Despite extensive research on pharmacokinetic interactions between hydroxymethylglutaryl-CoA reductase inhibitors (statins) and fibrates, the underlying pharmacodynamic mechanisms contributing to the increased risk of rhabdomyolysis remain unclear. This study aimed to determine the differences among statins or fibrates in terms of their susceptibility to rhabdomyolysis. The data mining of FDA Adverse Event Reporting System (FAERS) suggested the association of both statins and fibrates with rhabdomyolysis and the add-on effect of their combinations. In rats, their administration was associated with outliers in creatine phosphokinase and myoglobin levels and a larger distribution of data than in the control. Additionally, co-administration of cerivastatin increased the gemfibrozil concentration in skin and muscle tissues by more than two-fold without an increase in systemic exposure to gemfibrozil, suggesting that an alteration in the pharmacokinetics of gemfibrozil might contribute to an increased risk of rhabdomyolysis when cerivastatin and gemfibrozil are co-administered. Taken together, caution is uniformly needed in combination therapy with statins and fibrates because of the increased risk of rhabdomyolysis.

OBJECTIVE: This study explored the predictors of abemaciclib discontinuation, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer. MATERIAL AND METHODS: Between November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to discontinuation for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis. RESULTS: Baseline weight < 54 kg, bone metastases, and hemoglobin level ≤ 12.4 g/dL were independent predictors of abemaciclib discontinuation for any reason. The main adverse events leading to abemaciclib discontinuation were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight < 54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea. CONCLUSION: Patients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment discontinuation. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy.

Rheumatoid arthritis (RA) patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) often experience treatment changes due to inefficacy or adverse events. The purpose of this study was to clarify the incidence and reasons for change of b/tsDMARDs in a cohort of Japanese patients with RA and to identify the predictors of treatment change. This was a retrospective observational study of RA patients prescribed b/tsDMARD between April 2011 and December 2020 at the Kindai University Nara Hospital. We focused on the change of first-line b/tsDMARDs and identified the reasons for change using the electronic medical records. Logistic regression analysis was performed to identify predictors of treatment change as the objective variable and baseline characteristics as the explanatory variable. The reasons for treatment change were inefficacy in 69.6% of cases and adverse events in 29.7% of cases. Concomitant administration of higher dose prednisolone at baseline (adjusted odds ratio: [95% confidence interval]: 2.52 [1.19-5.33]) and old age (2.00 [1.03-3.87]) were associated with change in b/tsDMARD treatment due to inefficacy within 2 years of initiation. A better understanding of b/tsDMARDs persistence and elucidating the predictors of treatment change can help improve treatment outcomes for RA.

Tolvaptan-associated hepatic disorder is a rare, but lethal adverse event; however, the precise risk and time of onset remain unclear. This study aimed to characterize the severity, time‑to‑onset, and outcomes of hepatic disorder based on patient age and sex. Patient data were acquired from the Japanese Adverse Drug Event Report database (JADER) and the JAPIC AERS database, which consists of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) processed by the Japan Pharmaceutical Information Center. Hepatic disorder was classified as severe or nonsevere. Tolvaptan use was associated with hepatic disorder in analyses using the FAERS [Severe hepatic disorder: reporting odds ratio (ROR) 4.93, 95% confidence interval (CI) 4.33‒5.61; information component (IC) 2.11, 95% CI 1.92‒2.29; nonsevere hepatic disorder: ROR 6.78, 95% CI 6.01‒7.65; IC 2.51, 95% CI 2.33‒2.68] and the JADER (severe hepatic disorder: ROR 4.21, 95% CI 3.57‒4.97; IC 1.86, 95% CI 1.63‒2.10; nonsevere hepatic disorder: ROR 4.27, 95% CI 3.68‒4.95; IC 1.83, 95% CI 1.62‒2.04). A time‑to‑onset analysis revealed that the median onset time was significantly longer in patients aged < 60 years compared with patients aged ≥ 60, regardless of the severity (FAERS: severe hepatic disorder 7 vs. 58 days, p < 0.0001; nonsevere hepatic disorder 8 vs. 52.5 days, p < 0.0001; JADER: severe hepatic disorder 9.5 vs. 32 days, p = 0.0017; nonsevere hepatic disorder 9 vs. 89 days, p < 0.0001). Severe outcomes were observed, regardless of the severity of hepatic disorder. Patients should be monitored for liver function based on age to prevent fatal outcomes.

To assess the safety of molnupiravir capsules (MOV) and the adherence of patients taking these capsules, we conducted a survey of patients who were dispensed MOV at the Maruzen Pharmacy from January 1st to September 30th, 2022. In the survey, a sample of 134 patients were requested to complete a questionnaire, from whom we received 56 responses (response rate: 41.8%). Among the respondents, 11 (19.6%) failed to complete their medication, and those aged 60 years or older tended to have poor adherence (P<0.001). Apart from age, we detected no statistical differences with respect to other assessed factors (gender, capsule size, occurrence of side effects, and evaluation of pharmacist’s explanations). Side effects were reported by 11 individuals (19.6%) taking the drug, although these were mainly consistent with those that have been reported in clinical trials. In addition, 20 individuals (35.7%) experienced COVID-19 after-effects after taking MOV. When requested to evaluate pharmacies and pharmacists, five individuals (8.9%) reported feeling dissatisfied. Although the results obtained in this survey are based on a limited number of patients, they do reveal a concerning lack of adherence among patients over 60 years of age; and there are needs for future improvements in the size of MOV capsules.

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.

ブリンゾラミド懸濁性点眼液の先発品と後発品2種を対象に再分散性を評価するとともに、フルオロメトロン懸濁点眼液の品質上の課題がブリンゾラミド懸濁性点眼液にも該当するのかについて検討した。先発品エイゾプト懸濁性点眼液1%(original drug)と後発品2品目(generic drug AおよびB)を検討対象とした。再分散性に関する目視観察の結果、いずれの製品も保管期間に関係なく、容器底面に懸濁点眼液特有の固化沈殿物は認められず評価は「0」であった。エイゾプト懸濁性点眼液1%では後発品と比較し、一次粒子が密着に集合した形状を示し1μm程度の微細な粒子もこれら二次粒子体に付着していることが確認された。ブリンゾラミド懸濁性点眼液は製品間で初回1滴に含まれる薬物量に差が生じるため、治療効果の低下を回避するためにも十分な服薬指導が必要であると考えられた。

Hyperuricemia is defined as high uric acid levels within the bloodstream and is commonly associated with gout, type 2 diabetes mellitus, and kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel drugs that prevent glucose reabsorption; additionally, this drug has shown promising results in patients at risk of developing cardiovascular or renal complications by lowering uric acid levels. This study aimed to investigate the association between SGLT2i and hyperuricemia. Here, a self-controlled sequence symmetry analysis using the JMDC administrative claims database (January 2005 to September 2022) consisting of 12396 patients, who were newly prescribed both SGLT2i and hypouricemic agents, was conducted. Trend-adjusted sequence ratios (SR) at intervals of 6, 12, 18, and 24 months were calculated. Significant inverse signals across all intervals were observed between SGLT2i and hypouricemic agents, with the strongest effect observed in the 24-month interval [adjusted SR 0.52 (95% CI 0.49-0.55)]. Significant inverse signals were observed for each of the six types of SGLT2i across all intervals. This indicates that SGLT2i initiation may be associated with a decreased risk of hyperuricemia. Further investigation of the efficacy of SGLT2i is needed in hypothesis-testing designs such as cohort studies.

