Development and validation of an automated antimicrobial surveillance system based on indications for antimicrobial administration.

INTRODUCTION: We developed an antimicrobial and patient background surveillance system (APBSS), an automated surveillance system that can calculate surveillance data such as antimicrobial use and detection of antimicrobial resistance for each indication of antimicrobial administration. We evaluated the validity of the APBSS data. METHODS: Eligible patients were hospitalized at the Toyota Kosei Hospital on July 7, 2022. Evaluated surveillance data included antimicrobial administration, indications for antimicrobial administration, and diagnosis. In the APBSS, surveillance data were calculated using the Diagnosis Procedure Combination data and Japan Nosocomial Infections Surveillance laboratory data. Using surveillance data collected by the Point Prevalence Survey (PPS) as a reference standard, the agreement between the results calculated based on the APBSS was evaluated using Cohen's kappa coefficient. Indications for antimicrobial administration and diagnosis were analyzed in patients identified for antimicrobial administration in PPS or APBSS. RESULTS: A total of 582 patients were included in this study, 223 of whom were evaluated for indications for antimicrobial administration and diagnosis. For the indications of antimicrobial administration, the Cohen's kappa coefficient was almost perfect (0.81-1.00) for all items. Cohen's kappa coefficient for the diagnosis of healthcare-associated infections was low. However, in major diseases (pneumonia and intra-abdominal, and symptomatic upper urinary tract infections) among community-acquired infections (CAIs) diagnosis, Cohen's kappa coefficient was substantial (0.61-0.80). CONCLUSIONS: The APBSS can identify indications for antimicrobial administration and major CAIs with high accuracy. Therefore, the APBSS can calculate surveillance data, such as antimicrobial use and detection of antimicrobial resistance, for each of these items.

Effect of rapid cefpodoxime disk screening for early detection of third-generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae bacteremia.

BACKGROUND: Several methods have been reported for detecting resistance genes or phenotypic testing on the day of positive blood culture in Escherichia coli or Klebsiella pneumoniae bacteremia. However, some facilities have not introduced these methods because of costs or other reasons. Toyota Kosei Hospital introduced cefpodoxime (CPDX) rapid screening on May 7, 2018, to enable early detection of third-generation cephalosporin resistance. In this study, we aimed to evaluate the effects of intervention with an Antimicrobial Stewardship Team using CPDX rapid screening. METHODS: Cefotaxime (CTX)-resistant E. coli or K. pneumoniae bacteremia cases were selected retrospectively and divided into two groups: the pre-CPDX screening (June 1, 2015, to May 6, 2018) and CPDX screening groups (July 7, 2018, to August 31, 2021). The primary outcome was the proportion of cases in which modifications were made to the administration of susceptible antimicrobial agents within 24 h of blood culture-positive reports. RESULTS: Overall, 63 patients in the pre-CPDX screening group and 84 patients in the CPDX screening group were eligible for analysis. The proportion of patients who modified to susceptible antimicrobial agents within 24 h of blood culture-positive reports was significantly increased in the CPDX screening group compared to that in the pre-CPDX screening group (6.3% vs. 22.6%, p = 0.010). CONCLUSION: The results demonstrated that in CTX-resistant E. coli or K. pneumoniae bacteremia, CPDX rapid screening increased the proportion of early initiation of appropriate antimicrobial agents.

Analysis of factors affecting pharmacists' ability to identify and solve problems.

BACKGROUND: Among Japanese pharmacists, there is a gap in their commitment to self-improvement and a possible gap in their ability to identify and solve problems. However, the factors causing this situation have not yet been clarified. This study was conducted to identify factors that influence the abilities of Japanese pharmacists to identify and solve problems, which are skills considered essential for this profession. A prior history of presenting at academic conferences was set as a surrogate outcome to clarify whether having this experience affects the factors. METHODS: A nationwide internet-based survey was conducted among 300 participating hospitals and 300 community pharmacists. The survey was discontinued when the sample size of each group reached 300. The respondents were categorized into two groups on the basis of their experience of presenting at academic conferences in the survey item "status of self-improvement after employment." Their association with other survey items was determined using univariate and multivariate logistic regression analyses. RESULTS: The multivariate analysis revealed that 152 (50.7%) hospital pharmacists and 41 (13.7%) community pharmacists had presented at academic conferences. Among the hospital pharmacists, the experience of presenting at academic conferences was significantly associated with the "age 30 s (*references 20 s)," "presence of pharmacists to consult," "experience supervising interns," and "number of types of self-improvement" factors. For the community pharmacists, prior conference presentation experience was significantly associated with "age over 70 s," "highest educational background (doctoral or master's degree)," and "number of types of self-improvement." CONCLUSION: This pioneering study suggests that having prior experience of presenting at academic conferences as a surrogate outcome of pharmacists' problem-finding and problem-solving skills may be related to the support provided by human environmental factors at the facility, the status of self-improvement, and the highest educational background.

