth of first nonfatal infant injuries occurred within 4 months of age. Healthcare providers should provide early education about injury prevention, especially to caregivers of first-born infants.

Background and Objective: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer presents considerable treatment challenges owing to its aggressive nature. Global guidelines have endorsed a full year of HER2-targeted therapy for early-stage breast cancer. However, previous cost-effectiveness analyses of dual HER2-targeted therapies have been limited. This study aimed to examine the cost effectiveness of dual HER2-targeted therapy for early-stage breast cancer within the Japanese healthcare system context., Methods: In the Markov model-based study, the cost effectiveness of dual anti-HER2 therapy, combining pertuzumab and trastuzumab, was assessed in comparison to trastuzumab monotherapy. Patients in whom treatment was initiated at a median age of 51 years were included. The study utilized quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) as comparison units. Subgroup analyses were conducted to explore variations in cost effectiveness, focusing on node-positive and node-negative patients. Both one-way deterministic and broader probabilistic sensitivity analyses using Monte Carlo simulations with 10,000 samples were performed from the Japanese healthcare payers perspective., Results: Dual HER2-targeted therapy led to 0.17 QALYs increment at an additional cost of $US15,289, resulting in an ICER of $US92,232 per QALY. In the subgroup of node-positive patients, the benefit of the dual HER2-targeted therapy was more pronounced, with an increase of 0.64 QALYs and an ICER of $US24,561 per QALY. Sensitivity analyses revealed the model's susceptibility to changes in the transition probabilities from invasive disease-free survival to death, from invasive disease-free survival to first-line metastatic breast cancer, and to costs associated with pertuzumab. Probabilistic sensitivity analysis suggests that for node-positive patients, dual HER2-targeted therapy may be a cost-effective option., Conclusions: The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases., (© 2024. The Author(s).)

Objectives: Polypharmacy is an important healthcare issue, especially in elderly patients with dementia. As an incentive to reduce polypharmacy, a health insurance reimbursement scheme was introduced in 2016 for medication review and the reduction of medications for inpatients in Japan. However, the effects of these incentive schemes were not evaluated., Methods: We identified 1,465,881 inpatients aged ≥65 years with dementia. An interrupted time-series analysis was conducted by fitting a Prais-Winsten linear regression model. The outcome measure was the number of classes of medications prescribed during discharge., Results: No significant changes were observed in the average number of medication classes at discharge immediately after the introduction of the scheme (coefficient: -0.022, 95% confidence interval [CI]: -0.17 to 0.13). The slope change, representing the effect of the intervention over time, was also not significant (coefficient: -0.00053, 95% confidence interval: -0.0012 to 0.00018)., Conclusions: The incentive scheme was not associated with a reduction in the number of medication classes at discharge among older inpatients with dementia., Competing Interests: Conflict of interest: Department of Real-world Evidence has received research funding from DeSC Healthcare, Inc. Yusuke Sasabuchi is affiliated with this institution. The funding source had no involvement in the study design; data analysis, and interpretation of data; the writing of the report; or the decision to submit the article for publication., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Perinatal mood disorders affect both parents, impacting their children negatively. Little is known on the association between parental perinatal mood disorders and pediatric outcomes in Japan considering relevant covariates. Our objective was to investigate the association between paternal and maternal perinatal mood disorders and adverse physical and psychological child outcomes by the age of 36 months, adjusting for covariates such as the child's sex, age of parent at child's birth, perinatal mood disorders of the other parent, and perinatal antidepressant use., Methods: We identified parents in the JMDC Claims Database in Japan from 2012 to 2020. Perinatal mood disorders were defined using International Classification of Diseases, 10th codes for mood disorders during the perinatal period combined with psychiatric treatment codes. We evaluated the association between parental perinatal mood disorders and pediatric adverse outcomes by the age of 36 months using Cox proportional hazard models adjusted for the covariates., Results: Of the 116,423 father-mother-child triads, 2.8% of fathers and 2.3% of mothers had perinatal mood disorders. Paternal perinatal mood disorders were not significantly associated with adverse child outcomes. After adjusting for paternal perinatal mood disorders and antidepressant use, maternal perinatal mood disorders were associated with delayed motor development, language development disorders, autism spectrum disorders, and behavioral and emotional disorders (adjusted hazard ratio [95% confidence interval]: 1.65 [1.01-2.69], 2.26 [1.36-3.75], 4.16 [2.64-6.55], and 6.12 [1.35-27.81], respectively)., Conclusions: Paternal perinatal mood disorders were not associated with adverse child outcomes in this population. Maternal perinatal mood disorders were associated with multiple child outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: To clarify the risk of adverse ocular events following influenza vaccination., Methods: This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0-56 days after vaccination) compared to the control period., Results: A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis., Conclusions: This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events., Abbreviation: HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series.

