Comparative Effectiveness of Long-Acting Injectable Versus Oral Antipsychotics in Patients With Schizophrenia Using the Prevalent New User Design and Subgroup Analyses.

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.

Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

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.

Risk of major congenital malformations associated with first-trimester exposure to propulsives: A health administrative database study in Japan.

PURPOSE: To evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to propulsives with a special focus on domperidone using a large administrative database in Japan. METHODS: A large claims database was used from January 2005 to August 2016. The dates of pregnancy onset and delivery were estimated using the developed algorithms. MCMs were defined according to the International Classification of Diseases, 10th revision codes. We compared the infants' risk of overall MCMs between women with or without first-trimester prescriptions of propulsives and estimated the odds ratios (ORs) with unadjusted and adjusted analyses. We also compared the risk of overall MCMs between women with domperidone prescriptions and those with other propulsive prescriptions during the first trimester. RESULTS: Among 38 270 women, propulsives were prescribed to 3197 women (8.4%) in the first trimester, including domperidone to 371 women (1.0%). Propulsive prescriptions in the first trimester were not significantly associated with an increased risk of overall MCMs (adjusted OR [aOR] 1.030, 95% confidence interval [CI] 0.843-1.257). Compared to the prescription of other propulsives in the first trimester, the prescription of domperidone in the first trimester was not associated with an increased risk of overall MCMs (aOR 0.724, 95% CI 0.363-1.447). CONCLUSIONS: The first-trimester prescription of propulsives, including domperidone, was not associated with an increased risk of overall MCMs.

Effects of medical service fee revision on reducing irrational psychotropic polypharmacy in Japan: an interrupted time-series analysis.

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.

Relationships between developmental strategies for additional indications and price revisions for anticancer drugs in Japan.

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.

Antimicrobial utilization and antimicrobial resistance in patients with haematological malignancies in Japan: a multi-centre cross-sectional study.

BACKGROUND: Infection is a major complication for patients with haematological malignancies. It is important to better understand the use of antimicrobial agents and antibiotic resistance for appropriate treatment and prevention of drug resistance. However, very few multi-centre analyses have focused on the use of antimicrobial agents and antibiotic resistance have been carried out in Japan. This study aimed to describe the characteristics of the use of antimicrobial agents and antibiotic resistance in patients with haematological malignancies. METHODS: We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in Japan. We included patients diagnosed with haematological malignancies, who were hospitalized in a haematology ward between 1 April 2015 and 30 September 2017 in 37 hospitals. Descriptive statistics were used to summarize patient characteristics, antimicrobial utilization, bacterial infections, and antibiotic resistance. RESULTS: In total, 8064 patients were included. Non-Hodgkin lymphoma (50.0%) was the most common malignancy. The broad-spectrum antibiotics displayed a following antimicrobial use density (AUD): cefepime (156.7), carbapenems (104.8), and piperacillin/tazobactam (28.4). In particular, patients with lymphoid leukaemia, myeloid leukaemia, or myelodysplastic syndromes presented a higher AUD than those with Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. The most frequent bacterial species in our study cohort was Escherichia coli (9.4%), and this trend was also observed in blood specimens. Fluoroquinolone-resistant E. coli (3.6%) was the most frequently observed antibiotic-resistant strain, while other antibiotic-resistant strains were rare. CONCLUSIONS: Broad-spectrum antibiotics were common in patients with haematological malignancies in Japan; however, antibiotic-resistant bacteria including carbapenem-resistant or multidrug-resistant bacteria were infrequent. Our results provide nationwide, cross-sectional insight into the use of antimicrobial agents, prevalence of bacteria, and antibiotic resistance, demonstrating differences in antimicrobial utilization among different haematological diseases.

Reduction in the Doses of Direct Oral Anticoagulants and Risk of Ischemic Stroke Events: A Hospital Survey.

