Relationship between body adiposity parameters and insulin resistance: a preliminary study of surrogate markers in Japan.

PURPOSE: According to the Japan National Health and Nutrition Survey 2019, the proportion of people with prediabetes is estimated to be 27.3%. Western-style dietary habits can lead to obesity and a functional abnormality of the adipose tissue, which can cause insulin resistance and predispose one to diabetes. We examined the relationship between insulin resistance using body adiposity parameters as surrogate markers. METHODS: This study enrolled 248 healthy participants to determine the association of six body adiposity parameters, namely, body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI), lipid accumulation product index (LAP), waist circumference-triglyceride index (WTI), and triglyceride (TG)/high-density lipoprotein (HDL) ratio with insulin resistance. Receiver operating characteristics curve analyses were performed to assess the accuracy of these parameters in identifying insulin resistance. RESULTS: The data of the 248 participants (women 79 and men 169) were examined in this study. WC showed the highest accuracy in the obese women group (cut-off value: 89.8 with sensitivity: 0.900 and specificity: 0.522, AUC: 0.680) and men group (cut-off value: 90.0 with sensitivity: 0.862 and specificity: 0.508, AUC: 0.701). The TG/HDL ratio showed the highest accuracy in men with non-obesity (cut-off value: 0.8 with sensitivity: 0.857 and specificity: 0.649, AUC: 0.780). CONCLUSION: Application of this finding should be useful in the early screening of obesity in men with non-obesity, such as during regular health check-up with the TG/HDL ratio in addition to the usually used WC, to assess insulin resistance and prevent lifestyle-related diseases that can lead to cardiovascular events.

Extracting the latent needs of dementia patients and caregivers from transcribed interviews in japanese: an initial assessment of the availability of morpheme selection as input data with Z-scores in machine learning.

BACKGROUND: Given the increasing number of dementia patients worldwide, a new method was developed for machine learning models to identify the 'latent needs' of patients and caregivers to facilitate patient/public involvement in societal decision making. METHODS: Japanese transcribed interviews with 53 dementia patients and caregivers were used. A new morpheme selection method using Z-scores was developed to identify trends in describing the latent needs. F-measures with and without the new method were compared using three machine learning models. RESULTS: The F-measures with the new method were higher for the support vector machine (SVM) (F-measure of 0.81 with the new method and F-measure of 0.79 without the new method for patients) and Naive Bayes (F-measure of 0.69 with the new method and F-measure of 0.67 without the new method for caregivers and F-measure of 0.75 with the new method and F-measure of 0.73 without the new method for patients). CONCLUSION: A new scheme based on Z-score adaptation for machine learning models was developed to predict the latent needs of dementia patients and their caregivers by extracting data from interviews in Japanese. However, this study alone cannot be used to assign significance to the adaptation of the new method because of no enough size of sample dataset. Such pre-selection with Z-score adaptation from text data in machine learning models should be considered with more modified suitable methods in the near future.

Differences in the Perception of Dietary Supplements between Dietary Supplement/Medicine Users and Non-Users.

Some patients use dietary supplements and medicines concomitantly, with an inappropriate perception of their safety and efficacy. To clarify the perception between dietary supplement and medicine users and non-users, we conducted an internet survey. In this survey, 38.9% of participants used dietary supplements, 32.6% used prescription medicines, and 14.7% used dietary supplements and prescription medicines concomitantly. Then, we conducted a further survey on four groups, dietary supplement and prescription medicine users, dietary supplement only users, prescription medicine only users, and non-users (500 each). Dietary supplement users had favorable outcomes in terms of both the safety and efficacy of dietary supplements compared to dietary supplement non-users. This perception of dietary supplements was independent from medicine use. The awareness of the Health Food Network consumer navigation site, which provides information about dietary supplements for consumers, was the highest among dietary supplement and prescription medicine users, but it was still low (2.2%). In conclusion, consumers who use dietary supplement and prescription medicine concomitantly have favorable outcomes for their safety and efficacy and a low awareness of their interaction. There is a need to provide information, especially regarding the risk of interaction, that takes into account the consumer's situation.

The usefulness of a checklist approach-based confirmation scheme in identifying unreliable COVID-19-related health information: a case study in Japan.

