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Objective: To estimate the incidence of muscle toxicity in patients receiving statin therapy by examining study populations, drug exposure status and outcome definitions. Design: A retrospective cohort study. Setting: 16 medical facilities in Japan providing information on laboratory tests performed in and claims received by their facilities between 1 April 2004 and 31 December 2010. Participants: A database representing a cohort of 35 903 adult statin (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin) users was studied. Use of interacting drugs (fibrates, triazoles, macrolides, amiodarone and ciclosporin) by these patients was determined. Main outcome measure: Statin-associated muscle toxicity (the 'event') was identified based on a diagnosis of muscle-related disorders (myopathy or rhabdomyolysis) and/or abnormal elevation of creatine kinase (CK) concentrations. Events were excluded if the patients had CK elevation-related conditions other than muscle toxicity. Incidence rates for muscle toxicity were determined per 1000 person-years, with 95% CI determined by Poisson regression. Results: A total of 18 036 patients accounted for 42 193 person-years of statin therapy, and 43 events were identified. The incidence of muscle toxicity in the patients treated with statins was 1.02 (95% CI 0.76 to 1.37)/1000 person-years. The estimates varied when outcome definitions were modified from 0.09/1000 person-years, which met both diagnosis and CK 10 x greater than the upper limit of normal range (ULN) criteria, to 2.06/1000 person-years, which met diagnosis or CK 5 x ULN criterion. The incidence of muscle toxicity was also influenced by the statin therapies selected, but no significant differences were observed. Among 2430 patients (13.5%) received interacting drugs with statins, only three muscle toxicity cases were observed (incidence: 1.69/1000 person-years). Conclusions: This database study suggested that statin use is generally well tolerated and safe; however, the risk of muscle toxicity related to the use of interacting drugs requires further exploration. [ABSTRACT FROM AUTHOR]

To compare the effectiveness of different long-acting injectable antipsychotics (LAIs) (aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol) in patients with schizophrenia in Japan. We conducted a retrospective cohort study using two administrative claims databases. The study population consisted of outpatients with schizophrenia who initiated LAIs between May 1, 2015, and November 30, 2019. We directly compared the risk of psychiatric hospitalization and LAI discontinuation among the LAIs based on hazard ratios (HRs) using Cox proportional hazards regression models. The numbers of eligible patients who initiated aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol were 303, 124, 73, and 123, respectively. Regarding psychiatric hospitalization, aripiprazole and paliperidone were associated with significantly lower risk compared to fluphenazine/haloperidol (HR of aripiprazole: 0.47, 95 % CI: 0.28–0.78, HR of paliperidone: 0.50, 95 % CI: 0.28–0.89); HR of risperidone showed the same trend as the aripiprazole and paliperidone. Regarding LAI discontinuation, aripiprazole and paliperidone were associated with significantly lower risk of LAI discontinuation compared to fluphenazine/haloperidol (HR of aripiprazole: 0.53, 95 % CI: 95 % CI: 0.35–0.80, HR of paliperidone: 0.57, 95 % CI: 0.35–0.92). Aripiprazole was also associated with a significantly lower risk compared to risperidone (HR: 0.56, 95 % CI: 0.32–0.98). Our study suggests that aripiprazole and paliperidone are superior to fluphenazine/haloperidol in the risk of psychiatric hospitalization and LAI discontinuation. Aripiprazole is superior to risperidone in the risk of LAI discontinuation. [ABSTRACT FROM AUTHOR]

We compared the cost-effectiveness of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX)—standard first-line treatments for metastatic pancreatic cancer in Japan. This retrospective cohort study included patients with metastatic pancreatic cancer treated at the National Cancer Center Hospital East in Japan between December 2013 and February 2017. A partitioned survival model, featuring five mutually exclusive health states, was developed. A cost-effectiveness analysis was performed to obtain total costs and quality-adjusted life-years (QALYs). A 2% annual discount rate was applied to costs and outcomes. Parameter uncertainty effect was assessed using a one-way sensitivity analysis. mFFX treatment involved intravenous infusions of oxaliplatin, levofolinate, and irinotecan, whereas GnP treatment involved weekly intravenous administration of nab-paclitaxel and gemcitabine. Dosages were adjusted based on observed adverse events. The total costs of the mFFX and GnP arms were JPY 3,193,597 (USD 31,006) and JPY 3,913,171 (USD 37,992), respectively. Incremental total costs of JPY 719,574 (USD 6,986) were associated with GnP compared to mFFX. Total QALYs were 0.427 and 0.435 for mFFX and GnP, respectively. Therefore, GnP has slightly higher QALYs than mFFX in Japanese real-world clinical practice, suggesting it has a potentially better safety profile, although the impact on healthcare costs persists. [ABSTRACT FROM AUTHOR]