Pharmacist's interventions in factors contributing to medication errors reduces medication errors in self-management of patients in the rehabilitation ward.

BACKGROUND: The number of medications, number of administrations per day, dosing frequency on indicated day, and medication from multiple prescriptions are the medication factors prone to medication errors in self-management that have been previously reported. However, whether pharmacists actually intervene in medication factors that affect medication error occurrences in self-management is unclear. Therefore, we conducted this study to clarify these issues. METHOD: This study included patients who underwent self-management in the rehabilitation ward of Higashinagoya National Hospital. From April 2019 to March 2020, a one-pharmacist period existed, and from April 2020 to March 2021, a two-pharmacist period existed. The number of patient instructions and interventions were expected to increase with an increase in the number of pharmacists. Considering this to be an environment of differential interventions by pharmacists, a pre-post-test design was conducted with all self-managed patients in both the time periods. The primary and secondary endpoints were the proportion of medication error occurrences and proportion of pharmacist's interventions in medication factors, respectively. RESULT: The proportions of medication error occurrences during the one-pharmacist and two-pharmacist periods were 41% (71/173) and 28% (51/180) (relative risk 0.690, 95% confidential interval 0.515-0.925), respectively. The proportion of pharmacist's interventions in medication factors in the one-pharmacist period was 13% (22/173) and 22% (40/180) in the two-pharmacist period; there was an increase in the proportion of pharmacist's interventions in medication factors in the two-pharmacist period. CONCLUSION: The proportion of medication error occurrences was significantly lower in the two-pharmacist period than that in the one-pharmacist period. This can be attributed to the increase in the proportion of pharmacist's interventions in medication factors. Therefore, an environment in which pharmacists could intervene in the medication factors to prevent medication errors in advance is necessary.

Potential safety signal of pregnancy loss with vascular endothelial growth factor inhibitor intraocular injection: A disproportionality analysis using the Food and Drug Administration Adverse Event Reporting System.

Objectives: Intraocular administration of vascular endothelial growth factor (VEGF) inhibitors may be associated with pregnancy loss. However, little is known about intraocular anti-VEGF therapy during pregnancy. Here, we conducted a pharmacovigilance study using a spontaneous reporting database to evaluate the relationship between intraocular VEGF inhibitors and pregnancy loss. Methods: We used the JAPIC AERS database which is composed of the Food and Drug Administration Adverse Event Reporting System (FAERS) dataset preprocessed by the Japan Pharmaceutical Information Center (JAPIC) to investigate the VEGF inhibitors ranibizumab, aflibercept, and bevacizumab. Disproportionality analyses were conducted for VEGF inhibitors and pregnancy loss. The lower limit of the 95% confidence interval (CI) of the reporting odds ratio (ROR) > 1 and a minimum of three reported cases of pregnancy loss were the detection criteria used in the current study. Results: In the FAERS, 19 pregnancy loss cases were reported for ranibizumab with an ROR of 4.44 (95% CI: 2.42-8.16), 6 for intraocular bevacizumab with an ROR of 32.25 (95% CI: 3.88-267.9), and 4 for intraocular aflibercept with an ROR of 5.37 (95% CI: 1.34-21.49). All these drugs met the detection criteria. Conclusion: Potential safety signals of pregnancy loss were obtained from intraocular administration of VEGF inhibitors during pregnancy. These signals should be validated using a causal design study.

Analysis of medication and prescription background risk factors contributing to oral medication administration errors by nurses: A case-control study.