Aim: The importance of comprehensive geriatric assessment (CGA) is increasing in aging societies worldwide. However, there are few comprehensive studies on CGA, resulting in a limited understanding of its implementation rate, temporal changes and factors associated with its implementation. We aimed to investigate the implementation status of CGA and its regional variance in Japan., Methods: Using the Diagnosis Procedure Combination database, we investigated CGA trends, and identified the patient, hospital and regional factors associated with its implementation. We identified patients aged ≥65 years who were admitted for the first time between 2016 and 2020 with a diagnosis of stroke, heart failure, pneumonia, bone fracture or colorectal cancer. We examined the CGA implementation rate according to patient and hospital characteristics. We also investigated temporal changes and tendencies to carry out CGA in different prefectures., Results: A total of 1 974 817 patients were analyzed, of whom 570 696 (28.9%) underwent CGA. The implementation trend increased steadily from 25.3% in fiscal year 2016 to 33.4% in fiscal year 2019. The implementation rate also increased with patient age (30.3% in patients aged ≥95 years). Regional variations in its implementation status were observed, with a higher tendency to be implemented in areas near major metropolitan regions. A trend toward carrying out CGA for colorectal cancer, but not for other diseases, has been observed in eastern Japan., Conclusion: Although CGA is increasingly carried out, considerable regional differences remain in its implementation status. Initiatives to reduce variations are necessary. Geriatr Gerontol Int 2024; 24: 904-911., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Objective: The study aimed to investigate treatment options for older women with pelvic organ prolapse (POP) and postoperative outcomes based on their long-term care (LTC) status., Methods: We used the medical and LTC insurance claims databases of Tochigi Prefecture in Japan, covering 2014 to 2019. We included women 65 years and older with POP and evaluated their care status and treatment, excluding women with an observation period <6 months. Among women with a postsurgical interval ≥6 months, we compared care level changes and deaths within 6 months and complications within 1 month postoperatively between those with and without LTC using Fisher exact test., Results: We identified 3406 eligible women. Of the 447 women with LTC and 2959 women without LTC, 16 (3.6%) and 415 (14.0%), respectively, underwent surgery. Among 393 women with a postsurgical interval ≥6 months, 19 (4.8%) required LTC at surgery. Two of the 19 women with LTC (10.5%) and eight of 374 women without LTC (2.1%) experienced worsening care-needs level. No deaths were recorded. Urinary tract infection (UTI) was significantly more frequent in women with LTC than in women without LTC (36.8% vs 8.6%). Other complications were rare in both groups., Conclusion: The proportion of patients who underwent surgery for POP was lower in women with LTC than in women without LTC. Postoperative UTI was common and 11% had a worsening care-needs level postoperatively, whereas other complications were infrequent. Further detailed studies would contribute to providing optimal treatment to enhance patients' quality of life., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Vertebral compression fractures (VCFs) in older adults cause considerable health and socioeconomic burdens due to worsening ability to perform activities of daily living. The long-term effects of VCFs on patient outcomes, particularly prolonged analgesic use and functional decline, remain unknown. The aims of this study were to examine long-term clinical outcomes and to determine the risk factors for persistent pain and functional disability after VCFs., Methods: This retrospective cohort study evaluated mortality, duration of analgesic use, and changes in care requirements in older adults with VCFs using claims data from a suburban prefecture in the Greater Tokyo Area. Patients were included if they were ≥65 years of age and had been diagnosed with a VCF between June 2014 and February 2019, as determined on the basis of International Classification of Diseases, Tenth Revision (ICD-10) codes; we also used claims data that could determine whether the patients underwent imaging examinations. Patients who discontinued outpatient visits within 1 month after the VCF diagnosis were excluded., Results: We included 18,392 patients with VCFs and a mean age of 80 years. Seventy-six percent of patients were women, and the median follow-up period was 670 days. At the index VCF diagnosis, 3,631 patients (19.7%) were care-dependent. Overall, 968 patients (5.3%) died within 1 year. Among the 8,375 patients who received analgesics, 22% required analgesics for >4 months. Factors associated with prolonged analgesic use for >1 year were female sex (odds ratio [OR], 1.39 [95% confidence interval (CI), 1.16 to 1.65]) and VCFs in the thoracolumbar region (OR, 1.95 [95% CI, 1.50 to 2.55]) or lumbar region (OR, 1.59 [95% CI, 1.23 to 2.04]) (the reference was the thoracic region). The care needs of 1,510 patients (8.2%) increased within 1 year. Patients with a preexisting care dependency had a 10 times higher risk of increased care need (30.2% [1,060 of 3,509]) than those who had been independent at the time of the index diagnosis (3.0% [450 of 14,761]) (p < 0.001)., Conclusions: Individuals with preexisting care dependency were more likely to experience functional decline following VCFs than those who were independent, which underscores the need for intensive and appropriate allocation of health-care resources to care-dependent patients., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This work was supported by grants from the Ministry of Health, Labour, and Welfare, Japan (23AA2003) and the Cross-ministerial Strategic Innovation Promotion Program (SIP) (“Integrated Health Care System”, JPJ012425). The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I73 )., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier's gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan., Methods: In this retrospective cohort study, we utilized the JMDC Claims Database. The study included patients aged 18 years or older diagnosed with type 2 diabetes mellitus, identified by a diagnostic code, who received new prescriptions for SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors between April 2014 and August 2020. Using one-to-one propensity score (PS) matching, we compared the incidence of perineal soft tissue infections, including FG, genital bacterial infection, and UTIs between groups treated with SGLT2 and DPP-4 inhibitors. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using the Cox proportional hazards model., Results: We identified 34,897 patients in the SGLT2 inhibitor group and 135,311 patients in the DPP-4 inhibitor group. After one-to-one PS matching, 31,665 pairs were generated. The mean age of the patients was 51 years, with approximately 70% being male. The use of SGLT2 inhibitors was associated with a decreased risk of UTI (HR 0.90, 95% CI 0.83-0.98) and an increased risk of genital bacterial infection (HR 1.23, 95% CI 1.03-1.46) compared to DPP-4 inhibitors. However, no significant association was observed with perineal soft tissue infection (HR 1.05, 95% CI 0.61-1.81)., Conclusions: SGLT2 inhibitors were associated with a reduced risk of UTI and an increased risk of genital bacterial infection. They showed no significant association with perineal soft tissue infection when compared to DPP-4 inhibitors. Future research should explore broader demographics, focusing on the elderly and achieving gender balance, to gain a comprehensive understanding of infection risks., (© 2024. The Author(s).)

Background: Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination., Methods: Data obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates., Results: Among the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model with reference of non-vaccine group revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63-0.91]), two-dose (0.89 [0.85-0.93]), three-dose (0.80 [0.76-0.85]), four-dose (0.93 [0.88-1.00]), and five-dose (0.72 [0.62-0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21-0.81]), two-dose (0.44 [0.35-0.56]), three-dose (0.38 [0.30-0.47]), four-dose (0.20 [0.14-0.28]), and five-dose (0.11 [0.014-0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model with reference of non-vaccine group revealed significant preventive effects of the vaccine for 4 months for the incidence of COVID-19 and ≥ 6 months for hospitalization., Conclusions: Vaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic., (© 2024. The Author(s).)

Background: The prevalence of diabetes has risen fast with a considerable weighted prevalence of undiagnosed diabetes or uncontrolled diabetes. Then it becomes more necessary to timely screen out and monitor high-risk populations who are likely to be ignored during the COVID-19 pandemic. To classify and find the common risks of undiagnosed diabetes and uncontrolled diabetes, it's beneficial to put specific risk control measures into effect for comprehensive primary care. Especially, there is a need for accurate yet accessible prediction models., Objective: Based on a cross-sectional study and secondary analysis on the health examination held in Changchun City (2016), we aimed to evaluate the factors associated with hyperglycemia, analyze the management status of T2DM, and determine the best cutoff value of incidence of diabetes in the first-degree relatives to suggest the necessity of early diagnosis of diabetes after first screening., Results: A total of 5658 volunteers were analyzed. Prevalence of T2DM and impaired fasting glucose were 8.4% (n=477) and 11.5% (n=648), respectively. There were 925 participants (16.3%) with a family history of T2DM in their first-degree relatives. Multivariable analysis demonstrated that family history was associated with hyperglycemia. Among the 477 patients with T2DM, 40.9% had not been previously diagnosed. The predictive equation was calculated with the following logistic regression parameters with 0.71 (95% CI: 0.67-0.76) of the area under the ROC curve, 64.0% of sensitivity and 29% of specificity ( P < 0.001): P = \frac{1}{1 + e^{-z}}, where z = -3.08 + [0.89 (Family history-group) + 0.69 (age-group)+ 0.25 (BMI-group)]. Positive family history was associated with the diagnosis of T2DM, but not glucose level in the diagnosed patients. The best cutoff value of incidence of diabetes in the first-degree relatives was 9.55% ( P < 0.001)., Conclusions: Family history of diabetes was independently associated with glucose dysfunction. Classification by the first-degree relatives with diabetes is prominent for targeting high-risk population. Meanwhile, positive family history of diabetes was associated with diabetes being diagnosed rather than the glycemic control in patients who had been diagnosed. It's necessary to emphasize the linkage between early diagnosis and positive family history for high proportions of undiagnosed T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Yamana, Yasunaga, Li and Wang.)