Management of tumor lysis syndrome (TLS) associated with cancer chemotherapy for malignant tumors is important because of its potentially fatal course. The use of rasburicase, a recombinant urate oxidase, is recommended for TLS; however, because rasburicase is an enzymatic drug, one should be cautious of anaphylaxis during administration. Using claims data in Japan, we investigated the rate of rasburicase re-administration and the occurrence of anaphylaxis during re-administration in patients with hematopoietic malignancies in a multicenter setting. Re-administration of rasburicase was defined as administration after an interval of 21 days from the first dose. Of 373 patients, 18 were re-administered rasburicase (re-administration rate: 4.8%). No patient developed anaphylaxis. The median number of days from the first to the last dose of rasburicase was 256.5 days (interquartile range: 138.8–455.8 days). The median daily dose was 7.5 mg (4.5–11.3 mg), and the median total dose was 33.8 mg (19.1–64.1 mg). This claims database analysis revealed that the re-administration rate of rasburicase was low in Japanese patients with hematopoietic malignancies, suggesting that rasburicase was being used appropriately, and that associated anaphylaxis was not observed. [ABSTRACT FROM AUTHOR]

Background: This study aimed to clarify the treatment patterns of pancreatic cancer patients receiving systemic chemotherapy in Japan and to estimate the direct medical costs in actual practice. Research Design and Methods: This retrospective cohort study used electronic health record data between April 2008 and December 2018 in Japan. Participants had a confirmed pancreatic cancer diagnosis and received at least one systemic chemotherapy, including FOLFIRINOX, gemcitabine plus nab‐paclitaxel, gemcitabine, and S‐1. The outcomes were treatment patterns and monthly medical costs and the distribution of monthly medical costs across healthcare resource categories. Results: Of the 4514 selected patients, 40.7%, 7.1%, 24.4%, and 21.3% used gemcitabine plus nab‐paclitaxel, FOLFIRINOX, gemcitabine, and S‐1 as first‐line chemotherapy, respectively. The median monthly medical costs were the highest in the first month, with gemcitabine plus nab‐paclitaxel ranking first (6813 USD), followed by FOLFIRINOX, gemcitabine, and S‐1. The health resource categories with the highest shares of monthly medical costs during the first‐line treatment period with gemcitabine plus nab‐paclitaxel and FOLFIRINOX were hospitalization costs (FOLFIRINOX: 41%–37%; gemcitabine plus nab‐paclitaxel: 40%–34%) and medicine costs (FOLFIRINOX: 51%–42%; gemcitabine plus nab‐paclitaxel: 49%–38%). Conclusions: This study sheds light on the current treatment patterns and direct medical costs of systemic chemotherapy for pancreatic cancer in Japan. [ABSTRACT FROM AUTHOR]

Background: The relationships between developmental strategies for additional indications and drug price revisions have not been thoroughly studied. Here, we investigated the price revisions for anticancer drugs approved in Japan.Methods: The study was based on published information on anticancer drugs approved between January 2009 and March 2020 in Japan. We investigated the relationships between the pharmacological and regulatory characteristics of anticancer drugs and occurrence/non-occurrence of the Japanese National Health Insurance (NHI) price revisions.Results: Eighty-one new anticancer drugs were given NHI price listings during the survey. On April 1, 2020, the prices of 23 anticancer drugs had been revised from the initial pricing, the prices were reduced for 21 drugs (91.3%). Several parameters showed the relationships between drug characteristics and NHI price revisions. The achievement of additional indications and compound type were identified as explanatory factors for these relationships. Additional indication profiles were defined to assess the relationships between the methods for additional indication achievement and price revisions. When the type of additional indication was "Expansion", the percentage of drugs received NHI price revisions was the highest (P<0.001).Conclusions: NHI price revision was significantly related to the achievement of additional indications and compound type. The strategy for additional indications was found to affect the occurrence/non-occurrence of NHI price revisions. [ABSTRACT FROM AUTHOR]

