Insights into Current Veterinary Pharmaceutics for Companion Animals in Japan: A Study Based on Data from the Veterinary Drug Side Effect Database.

In veterinary medicine, various drugs are used on a daily basis. Using inappropriate medications poses health hazards to companion animals and humans; thus, assessing adverse events in veterinary medicine has great social significance but remains an untapped area of research. In this study, to promote the appropriate use of veterinary drugs and clarify common pharmaceutical issues in Japanese veterinary medicine, we analyzed information in the Veterinary Drug Side Effects Database (National Veterinary Assay Laboratory of the Ministry of Agriculture, Forestry and Fisheries, Japan). We found that the number of reports has been increasing annually, including those on high-risk drugs, molecular-targeted drugs, and antibody-based drugs. The details of the reports were similar to those from the United States, including the misadministration of veterinary drugs to humans, improper drug management, and re-administering drugs with a history of side effects. Furthermore, 46.50% of all reports mentioned the administration of one or more drugs, with the highest number of concomitant drugs being 10. In addition, 37.78% of all reports described the use of drugs in manners deviating from the intended use indicated in the package insert. Therefore, to avoid adverse events, pharmacists may have to be involved in dispensing and aseptically preparing veterinary medicines and providing drug information and medication guidance. To optimize pharmacotherapy for ill companion animals, "veterinary pharmacy" and "veterinary medicine pharmacy" must be developed in line with clinical situations in Japan, while considering knowledge from countries that are advanced in terms of veterinary medicine.

[Survey on the Pharmacists Perceptions of Clinical Trial Literature Accessibility].

The purpose of this study is to understand the reading habits of Japanese pharmacists regarding clinical trial literature in 2014. Questionnaires were mailed to 1997 pharmacists in Miyagi Prefecture. Six hundreds and five [342 (56.5%) hospital pharmacists and 254 (42.0%) community pharmacists] responded to questionnaires (Response rate: 30.3%). Regarding the question, "Do you habitually read clinical trial literature?", 19.5% of hospital and 8.3% community pharmacists responded "yes", respectively, which showed both pharmacists are not habitual readers of clinical trial literature. That would be because they did not study critical reading of clinical trial literature at pharmacy schools as well as their work environments to access and retrieve clinical trial literature were limited.

Characteristics of pediatric adverse drug reaction reports in the Japanese Adverse Drug Event Report Database.

BACKGROUND: There are no reports on investigations of the characteristics of adverse drug reaction (ADR) reports for pediatric patients in the Japanese Adverse Drug Event Report database (JADER) and the utility of database for drug safety surveillance in these patients. METHOD: We aimed to evaluate ADR reports for pediatric patients in the JADER. We used spontaneous ADR reports included in the JADER since April 1, 2004, to December 31, 2017, which was downloaded in April 2018. In a total of 504,407 ADR reports, the number of spontaneous reports was 386,400 (76.6%), in which 37,534 (7.4%) were unknown age reports. After extraction of 27,800 ADR reports for children aged < 10 and 10-19 years, we excepted for ADR reports associated with a vaccine (n = 6355) and no-suspected drug reports (n = 86). A total of 21,359 (4.2%) reports were finally included in this analysis. RESULTS: More than half of the ADR reports were for children aged < 10 years. Approximately 30% of ADR reports had multiple suspected drugs, which did not differ by age. The percentages of fatal outcomes of ADRs among patients aged < 10 and 10-19 years were 4.7 and 3.9%, respectively. The most frequently reported drug, reaction, and drug-reaction pair were oseltamivir, abnormal behavior, and oseltamivir and abnormal behavior, respectively. CONCLUSION: We clarified the characteristics of ADR reports for Japanese children by using the JADER. ADR report databases, especially those for pediatric patients, are valuable pharmacovigilance tools in Japan and other countries. Therefore, a proper understanding of the characteristics of the ADR reports in the JADER is important. Additionally, potential signals for ADRs in pediatric patients should be monitored continuously and carefully.

Update on the prevalence and determinants of folic acid use in Japan evaluated with 91,538 pregnant women: the Japan Environment and Children's Study.

Objective: To provide the latest and most promising evidence on the prevalence and determinants for folic acid supplementation in pregnant women in Japan, including differences in prevalence between interview years and determinants across regions.Materials and methods: The study participants were enrolled from 15 regional centers across Japan between January 2011 and March 2014. Information on the use of folic acid supplementation before and during pregnancy and the characteristics of the participants were collected using questionnaires, medical chart reviews, and interviews by research coordinators.Results: Data for 91,538 women who provided sufficient data on folic acid supplementation were analyzed. The prevalence of adequate users was 8.0%, which, although low, tended to improve over the 4-year recruitment period. Various kinds of sociodemographic factors, lifestyle habits, and obstetrical and medication use history were significant and independent determinants for folic acid use. Associations between adequate preconception folic acid use and its major determinants tended to be similar across regions.Conclusions: Although the prevalence of adequate folic acid use was low, it increased from 2011 to 2014. Reproductive-aged women who have determinants for inadequate folic acid use should be informed about the need for preconception folic acid supplementation to help prevent neural tube defects.