Inappropriately reduced doses (IRDs) of direct oral anticoagulants (DOACs) are common in clinical practice. We performed a retrospective review using electronic medical records of St. Marianna University School of Medicine Hospital (a 1200-bed teaching hospital in Japan) to address the prevalence of IRDs and patient-related factors that result in IRDs. We also surveyed DOAC-treated patients who were hospitalized due to a stroke during the 5-year study period to analyze the association between stroke events and IRDs. We found that one in five patients who were newly prescribed a DOAC was treated with IRDs. Patients treated with edoxaban received the most IRDs (64%, 7/11), followed by those treated with dabigatran (50%, 1/2), apixaban (32%, 19/61), and rivaroxaban (27%, 12/44). Our analysis showed that the renal function (measured as serum creatinine and creatinine clearance values) and age are possible factors influencing dose reduction. The HAS-BLED score and antiplatelet use were not associated with IRD prescription. An analysis of the 5-year hospital records revealed 20 stroke cases despite ongoing treatments with DOACs, and IRDs were noted in three of these cases. In all three cases, the patients had been on an IRD of rivaroxaban. To prevent IRDs of DOACs, we suggest that a clinical protocol be incorporated into formularies to support the prescription process.

Validity of administrative database detection of previously resolved hepatitis B virus in Japan.

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person-years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%-89.3%). This study evaluated the PPV of the algorithm of HBV-DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person-years.

Examination of the prescription of antiepileptic drugs to prenatal and postpartum women in Japan from a health administrative database.

PURPOSE: To evaluate the prevalence and patterns of prescriptions of antiepileptic drugs (AEDs) to prenatal and postpartum women in Japan using a large administrative database. METHODS: The dates of pregnancy onset and delivery were estimated using published algorithms and infant birth months. The prevalence of prescribed AEDs, the maximum dose of some AEDs, and the frequency of potential combination therapy with AEDs were evaluated for the 180 days before pregnancy onset, during pregnancy, and at 180-day postpartum. RESULTS: In total, 33 941 pregnant women were eligible for analysis. At least one AED was prescribed to 225 women (66 per 10 000 deliveries) between 180 days before pregnancy and 180-day postpartum and for 135 women (40 per 10 000 deliveries) during pregnancy. The prevalence of AED prescription declined during the first and second trimesters and increased in the third trimester and postpartum. Valproate was the most frequently prescribed drug, followed by clonazepam, lamotrigine, and carbamazepine. Nine (18.4%) of the 49 women with at least one prescription record of valproate in the first trimester were prescribed more than 600 mg/day of valproate. Concerning potential combination therapy, 40 (12 per 10 000 deliveries) concurrently received two or more AEDs between 180 days before pregnancy and 180-day postpartum, respectively, 31 (9 per 10 000 deliveries) women received these drugs during pregnancy. CONCLUSIONS: Various AEDs were prescribed to pregnant Japanese women. Women of reproductive age should select the appropriate AED before becoming pregnant, depending on the risk benefit profile.

Characteristics and Early Hypoglycemic Medications of Patients at Risk of Progression to Type 2 Diabetes in Japan: A Retrospective Cohort Study of Health Checkup and Claims Data.

Medication therapy management by tracking patients with risk of progression to type 2 diabetes has not been investigated in Japan. We aimed to assess the characteristics of these patients and their early medications. Claims (n = 190507) and health checkup data (n = 106984) between April 2005 and March 2015 in Japan were selected. We selected patients aged ≥40 years with fasting plasma glucose levels of 100-125 mg/dL or glycated hemoglobin A1c values of 5.7-6.4%. The early-medication group comprised patients who received hypoglycemic medications within 6 months after their first clinic visit, while the no-medication group comprised patients who did not receive any hypoglycemic medications. Main outcome measures were characteristics and early hypoglycemic medications of patients at risk of progression to type 2 diabetes. Of 5676 individuals, hypoglycemic medications were initiated in 276 (5%). The early-medication group had a higher proportion of individuals with a body mass index ≥25 kg/m2 and current smokers and drinkers than the no-medication group. Approximately 83% of patients in the early-medication group were prescribed a single hypoglycemic medication, and since 2010, dipeptidyl peptidase-4 inhibitors were prescribed to one-third of these patients. In our population, early hypoglycemic medication was initiated within 6 months of the first clinic visit, indicating that initiation took place earlier than recommended by current guidelines. Early hypoglycemic medications, especially dipeptidyl peptidase-4 inhibitors with low risks of hypoglycemia, might be prescribed based on patient characteristics. Further epidemiological studies are needed to confirm the suitability of early hypoglycemic medication.