Background: The prevalence and pattern of perinatal antidepressant prescriptions in Japan are unknown.Methods: The prevalence of antidepressant prescriptions between 180 days before pregnancy onset and 180 days postpartum was evaluated using a large administrative database. The dates of pregnancy onset and delivery were estimated using developed algorithms.Results: Of 33,941 women, at least one antidepressant was prescribed to 451 (133/10,000 deliveries) between 180 days before pregnancy and 180 days postpartum and to 241 (71/10,000 deliveries) during pregnancy. The prevalence of antidepressant prescriptions decreased during the first and second trimesters and increased in the postpartum period. Of 339 women with antidepressant prescriptions before pregnancy, 151 (44.5%) discontinued it during pregnancy. Selective serotonin-reuptake inhibitors were the most frequently prescribed class of antidepressants in the time period studied (356 women, 105/10,000 deliveries), followed by tricyclic/non-tricyclic antidepressants (101 women, 30/10,000 deliveries). Of the 57 women who had at least one record of paroxetine prescription in the first trimester, 13 (22.8%) were prescribed >25 mg/day. Fifty-seven women (17/10,000 deliveries) were concurrently prescribed two or more classes of antidepressants between 180 days before pregnancy and 180 days postpartum.Limitations: It may not always have been the case that the prescribed antidepressants were used. Women whose pregnancy ended in an abortion or stillbirth were not included.Conclusions: Various antidepressants were prescribed to prenatal and postpartum women in Japan. Approximately half of pregnant women discontinued treatment with antidepressants after becoming pregnant. Women of childbearing age should select an appropriate antidepressant considering the risk/benefit profile. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of syphilis is increasing in Japan. A new treatment, penicillin intramuscular injection, was launched in January 2022. This study aimed to determine syphilis treatments in Japan and investigate the impact of the new intramuscular penicillin formulation., Materials and Methods: Data from the Japanese Administrative Claims Database from January 2016 to September 2023 were used to identify patients diagnosed with syphilis, and the types and annual trends of antimicrobials prescribed were investigated. Furthermore, the characteristics of patients prescribed an intramuscular injection of benzathine penicillin G were compared with those of patients who were not., Results: Overall, 7867 patients were included in the analysis ( 81%, male; 5.4% positive for human immunodeficiency virus). Seventy-five percent of patients were diagnosed with syphilis in facilities with 0-19 beds. Annual trends showed oral amoxicillin as the most prescribed drug to 80% of patients throughout the study period. In 2023, 10.6% of patients received a prescription for an intramuscular penicillin formulation. Compared with those who did not receive this treatment, those who received it tended to have fewer clinic visits over 1 month (p = 0.0256)., Conclusions: Oral amoxicillin is the primary treatment for syphilis in Japan; however, the number of patients receiving intramuscular injection of benzathine penicillin G is increasing. Prescribed mainly by clinics, an intramuscular injection of benzathine penicillin G may contribute to a decreased number of office visits., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 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: Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public., Methods: A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients' health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values., Results: Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: -0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios., Conclusions: The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Sasahara, Takumoto, Watanabe, Takeda, Umemoto, Sunakawa, Suzuki, Yoshioka, Kobayashi, Ueno, Nakamura, Akazawa and Narimatsu.)