In patients with type 2 diabetes mellitus (T2DM), controlling serum uric acid (SUA) and blood glucose levels is important. Moreover, sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease SUA levels by accelerating urinary uric acid excretion. We investigated the effect of baseline urinary glucose levels on the relationship between SGLT2 inhibitors and SUA levels. We conducted a retrospective observational study using the electronic medical records of patients with T2DM of Kindai University Nara Hospital (April 2013 to March 2022). We divided the patients into two groups according to their baseline urinary glucose levels: the N-UG group, which included patients with negative urinary glucose strip test results (-), and the P-UG group, which included patients with positive urinary glucose strip test results (± or more). The changes in SUA levels before and after SGLT2 inhibitor administration were investigated. For comparison, the changes in SUA levels before and after the prescription of antidiabetic agents, excluding SGLT2 inhibitors, were also investigated. Our results revealed that SGLT2 inhibitors significantly decreased the SUA levels in patients in the N-UG group but tended to decrease its levels in those in the P-UG group. Regardless of the urinary glucose status at baseline, the administration of SGLT2 inhibitors may be useful for patients with T2DM to prevent the complications of hyperuricemia.

OBJECTIVE: Pancreatic cancer-related mortality is increasing worldwide, and prevention methods and effective novel therapies are required. In pancreatic cancer, sodium-glucose cotransporters (SGLT) are involved in glucose uptake. This study aimed to clarify the association between SGLT2 inhibitors and pancreatic cancer development. MATERIALS AND METHODS: A nested case-control study was conducted using the JMDC administrative claims database (January 2005 to June 2020). Patients newly diagnosed with type 2 diabetes mellitus (T2DM) were included, and cases were defined as patients who developed pancreatic cancer. Patients with outcomes were randomly matched to a maximum of 20 controls according to age (± 5 years), sex, and calendar date (month and year) of the first T2DM diagnosis through risk set sampling. RESULTS: Of the 181,107 T2DM patients, 363 cases and 7,043 controls were selected with 14 and 457 patients prescribed SGLT2 inhibitors, respectively. Cumulative administration of SGLT2 inhibitors for > 180 days was significantly inversely associated with the development of pancreatic cancer (adjusted odds ratio: 0.58, 95% confidence interval: 0.31 - 0.99). CONCLUSION: SGLT2 inhibitors may reduce the risk of developing pancreatic cancer in T2DM patients. The number of patients over 65 years of age was small in this study due to the nature of the data source. Further studies with larger sample sizes including older patients are needed.

OBJECTIVE: To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. MATERIALS AND METHODS: Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. RESULTS: Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×104/μL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. CONCLUSION: Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.

The association between statins and open-angle glaucoma (OAG) remains controversial. This study investigated the relationship between statins and OAG in Japanese patients with dyslipidemia using the Japanese administrative claims database. A nested case-control study using two models was conducted using the JMDC claims database (01/2005-01/2020). The onset of OAG: index date was defined as the diagnosis of glaucoma, prescription of anti-glaucoma drugs, or surgery of glaucoma. For each case, a maximum of 10 age-, sex-, and calendar year/month-matched controls were randomly selected by risk-set sampling with replacement. The number of statin prescriptions during the exposure assessment period, which was identified as the 12-month (model 1) or 24-month (model 2) periods prior to the index date, was used as an indicator for statin exposure. Adjusted odds ratios (aORs) and 95% confidence interval (CI) were estimated using conditional logistic regression analyses. We identified 375,373 patients with newly diagnosed dyslipidemia. Of these, 6180 cases and 61,792 controls (model 1) and 4153 cases and 41,522 controls (model 2) were selected. Statin use was not identified as a significant risk factor for OAG (model 1: aOR 0.98, 95% CI 0.93-1.03, model 2: aOR 0.97, 95% CI 0.91-1.04). Compared with nonexposure, short-term exposure (< 2 years) to statins was not related to an increased risk of OAG in the Japanese working-age population with dyslipidemia.

With the development of information technology, patient information is stored as electronic data, and huge amounts of such data are collected every day. Such a collection compiled over the course of clinical practice is called real-world data and is expected to be used for evaluating drug efficacy and safety. Real-world data such as health insurance association-based administrative claims databases, pharmacy-based dispensing databases, and spontaneous reporting system databases are mainly used in pharmaceutical research. Among them, claims databases are used for various observational studies such as studies on nationwide prescription trends, pharmacovigilance studies, and studies on rare diseases due to their large sample size. Although the nature of omics data is different from that of real-world data, it has become accessible on cloud platforms and are being used to broaden the scope of research in recent years. In this paper, we introduce a method for generating and further testing hypotheses through integrated analysis of real-world data and omics data, with a focus on administrative claims databases.

BACKGROUND: Statins are expected to have beneficial effects on nonalcoholic fatty liver disease (NAFLD); however, evidence remains insufficient. OBJECTIVE: In this study, we aim to investigate the association between statin adherence and NAFLD development. METHODS: We conducted a nested case-control study of statin users using the Japan Medical Data Center administrative claims database (January 2005 to January 2020). Individuals who developed NAFLD were designated as cases. For each case, we randomly selected a maximum of 10 controls using risk set sampling. Good adherence was defined as the proportion of days covered (PDC) of ≥0.80. Higher intensity was defined as the median or higher of a cumulative defined daily dose (cDDD) per day covered by statin prescription. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In this study, 253 383 patients with the first statin prescription were identified. Of them, 7080 were selected and matched to 70 734 controls. The medians of PDC and intensity were 0.88 (interquartile range [IQR], 0.61-0.96) and 0.32 (IQR, 0.25-0.50) cDDD/day, respectively. Good adherence was significantly associated with a reduced risk of NAFLD development (adjusted OR, 0.82; 95% CI, 0.78-0.86). Higher intensity was not significantly associated with a reduced risk of NAFLD development (adjusted OR, 1.02; 95% CI, 0.97-1.08). CONCLUSION AND RELEVANCE: Good adherence to statins is associated with a reduced risk of NAFLD development, regardless of the statin intensity. Appropriate statin therapy could reduce the risk of NAFLD development.