Antihypertensives prescribed for pregnant women in Japan: Prevalence and timing determined from a database of health insurance claims.

PURPOSE: The purpose of the study is to evaluate the status of prescribed antihypertensives primarily during pregnancy, but also before pregnancy and after delivery, using a large claims database in Japan. METHODS: The dates of pregnancy onset and delivery were identified using reported algorithms and the birth months of infants. The prevalence and timing of prescribed antihypertensives during pregnancy were descriptively evaluated. Time trends in prescriptions were evaluated using multivariate logistic regression analyses. We also evaluated the prevalence of antihypertensives prescribed within 180 days before pregnancy and 180 days after delivery among women who were covered by health insurers during the entire period. RESULTS: At least one antihypertensive agent was prescribed for 1144 (2.74%) of 41 693 pregnant women. The most frequently prescribed oral antihypertensive during pregnancy was nifedipine, followed by methyldopa, hydralazine, and furosemide. Drugs targeting the renin-angiotensin system were prescribed for 21 pregnant women (0.05%), including angiotensin II receptor blockers that were prescribed for 19 (0.05%) of them. Nicardipine was the most frequently prescribed injectable antihypertensive during pregnancy, followed by furosemide, hydralazine, and nitroglycerin. Annual prescription trends remained similar except for a significant decrease in those for oral and injectable furosemide and an annual increase in those for organic nitrate. Based on an evaluation of 33 941 pregnant women, the number of prescriptions for antihypertensives increased particularly during the third trimester, then decreased from 91 to 180 days after delivery. CONCLUSIONS: Various types of antihypertensives are prescribed for Japanese pregnant women. The effects of exposing pregnant Japanese women to these agents should be evaluated.

Identifying drug substances of screening tool for older persons' appropriate prescriptions for Japanese.

BACKGROUND: In 2015, the Japan Geriatric Society (JGS) updated "the Guidelines for Medical Treatment and its Safety in the elderly," accompanied with the Screening Tool for Older Persons' Appropriate Prescriptions for Japanese (STOPP-J): "drugs to be prescribed with special caution" and "drugs to consider starting." The JGS proposed the STOPP-J to contribute to improving prescribing quality; however, each decision should be carefully based on medical knowledge. The STOPP-J shows examples of commonly prescribed drug substances, but not all relevant drugs. This research aimed to identify substances using such coding, as a standardized classification system would support medication monitoring and pharmacoepidemiologic research using such health-related information. METHODS: A voluntary team of three physicians and two pharmacists identified possible approved medicines based on the STOPP-J, and matched certain drug substances to the Anatomical Therapeutic Chemical Classification (ATC) and the Japanese price list as of 2017 February. Injectables and externally used drugs were excluded, except for self-injecting insulin, since the STOPP-J guidelines are intended to cover medicines used chronically for more than one month. Some vaccines are not available in the Japanese price list since they not reimbursed through the national health insurance. RESULTS: The ATC 5th level was not available for 39 of the 235 identified substances, resulting in their classification at the ATC 4th level. Furthermore, among 26 combinations, 10 products were matched directly to the ATC 5th level of the exact substances, and others were linked to the ATC representing the combination or divided into multiple substances for classification if the combination was not listed in the ATC. CONCLUSION: This initial work demonstrates the challenge of matching ATC codes and the Japan standard commodity classification codes corresponding to STOPP-J substances. Since coding facilitates database analysis, the proposed drug list could be applied to research using large databases to examine prescribing patterns in patients older than 75 years or who are frail. Since ATC is not available for some substances, Japanese medicines need the process to be registered in the ATC for an effective screening tool to be developed for STOPP-J.