Background: Patients who receive invasive mechanical ventilation (IMV) in the intensive care unit (ICU) have exhibited lower in-hospital mortality rates than those who are treated outside. However, the patient-, hospital-, and regional factors influencing the ICU admission of patients with IMV have not been quantitatively examined., Methods: This retrospective cohort study used data from the nationwide Japanese inpatient administrative database and medical facility statistics. We included patients aged ≥ 15 years who underwent IMV between April 2018 and March 2019. The primary outcome was ICU admission on the day of IMV initiation. Multilevel logistic regression analyses incorporating patient-, hospital-, or regional-level variables were used to assess cluster effects by calculating the intraclass correlation coefficient (ICC), median odds ratio (MOR), and proportional change in variance (PCV)., Results: Among 83,346 eligible patients from 546 hospitals across 140 areas, 40.4% were treated in ICUs on their IMV start day. ICU admission rates varied widely between hospitals (median 0.7%, interquartile range 0-44.5%) and regions (median 28.7%, interquartile range 0.9-46.2%). Multilevel analyses revealed significant effects of hospital cluster (ICC 82.2% and MOR 41.4) and regional cluster (ICC 67.3% and MOR 12.0). Including patient-level variables did not change these ICCs and MORs, with a PCV of 2.3% and - 1.0%, respectively. Further adjustment for hospital- and regional-level variables decreased the ICC and MOR, with a PCV of 95.2% and 85.6%, respectively. Among the hospital- and regional-level variables, hospitals with ICU beds and regions with ICU beds had a statistically significant and strong association with ICU admission., Conclusions: Our results revealed that primarily hospital and regional factors, rather than patient-related ones, opposed ICU admissions for patients with IMV. This has important implications for healthcare policymakers planning interventions for optimal ICU resource allocation., (© 2024. The Author(s).)

Although large-scale administrative databases may be useful for studies of infectious diseases, conventional databases lack microbiological data. To illustrate the applicability of the National Hospital Organization Clinical Data Archives, a novel database of electronic medical records in Japan, we conducted a descriptive study of the microbiological findings in patients with community-acquired pneumonia using the database. We identified patients aged ≥18 years who were hospitalized for community-acquired bacterial pneumonia between April 2016 and March 2019. We evaluated the results of bacterial culture and antibacterial susceptibility of specimens obtained on the first day of hospitalization, in addition to patient characteristics, diagnosis codes, and intravenous antibiotics administered. The analysis identified 2200 eligible patients from 15 hospitals. Sulbactam-ampicillin was the most frequently used initial antibiotic (32 %), followed by ceftriaxone (22 %) and tazobactam-piperacillin (19 %). Overall, 56 %, 95 %, 56 %, and 73 % of patients with pathogen-specific diagnosis codes in the database for Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa, respectively, also tested positive for the corresponding pathogen in their sputum or blood cultures. Antibacterial susceptibilities were consistent with a previous report from Japan; 81 % of S. pneumoniae cases were resistant to azithromycin, and 48 % of H. influenzae cases were resistant to ampicillin. These microbiological characteristics warrant the future use of this database for detailed real-world research on infectious diseases., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The association between weight loss and subsequent functional decline is uncertain. The study aims to elucidate the association between weight loss over a year and subsequent functional decline requiring assistance in performing their activities of daily living in older individuals., Methods: The study used data from the publicly funded Long-Term Care Insurance service in Japan, which provides coverage for long-term care services for individuals unable to perform activities of daily living due to physical or cognitive impairment. The study enrolled people born in or before 1949, who underwent health checkups in both 2014 and 2015. The participants were followed from 2015 to the worsening of functional decline requiring long-term care services, death, or February 28, 2019, whichever occurred first. The risk of subsequent functional decline in each weight loss category was estimated using a Cox regression model adjusted for age, sex, baseline body mass index, smoking, and Charlson comorbidity index., Results: We identified 67,452 eligible individuals from the database. The median follow-up period was 1,284 days. The hazard ratios (95 % confidence interval) of functional decline for -1 %, -2 %, -3 %, -4 %, and ≤-5% weight change compared to 0 % weight change were 1.17 (1.03-1.32), 1.26 (1.11-1.43), 1.29 (1.12-1.49), 1.61 (1.39-1.87), and 1.79 (1.58-1.99), respectively., Conclusions and Implications: Older people with weight loss of 1 % or more were at risk of functional decline. Close weight monitoring may serve as an easy and inexpensive means of identifying older individuals at risk of functional decline., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: /Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs., Methods: We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups., Results: Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group., Conclusions: The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Delayed vaccination is a well-studied and critical public health issue. However, limited studies have explored whether familial factors influence vaccination delay. This study aimed to determine whether family structure and comorbidities affect the refusal or delayed receipt of measles-rubella and varicella vaccines., Methods: We gathered data on all children from birth to 13 months of age between 2006 and 2020 using vaccination records linked with the administrative healthcare claims data from a Japanese city. Multivariable logistic regression analyses were conducted to examine the association of refusal or delay in receiving the first-dose measles-rubella and varicella vaccines with the following factors: the child's sex; presence of parents, siblings, and grandparents; parental and grandparental comorbidities; chronic pediatric comorbidities in the child and siblings; and year of vaccination., Results: We identified a total of 14,241 eligible children. Refusal or delayed receipt of the first-dose measles-rubella vaccine was associated with an adjusted odds ratio of 2.46 (95% confidence interval, 1.86-3.24) for maternal absence and 1.61 (1.44-1.80) for paternal absence. Similarly, the refusal or delay in receiving the first-dose varicella vaccine was associated with an adjusted odds ratio of 2.04 (95% confidence interval, 1.01-4.16) for maternal absence and 1.37 (1.12-1.69) for paternal absence. The presence of siblings and maternal comorbidities were significantly associated with vaccination delays., Conclusion: The absence of a parent, the presence of siblings, and maternal comorbidities were associated with the refusal or delay in receiving measles-rubella and varicella vaccines. Strategies for vaccine recommendation should therefore consider family structure and maternal comorbidities., Competing Interests: Nobuaki Michihata, Yamana Hayato, and Taisuke Jo were members of the Department of Health Services Research, a cooperative program between the University of Tokyo and Tsumura. Sachiko Ono is a member of the Department of Eat-loss Medicine, a cooperative program between the University of Tokyo and ITO EN Ltd and received grants from the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science and Technology, Japan, outside the submitted work. Hideo Yasunaga received grants from the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science and Technology, Japan, outside the submitted work. The other authors report no potential conflicts of interest., (© 2024 Society for Clinical Epidemiology.)