OBJECTIVE: The aim of this study was to investigate the risk of hemorrhage in concomitant therapy with direct oral anticoagulants (DOACs) and class IV antiarrhythmic drugs. MATERIALS AND METHODS: First, disproportionality analysis (DPA) was performed using the Japanese Adverse Drug Event Report (JADER) database to investigate the risk of hemorrhage with DOACs. Second, a cohort study was performed using electronic medical record data to confirm the results of the JADER analysis. RESULTS: In the JADER analysis, hemorrhage was significantly associated with treatment with edoxaban and verapamil (reporting odds ratio = 1.66; 95% confidence interval (CI) = 1.04 - 2.67). The cohort study revealed that hemorrhage incidence significantly differed between the verapamil-treated group and the bepridil-treated group, with a higher risk for hemorrhage in the verapamil group (log-rank test: p < 0.001). The multivariate Cox proportional hazards model also showed that the verapamil and DOAC combination was significantly associated with hemorrhage events compared with the bepridil and DOAC combination (hazard ratio (HR): 2.87, 95% CI: 1.17 - 7.07, p = 0.022). Furthermore, creatinine clearance (Ccr) ≥ 50 mL/min was significantly associated with hemorrhage events (HR: 2.72, 95% CI: 1.03 - 7.18, p = 0.043), and verapamil was significantly associated with hemorrhage in patients with Ccr ≥ 50 mL/min (HR: 3.58, 95% CI: 1.36 - 9.39, p = 0.010) but not in patients with Ccr < 50 mL/min. CONCLUSION: Verapamil increases the risk of hemorrhage in patients on DOACs. Dose adjustment of DOACs based on renal function may prevent hemorrhage when verapamil is concomitantly administered.

OBJECTIVE: To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia. MATERIALS AND METHODS: A health insurance claims database and a spontaneous adverse drug reaction database were used. RESULTS: Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years. CONCLUSION: It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.

OBJECTIVE: Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database. MATERIALS AND METHODS: Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 - 2019) with reporting odds ratio and information component being used to indicate a signal. RESULTS: Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi's sarcoma. CONCLUSION: mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi's sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi's sarcoma.

Abstract Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. “Colitis microscopic” (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.

Proton pump inhibitors (PPIs) are commonly used for the prevention or treatment of gastric ulcers, but they can induce hypomagnesemia. Little is known about the onset duration and risk factors related to patient characteristics of this adverse event in Japanese patients. Therefore, we analyzed the time-to-onset of PPI-induced hypomagnesemia and evaluated the association between hypomagnesemia and PPIs using the Japanese Adverse Drug Event Report (JADER) database. We analyzed hypomagnesemia cases between 2004 and 2021. The time-to-onset analysis was performed using the Weibull distribution, and the adjusted reporting odds ratio (aROR) or 95% confidence interval (95% CI) was calculated using a multiple logistic regression analysis. The analysis database comprised 236,525 cases, with 188 cases associated with hypomagnesemia. The median onset duration (interquartile range) of PPI-induced hypomagnesemia was 99.0 (51.8-285.5 ) days, which is considered the random failure type. The multiple logistic regression analysis revealed that hypomagnesemia is significantly associated with male sex (aROR, 95% CI: 1.66, 1.23-2.25) , age < 60 (1.59, 1.14-2.21) , estimated body-mass index (eBMI) (0.94, 0.91-0.98) , PPIs (1.66, 1.18-2.30) , and the interaction of age (<60)*PPIs (1.58, 1.13-2.19) . However, diuretics were not significantly associated with hypomagnesemia. Our results suggest that serum magnesium levels should be measured regularly regardless of the duration of PPI use, especially in patients with male sex, age < 60, or low BMI. These findings will assist health professionals in the adequate use of PPIs. These findings need to be evaluated by cohort studies and long-term clinical investigations.

BACKGROUND: Atrial fibrillation (AF) is a major risk factor for the development of stroke and silent cerebral infarct (SCI). Additionally, AF is independently associated with neurological disorders, including cognitive impairment and dementia. Although oral anticoagulants (OACs) are used to reduce the risk of development of stroke and SCI in patients with AF, it is unclear whether OACs reduce the risk of dementia. OBJECTIVE: This study aimed to investigate the association between OAC use and dementia in relatively young patients with AF. Moreover, the impact of medication adherence on the association between OAC use and the risk of dementia was examined. PATIENTS AND METHODS: This retrospective cohort study was conducted using a large claims database-Japan Medical Data Center, Inc. (JMDC)-from which newly diagnosed patients with AF younger than 75 years of age were identified. We analyzed medication adherence using the medication possession ratio (MPR). The dementia risk was compared between the OAC and non-OAC groups using Cox proportional hazards regression analysis and the Kaplan-Meier method after propensity score matching. Similarly, the MPR-classified and non-OAC groups were also compared. RESULTS: OAC administration was not associated with the risk of dementia in the entire cohort (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40-1.08; p = 0.098); however, OAC administration in patients with an MPR ≥90% was significantly associated with a lower risk of dementia (HR 0.45, 95% CI 0.25-0.81; p = 0.008). Meanwhile, direct OAC (DOAC) and warfarin (WF) administration was not associated with the risk of dementia regardless of MPR. Kaplan-Meier analysis revealed a significant difference in the incidence of dementia between the MPR ≥ 90% OAC and non-OAC groups (log-rank test: p = 0.006). However, no difference was observed in the incidence of dementia between the MPR ≥ 90% WF and non-OAC groups, or between the MPR ≥ 90% DOAC and non-OAC groups. CONCLUSIONS: OAC administration was not associated with the risk of dementia in relatively young patients with AF; however, when limited to patients with an MPR ≥ 90%, OAC administration reduced the risk of dementia. Our results suggest that the association between OAC use and dementia should be evaluated while considering medication adherence.

Objective: Pharmacy students learn the “brand names” of many drugs throughout clinical training, and their drug recognition skill in “generic names” might decline thereafter. To evaluate this, we conducted tests to assess students’ recognition of drugs in both “brand” and “generic” names before and after clinical training. Method: The participants were 64 students undergoing clinical pharmacy training at Kindai University Hospital. Mark-sheet tests concerning pharmacology of drugs in both “brand” and “generic” names were conducted 3 times, before and after community pharmacy training and after hospital pharmacy training. Results: After clinical pharmacy training, students’ drug recognition skill in “brand name” significantly elevated, but that in “generic name” remained constant. Conclusions: Unexpectedly, many students maintained their drug recognition skill in “generic name” after clinical pharmacy training. Nonetheless, educational programs to make students conscious of “generic name” linking with “brand name” during clinical training might be beneficial to promote overall skills in clinical pharmacy.