Prevalence and determinants of inadequate use of folic acid supplementation in Japanese pregnant women: the Japan Environment and Children's Study (JECS).

OBJECTIVE: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women. METHODS: This study was part of the Japan Environment and Children's Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire. RESULTS: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation. CONCLUSION: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.

Outcomes of a Long-term Case Review Program during the On-site Training of Pharmacy Students.

  This study sought to determine whether a long-term case review (LTCR) program helped pharmacy students develop their abilities as pharmacists, and how their level of satisfaction changed. LTCRs were comprised of four elements: self-learning, one-on-one bedside training with advising pharmacists, daily group sessions including three members, and weekly plenary sessions (case conferences). This program conducted on-site training in a hospital for 21 fifth-year students. The students were divided into 7 groups. One member of each group was assigned to a ward for bedside training for three weeks, while other member(s) of the central pharmacy provided support through daily group sessions. Each week, students training in the wards delivered case presentations in the case conference. All students, advising pharmacists, and teachers participated in these weekly case conferences. Upon conclusion of the on-site training, a survey was conducted on the program's efficacy. Through information sharing during group discussions, and in case conferences, continuous patient follow up was possible regardless of students' training schedules in wards or in the central pharmacy. After introducing the LTCR, the mean satisfaction level for case conferences (as scored using a 5-point Likert-type scale) increased from 3.4 to 4.3. Students' levels of understanding also improved. Statistically significant increases in students' self-evaluation scores on professional awareness, presentation skills, and logical thinking were also observed. We concluded that the program helped students to gain practical experience, made them more aware of clinical issues, and improved their presentation skills. Through this program, the students gained clinical competency through a deep understanding of the clinical courses of diseases and patient-oriented pharmaceutical care.

Effects of an evidence-based medicine workshop on Japanese pharmacy students' awareness regarding the importance of reading current clinical literature.

BACKGROUND: Drug literature evaluation has been taught at pharmacy schools in the United States, allowing pharmacy students to learn how to read clinical literature critically. In advanced pharmacy practice experiences, preceptors often assign pharmacy students to journal clubs in which they repeatedly train how to read such literature. This enables them to understand the importance of reading clinical literature prior to graduation. The objective of this study was to create evidence-based medicine (EBM) workshop that would enhance Japanese pharmacy students' awareness regarding the importance of reading up-to-date clinical literature. METHODS: The EBM workshop were designed as a one-day workshop consisting of student presentations regarding their opinions about reading clinical literature, a lecture on methods for reading required literature critically, and small group discussions using the KJ (Kawakita Jiro) Method. To evaluate the effectiveness of the EBM workshop, students were administered questionnaire surveys both before and after the workshop. The students also took a 15-question test on EBM. Regarding the questionnaires, students were asked to respond to dichotomous items (yes/no) and to indicate on a 7-point Likert scale the extent to which they agreed with statements about clinical literature. Student responses to both the pre- and post-workshop questionnaires were then compared to evaluate the effectiveness of the EBM workshop. RESULTS: A total of 37 students participated in the EBM workshop. Significant improvement was seen between the pre- and post-workshop questionnaires in responses regarding whether they thought that pharmacists should read clinical literature regularly (pre-workshop: 5.70 ± 0.17 versus 6.51 ± 0.13 post-workshop; p < 0.0001), whether they were confident in their ability to read clinical literature (1.81 ± 0.15 versus 3.92 ± 0.18; p < 0.0001), and whether they could discuss treatment with nurses and physicians based on the results of clinical literature if they were a hospital pharmacist (2.49 ± 0.22 versus 3.86 ± 0.21; p < 0.0001). Significant improvement was also seen in scores on the EBM tests (11.4 ± 0.29 versus 12.6 ± 0.22; p < 0.0001). CONCLUSION: Our EBM workshop significantly enhanced student awareness regarding the importance of reading up-to-date clinical literature. It is therefore expected that students who participated in our EBM workshop will contribute to improvements in the quality of the pharmacy profession in the future.

Pharmacists' awareness and attitude toward blood pressure measurement at home and in the pharmacy in Japan.