Aim: This study aimed to elucidate the impact of periodontal therapy on glycaemic control in individuals with type 2 diabetes and various baseline blood glucose levels using a large-scale claims database from Japan., Materials and Methods: Using the JMDC Claims Database, we identified individuals with type 2 diabetes who underwent health check-ups in the fiscal years 2018 or 2019 and were followed up until the next year's health check-up. We conducted a weighted cohort analysis using stabilized inverse probability weights for treatment and censoring to estimate the effect of periodontal therapy on changes in haemoglobin A1c levels within a year. Analysis was done for different baseline haemoglobin A1c categories: 6.5%-6.9%, 7.0%-7.9% and ≥8.0%., Results: Of the 4279 insured persons included in the study, 957 received periodontal therapy. Overall, there was a tendency towards improved glycaemic control among those who received periodontal therapy. Participants with baseline haemoglobin A1c levels of 7.0%-7.9% who received periodontal therapy exhibited significantly better glycaemic control compared with those without dental visits (difference; -0.094 [95% confidence interval: -0.181 to -0.007])., Conclusions: Periodontal therapy may improve glycaemic control in individuals with diabetes, especially in those with haemoglobin A1c levels ≥7.0%., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective The effect of Rikkunshito, a Japanese herbal Kampo medicine, on chemotherapy-induced nausea and vomiting (CINV) has been evaluated in several small prospective studies, with mixed results. We retrospectively evaluated the antiemetic effects of Rikkunshito in patients undergoing cisplatin-based chemotherapy using a large-scale database in Japan. Methods The Diagnosis Procedure Combination inpatient database from July 2010 to March 2019 was used to compare adult patients with malignant tumors who had received Rikkunshito on or before the day of cisplatin administration (Rikkunshito group) and those who had not (control group). Antiemetics on days 2 and 3 and days 4 and beyond following cisplatin administration were used as surrogate outcomes for CINV. Patient backgrounds were adjusted using the stabilized inverse probability of treatment weighting, and outcomes were compared using univariable regression models. Results We identified 669 and 123,378 patients in the Rikkunshito and control groups, respectively. There were significantly fewer patients using intravenous 5-HT 3 -receptor antagonists in the Rikkunshito group (odds ratio, 0.38; 95% confidence interval, 0.16-0.87; p=0.023) on days 2 and 3 of cisplatin-based chemotherapy. Conclusion The reduced use of antiemetics on day 2 and beyond of cisplatin administration suggested a beneficial effect of Rikkunshito in palliating the symptoms of CINV.

Molecular recognition features (MoRFs) are particular functional segments of disordered proteins, which play crucial roles in regulating the phase transition of membrane-less organelles and frequently serve as central sites in cellular interaction networks. As the association between disordered proteins and severe diseases continues to be discovered, identifying MoRFs has gained growing significance. Due to the limited number of experimentally validated MoRFs, the performance of existing MoRF's prediction algorithms is not good enough and still needs to be improved. In this research, we present a model named MoRF&#95;ESM, which utilizes deep-learning protein representations to predict MoRFs in disordered proteins. This approach employs a pretrained ESM-2 protein language model to generate embedding representations of residues in the form of attention map matrices. These representations are combined with a self-learned TextCNN model for feature extraction and prediction. In addition, an averaging step was incorporated at the end of the MoRF&#95;ESM model to refine the output and generate final prediction results. In comparison to other impressive methods on benchmark datasets, the MoRF&#95;ESM approach demonstrates state-of-the-art performance, achieving [Formula: see text] higher AUC than other methods when tested on TEST1 and achieving [Formula: see text] higher AUC than other methods when tested on TEST2. These results imply that the combination of ESM-2 and TextCNN can effectively extract deep evolutionary features related to protein structure and function, along with capturing shallow pattern features located in protein sequences, and is well qualified for the prediction task of MoRFs. Given that ESM-2 is a highly versatile protein language model, the methodology proposed in this study can be readily applied to other tasks involving the classification of protein sequences.

Background: Despite a strong association between nutritional indices and disease prognosis, evidence regarding the evaluation of nutritional indices after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC) is insufficient. We evaluated the clinical significance of the prognostic nutritional index (PNI) in patients with resectable (R-) and borderline resectable (BR-) PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by pancreatic resection., Methods: We assessed 153 patients with R- and BR-PDAC who underwent NACRT followed by curative resection between 2009 and 2022. We evaluated the association between preoperative PNI after NACRT and short- and long-term outcomes., Results: The median preoperative PNI value after NACRT was 42.1, and the optimal cutoff value from the time-dependent receiver operating characteristic curve was 38.6. The low PNI group (PNI < 38.6, n = 44) exhibited significantly worse inflammatory parameters, surgical outcomes, and prognoses than the high PNI group (PNI ≥ 38.6, n = 109). Multivariate analysis identified preoperative PNI ≤ 38.6 (hazard ratio [HR]: 2.32, 95% confidence interval [CI]: 1.00-5.38, p = .049), blood loss ≥1642 mL (HR: 3.05, 95% CI: 1.65-5.64, p < .001), node positive pathology (HR: 2.10, 95% CI: 1.32-3.34, p = .002), and lack of postoperative adjuvant chemotherapy (HR: 3.55, 95% CI: 2.05-6.15, p < .001) as significant predictors of overall survival., Conclusions: For patients with R- and BR-PDAC receiving preoperative treatment, it is imperative to closely monitor their nutritional status when determining the optimal surgical procedure timing., (© 2024 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objectives: Although amoxicillin is the first-line prophylactic drug for impacted mandibular third molar extraction, third-generation cephalosporins are widely prescribed in Japan. The lack of real-world evidence may be one reason for this inappropriate use. We evaluated differences in the incidence of surgical site infection between amoxicillin and third-generation cephalosporins for impacted mandibular third molar extraction., Methods: Using the JMDC Claims Database, we identified dental visits with fully or horizontally impacted mandibular third molar extraction from April 2015 to March 2020. One-to-one propensity-score matching was conducted between amoxicillin and third-generation cephalosporin groups. The incidence of surgical site infection following extraction was compared in the matched pairs using McNemar's test., Results: We identified 109,266 dental visits, including 39,514 (36.2%) patients who received amoxicillin and 69,752 (63.8%) patients who received third-generation cephalosporins. In the 39,514 matched pairs, the incidence of surgical site infection was 3.5% (n = 1399) for amoxicillin group and 3.7% (n = 1467) for third-generation cephalosporin group (p = 0.003)., Conclusions: Amoxicillin was associated with a lower incidence of surgical site infection after impacted mandibular third molar extraction compared with third-generation cephalosporins. This result supports current guidelines and strengthens the importance of disseminating and implementing antimicrobial resistance control in dentistry., (© 2022 Wiley Periodicals LLC.)