Background: We compared the effectiveness of long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in treating schizophrenia, focusing on whether the benefits of LAIs over OAs are evident even in the prevalent new user design and on effect heterogeneity., Methods: We conducted a prevalent new user cohort study using 2 administrative claims databases in Japan. We included patients with schizophrenia initiated on LAIs and propensity score-matched patients on OA. We compared the risks of psychiatric hospitalization and treatment discontinuation based on hazard ratios (HRs) using the Cox proportional hazards model. Effect heterogeneity was evaluated using subgroup analyses., Results: In total, 2520 patients using LAI and OA were identified as matched cohorts. Long-acting injectable antipsychotics were associated with a higher psychiatric hospitalization risk than OAs (HR, 1.41; 95% confidence interval [CI], 1.06-1.88) in the entire population; however, LAIs were associated with lower risk in the group with a low proportion of days covered and psychiatric hospitalization history (HR, 0.51; 95% CI, 0.30-0.89). Long-acting injectable antipsychotics were associated with a lower risk of treatment discontinuation than OAs (HR, 0.76; 95% CI, 0.66-0.87) in the entire population; in the subgroup analyses, a consistent trend was observed in all strata (LAIs had a lower risk)., Conclusions: Using a prevalent new user design, this study confirmed that LAIs have an advantage regarding treatment continuity. Long-acting injectable antipsychotics had higher psychiatric hospitalization risk than OAs in the entire population; however, this study suggested the presence of effect heterogeneity due to psychiatric hospitalization history., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The days of therapy (DOT) metric, used to estimate antimicrobial consumption, has some limitations. Days of antibiotic spectrum coverage (DASC), a novel metric, overcomes these limitations. We examined the difference between these 2 metrics of inpatient intravenous antimicrobial consumption in assessing antimicrobial stewardship efficacy and antimicrobial resistance using vector autoregressive (VAR) models with time-series analysis., Methods: Differences between DOT and DASC were investigated at a tertiary-care center over 8 years using VAR models with 3 variables in the following order: (1) the monthly proportion of prospective audit and feedback (PAF) acceptance as an index of antimicrobial stewardship efficacy; (2) monthly DOT and DASC adjusted by 1,000 days present as indices of antimicrobial consumption; and (3) the monthly incidence of 5 organisms as an index of antimicrobial resistance., Results: The Granger causality test, which evaluates whether incorporating lagged variables can help predict other variables, showed that PAF activity contributed to DOT and DASC, which, in turn, contributed to the incidence of drug-resistant P. aeruginosa . Notably, only DASC helped predict the incidence of drug-resistant Enterobacterales. Another VAR analysis demonstrated that a high proportion of PAF acceptance was accompanied by decreased DASC in a given month, whereas increased DASC was accompanied by an increased incidence of drug-resistant Enterobacterales, unlike with DOT., Conclusions: The VAR models of PAF activity, antimicrobial consumption, and antimicrobial resistance suggested that DASC may more accurately reflect the impact of PAF on antimicrobial consumption and be superior to DOT for predicting the incidence of drug-resistant Enterobacterales.

Background: About one-third of caregivers of pediatric or adolescent growth hormone deficiency (pGHD) patients in Japan have reported poor treatment adherence. However, few studies have examined factors related to adherence for that group., Objective: The aim of this study is to consider factors related to poor adherence to daily treatment among caregivers of pGHD patients in Japan., Methods: A cross-sectional survey was conducted among caregivers of pGHD patients in Japan. Caregivers were asked about demographic and treatment characteristics, health literacy, treatment satisfaction, opinions about treatment, and treatment adherence. Health literacy was assessed using the 14-item health literacy scale (HLS-14). Adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8). Statistical association with adherence was considered using Chi-square and Student's t -testing. An exploratory factor analysis (EFA) and K-means cluster analysis was conducted to consider the influence of treatment satisfaction and opinions concerning treatment on adherence., Results: Responses were collected from 112 caregivers. The caregiver's age being 30-39 years old, the primary caregiver being male, the primary caregiver being employed, and low functional health literacy for the caregiver were associated with poor adherence. Patients being pre-elementary school age was also associated with poor adherence. Low satisfaction with drug treatment and/or their device and communication with healthcare professionals (HCPs), and lack of agreement with the importance of treatment management (eg, keeping injection records, getting informed about the disease/therapy, reporting non-adherence, and sticking to an administration schedule), were also associated with poor adherence., Conclusion: Strategies to improve treatment adherence among caregivers of pGHD patients in Japan should consider the age, gender, and employment status of the caregiver - as well as their functional literacy. Improvement in satisfaction with the drug or device used, better communication with HCPs, and greater awareness of the importance of treatment management, may also lead to better adherence., Competing Interests: MA has received honoraria and manuscript fees from Pfizer, Jansen, GSK, Novartis, Takeda, Shionogi and Astellas. TS and NE are full-time employees of Pfizer Japan Inc. ML and RN are full-time employees of INTAGE Healthcare Inc., which received funding from Pfizer Japan Inc. to conduct the analysis and reporting for this study. The authors report no other conflicts of interest in this work., (© 2024 Akazawa et al.)