Medication errors, including overdose and underdose, have a significant impact on patients and the medical economy. We need to prevent or avoid recurring medication errors. Therefore, we conducted a survey to identify medication and prescription background risk factors contributing to the administration of medication by nurses. This study surveyed cases of medication administration errors. This study was conducted at Higashinagoya National Hospital from April 1, 2018, to October 31, 2019. Patients' backgrounds and medication and prescription background risk factors were investigated. Three control cases were randomly selected for each medication error case. We defined the group of medication error cases as the medication error group and the group of control cases as the no-medication-error group. A logistic regression analysis was performed for factors related to medication errors. A total of 202 patients were included in the medication error group. The median age and number of medications were 78 years and 7, respectively. A total of 606 cases were included in the no-medication-error group. The median age and number of medications were 77 years and 6, respectively. The factors that exhibited a relationship with the medication error group were the number of administrations per day, dosing frequency on indicated days, prescription and start dates were the same, medications from multiple prescriptions, and continuous use of a medication received prior to admission. This study identified existing medication and prescription background risk factors. Overlapping risk factors from these groups might contribute to medication administration errors. Therefore, reviewing these factors is necessary to avoid recurring medication administration errors.

Analysis of factors contributing to medication errors during self-management of medication in the rehabilitation ward: a case control study.

BACKGROUND: In the rehabilitation ward, many elderly patients require continuous use of medication after a stroke or bone fracture, even after discharge. They are encouraged to self-manage their medications from the time of admission. Medication errors, such as a missed dose or incorrect administered medication can worsen conditions, resulting in recurrent strokes, fractures, or adverse effects. The study was aimed to identify risk factors, such as medication and prescription, contributing to errors in self-management of medication. METHODS: This study was conducted on patients who self-managed their medication in the rehabilitation ward of Higashinagoya National Hospital from April 2018 to March 2020. The patient background including age and sex were investigated. The medication factors examined include the number of medications and administrations per day, dosing frequency on indicated days, prescription and start date are the same, medications from multiple prescriptions, and one package or one tablet at each dosage. The group of medication error cases were defined as the medication error group and that of control cases as the no-medication error group. A logistic regression analysis was performed for factors related to medication errors. RESULTS: A total of 348 patients were included in the study, of which 154 patients made medication errors, with 374 total medication error cases. The median number of medications in the medication error group was six, and that in the no-medication error group was five. Statistically significant factors correlated with errors made during self-management of medication were the number of medications, number of administrations per day, dosing frequency on indicated days, and medication from multiple prescriptions. CONCLUSIONS: When a patient is self-managing their medications, errors are likely to occur due to a high number of medicines they are taking and the complexity of the dosage regimen. Therefore, to prevent medication errors, reviewing the prescribed medications and devise ways to simplify the dosage regimens is crucial.

Pregnancy Loss Signal from Prostaglandin Eye Drop Use in Pregnancy: A Disproportionality Analysis Using Japanese and US Spontaneous Reporting Databases.

BACKGROUND: There is limited research regarding the use of glaucoma medicines during pregnancy. Prostaglandins contract uterine smooth muscle; however, it is not clear whether prostaglandin eye drops are associated with pregnancy loss in pregnant women. OBJECTIVES: We conducted a pharmacovigilance study using spontaneous report databases from Japan and the USA to evaluate the association between pregnancy loss and the use of prostaglandin eye drops during pregnancy. METHODS: The Japanese Adverse Drug Event Report database and the Food and Drug Administration Adverse Event Reporting System were used for analysis. Disproportionality analyses and a review of individual case safety reports were conducted. RESULTS: As for prostaglandin eye drops in pregnancy-related reports, there were eight reports involving latanoprost in the Japanese Adverse Drug Event Report database and no reports of pregnant women using other prostaglandin eye drops. In the Food and Drug Administration Adverse Event Reporting System, there were 25 reports involving latanoprost, 23 involving bimatoprost, 13 involving travoprost, and three involving tafluprost. The drug safety signal was detected during latanoprost usage and pregnancy loss. In the Japanese Adverse Drug Event Report database, there were five reports of pregnancy loss related to latanoprost, with a reporting odds ratio of 12.84 (95% confidence interval 3.06-53.86), and in the Food and Drug Administration Adverse Event Reporting System, pregnancy loss was reported in 12 cases of latanoprost usage with a reporting odds ratio of 4.35 (95% confidence interval 1.98-9.54). Uterine contractions were observed as concomitant adverse events in one case. CONCLUSIONS: Although a disproportionality analysis cannot determine causality, we need to keep an eye on the signal detected in this study. This signal should be validated using a causal design study.

Medication Errors in the Operating Room: An Analysis of Contributing Factors and Related Drugs in Case Reports from a Japanese Medication Error Database.