Background : The efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by pancreatoduodenectomy (PD) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods : This retrospective analysis of prospectively collected data examined the effect of NACRT followed by PD in elderly patients with PDAC. A total of 112 patients with resectable (R-) and borderline resectable (BR-) PDAC, who were planned for PD and received NACRT between 2009 and 2022, were assessed. Changes induced by NACRT, surgical outcomes, nutritional status, renal and endocrine functions, and prognosis were compared between elderly (≥75 years, n = 43) and non-elderly (<75 years, n = 69) patients over two years following PD. Results : Completion and adverse event rates during NACRT, nutritional status, renal function, endocrine function over two years postoperatively, and prognosis did not significantly differ between the two groups. Low prognostic index after NACRT and the absence of postoperative adjuvant chemotherapy may be adverse prognostic indicators for elderly patients undergoing NACRT for R- and BR-PDAC. Conclusions : Despite a higher incidence of postoperative complications, NACRT followed by PD can be safely performed in elderly patients, resulting in a prognosis similar to that in non-elderly patients.

Background: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations., Methods: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated., Results: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models., Conclusion: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Aim: Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis., Methods: We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis., Results: The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups., Conclusions: Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship., (© 2023 Japan Society of Obstetrics and Gynecology.)

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 &lt; 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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Anti-glomerular basement membrane (anti-GBM) disease is treated with immunosuppressive medications and plasma exchange. However, whether plasma exchange, in addition to pulse glucocorticoid therapy, would benefit patients with anti-GBM disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage remains unclear., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients diagnosed with anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage from July 2010 to March 2020. We compared in-hospital mortality within 10 days of hospitalization between patients who received therapeutic plasma exchange in addition to pulse glucocorticoid therapy and those who received pulse glucocorticoid therapy alone. Overlap weighting based on propensity score was performed to adjust for potential confounders., Results: We identified 207 eligible patients; 168 patients received therapeutic plasma exchange plus pulse glucocorticoid therapy, while 39 patients received pulse glucocorticoid therapy alone. The mean dose of therapeutic plasma exchange was 52.2 ml/kg/day of albumin and/or fresh frozen plasma. Therapeutic plasma exchange in addition to pulse glucocorticoid therapy was associated with a lower in-hospital mortality risk in the unweighted (10.7% versus 28.2%; risk difference, 17.5%; 95% confidence interval, 2.6-32.4%; P = 0.02) and weighted analyses (11.5% versus 28.4%; risk difference, 17.0%; 95% confidence interval, 1.5-32.5%; P = 0.03) than pulse glucocorticoid therapy alone., Conclusions: This retrospective cohort study using a national database suggests that therapeutic plasma exchange may improve the in-hospital prognosis of anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage., (© 2023. The Author(s).)

Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kiyomi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/aim: Galectin-9 (Gal-9) induces tumor cell apoptosis in lymphoma and other malignant cell types. Duodenal adenocarcinoma is a rare malignancy, and there are insufficient data to determine a standard therapeutic approach. Here, we investigated the antitumor effect of Gal-9 in HuTu-80 duodenal adenocarcinoma cells., Materials and Methods: Cell proliferation was examined in HuTu-80 cells using a Cell Counting Kit-8 assay. Cell cycle analysis, apoptosis array, and microRNA expression analysis were performed to identify the effect of Gal-9 on HuTu-80 cells. The antitumor effect of Gal-9 was also examined using xenograft mouse models., Results: Gal-9 suppressed the proliferation of HuTu-80 via blockade of the G 0 to G 1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1 and phosphorylated Rb, suggesting a G 1 arrest. Additionally, Gal-9 induced apoptosis, and the expression of cleaved caspase-3 was increased in Gal-9-treated HuTu-80 cells according to the apoptosis array. MiRNA microarrays revealed that Gal-9 altered the expression of miRNAs in HuTu-80 cells., Conclusion: These data demonstrate the therapeutic potential of Gal-9 and provide molecular mechanistic insights into its antitumor effect in HuTu-80 cells., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims: We aimed to explore the association between short-term exposure to temperature variability (TV), and cardiovascular hospitalization stratified by the presence of comorbid diabetes., Methods: We collected data on nationwide hospitalization for cardiovascular diseases and daily weather conditions during 2011-2018 in Japan. TV was calculated as the standard deviation of daily minimum and maximum temperatures within 0-7 lag days. We applied a two-stage time-stratified case-crossover design to estimate the association between TV and cardiovascular hospitalization with and without comorbid diabetes, adjusting for temperature and relative humidity. Furthermore, specific cardiovascular disease causes, demographic characteristics, and seasons were used for stratification., Results: In 3,844,910 hospitalizations for cardiovascular disease, each 1 °C increase in TV was associated with a 0.44% (95% CI: 0.22%, 0.65%) increase in the risk of cardiovascular admission. We observed a 2.07% (95% CI: 1.16%, 2.99%) and 0.61% (95% CI: -0.02%, 1.23%) increase per 1 °C in risk of heart failure admission in individuals with and those without diabetes, respectively. The higher risk among individuals with diabetes was mostly consistent in the analyses stratified by age, sex, body mass index, smoking status, and season., Conclusion: Comorbid diabetes may increase susceptibility to TV in relation to acute cardiovascular disease hospitalization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A 40-year-old woman visited our hospital with a several-year history of right hypochondriac pain and vomiting after eating. She had been treated for functional dyspepsia, with no improvement in her symptoms. No gallstones were detected on imaging tests, but papillary insufficiency or dyskinesia of the gallbladder was suspected and biliary scintigraphy was performed. Biliary scintigraphy showed delayed excretion of radionuclides from the gallbladder and bile ducts into the duodenum. We initially suspected papillary dysfunction and performed endoscopic sphincterotomy, but there was no improvement in her symptoms. Biliary scintigraphy also showed delayed excretion of radionuclides, especially stagnation of radionuclides in the gallbladder. We suspected gallbladder dyskinesia and performed endoscopic gallbladder stenting, after which her symptoms disappeared and biliary scintigraphy showed improved excretion of radionuclides into the duodenum. Endoscopic gallbladder stenting may be useful for the diagnosis of gallbladder dyskinesia and for determining the efficacy of cholecystectomy., (© 2023. Japanese Society of Gastroenterology.)

Competing Interests: The authors declare no conflicts of interest in relation to the work presented in the manuscript.