Background: Accurate prognosis in terminal cancer patients is useful to improve their quality of life and also to decide the cessation of fluid administration. Nonetheless, few prognostic indicators are available for prediction of such a short-term life expectancy. Objectives: The present study aimed at evaluating the efficacy of C-reactive protein (CRP)/albumin (CRP/Alb) ratio, prognostic nutritional index (PNI), fibrosis-4 (FIB-4) index, and albumin-bilirubin (ALBI) score in identifying terminal cancer patients who have a life expectancy less than two weeks. Design: Retrospective study. Setting/Subjects: Of 483 patients who died between April 2019 and March 2020 at a single center in Japan, 102 who met the inclusion criteria were enrolled in this study. Measurements: CRP/Alb, PNI, FIB-4, and ALBI were calculated from the laboratory data collected 1-13, 14-27, 28-83, and 168-365 days before death and subjected to statistical analyses. Results: CRP/Alb, PNI, FIB-4, and ALBI values were significantly associated with the time before death during terminal 365 days. CRP/Alb ≥4.4, PNI <30, FIB-4 ≥ 9.4, and ALBI ≥ -1.26 were significantly associated with the transition from the first half to the second half of terminal four weeks. Of those prognostic indicators, three and four combinations provided significantly reliable estimation of a life expectancy less than two weeks. Conclusions: CRP/Alb, PNI, FIB-4, ALBI, and their combinations are considered to help identify cancer patients who have a life expectancy less than two weeks, which is useful to make appropriate end-stage treatment decisions, for example, cessation of artificial hydration therapy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of cancer treatment; however, no drug is recommended for the prevention of CIPN. In Japan, several drugs such as Gosha-Jinki-Gan and duloxetine are frequently administered as a treatment for CIPN. The aim of this study was to elucidate prescription patterns of drugs administered for CIPN caused by oxaliplatin and the association between these drugs and the duration of oxaliplatin treatment. METHODS: We conducted a retrospective nationwide study using the JMDC administrative claims database (January 2005-June 2020; JMDC Inc., Japan). Patients newly treated with oxaliplatin were identified, and prescription patterns of CIPN medication including Gosha-Jinki-Gan, pregabalin, duloxetine, mecobalamin, and mirogabalin were investigated. The primary outcome was the duration of oxaliplatin treatment. Multivariable logistic regression analysis was performed to examine the association between CIPN medication and duration of oxaliplatin treatment. RESULTS: A total of 4,739 patients who newly received oxaliplatin were identified. Of these, 759 (16.0%) had received CIPN medication. Duloxetine was administered in 99 (2.1%) patients. Multivariable logistic regression analysis revealed that CIPN medication was significantly associated with the prolonged duration of oxaliplatin treatment (odds ratio: 2.35, [95% confidence interval: 1.99-2.77]). CONCLUSION: Real-world data demonstrated that the administration rate of CIPN medication was higher in patients who received oxaliplatin treatment for over 6 months.

In this study, we focused on the storage conditions and investigated the effects of low-temperature storage (10°C) on the dispersibility of active components in three formulations of fluorometholone (FLU) suspension eye-drops (one original drug and two generic drugs, P1-P3). For all three eye-drop products, before shaking by hand, white sediment anticipated to be the principal active component was seen at the vial base. In the ordinary-temperature storage group, the FLU contents per drop after shaking by hand were 0.076% in P1, 0.023% in P2, and 0.100% in P3, and the content in P2 was significantly lower than that in P1 and P3. In contrast, almost no dispersion was observed in the low-temperature group. The results after sufficient shaking of these samples with a vortex, in contrast, were such that the FLU contents per drop were 0.063% in P1, 0.086% in P2, and 0.088% in P3; the content in P1 was significantly lower than that in P2 and P3, and there was no difference between P2 and P3. Moreover, we evaluated the dispersibility according to the evaluation "Vs / (ρg - ρf) g." In both the low- and ordinary-temperature storage groups, the value of Vs / (ρg - ρf) g, proportional to the terminal velocity, decreased in the following order: P3 > P1 ≫ P2, and each value in the ordinary-temperature was higher than that in low temperature. The zeta potential decreased in the following order: P2 > P3 ≫ P1. In conclusion, when FLU suspension eye drops are stored at low temperatures until use, such as in a refrigerator, ordinary shaking does not help achieve dispersion to the specified concentration, and even with vigorous shaking with some formulations, the specified concentration cannot be achieved.

A retrospective data analysis was performed to investigate the association between polypharmacy and adverse events using three different spontaneous adverse event reporting system databases. Multivariate logistic regression analyses were performed to investigate the association between the number of drugs and adverse events, including hepatic disorders, renal disorders, hypersensitivity, and extrapyramidal syndrome. The results showed that the risk of hepatic and renal disorders increased with the number of drugs. Thus, decreasing the number of drugs may reduce the risk of hepatic and renal disorders. Furthermore, attention should be given to specific drugs that may cause hypersensitivity and extrapyramidal syndrome.

INTRODUCTION: Treatment of rheumatoid arthritis (RA) has advanced with the introduction of biological disease-modifying antirheumatic drugs. However, more than 20% of patients with RA still have moderate or severe disease activity. Hence, novel antirheumatic drugs are required. Recently, drug repurposing, a process of identifying new indications for existing drugs, has received great attention. Furthermore, a few reports have shown that antipsychotics are capable of affecting several cytokines that are also modulated by existing antirheumatic drugs. Therefore, we investigated the association between antipsychotics and RA by data mining using real-world data and bioinformatics databases. METHODS: Disproportionality and sequence symmetry analyses were employed to identify the associations between the investigational drugs and RA using the US Food and Drug Administration Adverse Event Reporting System (2004-2016) and JMDC administrative claims database (January 2005-April 2017; JMDC Inc., Tokyo, Japan), respectively. The reporting odds ratio (ROR) and information component (IC) were used in the disproportionality analysis to indicate a signal. The adjusted sequence ratio (SR) was used in the sequence symmetry analysis to indicate a signal. The bioinformatics analysis suite, BaseSpace Correlation Engine (Illumina, CA, USA) was employed to explore the molecular mechanisms associated with the potential candidates identified by the drug-repurposing approach. RESULTS: A potential inverse association between the antipsychotic haloperidol and RA, which exhibited significant inverse signals with ROR, IC, and adjusted SR, was found. Furthermore, the results suggested that haloperidol may exert antirheumatic effects by modulating various signaling pathways, including cytokine and chemokine signaling, major histocompatibility complex class-II antigen presentation, and Toll-like receptor cascade pathways. CONCLUSION: Our drug-repurposing approach using data mining techniques identified haloperidol as a potential antirheumatic drug candidate.

Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH. Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192). Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84). Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.

OBJECTIVE: Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil. MATERIALS AND METHODS: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. Patients with atrial fibrillation who were treated with bepridil from January 2014 to December 2015 were enrolled in the study. Serum bepridil concentrations and electrocardiogram data collected more than 21 days after the initiation of bepridil were used for analysis. RESULTS: A total of 60 patients were included in this study. There was a significant difference in mean QTc interval before and after initiation of bepridil (p < 0.0001). A significant relationship was observed between bepridil dose (p = 0.014) or serum bepridil concentration (p < 0.001) and QTc interval. Additionally, a significant relationship was observed between serum bepridil concentration and ΔQTc (p = 0.034). In the study, 4 patients developed QTc prolongation ≥ 500 ms after the initiation of bepridil. Serum bepridil concentration in this group was significantly higher compared with the group that did not display prolonged QTc (973 ± 651 vs. 526 ± 310 ng/mL, p = 0.01). CONCLUSION: This study revealed that the QTc interval was significantly associated with serum bepridil concentration. Serum bepridil concentration beyond a therapeutic range may be a critical risk factor for developing QTc prolongation.

OBJECTIVE: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases. MATERIALS AND METHODS: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated. RESULTS: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 - 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD). CONCLUSION: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.