OBJECTIVE: The aim of this study was to prevent drug-related medication errors in the operating room by clarifying the association between the medication error category with related drugs and contributing factors. METHODS: We used data from the Japan Council for Quality Health Care's open database on the web. We researched the medication error category, related drugs, and contributing factors. We classified each medication error category into case groups and other medication error categories into control groups. We compared the medication error factors of the 2 groups using multivariate logistic regression analysis on the medication error factors. RESULTS: The total number of analyzed cases was 541. Incorrect dose was the most common medication error category in 170 cases, followed by incorrect drug in 152 cases. Medication error factors (odds ratio, 95% confidence interval) that were found to be significantly positively associated with incorrect dose were "pressor drugs" (3.0, 1.4-6.4), "anesthesia-inducing drugs" (6.3, 1.7-23.4), "lack of knowledge" (2.0, 1.3-3.3), and "drug administration" (3.4, 1.6-7.4). The medication error factors that were found to be significantly positively associated with incorrect drug were "preparation" (5.7, 3.1-10.5) and "medication passed or picked up" (102.2, 35.7-292.8). CONCLUSIONS: Medication errors are frequently occurring during drug preparation and administration in the operating room. Medical staff should thoroughly learn about operating room-specific drugs and closely monitor every step of the drug preparation and administration process. It is also important to create a workflow and improve the environment so that it reduces the likelihood of medication errors.

Visualization of Kinase Inhibition-Related Adverse Events Using the Japanese Adverse Drug Event Report Database.

INTRODUCTION: Small molecule tyrosine kinase inhibitors (TKIs) inhibit not only the target kinase but also various kinases as off-target inhibitors not mentioned in the package insert. However, there are no reports that comprehensively examine the relationship between adverse events and kinase affinity. OBJECTIVE: In this study, we combined basic data and clinical data to visualize the relationship between kinase affinity and adverse events, which will be useful for the management of adverse events in clinical practice. METHODS: We targeted TKIs that have been used domestically and for which the dissociation constant was obtained as reported by Davis et al. Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2018 were used. We calculated the reporting rates of the Standardized MedDRA Queries (SMQ) for the adverse events of interest and visualized the correlation coefficients with kinase affinity. We used the adverse events associated with VEGFR2 and EGFR to assess their validity. RESULTS: We found a correlation among known kinase-related adverse events, suggesting that the methodology may be used as a signal detection method to generate hypotheses for clinical and basic research. CONCLUSION: Our comprehensive analysis of the kinase affinity of TKIs in this study, which was based on basic TKI kinase affinity data and the clinical data of the reporting rates, suggested that our comprehensive analysis method is useful for generating hypotheses about possible causal relationships between pharmacological effects and adverse events.

Identification of target small molecule tyrosine kinase inhibitors that need monitoring and clinical application of protocol for early detection of cancer therapeutics-related cardiac dysfunction using signal detection: An investigation of real world data.

PURPOSE: In order to detect cancer therapeutics-related cardiac dysfunction (CTRCD) early, we identified which drugs were to be monitored using signal detection and the package insert, and created and applied a protocol to address this. METHODS: Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and January 2018 were used. Among small molecule tyrosine kinase inhibitors that are not described in the serious side-effects section of the package insert despite signal detection, tyrosine kinase inhibitors with severe side-effects in the background of cases reported by JADER database were selected to be monitored in clinical practice. We applied our findings clinically by creating a protocol to detect CTRCD early. All cases at Tosei General Hospital where the target tyrosine kinase inhibitors were administered from when they were first released in November 2019 were included. We compared the results from before and after we began the protocol to clarify its effects. RESULTS: We found that CTRCD was not described in the serious side-effect section of the package inserts for Bosutinib, Alectinib, and Osimertinib even though CTRCD signals were detected for them. Therefore, it is possible that we may have previously overlooked CTRCD. When we applied our protocol using Osimertinib as the target drug, we were able to detect CTRCD early in 5/21 (24%) patients. CONCLUSIONS: It was clarified that the drug identification method used in this study for early detection of adverse events leads to early detection of adverse events when applied clinically.

[The Effectiveness of Counseling Using Preventative Informational Sheets with Climate and Environmental Data from Insurance Pharmacies in Preventing Worsened Asthma Symptoms].