Objectives: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in preventing pneumonia in older adults remains controversial. Some studies have suggested differences in their effectiveness according to age or sex., Methods: We conducted an observational study using a database of vaccine subsidization data and health insurance claims for a city in Japan. Participants were residents from 2014 to 2018 turning 65, 70, 75, 80, 85, 90, or 95 years during a given fiscal year, and PPV23 during the first year of observation were identified. We matched vaccinated and non-vaccinated individuals of the same age using propensity scores for vaccination. The incidence of hospitalization with pneumonia was compared using the Fine-Gray regression model. We summarized the results for each age using random-effects meta-analysis and conducted a subgroup analysis by sex., Results: A total of 102 136 participants were included, of whom 35% received PPV23. Propensity score matching selected 32 510 pairs of vaccinated and non-vaccinated individuals. Overall, PPV23 administration was associated with a decreased incidence of hospitalization with pneumonia (17.2 vs. 20.4 per 1000 person-years, sub-distribution hazard ratio: 0.84, 95% CI: 0.77 to 0.91). Vaccine effectiveness was the highest among those aged 70 years and decreased with increasing age. No statistically significant effect was observed in those aged 90 or 95 years. Vaccine effectiveness was observed in both males and females., Conclusions: PPV23 was associated with an overall decrease in hospitalization with pneumonia in older adults. However, vaccine effectiveness was significant in those aged 65 to 85 years but not in the older population., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: Large-scale administrative health care databases are increasingly being utilized for research. However, there has not been much literature that validated administrative data in Japan; a previous review identified six validation studies published between 2011 and 2017. We conducted a literature review of studies that assessed the validity of Japanese administrative health care data., Methods: We searched for studies published by March 2022 that compared individual-level administrative data with a reference standard from another data source, as well as studies that validated administrative data using other data within the same database. The eligible studies were also summarized based on characteristics which included data types, settings, reference standard used, numbers of patients, and conditions validated., Results: There were 36 eligible studies, including 29 that used external reference standard and seven that validated administrative data using other data within the same database. Chart review was the reference standard in 21 studies (range of the numbers of patients, 72-1674; 11 studies conducted in single institutions and nine studies in 2-5 institutions). Five studies used a disease registry as the reference standard. Diagnoses of cardiovascular diseases, cancer, and diabetes were frequently evaluated., Conclusions: Validation studies are being conducted at an increasing rate in Japan, although most of them are small scale. Further large-scale comprehensive validation studies are necessary to effectively utilize the databases for research., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Aim: Hypnotics might increase the risk of falls and fractures in older patients with neurocognitive disorders. Orexin receptor antagonists have recently been approved, but the relationship between the new drugs and fractures remains unclarified. This study aimed to evaluate the association between the type of hypnotic and in-hospital fractures in older patients with neurocognitive disorders using a nationwide inpatient database., Methods: Using the Japanese Diagnosis Procedure Combination database, we collected information on inpatients aged ≥65 years with neurocognitive disorders between April 2014 and March 2021. We examined trends in the prescription patterns of benzodiazepine drugs, Z-drugs, orexin receptor antagonists and melatonin receptor agonists. We also carried out a 1:4 matched case-control analysis of in-hospital fractures. The odds ratio of each hypnotic drug was estimated using a generalized estimating equation with adjustment for walking ability, comorbidities, osteoporosis, dialysis, selective serotonin reuptake inhibitor use and anti-dementia drug use., Results: The prescription of benzodiazepine hypnotics decreased and that of orexin receptor antagonists increased. This case-control analysis included 6832 patients with fractures and 23 463 controls. Ultrashort-acting benzodiazepines, short-acting benzodiazepines and Z-drugs were associated with an increased risk of bone fracture (odds ratio [95% confidence interval] 1.38 [1.08-1.77], 1.38 [1.27-1.50], 1.49 [1.37-1.61], respectively). Orexin receptor antagonists were not associated with an increased risk of bone fracture (1.07 [0.95-1.19])., Conclusions: In contrast to other types of hypnotics, orexin receptor antagonists were not associated with in-hospital fractures in older patients with neurocognitive disorders. Geriatr Gerontol Int 2023; 23: 500-505., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database., Methods: Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups' baseline patient characteristics and treatments were compared., Results: The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child-Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis., Conclusions: HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice., (© 2023. The Author(s).)