The aim of this study is to investigate the status of Japanese pharmacists' awareness and attitude toward blood pressure (BP) measurement at home (HBP) and in the pharmacy. Of the 708 community pharmacists and the 117 hospital pharmacists, more than 90% of pharmacists answered that HBP was equally important to or more important than clinic BP, 71.9% (community) and 48.7% (hospital) recommended HBP measurement to the hypertensive patients, and about 15% correctly recognized the reference values of HBP hypertension. Among community pharmacists, 54.0% answered that BP-measuring devices were available in their pharmacy. More aggressive promotion of HBP measurement among pharmacists is warranted.

[Introducing hazard prediction training 'KYT' to undergraduate pharmacy education on patient safety].

To develop students' sensitivity toword medication hazards, we have introduced a behavioral approach, "Kiken-Yochi Training" (KYT) for hazard prediction training to pharmacy education. KYT was originally implemented in the field of occupational health and safety in Japan. Only recently it has been introduced in the medical arena. The process consists of four steps; identification of hazards, assessing risks, planning countermeasure, and making action plan. One facilitator organizes the KYT class (20 students divided into four or five small groups). Watching a photo or illustration of everyday occurrences, each group follows the above four steps to discuss predictable hazards. Concepts are intensively presented in short time with brainstorming. KYT has been used with five classes thus far. Students learned KYT theory and exhibited desired attitudes and behaviors. Students presented many ideas, then formulated their own action plan within about one hour. More than 95% of KYT-naïve students assessed themselves as capable of applying the methodology in various situations. They also assessed themselves as being more aware of potential hazards and new points of view through the KYT process. Pharmacists must work for safer and more effective pharmacotherapy, predicting hazards as side effect or human error and solving the problems on each patient. KYT is a very useful and effective tool for pro-active safety training for the skill and attitude development. Repeating problem-based learning like KYT at intervals through undergraduate education should improve patient safety.

[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

The development and progress of antidiabetic drugs (e.g., insulin preparations and hypoglycemic drugs) are retrospectively investigated in Japan. Their influences on the treatment of diabetes mellitus (DM) and its epidemiological aspects are also discussed. 1) Insulin preparations: Insulin was introduced for DM therapy in 1925, two or three years after its discovery in Canada. The preparations were raw extracts of bovine or porcine pancreas. These did not prevail widely in Japan because of the low incidence of DM before World Wan II. After the war, a shortage of mammalian materials compelled the use of fish pancreatic tissues such as bonito and/or tuna for insulin production. Insulin infection, so-called regular insulin, was first promoted in the 6th "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present edition (JP14, 2001). Although depot-type insulin preparations were developed in the USA and Europe during the war, the introduction of those preparations to Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc insulin and Isophane insulin were introduced for clinical use in 1952 and 1955, respectively. These were also adopted for JP7 (1961). Biphasic-type insulin, which has a rapid onset and long duration of activity, appeared in 1965. Purified preparations from bovine or porcine sources have been available since 1980, which might be a strong reason for the decrease in insulin allergy. Insulin from animal origin has been supplied for almost 60 years since its discovery. Amino acid sequences of insulins from various species of animals were determined by the pioneering studies of Sanger and his associates. Human insulin, which differs from porcine insulin by only one amino acid, was produced by Novo researchers in 1982 using a semi-synthetic method. Then the Lilly group soon succeeded in obtaining human insulin by recombinant DNA technology in the same year. Both products were introduced to Japan in 1985, and the recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after-meal hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society proposed a guideline on diagnostic criteria and treatment of diabetes mellitus (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM, requires insulin therapy to prevent ketosis and to sustain life. Treatment of type 2, adult onset DM, is recommended as a step-by-step method, starting with dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin therapy. DM patients with complications should have a therapy devised to match their circumstances. 5) Epidemiological aspects: The mortality rate of DM compared to the time of drug appearance was traced from 1920 to 2000. The curve goes down slowly in the time frame of World War II, but rises from 1950 to 1970. The elevation could not be suppressed by the appearance of SUs, BGs or improved insulin preparations. The curve runs flat from 1980 to 1990, which might be related to the use of purified insulin or human insulin therapy. The mortality rate of DM indicates that death by hyperglycemic coma and other deaths resulting from complications are excluded. The survey of the principal cause of death by DM during the period of 1981-1990 indicates that the death rate due to hyperglycemic coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on all of the death resulting from DM is not detected. Hospital visitation and admission rates of the DM patients have been recorded since 1952 in Japan. This curve is rising continuously, and none of the antidiabetic drugs has been able to suppress it. These data show that the antidiabetic drugs relieve DM symptoms through their effective hypoglycemic actions, but that they cannot suppress the mortality rate of DM. It is possible that none of the drugs currently available can suppress the increasing tendency of DM patients.