Background: Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made., Objective: To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups., Methods: A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model., Results: Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]., Conclusion: Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

Objectives: To evaluate the major congenital malformation (MCM) risk of first-trimester antihypertensive exposure, specifically of amlodipine and methyldopa., Study Design: A large administrative claims database was used., Main Outcome Measures: The prevalence of antihypertensive prescriptions during pregnancy was described in 91,390 women giving birth between 2010 and 2019. The MCM risk of first-trimester antihypertensives was evaluated in 1,185 women diagnosed with hypertensive disorders in the first trimester. The MCM risk of first-trimester amlodipine and methyldopa was evaluated in 178 women who were prescribed antihypertensives in the first trimester., Results: Antihypertensives were prescribed to 278 (0.30%) women during their first trimester. The prescription prevalence in the first trimester was highest for methyldopa (115, 0.13%), followed by amlodipine (55, 0.06%). Antihypertensives were prescribed to 2,955 (3.23%) women during pregnancy. Nifedipine (903, 0.99%) and nicardipine (758, 0.83%) were the most frequently prescribed oral and injectable antihypertensives during pregnancy, both with a significant increase in annual prevalence. Of the 1,185 women diagnosed with hypertensive disorders in the first trimester, antihypertensives were prescribed to 178 women. The adjusted odds ratio (aOR) of MCMs in the first-trimester prescription of any antihypertensive medication was 1.124 (95% confidence interval [CI], 0.618-2.045). Amlodipine and methyldopa were prescribed to 44 and 93 of the 178 women, respectively. The aORs of MCMs in the first-trimester prescription of amlodipine and methyldopa were 1.219 (95% CI, 0.400-3.721) and 0.921 (0.331-2.564), respectively., Conclusions: The MCM risk of first-trimester exposure to antihypertensives, including amlodipine and methyldopa, was not suggested., Competing Interests: Declaration of Competing Interest Tomofumi Ishikawa is an employee of Pfizer R&D in Japan and a research collaborator at Tohoku University and has contributed to the present study independently of Pfizer R&D, Japan. Manabu Akazawa received consultation fees from RAD-AR: Risk/Benefit Assessment of Drugs Analysis and Response. Nariyasu Mano received presentation fees from Daiichi Sankyo Co. Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2023 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Backgrounds: Limited information is available on the utility values of metastatic pancreatic cancer, focusing on different health statuses, selected chemotherapy, and related grades 1/2 and 3/4 adverse events (AEs). We evaluated Japanese societal-based health-related utility values for metastatic pancreatic cancer by considering different grade toxicities commonly associated with chemotherapy using the vignette-based method., Methods: We developed health status scenarios for patients with metastatic pancreatic cancer undergoing chemotherapy and conducted utility research using the developed scenarios in four steps: 'literature review,' 'exploratory interview,' 'content validation', and 'utility research'. In the development process, to consider the impact of AEs of chemotherapy for metastatic pancreatic cancer on health state utility values, we selected neutropenia, febrile neutropenia, diarrhea, nausea and vomiting, and neuropathy as representative AEs. Each AE was classified as either grade 1/2 or 3/4. We confirmed our created scenarios through cognitive interviews with the general population and clinical experts to validate the content. Finally, we developed 11 scenarios for using 'utility research,' evaluated in a societal-based valuation study using the face-to-face method. Participants for 'utility research' were the general population, and they evaluated these scenarios in the composite time trade-off (cTTO) and visual analog scale (VAS) of the European quality of life (EuroQol) valuation technology to derive health state utility scores., Results: Of 220 responders who completed this survey, 201 were adapted into the analysis population. Stable disease with no AEs (reference state) had a mean utility value of 0.653 using cTTO. The lowest mean utility score in the stable state was 0.242 (stable disease + grade 3/4 vomiting). VAS results ranged from 0.189 to 0.468, depending on the various grades of AEs in stable disease. In addition, grade 3/4 AEs and grade 1/2 nausea/vomiting were associated with significantly greater disutility. Utility values were also strongly influenced by the direct impact of AE on physical symptoms, severity and their experience. In addition, 95.9% of the respondents agreed that they understood the questions in the post-response questionnaire., Conclusions: We clarified the health state utility values of patients with metastatic pancreatic cancer based on the general population in Japan. The effect on utilities should be considered not only for serious AEs, but also for minor AEs., (© 2022. The Author(s).)