フィジカルアセスメント(PA)が実際に必要となる在宅医療に対する模擬患者(SP)の知識を調査した。さらにSPが薬剤師や薬学生から聴診や血圧測定等を受けることについてどのように考えているかを把握し、SPが負担なくPA課題を実施できる方法について検討した。対象は、2016年7月に実施した本学模擬患者講習会に参加したSP37名で、PA関連課題の説明を行った後にアンケートを配布し、回答を依頼した。まず、SPが在宅医療をどの程度理解しているか検証した結果、97%のSPが「在宅医療という言葉を聞いたことがある」を意味する3以上の認知度であったことから、SPは「在宅医療」という言葉は知っており、少なからず知識や関心を持っていることが示された。また、41%のSPが「PAと言う言葉を聞いたことがある」を意味する3以上の回答をしており、一部のSPはPAという言葉を知っているものの「在宅医療」よりもその認知度は低いことが明らかとなった。次に、実際に薬剤師や薬学生から聴診や脈拍測定などを受けることについてSPがどのように考えているかについて調査したところ、聴診や脈拍測定等を薬剤師や薬学生から受けることについて非常に肯定的(前向き)であることが明らかとなった。さらに、これらの結果を詳しく見てみると、聴診に対する態度は、血圧測定や脈拍測定等に対する態度ほど肯定的でないことが示唆された。男女別で見てみると、女性の方が男性よりもその傾向は高かった。

<p>In the areas of home medical care and self-medication, the role of the pharmacist is growing, partly as a result of Japan's aging society and the need to reduce medical costs. In response, the Kinki University Faculty of Pharmacy implemented a physical assessment practical training seminar in order to improve the physical assessment skills of practicing pharmacists. A series of questionnaires were conducted among pharmacists to investigate their perceptions of physical assessment practical training seminars. The results of the questionnaires were analyzed using Customer Satisfaction (CS) analysis and text mining. Based on a 5-point scale (1-low∼5-high), questionnaires revealed satisfaction for physical assessment practical training seminars was 4.6±0.6 (Ave.±S.D.). CS analysis revealed that the items "lectures" and "case seminars" had the highest level of satisfaction. However, items showing low levels of satisfaction were "auscultation of respiratory sounds" and "SBAR (Situation, Background, Assessment, Recommendation)." Results of text mining suggested a relationship between "physical assessment" and "difficult". Analysis of the questionnaires showed a high level satisfaction with physical assessment practical training seminars, notably physical assessment practice methods. However, CS analysis and text mining indicate the finer techniques of physical assessment were difficult to acquire.</p>

Atypical antipsychotics are less likely to cause extrapyramidal symptoms (EPS) compared to typical antipsychotics. However, recent studies have suggested that both atypicals and typicals produce a similar risk for EPS. We performed data mining using the Japanese national insurance claims database (NDB) constructed by the Ministry of Health, Labour and Welfare in Japan. Sequence symmetry analysis was performed to identify the risk of EPS after antipsychotic use. In this study, antiparkinsonian drugs with anticholinergic action were used as a marker of EPS. Antipsychotics in combination with antiparkinsonians was examined by prescription sequence symmetry analysis (PSSA). Likewise, event sequence symmetry analysis (ESSA) was undertaken to evaluate the association between antipsychotics and EPS diagnosis. Adjusted sequence ratios (ASRs) with 95% confidence intervals (CI) were calculated. In PSSA, significant associations with antiparkinsonians were found for the whole class of antipsychotics and atypicals with ASRs of 4.82 (95%CI 4.74-4.91) and 2.97 (2.93-3.01), respectively. A significant association between typicals and antiparkinsonians was not found. In ESSA, significant associations with EPS were found for the whole class of antipsychotics and atypicals with ASRs of 1.67 (1.65-1.69) and 1.49 (1.47-1.50), respectively. A significant association between typicals and EPS was not found. The number of patients who were prescribed atypicals first was 1.5 times larger than the number of patients who had typicals initially prescribed. Analysis of NDB demonstrated that antipsychotics increase the risk of EPS. Significant associations between EPS and atypicals (but not typicals) were found. This finding may be attributed to the prescribing sequence of antipsychotics.

Objective: To examine the association between atypical and typical antipsychotics and extrapyramidal symptoms (EPS), we analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) from the Pharmaceuticals and Medical Devices Agency (PMDA).
Methods: A reporting odds ratio was calculated and used to detect spontaneous report signals, with detection defined as a lower limit >1 in a 95% confidence interval.  In addition, time to onset and age at onset of EPS were investigated.
Results: Drug-reaction pairs were identified in both FAERS (n=29,017,485) and JADER (n=2,079,653).  In analyses of both databases, significant associations were found between atypical and typical antipsychotics and EPS.  Atypical antipsychotics cause EPS with a longer duration of therapy compared to typical ones.  EPS in patients treated with atypical antipsychotics was observed at a broad range of ages compared to the patients treated with typical ones.
Conclusion: Atypical antipsychotics, like typical ones, may increase the risk of EPS.  Because of the longer latency of onset, it may be difficult to find EPS associated with atypical antipsychotics.  Therefore, the severe symptom may be developed in patients treated with atypical antipsychotics.  The attention should be paid to the EPS in patients of all ages treated with atypical antipsychotics.

Objective: Signal detection by analyzing adverse event spontaneous report databases is used to monitor drug safety.  One of the major spontaneous report databases is the FDA Adverse Event Reporting System (FAERS).  Recently, the Japanese Adverse Drug Event Report database (JADER) was released.  To compare FAERS and JADER, we calculated the signals of adverse events by new quinolones (NQs).
Methods: We extracted reports of adverse events by NQs from FAERS and JADER, and analyzed them using the ROR data mining algorithm.  Thirteen kinds of NQs were extracted, and the terms of adverse events extracted were defined by MedDRA.
Results: There were 35,990,645 reports in FAERS and 1,643,404 reports in JADER.  Significant RORs were found for hypersensitivity (FAERS: 1.78, JADER: 1.47), arrhythmia (1.07, 0.68), hypoglycemia (1.80, 2.03), hyperglycemia (0.72, 0.78), rhabdomyolysis (1.01, 0.78), tendon disorders (15.18, 6.59), psychiatric symptoms (1.12, 0.45) and convulsion (0.99, 1.31).  We identified 4 types of adverse events by comparing FAERS and JADER: 1) Signal detection in both, 2) No signal detection in either, 3) Signal detection only in FAERS, 4) Signal detection only in JADER.
Conclusion: Analyzing spontaneous report databases has several limitations, but is still a valuable tool for identifying potential associations between drugs and adverse events.  Spontaneous report databases may also be useful for detecting differences in adverse events between different races, countries and regions.

To examine the association between biologics for rheumatoid arthritis and serious infections (hepatitis B, hepatitis C, tuberculosis, pneumonia and sepsis), we analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of Pharmaceuticals and Medical Devices Agency (PMDA). The reporting odds ratio was calculated and used to detect spontaneous report signals, with detection defined as a lower limit >1 in a 95% confidence interval. In addition, time to onset and age at onset of tuberculosis were investigated. Drug-reaction pairs were identified in both FAERS (n = 29,017,485) and JADER (n = 2,079,653). In both databases, significant associations were observed between biologics and infections (hepatitis B, tuberculosis, pneumonia and sepsis). JADER data revealed a significant association of etanercept with hepatitis C. In FAERS, the majority of tuberculosis events, associated with all drugs, were observed within 1 month of administration, whereas most tuberculosis infections associated with biologics were observed during the 5 months following administration. In JADER, most cases of tuberculosis associated with all drugs and with biologics, respectively, were observed during the 2 months after administration. In conclusion, hepatitis C associated with etanercept treatment should be closely monitored in clinical practice. In addition, tuberculosis associated with biologics should be carefully monitored for 5 months following drug administration. Further studies are needed to confirm these findings.