Consumers are increasingly able to easily access health information online about food products. However, consumers have difficulty identifying reliable health information from diverse sources along with information about the coronavirus disease (COVID-19) pandemic because the inundation of information (both true and false) overwhelm consumers. We investigated the usefulness of a checklist confirmation scheme for identifying unreliable COVID-19-related health information. Data were collected from June 30-July 1, 2021. First, we measured 700 participants' baseline health literacy levels by having them read unreliable health information about the efficacy of green tea intake in preventing COVID-19 based on the results of animal experimentation. Second, participants read an explanation with a five-step flowchart of how to identify reliable health information. Thereafter, we remeasured participants' health literacy levels. To identify the factors hindering the effect of the confirmation scheme, a logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 77.9% (293/376) of those with low health literacy levels at baseline still had low literacy after the intervention. The factor that hindered the confirmation scheme's usefulness was benefit perceptions of food ingredients (OR: 0.493; 95% CI: 0.252-0.966). Consumers with higher benefit perceptions of a target product faced more difficulties using the confirmation scheme effectively. Therefore, the most effective strategies involve filtering information at the organizational level rather than the individual level, which should help consumers correctly identify misinformation concerning food and health and promote accurate decision-making.

The Prevalence of Dietary Supplement Use for the Purpose of COVID-19 Prevention in Japan.

COVID-19 is still the biggest issue worldwide. Many dietary supplements on the market claim to have anti-COVID-19 effects without scientific evidence. To elucidate the prevalence of dietary supplement usage for the prevention of COVID-19, we conducted an online cross-sectional questionnaire survey among Japanese adults in January 2022. The prevalence of dietary supplement use for the prevention of COVID-19 was 8.3%, and there was no gender difference. We also conducted additional research on these dietary supplement users (1000 males and 1000 females). The most popular ingredient used was vitamin C (61.0%), with vitamin D (34.9%) and probiotics (33.4%) following. Half of these participants reported using supplements for more than one year. The information sources that reportedly led them to start using dietary supplements for the prevention of COVID-19 were the Internet (44.0%), television and radio (29.9%), and family or friends (26.0%), and these information sources differed among generations. In conclusion, some of the population used vitamin/mineral supplements for the prevention of COVID-19 that might be beneficial for their health, but some used ingredients with no scientifically proven effects against the virus at this time. Therefore, information-based scientific evidence is important to prevent the inappropriate use of dietary supplements by consumers.

The Perception of Minerals and Their Prevalence in Fortified Foods and Supplements in Japan.

People's intake of some minerals does not meet the nutrient reference values even in high-income countries. Recently, the deficiency of zinc and/or selenium has been considered to cause greater risk of COVID-19 infection and severity. To investigate consumer awareness, we conducted a cross-sectional questionnaire online survey among Japanese people (7500 males and 7500 females) concerning their perceptions of each mineral and the prevalence of mineral-fortified foods and/or mineral supplements. People's perception of each mineral varied: the highest was for calcium (91.8%) and the lowest was for selenium (44.7%). In addition, only a portion of participants believed that they consumed a sufficient amount of each mineral; the highest was sodium (23.7%), and the lowest was manganese (5.2%). In addition, 18.2% of them felt that they could not consume enough sodium, even though most of the Japanese's intake is excessive. Among mineral-fortified-food and/or mineral-supplement users, the purposes for these products were to maintain health (80.6%), supplement nutrients (48.0%), and prevent infectious diseases (23.2%). Only 18.4% of participants knew what amount they took. In conclusion, education is needed to prevent not only the insufficiency/deficiency of each mineral but also an excess intake of sodium.

[Recognition and Prevalence of "Designated Ingredient, etc." in Health Foods].

From 2012 to 2017, many adverse events, such as irregular vaginal bleeding and menstrual disorders, associated with the use of health foods containing Pueraria mirifica were reported in PIO-NET. Health foods containing P. mirifica claim mastogenic or body shaping effects, and it is for this reason that many women use these products. As a result, the Japanese government investigated and assessed the possibility of the occurrence of adverse effects associated with the use of other ingredients in health foods and labelled P. mirifica, Coleus forskohlii, black cohosh, and greater celandine as "designated ingredient, etc."The present study showed that recognition of "designated ingredient, etc." was 45.9% and that there was a difference between consumers and healthcare professionals. The prevalence of food containing P. mirifica use was 1.2%. Almost half of users experienced adverse events, such as irregular vaginal bleeding and menstrual disorder. Some subjects had a good perception towards "designated ingredient, etc.," such as "It seems effective"(32.7%) and "It seems good for health"(18.9%). After reading the descriptive text, their positive perceptions decreased.In conclusion, the recognition of "designated ingredient, etc." is insufficient. To avoid adverse events associated with "food containing designated ingredient, etc.," detailed information should be provided.