Background: Poor adherence to daily human growth hormone (hGH) treatment has been shown to be associated with poor clinical outcomes for growth hormone deficiency (GHD) patients. However, few studies have examined the perception of adherence to hGH treatment among both physicians and caregivers in Japan., Objective: The aim of this study is to examine the perception of adherence for daily hGH treatment among physicians and caregivers of pediatric and adolescent patients treated with GH in Japan. Moreover, we explore reasons for skipping treatment and the potential impact of a once-weekly treatment on adherence., Methods: A cross-sectional survey was conducted in Japan among physicians that prescribe daily hGH treatment and caregivers that have administered daily hGH treatment to children/adolescents for 3 months or longer. The Morisky Medication Adherence Scale (MMAS-8) was used to gauge perceived adherence for both physician and caregiver groups. Caregivers were also questioned regarding reasons for missing injections. Moreover, both groups were asked about the impact of a once-weekly treatment on adherence., Results: Responses were collected from 123 physicians and 112 caregivers. Physicians reported that 18.1% of patients have poor adherence based on the MMAS-8 instrument. In contrast, 32.1% of the caregivers reported poor adherence. "Simply forgetting", "Patient refused/resisted", and being "Busy with school activities, etc" were the most commonly selected reasons by caregivers for missing an injection. Physicians felt that a once-weekly injection could improve adherence for 64.5% of patients with poor adherence. Moreover, 56.9% of the caregivers that reported an experience of missed injections felt that a once-weekly injection would improve their adherence., Conclusion: Approaches to improve adherence to hGH treatment in Japan are continuously needed. While further research is needed to understand factors most likely to improve adherence, availability of a once-weekly treatment is expected to help improve adherence., Competing Interests: MA is a full-time employee of Meiji Pharmaceutical University and has received some payments from Pfizer Japan Inc for lectures. DS, TS and ES are full-time employees of Pfizer Japan Inc. ML and RN are full-time employees of INTAGE Healthcare Inc., which received funding from Pfizer Japan Inc. to conduct, analysis and reporting for this study. The authors report no other conflicts of interest in this work., (© 2022 Akazawa et al.)

Purpose: According to the revised Japanese medical service fees aimed at reducing irrational psychotropic polypharmacy, medical service fees are reduced if the number of simultaneously prescribed psychotropic drugs exceeds the standard. This study primarily aims to examine the effect of the 2018 revision., Methods: Using a large Japanese administrative claims database, we retrospectively identified five groups (April 2013-September 2018) prescribed at least one drug from the following drug groups: anxiolytics, hypnotics, sum of anxiolytics and hypnotics, antipsychotics, and antidepressants (study population in each group: 547,511, 406,524, 759,137, 112,929, and 201,046, respectively). We used an interrupted time-series design to evaluate changes in the proportion of patients prescribed more than the standard number of drugs., Results: After the 2018 revision, the proportion of patients prescribed more than the standard number of drugs significantly decreased only for the sum of anxiolytics and hypnotics; estimated changes in level and trend were - 0.60% [- 0.69%, - 0.52%] and - 0.04% [- 0.06%, - 0.02%] per month, respectively. The proportion of patients exhibiting a decrease in the number of prescribed drugs from more than the standard to within the standard increased when the revision was enforced (April 2018); this proportion in April 2018 was 36.3%, while all other proportions were in the range of 12.1-22.3%., Conclusion: The 2018 revision promoted a reduction in the number of prescribed drugs, which served as an important factor in the decrease in the proportion of patients prescribed more than the standard number of drugs for the sum of anxiolytics and hypnotics., (© 2021. The Author(s).)

Background: Clinical pharmacists play a role in limiting the disadvantages of pharmacotherapy for patients by detecting and resolving drug-related problems (DRPs) through medication reviews. Although their contributions to patient care have been analyzed and understood in various countries, the role of Japanese clinical pharmacists in this context remains to be clearly elucidated. Thus, in this study, we aimed to elucidate the detection of DRPs by clinical pharmacists and determine the potential impact of pharmacist interventions in Japan., Methods: This study was conducted in a 273-bed hospital and targeted hospitalized patients over a period of 6 months. DRPs detected by clinical pharmacists during the study period were investigated and classified into 10 types. Furthermore, medications were categorized according to the Anatomical Therapeutic Chemical classification. A review committee consisting of two pharmacists independently reviewed the pharmacist interventions on a six-point scale (extremely significant, very significant, significant, somewhat significant, no significance, adverse significance) according to the potential impact on patient care., Results: During the study period, 1711 patients (mean age: 71.2 years, 54.1% male) were included, and 2149 DRPs were detected (1.26 DRPs/patient). Pharmacists intervened in all the DRPs detected. The most common DRP was supratherapeutic dosage (19.3%), followed by untreated indication (18.1%). The most common medication classification causing DRPs was "Antiinfectives for Systemic Use" (25.1%), followed by "Alimentary Tract and Metabolism" (19.9%). Most of the pharmacist interventions (99.6%) were rated "somewhat significant" or more significant, of which 1.1% were rated "extremely significant," and none were rated as "adverse significance.", Conclusions: Our results show that in Japan, as in other countries, clinical pharmacists detect and resolve DRPs in hospitalized patients through medication review. Our findings also show that clinical pharmacists have a positive impact on patient care and suggest the need for their involvement., (© 2021. The Author(s).)