Several case reports of hepatitis B virus reactivation after rituximab administration have been documented. We investigated the association between hepatitis B and C and 15 kinds of molecular-targeted drugs for cancer. We compared two databases, the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency (PMDA). Quantitative analysis involved calculating the reporting odds ratio (ROR) and 95％ confidence interval (95% CI) as a measure of disproportionality. ROR is a tool that detects signals of adverse events for individual drugs, with signals detected when the lower limit of the 95% CI of ROR is > 1. We also investigated the timing of the adverse events and the age of the patients. There were 29,017,485 reports in FAERS and 2,079,653 reports in JADER. Signals were detected for rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B. In FAERS, hepatitis B often occurred within 1 month, whereas rituximab-associated hepatitis B often occurred 2-6 months after administration. In JADER, hepatitis B and rituximab-associated hepatitis B often occurred 1-3 months after administration. We conclude that signals of rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B are marked. Analyzing the timing and age of the patient at the occurrence of adverse events may suggest a relationship between drugs and these events.

Objective: To examine the signal of gastrointestinal tract injury induced by aspirin and other drugs, we analyzed the US FDA Adverse Event Reporting System (FAERS).
Methods: After deleting duplicate submissions, we analyzed the reports involving gastrointestinal tract injury associated with aspirin, H2-receptor antagonists (H2RAs), proton pump inhibitors (PPIs), ACE inhibitors, angiotensin II receptor blockers (ARBs), and antiplatelet and antithrombotic drugs.  The reporting odds ratio (ROR), a recognized pharmacovigilance tool, was used for the quantitative detection of signals.
Results: Based on 29,017,485 co-occurrences, i.e., drug-adverse event pairs, found in 1,645,605 reports from 2004 to 2009, the ROR-associated gastrointestinal tract injury for aspirin alone, aspirin with H2RAs, aspirin with PPIs, aspirin with ACE inhibitors, aspirin with ARBs, and aspirin with antiplatelet and antithrombotic drugs were 2.88, 1.42, 1.46, 1.00, 1.05, and 2.98-8.26, respectively.  The following summarizes the types of listed reports: 86 reports described the daily aspirin doses, and 36/86 were between 75 and 100 mg; 343 reports described the periods between the start-date for aspirin and the date when gastrointestinal tract injury occurred, of which 128/343 were within one month while 215/343 were over one month; additionally, 78 reports described the total cumulative doses of aspirin, and 17/78 were between 1 and 5 g.
Conclusion: The data suggest that H2RAs, PPIs, ACE inhibitors, and ARBs may reduce gastrointestinal tract injury associated with aspirin in possibility.

Objective: To examine the association between statin use and the risk of sleep disturbances, data mining was performed on a claims database.
Methods: Symmetry analysis was carried out to identify the risk of sleep disturbances after statin use during the period from January 2005 to December 2011.  Statin use in combination with hypnotic drugs was examined by prescription sequence symmetry analysis.  In this study, hypnotic drugs that are commonly prescribed for the treatment of insomnia were used as markers of sleep disturbances produced by statins. Likewise, event sequence symmetry analysis was undertaken to evaluate the association between statin use and the diagnosis of sleep disturbances.
Results: Significant associations of statin use with short-acting hypnotic drugs were found, with an adjusted SR (sequence ratio) of 1.23 (95%CI: 1.04-1.45) at an interval of 12 months.  Otherwise, significant associations between individual statin use and hypnotic drug use were not found.  Significant associations between use of statins and the diagnosis of sleep disturbances were not also found in this study.
Conclusions: Analysis of the claim database demonstrated that statin therapy might be associated with an emergence of sleep disturbances.  Therefore, individuals prescribed statins should be considered as having an increased risk of sleep disturbances.

薬学教育モデル・コアカリキュラムに沿った実習の実施状況を検証し、6年制長実務実習の問題点の検討と改善を目的に学生アンケートを実施した。アンケート結果は、薬学教育において改善項目の抽出などに使用されている顧客満足度(CS)分析より検討した。病院実務実習の実習内容は、「TDMについての演習あるいは実習を受けましたか?」が「要改善項目」として抽出され、薬局実務実習の実習内容は、「薬品管理に関する説明を受けましたか?」が「要改善項目」として抽出された。また、実務実習の指導にあたる指導薬剤師に関しては病院薬局共に、「指導薬剤師の言動に不快だと感じたことがありましたか?」が「改善検討項目」として抽出された。言動は実務実習を円滑に遂行する上で非常に重要かつ基本的な問題で、大学教員と実習指導薬剤師がワークショップなどで共にコミュニケーションとは何かを学び、スキルを検討する必要があった。

We conducted a survey on the practical training of pharmacy students in 47 community pharmacies and 76 hospital pharmacies in Hyogo Prefecture. Items surveyed included the acceptance system for pharmacy students, practical training curriculum, problems and difficulties. In many community pharmacies and hospital pharmacies, instruction in practical training was recognized as worthwhile despite the workload involved. Though the content of the practical training varied, dispensing and medication instruction were the most common items in the practical training for both community pharmacies and hospital pharmacies. Communication with patients and management of medication history were the focus of training in community pharmacies, while the major aspects of training in hospital pharmacies were dispensing of injections and TDM (therapeutic drug monitoring).
Many pharmacists were of the opinion that the content and goals of the training should be reviewed and that it needed to be further evaluated. Revision of the practical training in universities was also recommended. Further, in order to achieve an efficient practical training curriculum it was felt that the training should be more linked to the special characteristics of community pharmacies and hospital pharmacies.

We examined the clinical efficacy of shitei-decoction in 108 patients with hiccups with respect to various factors influencing them : sex, age, other drugs for hiccups, use of benzodiazepines, malignant tumors, use of antitumor agents, metastasis, complications and stress. Hiccups completely disappeared in 63 of the 108 patients following the administration of shitei-decoction, a rate of 58.3%. However, if we judge efficacy by the sum of patients whose hiccups disappeared and those who experienced remission, the efficacy rate for shitei-decoction was 82.4%. The chi-square test showed that there was no significant correlation between the above hiccup influencing factors and the efficacy of shitei-decoction. Despite previous reports to the contrary, there was no correlation between the efficacy of shitei-decoction and co-administration of benzodiazepines. However, the efficacy of shitei-decoction tended to be higher in patients with brain metastasis, suggesting that efficacy may be greater for central hiccups than peripheral hiccups.

This report describes how good medication guidance may be provided to patients with blood cancer and discusses the role of the pharmacist in raising the satisfaction of patients and family members with treatment. Chemotherapy for blood cancer causes a variety of severe adverse reactions, giving patients and their families a feeling of anxiety towards it. It is therefore necessary for pharmacists to provide medication guidance in order to reduce anxiety towards drugs during long-term chemotherapy.
In the present study, we examined questions regarding chemotherapy from patients and their families for 32 cases in the past 3 years. The 485 questions asked were classified according to subject as follows : 1) Adverse reactions-40%, 2) Chemotherapy protocol-12%, 3) Blood transfusions-7%, 4) Effects of chemotherapy-6%, 5) Granulocyte-colony stimulating factor (G-CSF) -6%, 6) Method of use-4%, 7) Drugs preventing opportunistic infections-4%, 8) Administration method-3%, 9) Chemotherapy in outpatient ward-3 %, 10) High-dose chemotherapy-3 %, 11) Discharge and short stay at home-1%, 12) Drop-out-1 %, 13) Drawing blood-1 %, 14) Color of chemotherapy agents for injection-1%, and 15) Differences between treatment strategies at other hospitals-1%.