Background: Substantial evidence suggests that non-optimal temperatures can increase the risk of cardiovascular disease (CVD) mortality and morbidity; however, limited studies have reported inconsistent results for hospital admissions depending on study locations, which also lack national-level investigations on cause-specific CVDs., Methods: We performed a two-stage meta-regression analysis to examine the short-term associations between temperature and acute CVD hospital admissions by specific categories [i.e., ischemic heart disease (IHD), heart failure (HF), and stroke] in 47 prefectures of Japan from 2011 to 2018. First, we estimated the prefecture-specific associations using a time-stratified case-crossover design with a distributed lag nonlinear model. We then used a multivariate meta-regression model to obtain national average associations., Results: During the study period, a total of 4,611,984 CVD admissions were reported. We found cold temperatures significantly increased the risk of total CVD admissions and cause-specific categories. Compared with the minimum hospitalization temperature (MHT) at the 98 th percentile of temperature (29.9 °C), the cumulative relative risks (RRs) for cold (5 th percentile, 1.7 °C) and heat (99 th percentile, 30.5 °C) on total CVD were 1.226 [95% confidence interval (CI): 1.195, 1.258] and 1.000 (95% CI: 0.998, 1.002), respectively. The RR for cold on HF [RR = 1.571 (95% CI: 1.487, 1.660)] was higher than those of IHD [RR = 1.119 (95% CI: 1.040, 1.204)] and stroke [RR = 1.107 (95% CI: 1.062, 1.155)], comparing to their cause-specific MHTs. We also observed that extreme heat increased the risk of HF with RR of 1.030 (95% CI: 1.007, 1.054). Subgroup analysis showed that the age group ≥85 years was more vulnerable to these non-optimal temperature risks., Conclusions: This study indicated that cold and heat exposure could increase the risk of hospital admissions for CVD, varying depending on the cause-specific categories, which may provide new evidence to reduce the burden of CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness., Methods: We used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases)., Results: We identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43-0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53-1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65-69 and 80-years, 5 months in 70-79 years., Conclusions: Our study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database., Methods: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined., Results: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals., Conclusions: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Hepatocyte transplantation has been reported to be useful for metabolic diseases and acute liver failure. However, the shortage of donors limits its widespread use. The use of livers from donors after circulatory death, which are currently unavailable for liver transplantation, may alleviate donor shortage. In this study, we investigated the effects of mechanical perfusion on cardiac arrest hepatocytes in a rat model using cardiac arrest donor livers, and we evaluated the function of cardiac arrest hepatocytes., Methods: F344 rat hepatocytes isolated from livers removed during cardiac pulsation were compared with those isolated from livers removed after 30 minutes of warm ischemia after cardiac arrest. We then compared hepatocytes isolated from livers removed after 30 minutes of warm ischemia with those isolated after 30 minutes of mechanical perfusion before isolation. The yield per liver weight, ammonia removal capacity, and adenosine diphosphate/adenosine triphosphate ratio were evaluated., Results: Thirty minutes of warm inhibition reduced hepatocyte yield but did not alter ammonia removal capacity and energy status. Mechanical perfusion increased hepatocyte yield and improved the adenosine diphosphate/adenosine triphosphate ratio after 30 minutes of warm inhibition., Conclusion: Thirty minutes of warm ischemic time may decrease isolated hepatocyte yield without degrading their function. If increased yields are obtained, livers from donors dying of cardiac arrest could be used for hepatocyte transplantation. The results also suggest that mechanical perfusion may positively affect the energy status of hepatocytes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: After pediatric liver transplantation, liver fibrosis may occur during long-term follow-up. Noninvasive markers for assessing this liver fibrosis are desired. Mac-2 binding protein glycosylated isomer (M2BPGi) has recently been reported as a useful biomarker for liver fibrosis. However, its usefulness in the pediatric population is yet to be established. This study investigated the clinical significance of M2BPGi levels as a surrogate marker of graft fibrosis after pediatric liver transplantation., Methods: We retrospectively identified 96 patients who underwent pediatric liver transplantation at our institution between 1991 and 2015. The association between M2BPGi levels and other fibrosis markers was analyzed in 60 patients in whom fibrosis markers were measured. The association between fibrosis marker levels and graft fibrosis was assessed in 42 patients who underwent biopsies between 2016 and 2022., Results: The M2BPGi levels were statistically correlated with the hyaluronic acid and type-IV collagen levels. None of the fibrosis markers were significantly associated with liver graft fibrosis, although the levels of these markers were slightly higher in patients with severe liver fibrosis than in those with mild fibrosis., Conclusions: The M2BPGi levels had a limited ability to assess liver graft fibrosis after pediatric liver transplantation, similar to other fibrosis markers. Further studies with larger cohorts are required to validate these findings externally., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Influenza-related bacterial pneumonia is a leading complication of influenza infection. However, the differences in the incidence rates and risk factors associated with concomitant viral/bacterial pneumonia (CP) and secondary bacterial pneumonia following influenza (SP) remain unclear. This study aimed to clarify the incidence rates of CP and SP following seasonal influenza and identify factors associated with their development., Methods: This retrospective cohort study was conducted using the JMDC Claims Database, a health insurance claims database in Japan. All patients aged <75 years who developed influenza during 2 consecutive epidemic seasons, 2017/2018 and 2018/2019, were analyzed. CP was defined as bacterial pneumonia diagnosed between 3 days before and 6 days after the date of influenza diagnosis, and SP was defined as pneumonia diagnosed 7-30 days after the date of diagnosis. Multivariable logistic regression analyses were performed to identify factors associated with the development of CP and SP., Results: Among the 10 473 014 individuals registered in the database, 1 341 355 patients with influenza were analyzed. The average age at diagnosis (SD) was 26.6 (18.6) years. There were 2901 (0.22%) and 1262 (0.09%) patients who developed CP and SP, respectively. Age 65-74 years, asthma, chronic bronchitis/emphysema, cardiovascular disease, renal disease, malignant tumor, and immunosuppression were significant risk factors for both CP and SP, whereas cerebrovascular disease, neurological disease, liver disease, and diabetes were risk factors specific to CP development., Conclusions: The results determined the incidence rates of CP and SP and identified their risk factors, such as older age and comorbidities., Competing Interests: Potential conflicts of interest. M.S., I.I., T.I., I.O., N.H., K.N., T.N., H.Yas., T.H.: no conflict. T.J. and H.Yam. have academic affiliations with the Department of Health Services Research, which is a cooperative program between the University of Tokyo and Tsumura and Company, outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Prcis: Diagnostic or antiglaucoma drug records in the Japanese claims data showed a high validity in identifying glaucoma patients. Specific subtypes were identified with high specificity and negative predictive values but low sensitivity and positive predictive values., Purpose: Despite the widespread use of administrative claims data in epidemiological research on glaucoma, only a few studies have investigated the validity of the methods in defining patients with glaucoma using diagnoses and drug records. We aimed to evaluate the validity of these algorithms in identifying patients with glaucoma using the Japanese claims data., Methods: Two ophthalmologists independently reviewed the medical charts and administrative claims data of 500 randomly selected patients who visited the Department of Ophthalmology of an academic hospital in 2019. We constructed 12 algorithms to identify patients with any type and specific subtypes of glaucoma using the claims records of diagnosis, antiglaucoma drugs, and visual field tests. We regarded the diagnosis of glaucoma based on the medical charts as the reference standard and calculated the sensitivity, specificity, and positive and negative predictive values of each algorithm based on the claims data., Results: The algorithms of ≥1 diagnostic record per year and ≥1 antiglaucoma drug record per year exhibited sensitivities of 94.6% and 89.2%, respectively, and specificities of 88.9% and 98.3%, respectively. An increase in the frequency of records resulted in a decreased sensitivity and slightly increased specificity. The addition of visual field tests did not improve the validity. The algorithms for specific subtypes of glaucoma exhibited high specificity and relatively low sensitivity., Conclusion: Diagnostic or antiglaucoma drug records in the Japanese claims data were useful for identifying patients with glaucoma. Researchers should select identification algorithms based on the study design., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination., Design: Matched cohort and self-controlled case series (SCCS) studies., Participants: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events., Methods: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods., Main Outcome Measures: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis., Results: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively., Conclusions: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Direct comparative effectiveness of booster doses of BNT162b2 and mRNA-1273 after BNT162b2 primary vaccination is unknown., Methods: We investigated comparative effectiveness of BNT162b2 and mRNA-1273 booster dose using data from registry systems for vaccination and coronavirus disease 2019 (COVID-19) infection in a local city in Japan. We followed participants aged ≥16 years who completed the BNT162b2 primary vaccination between 22 November 2021, and 15 April 2022. We collected information on age, sex, vaccination status, vaccine type, and infection status. Age was categorized as 16-44, 45-64, 65-84, and ≥85 years. Vaccine effectiveness for mRNA-1273 and no booster vaccination against BNT162b2 was estimated using age-stratified Cox regression adjusted for age, sex, and days since the second vaccination. The estimated hazard ratios for mRNA-1273 and no booster vaccinations were integrated separately using random effects meta-analyses., Results: During the study period, we identified 62 586 (40.4%), 51 490 (33.2%), and 40 849 (26.4%) participants who received BNT162b2, mRNA-1273, and no booster dose, respectively. The median age was 69, 71, and 47 years for BNT162b2, mRNA-1273, and no booster dose, respectively. The integrated hazard ratio with reference to BNT162b2 was 1.72 for no booster vaccination and 0.62 for mRNA-1273. The comparative effectiveness of mRNA-1273 was similar across age categories., Conclusions: Both homologous and heterologous vaccinations are effective against Omicron variants. In the head-to-head comparison, the effect was stronger in people who received heterologous vaccination than in those who received homologous vaccination. These findings may help improve logistics and decision making in future vaccination programs., Competing Interests: Potential conflicts of interest. S. O. is a member of the Department of Eat-loss Medicine, a cooperative program between the University of Tokyo and ITO EN Ltd and received grants from the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science and Technology, Japan, outside the submitted work. N. M., H. Y., and T. J. are member of the Department of Health Services Research, a cooperative program between the University of Tokyo and Tsumura. T. J. and H. Y. received grants from the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science and Technology, Japan, outside the submitted work. Y. O. reports grants or contracts from Japan Medical Education Foundation (https://www.jmef.or.jp/). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Several studies have demonstrated the efficacy of prednisolone and cyclosporine as initial combination treatments for the prevention of coronary artery abnormalities (CAA) in patients with Kawasaki disease. However, whether prednisolone or cyclosporine results in superior clinical outcomes is unknown. Thus, this study aimed to compare the outcomes of these two treatments., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients with Kawasaki disease who had received prednisolone or cyclosporine in addition to initial intravenous immunoglobulin treatment between April 2014 and March 2021. The primary outcome was the proportion of CAA; secondary outcomes included intravenous immunoglobulin resistance, medical costs, and length of hospital stay. Propensity score matching was conducted to compare outcomes between the two groups., Results: We identified 6288 patients with Kawasaki disease who had received prednisolone (n = 6147) or cyclosporine (n = 141) as an initial treatment in combination with intravenous immunoglobulin. Four-to-one propensity score-matched analysis demonstrated no significant difference in the proportion of CAA (0.7% vs. 2.8%; p = 0.098), intravenous immunoglobulin resistance, or medical costs between the treatment groups. The length of hospital stay was significantly longer in the prednisolone group (14 vs. 11 days, p < 0.001)., Conclusions: Prednisolone and cyclosporine used in the initial combination treatment for Kawasaki disease showed similar clinical outcomes regarding the risk of CAA, intravenous immunoglobulin resistance, and medical costs, whereas the length of hospital stay was longer in the prednisolone group than in the cyclosporine group., (© 2023 Japan Pediatric Society.)