Background: Studies have shown the efficacy of asthma biologics in real-world settings, confirming the generalizability of randomized controlled trial (RCT) results, but studies on more than one biologic are scarce. Accordingly, little is known about the different background characteristics in users of asthma biologics. This study aimed to describe the backgrounds of asthma patients using biologics (omalizumab, mepolizumab, benralizumab, and dupilumab) and examine the effectiveness of these biologics for reducing asthma exacerbations and total systemic corticosteroid doses., Methods: We conducted a retrospective cohort study using self-controlled methods to evaluate the association between the use of biologics and reduction in exacerbations and hospitalizations using a large-scale health insurance claims database in Japan., Results: Of 355 continuously treated asthma patients using biologics, 119, 82, 69, and 85 patients were assigned to the omalizumab, mepolizumab, benralizumab, and dupilumab groups, respectively. The baseline characteristics differed among users of biologics. The incidence ratios of exacerbations and hospitalizations during biologics use were 0.68 (95% confidence interval, 0.62-0.74) and 0.65 (0.55-0.77) compared with the period before biologics use. The total systemic corticosteroid dose equivalent to prednisolone per person-year was reduced from a median of 600 [interquartile range, 90-1713] mg to 164 [0-1010] mg ( P  < .001). Similar results were obtained for individual biologics with a few exceptions., Conclusions: The background characteristics of biologics users differed in a real-world setting. Our results confirmed findings from RCTs demonstrating that each biologic (omalizumab, mepolizumab, benralizumab, and dupilumab) is associated with decreased exacerbation numbers and corticosteroid-sparing effects, even outside of the controlled settings of RCTs., Competing Interests: Yuya Kimura, Norihiko Inoue, Shinobu Imai, Manabu Akazawa, and Hirotoshi Matsui declare no conflict of interest. Maho Suzukawa received research funding from Shionogi, MSD, Sanofi, Kyorin, AstraZeneca, and GlaxoSmithKline., (© 2021 The Author(s).)

Background and Aims: There are few reports on the association between malnutrition and hypoglycemia. The geriatric nutritional risk index (GNRI) allows risk classification by morbidity and mortality resulting from conditions often associated with malnutrition in older individuals. However, the association between GNRI and hypoglycemia is unclear. This study examined the associations between nutrition-related risk and hypoglycemia among older individuals with type 2 diabetes (T2D) using diabetes medication., Methods: This single-center historical cohort study included hospitalized patients aged ≥ 65 years with T2D on medication. Nutrition-related risk was assessed using the GNRI and classified into four risk groups. Hypoglycemia and serious hypoglycemia were determined by oral or intravenous glucose intake and blood glucose < 3.9 mmol/L (70 mg/dL) as hypoglycemia, among them blood glucose < 3.0 mmol/L (54 mg/dL) as serious hypoglycemia. Data were recorded at least once during hospitalization., Results: Patients who met the criteria ( n  = 1.754) were included in the study. The participants median age was 75.0 years. During the study, 81 patients (4.6%) experienced hypoglycemia and 7 patients (0.4%) experienced serious hypoglycemia. Hypoglycemia was observed in patients in the major risk (16.0%), moderate risk (9.7%), low risk (5.2%), and no risk (1.5%) groups ( p for trend < 0.001). After adjusting for other risk factors, the hazard ratios of hypoglycemic among people with major, moderate, and low risk were 5.50, 3.86, and 2.55, respectively., Conclusions: Hypoglycemia increased with increasing nutrition-related risk among older individuals with T2D using diabetes medication. The GNRI is a simple and useful assessment tool in the clinical setting., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Japan Diabetes Society 2021.)