Objective : This study investigated the significance of the multidisciplmary psychosocial support for pediatnc patients with cancer and their families Method : Patient's adjustment disorder, mother's post traumatic stress reaction (PTSR), and the other psychosocial problems were examined on 7 mpatients with cancer (5 : acute lymphoblastic leukemia, 2 : malignant lymphoma) admitted to pediatric ward of Nishi-Kobe Medical Center from September, 1998 to March, 2002 Practical details of the multidisciplmary psychosocial support were shown in one patient Results : Patient's adjustment disorder ranked severe for one patient, moderate for two and mild for four These disorders recovered during hospitahzation in all patients except one As for the severity of mother's PTSR, one mother was diagnosed as severe, four as moderate and two as mild Their PTSR recovered within one month The severity of mother's PTSR was well correlated with that of patient's adjustment disorder Conclusions : The multidisciplmary psychosocial support was effective for psychosocial support to pediatric patients with cancer and their families from the viewpoint of team approach, adjustment disorder, PTSR and narrative based medicine

A variety of medicines, such as digestive medicines in addition to psychotropic drugs including anxiolytics, antidepressants, hypnotics, antipsychotropic drugs and mania state medical treatment agents may be prescribed to the patients with eating disorder. We observed from the pharmacist's view "Regarding the anxiety about medicine" in the pediatric patients with eating disorder through pharmaceutical care, and examined the role of the pharmacist as a member of therapeutic team for eating disorder. Very important roles of the pharmacist are as in the following: 1. Finding out complaints about medicines by listening to patients 2. Informing patients of "mutual understanding of the anxiety about medicine". 3. Making patients aware of "a pharmacist is always with you" and creating an environment under which patients can take medicines despite anxiety. These trials are good factors to strengthen their ability for self-expression.

症例1(4歳男児).母親は病気を受容しきれず化学療法に対する理解も得られなかった.症例2(6歳女児).母親は副作用の重篤さや患児の服薬困難のために不安が増大していった.薬剤師は聞き手にまわり,不安を共感した上で,仲間がいること,目標が見えるようにすること,褒めながら母親を手伝う薬剤指導により,治療を受け入れる環境が整い,治療を最後まで円滑に進めることができた.また,薬剤指導中に得られた他職種に関係する情報を各チーム医療スタッフに伝達し,連携して対応することで,母親の信頼が生れ,癌化学療法に対する信頼にも繋がった

職種間の理解と連携を深めたチーム医療を確立するための「職種間チーム医療のための勉強会」を実施し、薬剤管理指導業務への影響を調査した。医師・看護師等各職種に、薬剤師が病棟にいることの評価が得られ、薬剤管理指導業務がチーム医療の質の向上を導き支援するものと受け入れられたことを明らかにした。

薬局薬剤師の在宅医療への参画について、薬剤師へのアンケート調査結果の単純集計ならびに因子分析による検討を行い、参画への現状と阻害要因を明らかにした。

テキストマイニング手法の医薬品および医療情報解析への応用の試みとして、薬剤師による医療薬学研究の論文タイトルを解析した。特徴的な語彙間の関係を抽出したことで、薬剤師の研究対象が、物質としての薬剤の研究から臨床で患者の治療を行うための薬剤の研究へ変化したことを明確に捉えることができた。

薬剤師によるNST広報の意義を検討した｡医師とは薬物療法､管理栄養士とは栄養剤など共通した話題が多く､生化学などの知識に精通した薬剤師には､最適な職種でありNST活動の質の向上に貢献できることを明らかにした。

がん化学療法の投与中止の事例に注目し、その理由について解析した。薬剤師の関わりとして適正使用や安全性の向上の観点のみならず、全人的なアプローチの必要性を明らかにした。

全自動散薬分包機135包型と従来の90包型と機能を比較し、その有用性を検討した。全自動散薬分包機の135包型を従来の90包型と比較すると、同等の機能を有し有用性があり従来の調剤業務はより効率化されることを明らかにした。

NST回診時に、薬剤師ごとに異なりがちな情報提供の内容を均一かつ高いレベルに保つため、NST薬剤師回診マニュアルを作成した。薬剤師の役割としては、輸液に関する情報の提供が最も期待されており、他職種が望む情報提供を優先して記載したため、回診時に他職種が欲する情報をリアルタイムに提供する事ができ、薬剤師がNST活動の質の向上に貢献していることを明らかにした。

NST回診時に、薬剤師ごとに異なりがちな情報提供の内容を均一かつ高いレベルに保つため、NST薬剤師回診マニュアルを作成した。薬剤師の役割としては、輸液に関する情報の提供が最も期待されており、他職種が望む情報提供を優先して記載したため、回診時に他職種が欲する情報をリアルタイムに提供する事ができ、薬剤師がNST活動の質の向上に貢献していることを明らかにした。

注射薬自動払出し装置に連動した注射薬調剤支援システムの活用により、外来化学療法注射薬調製業務の効率化を検討した。注射薬調剤支援システムの活用により、ラベルなどの書式準備および薬品の取り揃えの所要時間が大きく短縮され、外来化学療法注射薬調製業務の効率化に至った。

病院薬剤師が取り組む注射薬のリスクマネジメントに注目し、注射薬調剤での疑義照会について解析した。各薬剤師の経験量を問わず同レベルの実施が可能となるよう業務の標準化を行い、照会内容を医師と情報共有した。注射薬に関するリスクマネジメントへの関与は、薬剤師の職能を発揮する重要な位置づけであることを明らかにした。

疑義照会内容を病院全体に公開し、事故防止運用システムを構築した。疑義照会によるインシデントレポート的役割を果たし、医療の質を高めたことを明らかにした。

薬剤師の注射薬調剤の質的向上、医療スタッフヘの情報提供、業務の効率化をはかるために、注射薬自動払出し装置を導入し注射薬調剤支援システムを構築し、その有効活用の評価について検討した。薬剤師による職能の発揮を支援するシステムが構築されたことで、各薬剤師の経験量を問わず新人からベテランまで同レベルの業務内容が可能となり業務の標準化に導いた。病棟からの要望に対応した情報提供を行うことで医薬品適正使用を促進した。

がん化学療法施行中の患者の薬に対する不安を調査した。副作用に関する質問が最も多かったが、副作用以外に、治療方法、入院中・退院後のQOLの確保などの質問も過半数を占め、患者の不安は、薬の副作用にとどまらず多岐に亘っていることを明らかにした。（英文）

薬剤師が関わり骨髄移植（BMT）を受け入れた症例から、病院薬剤師は薬物療法の説明、および患者個々に応じた薬剤支援を行うことが重要であり、患者は心の支えを得ることでBMTが可能になることを明らかにした。