Background: Although there have been studies that compared outcomes of patients with acute myocardial infarction (AMI) across countries, little focus has been placed on institutional variance of outcomes. The aim of the present study was to compare institutional variance in mortality following percutaneous coronary intervention (PCI) for AMI and factors explaining this variance across different health systems., Methods: Data on inpatients who underwent PCI for AMI in 2016 were obtained from the National Health Insurance Data Sharing Service in Korea, the Diagnosis Procedure Combination (DPC) Study Group Database in Japan, and the National Health Insurance Research Database (NHIRD) in Taiwan. Multilevel analyses with inpatient mortality as the outcome and the hierarchical structure of patients nested within hospitals were conducted, adjusting for common patient-level and hospital-level variables. We compared the intraclass correlation coefficient (ICC) and the proportion of variance explained by hospital-level characteristics across the three health systems., Results: There were 17 351 patients from 160 Korean hospitals, 29 804 patients from 660 Japanese hospitals, and 10 863 patients from 104 Taiwanese hospitals included in the analysis. Inpatient mortality rates were 6.3%, 7.3%, and 6.0% in Korea, Japan, and Taiwan, respectively. After adjusting for patient and hospital characteristics, Taiwan had the lowest variation in mortality (ICC, 1.8%), followed by Korea (2.2%) and then Japan (4.5%). The measured hospital characteristics explained 38%, 19%, and 9% of the institutional variance in Korea, Taiwan, and Japan, respectively., Conclusion: Korea, Japan, and Taiwan had similarly uniform outcomes across hospitals for patients undergoing PCI for AMI. However, Japan had a relatively large institutional variance in mortality and a lower proportion of variation explainable by hospital characteristics, compared with Korea and Taiwan., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most devastating of all cancers with an extremely poor prognosis. It has few effective and reliable therapeutic strategies. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). Telmisartan inhibits cancer cell proliferation, but the underlying mechanisms in PDAC, remain unknown., Material and Methods: In the present study, we evaluated the effects of telmisartan on human PDAC cell proliferation in vitro. We assessed the effects of telmisartan on human PDAC cells using the cell lines PK-1 and PANC-1., Results: Telmisartan inhibited the proliferation of these cells via blockade of the G0 to G1 cell cycle transition. This was accompanied by a strong decrease in cyclin D1. Telmisartan was also shown by receptor tyrosine kinase and angiogenesis arrays to reduce the phosphorylation of epidermal growth factor receptor (EGFR), and miRNA expression was markedly altered by telmisartan in PK-1 cells., Conclusion: In conclusion, telmisartan inhibits human PDAC cell proliferation by inducing cell cycle arrest. Furthermore, telmisartan significantly altered miRNA expression in vitro. Taken together, our study demonstrated the therapeutic potential of telmisartan and provides molecular mechanistic insights into its anti-tumor effect on PDAC cells., Competing Interests: None

Objective: To clarify the fetal safety of herbal Kampo medicines, including Hange-koboku-to, Koso-san, Nyoshin-san, Yokukansan, Yokukansan-kachinpi-hange, Saiko-keishikankyo-to, Keishi-karyukotu-borei-to, and Kanbaku-taisou-to, when administered to pregnant women with depression using a large healthcare administrative database., Methods: We extracted data from the JMDC Claims Database (2005-2018) for this retrospective cohort study of pregnant women aged 19 years or older admitted to obstetric clinics or hospitals for delivery. Participants were classified into four groups: those without depression, those diagnosed with depression without medication, those given Kampo medicines for depression, and those given western medicines for depression. Neonatal outcomes (congenital anomalies, low birth weight, and preterm birth) were considered as the safety outcome measures., Results: We identified 179 707 eligible mothers. The adverse outcomes did not differ significantly between participants receiving Kampo medicine and those not diagnosed with depression during pregnancy. The proportion of low-birth-weight neonates did not differ significantly between the Kampo medicine and non-depression groups (adjusted odds ratio [aOR] 1.28; 95% confidence interval [CI] 0.86-1.91), but was significantly higher in the unmedicated depression group (aOR 1.31; 95% CI 1.07-1.61) and western medicine group (aOR 1.47; 95% CI 1.18-1.83)., Conclusion: Kampo medicines are safe for treating depression during pregnancy without increasing the incidence of congenital anomalies, low birth weight, or preterm birth., (© 2022 International Federation of Gynecology and Obstetrics.)