We investigated the possibility that having pharmacists give asthma patients informational sheets on climate and environmental changes at insurance pharmacies during patient counseling might prevent the worsening of asthma symptoms. Patients with hyperlipidemia were comparative subjects. We created informational sheets about climate and environmental changes and their influence on asthma. During patient counseling, pharmacists gave them to all asthma patients who visited insurance pharmacies over a period of 2 months, between November and December 2017. Based on previous studies, we called days which showed certain climate or environmental changes as compared to the previous day "change days". We compared the number of visiting patients on change days after preventative information was provided (between January and March 2018) with the number before information was provided (between January and March 2017). In addition, we compared those numbers with the number of patients who visited the target pharmacies between January and March 2016 in order to examine the influence of yearly climate change. The same procedure was used with hyperlipidemic patients. The number of visiting asthma patients after information was provided significantly decreased (5.1±2.1, p=0.03) compared with the number before information was provided, between January and March 2017 (6.1±2.8). The number of aforementioned visits compared to those between January and March 2016 also significantly decreased (p=0.01). Our results suggest that preventative information about climate and environmental changes provided by pharmacists during patient counseling might influence the number of asthma patient visits and prevent the exacerbation of their symptoms.

Quality of Web Information About Palliative Care on Websites from the United States and Japan: Comparative Evaluation Study.

BACKGROUND: Patients and their families are able to obtain information about palliative care from websites easily nowadays. However, there are concerns on the accuracy of information on the Web and how up to date it is. OBJECTIVE: The objective of this study was to elucidate problematic points of medical information about palliative care obtained from websites, and to compare the quality of the information between Japanese and US websites. METHODS: We searched Google Japan and Google USA for websites relating to palliative care. We then evaluated the top 50 websites from each search using the DISCERN and LIDA instruments. RESULTS: We found that Japanese websites were given a lower evaluation of reliability than US websites. In 3 LIDA instrument subcategories-engagability (P<.001), currency (P=.001), and content production procedure (P<.001)-US websites scored significantly higher and had large effect sizes. CONCLUSIONS: Our results suggest that Japanese websites have problems with the frequency with which they are updated, their update procedures and policies, and the scrutiny process the evidence must undergo. Additionally, there was a weak association between search ranking and reliability, and simultaneously we found that reliability could not be assessed by search ranking alone.

Signal of Miscarriage with Aripiprazole: A Disproportionality Analysis of the Japanese Adverse Drug Event Report Database.

INTRODUCTION: With recent advances in medicines, many patients with schizophrenia have become able to conceive. One common second-generation antipsychotic given to patients with schizophrenia is aripiprazole. The label information of aripiprazole in Japan states that according to one case report "there is a report of miscarriage in clinical trial". OBJECTIVE: The aim of this study was to evaluate the relationship between aripiprazole and miscarriage by conducting a disproportionality analysis of an adverse drug event report database. METHODS: We conducted a disproportionality analysis of second-generation antipsychotic exposure during pregnancy using the Japanese Adverse Drug Event Report database, which is a spontaneous reporting database in Japan. We investigated aripiprazole and other approved second-generation antipsychotics in Japan. In accordance with the previous report, we created a data set for analysis consisting of pregnancy-related reports. RESULTS: A potential signal for miscarriage was detected for aripiprazole [proportional reporting ratio: 2.39, χ 2: 13.77, reporting odds ratio (95% confidence interval): 2.76 (1.62-4.69); n = 18]. In contrast, no potential signal for miscarriage was detected for other second-generation antipsychotics. CONCLUSION: Through our analysis of the Japanese Adverse Drug Event Report database, we found a potential signal for miscarriage for aripiprazole. Safety information on the use of aripiprazole during pregnancy is very limited. Therefore, we suggest that the potential signal detected in our analysis be explored further.

Relationship between Physicochemical Properties of Medical Supplies and Serious Adverse Drug Reactions Listed in the Package Inserts.