摂食障害患児の薬剤指導で母親との薬の話題から、チーム医療で情報共有し、母親をサポートすることが重要であることを明らかにした。

薬系大学教員や保険薬局そして病院・診療所の薬剤師が医療に貢献することを目的として発足した勉強会について紹介した。薬剤師を取り巻く諸問題についてテーマを設定し、薬・薬・学それぞれの立場からの意見を交換する場として交流を図った。薬剤師を取り巻く問題に対応していくために、教育の場と臨床の場の相互理解・協力なくしてありえず、薬学部６年制で、さらにこの薬・薬・学連携の重要性が増してくることを明らかにした。

新薬等の情報が入手できるよう、新薬・最新薬物療法研究会を発足し、新薬情報の入手に関するアンケート調査を行った。情報の入手方法は、受動的ではあるが「MRから」の情報提供が重要であること、「インターネット利用」は思ったほど多くないこと、新薬情報に関して約20％が何らかのトラブルを経験していること、等を確認し、新薬情報において、全ての薬剤師が容易に情報を共有できるシステム整備の必要性を明らかにした。

Objective : This study investigated the significance of the multidisciplmary psychosocial support for pediatnc patients with cancer and their families Method : Patient's adjustment disorder, mother's post traumatic stress reaction (PTSR), and the other psychosocial problems were examined on 7 mpatients with cancer (5 : acute lymphoblastic leukemia, 2 : malignant lymphoma) admitted to pediatric ward of Nishi-Kobe Medical Center from September, 1998 to March, 2002 Practical details of the multidisciplmary psychosocial support were shown in one patient Results : Patient's adjustment disorder ranked severe for one patient, moderate for two and mild for four These disorders recovered during hospitahzation in all patients except one As for the severity of mother's PTSR, one mother was diagnosed as severe, four as moderate and two as mild Their PTSR recovered within one month The severity of mother's PTSR was well correlated with that of patient's adjustment disorder Conclusions : The multidisciplmary psychosocial support was effective for psychosocial support to pediatric patients with cancer and their families from the viewpoint of team approach, adjustment disorder, PTSR and narrative based medicine

薬学部６年制の実施に備え，適切な学生実習の受け入れ体制を検討するために，保険薬局および病院・診療所における学生実習の実態について調査し、明らかにした。

結核合併HIV感染症の薬剤指導を通して、多種多様の薬剤のコンプライアンスを長期間にわたり維持させることを目標に薬剤師の役割を検討した。服用方法を調節し自己管理の負担の軽減、公的援助利用の橋渡し等で、薬剤指導を通して患者の自己価値を高めていくことが重要であることを明らかにした。

多職種によるがん患者と家族への多角的心理援助を実施し、その意義を考察した。多職種による援助が円滑に進むためにはきめ細かい連携が必要であった。一般の総合病院でのがん治療における心理的サポートは、各職種が力を出し合う多角的アプローチが有用であることを明らかにした。

フェノチアジン系薬剤と金属含有薬剤による着色変化の問題点に対して、基礎薬学的な検討を実施した結果、着色変化を惹起した配合剤にはFT-ラマンスペクトルの変化が認められ、フェノチアジン系薬剤の構造変化を明らかにした。

Chiral bicyclo[3.3.0]octane derivatives 1 are useful as chiral synthons for efficient synthesis of cyclic natural products. Here we describe the asymmetric transformation using enzymatic method of δ-symmetric bicyclic diketones 2a-c and tetraester 9, and the application of chiral bicyclo[3.3.0]octane derivatives [ (+)-3b, (+)- and (-)-11] to natural products syntheses. 1. Baker's yeast-mediated asymmetric reduction of δ-symmetric bicyclic diketones 2a-c afforded the optical active ketols 3a-d in excellent enantioselectivity. Especially, ketol (+)-3b was the chiral intermediate for the total syntheses of (-)-cantabrenonic acids. Furthermore, usefulness of (+)-3b as a chiral bicyclic synthon was revealed by the short transformation of the ketol to the chiral intermediate (+)-4 in (+)-capnellenols syntheses (Scheme 5). 2. PPL-mediated asymmetric demethoxycarbonylation of achiral tetraester 9 obtained by Weiss reaction afforded the chiral triester (+)-10 in 98.3 %ee. The chiral triester was selectively demethoxycarbonylated to prepare chiral C_2-symmetry diester (+)-11. On the other hand, lipase AY-mediated asymmetric demethoxycarbonylation of achiral tetraester 9 directly afforded the chiral C_2-symmetry diester (-)-11 (100 %ee), having opposite chirality compared to the reaction with PPL. The results of lipase-mediated asymmetric transformation of achiral tetraester 9 are shown in Table 1. The chiral diesters (+)- and (-)-11 were very useful as chiral C_2-symmetry synthons for the total syntheses of (+)-carbacyclin, (-)-isoiridomyrmecin, (-)-ajmalicine (Scheme 7, 8, and 9).

データサイエンスの手法を駆使し、行政や医療機関による服薬適正化・ポリファーマシー対策の実施効果、およびRWDからデータマイニングによって生成された仮説の検証を研究の目的としている。地域医療における服薬適正化・ポリファーマシー対策を適切に支援・検証するために、指標となる因子を明確化するために、レセプトデータを解析し指標となる因子の抽出を引き続き検討した。 前年度よりも更新された処方情報データベース(2020年10月分)の解析を行い、ポリファーマシー特有の潜在的不適切処方（PIMs）について、性別、年齢別、疾患別のほか併用薬のカテゴリー別における関連性をあぶり出した。PIMsは2015年に日本老年医学会が作成した「特に慎重な投与を要する薬物のリスト」に従った。 感度分析としても、加齢に伴い5剤以上やPIMsを含む処方割合は増加するが、PIMsとの関連性には処方薬剤数が重要な因子であることを確認した。認知症患者におけるPIMsとの関連性が認められた薬効分類に変化は認められなかった。処方薬剤数が4剤以下のとき、末梢神経系用薬や抗生物質製剤は特定のPIMsとの併用が頻繁になされており、漫然とした処方との見分けに留意する必要がある。また、PIMsではない末梢神経系用薬がPIMsと関連を示し、末梢神経系用薬エペリゾンとの併用薬として、PIMsであるロキソプロフェンナトリウムとの組み合わせが最多であった。PIMsと末梢神経用薬の組み合わせに注意する必要があることが示唆された。

This is the study to evaluate the differences of the adverse event profiles among multiple databases (DBs). We comprehensively searched for the risk factors of adverse events using DBs from countries such as Japan, the United States, and Canada. We exposed country-specific profiles of adverse events. It is particularly worth noting for comparisons in polypharmacy among DBs. We found some inverse relationships between drugs and adverse events. This study will contribute to clinical practice.

有害事象自発報告データベースを用いて、口内炎の発現リスクを低下させる可能性のある薬剤をスクリーニングした結果、8剤が候補薬として選抜された。次に、ヒト口腔ケラチノサイト細胞に対して、5-フルオロウラシル(5-FU)および候補薬を添加し、細胞生存率を検討した結果、3剤の候補薬で5-FU添加による細胞生存率の低下が軽減された。今後は、選抜された候補薬についてin vivo研究などを実施し、有効性をさらに検証していく予定である。