Cost-Minimization Analysis of Deep-Brain Stimulation Using National Database of Japanese Health Insurance Claims.

OBJECTIVES: A new rechargeable dual-channel deep brain stimulation (DBS) system has been introduced for the treatment of Parkinson's disease and other movement disorders. However, the clinical value of the device, which has a high cost, remains unclear. MATERIALS AND METHODS: We conducted a cost-minimization analysis using a national database of health insurance claims in Japan. DBS-related costs were compared between rechargeable and non-rechargeable devices and estimated across a 20-year period. RESULTS: Although the price of rechargeable DBS was higher than that of non-rechargeable DBS, we observed total cost-savings of 8.4 million yen across 20 years by considering costs related to implantation surgery, frequency of replacement, and risk of complications. CONCLUSIONS: In this study, real-world evidence indicated that rechargeable dual-channel DBS is a reasonable choice for saving total medical costs. Price revisions should consider cost-effectiveness findings for medical devices.

Difference between days of therapy and days of antibiotic spectrum coverage in an inpatient antimicrobial stewardship program: Vector autoregressive models for time-series analysis.

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.

Factors Related to Treatment Non-Adherence Among Caregivers of Pediatric and Adolescent Growth Hormone Deficiency Patients in Japan.

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.

Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis.

BACKGROUND: The prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction. In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs. METHODS: Claims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC between December 2010 and April 2011 were compared to patients who did not receive FDC (control group). Changes in annual antihypertensive drug costs were compared using a difference-in-differences approach to adjust for patient characteristics and use of concomitant medication. Subpopulation analyses were also performed, taking into account pre-index treatment patterns and prescribers' characteristics. RESULTS: There were 542 patients who switched to FDC and 9664 patients in the control group. No significant differences were observed between the 2 groups, except for antihypertensive drug use patterns before the policy change and prescribers' characteristics. The switch to FDC was associated with an annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs. Approximately 20% of the FDC patients, however, switched from ARB alone, and their drug costs increased by 2376 yen (US$25.5). CONCLUSIONS: For hypertensive patients who required ARB-based combination therapy, switching to FDC drugs had a significant cost-saving effect. However, the policy change of relaxing the prescription-term restriction could encourage aggressive treatment, i.e., switching to a combination therapy from monotherapy, regardless of medical conditions. Further research is required to evaluate the possible negative aspects of FDC drugs.

Comparative effectiveness of long-acting injectable antipsychotics in patients with schizophrenia in Japan.

OBJECTIVE: To compare the effectiveness of different long-acting injectable antipsychotics (LAIs) (aripiprazole, paliperidone, risperidone, and fluphenazine/haloperidol) in patients with schizophrenia in Japan. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Treatment patterns and cost estimations of systemic chemotherapy for pancreatic cancer in Japan: A retrospective database study.

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.

Risk of major congenital malformations associated with first-trimester antihypertensives, including amlodipine and methyldopa: A large claims database study 2010-2019.

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.

[Clinical Research in Communities and the Importance of Patient Information].

In collaboration with community pharmacists, we have conducted research including drug utilization reviews since 2009 and patient registry and long-term follow-up since 2013. The results of these projects have influenced the establishment of healthcare policies and pharmacists' roles. Moreover, the number of clinical studies using electronic medical records by hospital pharmacists has increased. Findings from real-world clinical practice provide useful evidence to improve the quality of patient care provided by clinical pharmacists. When comparing research between community and hospital pharmacists, differences are observed in the efficiency of using patients' information. In hospitals, patients' medical records are important for sharing information among healthcare providers. However, in communities, the importance of maintaining patients' information tends to follow dispensing medications and counseling. This practice results in a lack of data for clinical research. Studies in community pharmacies would deepen our understanding of the needs for patient records and improve the quality of patient care.