We sought to clarify the relationship between the physicochemical properties of each medical supply and serious adverse drug reactions listed in the package inserts, by reviewing new information. We investigated 1) 1078 medicines currently available on the domestic Japanese market by using physicochemical data, such as cLogD, molecular weight (MW), and pKa and 2) the serious adverse drug reactions stated in the package inserts and the presence or absence of serious renal and liver disorders, as well as mental, extrapyramidal, and skin disorders. The renal disorders data showed: cLogD<0, adjusted odds ratio (aOR)=2.00; MW values ≥500, aOR=2.28; and pKa<7.4, aOR=1.95-2.06. The liver disorders data showed: pKa<8.4, aOR=1.83-1.95, and MW values ≥300, aOR=1.47-1.87. The mental disorders data showed: cLogD≥0, aOR=2.12, and MW values<400, aOR=2.46-2.85. The extrapyramidal disorders data showed: pKa≥6.4, aOR=4.50-11.32; cLogD≥0, aOR=4.71; and MW values<500, aOR=7.95-15.08. The skin disorders data showed: cLogD<0, aOR=1.46; MW values ≥500, aOR=1.69; and pKa<6.4, aOR=1.65 or<7.4-8.4, aOR=1.59. This information will be useful for investigating the relationships between new drugs entering the market and their potential future adverse drug reactions, and for establishing both precautionary and medical observational standards.

[The Synergistic Effect of Problem-based Learning Combined with the Jigsaw Method in a Pharmacotherapy Course].

To promote problem-solving ability within a pharmacotherapy course, we developed new problem-based learning (PBL) and information and communication technologies (ICT) support systems, and introduced the "Jigsaw Method," an active learning method in which, similar to parts of a jigsaw puzzle, students are dependent on each other to create the full picture, to succeed. We conducted 10 PBL modules (one case per module), each lasting one week. To encourage constructive group work, information sharing, and student understanding in the individual modules, we implemented a Jigsaw Method-based wiki worksheet system in which students were to identify patient problems and check each other's work on an e-portfolio system. After completing this new curriculum, students were able to create comprehensive therapeutic care plans. A significant correlation was observed between the students' care plan evaluation scores and their module test results, suggesting that constructive group work can enhance problem-solving ability in therapeutics. These results clearly indicate the benefit of combining our new PBL-ICT support system with the Jigsaw Method.

[Methodology for Estimating the Risk of Adverse Drug Reactions in Pregnant Women: Analysis of the Japanese Adverse Drug Event Report Database].

Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.

[Development and Validation of Estimate Equations for Adverse Drug Reactions Using Risk Factors and Subjective Symptoms].

The purpose of this study was to develop and validate estimate equations for preventing adverse drug reactions (ADRs). We conducted five case-control studies to identify individual risk factors and subjective symptoms associated with the following five ADRs: drug-induced ischemic heart disease; renal damage; muscle disorder; interstitial pneumonia; and leucopenia. We performed logistic regression analysis and obtained eight regression equations for each ADR. We converted these to ADR estimate equations for predicting the likelihood of ADRs. We randomly selected 50 cases with non-individual ADRs from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 65000 case reports of ADRs, and assigned these cases to a validation case group. We then calculated the predictive probability for 50 cases using the eight estimate equations for each ADR. The highest probability for each ADR was set as the probability of each ADR. If the probability was over 50%, the case was interpreted as ADR-positive. We calculated and evaluated the sensitivity, specificity, and positive likelihood ratio of this system. Sensitivity of the estimate equations for muscle disorder and interstitial pneumonia were ≥90%. Specificity and positive likelihood ratios of estimate equations for renal damage, interstitial pneumonia and leucopenia were ≥80% and ≥5, respectively. Our estimate equations thus showed high validity, and are therefore helpful for the prevention or early detection of ADRs.

[Risk factors and subjective symptoms of drug-induced leucopenia].

The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

[Development of new problem-based learning to promote problem-solving ability in therapeutics at Meijo University].

Pharmacy students in the six-year education system are expected to combine their knowledge obtained from many lectures and to develop problem-solving abilities in therapeutics. These two expectations are considered to be difficult in the conventional education system. Therefore we introduced a new problem-based learning (PBL) method in the class on "pharmacotherapeutics," which was held in the first semester of the fourth year. In the PBL modules, students studied the etiology, pathology, and appropriate drug therapeutics of a given disease and obtained the knowledge and skills necessary for monitoring patients during treatment. We conducted 12 PBL modules, and students studied one case per module, each lasting a week. To encourage constructive group work and to generate original input formats to provide students with a problem-solving road map, we developed new systems including a class review and portfolio. The new PBL method also included lectures on the overview of each disease and the therapeutic agents (action mechanism, physical properties, pharmacokinetics, and monitoring of the efficacy and adverse reactions). By integrating their knowledge and skills, we hope that the students will be able to acquire problem-solving abilities in therapeutics when they become pharmacists.