[Consultation and Information Source of Interaction between Drugs and Health Foods among Pharmacists and Dietitians].

The prevalence of health food use is increasing not only among healthy individuals but also among patients. Many patients consume drugs and health foods concomitantly, and most of them use more than one drug and one health food. In this regard, the interactions between drugs and health foods should be addressed. However, it is not clear where healthcare professionals can get sufficient information about the interactions between drugs and health foods. To address this issue, we conducted an online questionnaire about the consultation and attitude concerning and information source of interactions between drugs and health foods among pharmacists and dietitians. Only 29.7% of pharmacists and 14.0% of dietitians always confirmed the use of health foods among their patients, even though they work at pharmacies or hospitals. Regarding concomitant use, 79.2% of pharmacists and 60.2% of dietitians allowed their patients to continue concomitant use, and less than 20% of them advised their patients to avoid concomitant use. Most of them checked the manufacturer's website and could not obtain sufficient information about the interactions between drugs and health foods. However, they utilized the "Information system on safety and effectiveness for health foods (HFNet)," which is the website of the National Institutes of Biomedical Innovation, Health and Nutrition, to obtain information, if they were aware of this. In conclusion, pharmacists and dietitians need more information about the interactions between drugs and health foods, and HFNet may play an important role as information source.

The Perception of Vitamins and Their Prevalence in Fortified Food and Supplements in Japan.

Most vitamins are primarily ingested from foods. However, it has been reported that intakes of some vitamins do not meet the nutrition reference values even in high-income countries. In this case, vitamin-fortified foods and/or vitamin supplements are helpful to fix insufficient/deficient status. However, it is not clear whether consumers are aware of their nutritional status or whether they use these products efficiently. To address this issue, we conducted an online cross-sectional questionnaire survey among 14,741 Japanese adults (over 20 years old, 7489 males and 7252 females) concerning the perceptions and prevalence of vitamin-fortified food and/or vitamin supplements. Differences in distribution among groups were compared using the chi-squared test. According to dietary habits, 33.2% of the participants consumed a well-balanced diet every day, but 25.5% could not because of time (41.6%) or money (36.9%) constraints. The perception of each vitamin varied: the highest was for vitamin C (93.2%) and the lowest was for biotin (41.9%). In addition, only a portion of the participants believed that they took sufficient amounts of each vitamin; the highest was vitamin C (22.3%) and the lowest was biotin (5.2%). Despite this situation, most did not use vitamin-fortified food and/or vitamin supplements due to economic reasons. Among vitamin-fortified food and/or vitamin supplement users, the purposes for the usage of these products were varied, such as maintaining health (80.5%), supplementation of nutrients (47.8%), beauty-related purposes (27.5%), and to prevent infectious disease (23.2%). To remedy nutritional status in individuals, it is important to improve not only consumer awareness but also the environment, which can lead consumers to use acceptable vitamin products without any burden.

Study factors associated with the incompletion of clinical trials that include pediatric patients: a retrospective analysis of the European Clinical Trials Database and a lesson from the European region.

BACKGROUND: Incomplete clinical trials for pediatric drug development result in a lack of adequate scientific evidence for providing appropriate medication to pediatric populations; this is especially true for Japan. Thus, using the European Clinical Trials Database (EudraCT), this study aimed to identify the factors related to the study design and administration that lead to incompletion of clinical trials that included pediatric patients. METHODS: We focused on clinical trials that included patients under the age of 18 registered in the database, named as the European Clinical Trials Database between January 1, 2014, and December 31, 2018. Two groups of trials were identified: "all cases completed" and "not all cases completed," reflecting whether they were completed in all participating countries/regions or not. To identify the factors of the occurrence of "not all cases completed," a logistic regression analysis was performed to calculate the odds ratios and 95% confidence intervals. In total, 142 clinical trials (95 "all cases completed" and 47 "not all cases completed") were analyzed. RESULTS: The logistic regression analysis showed the number of countries in which a clinical trial was conducted to be the only significant factor (odds ratio: 1.3; 95% confidence interval: 1.1-1.5); this was identified as the primary factor for the occurrence of "not all cases completed" in the clinical trials that included pediatric patients. CONCLUSION: Our findings suggest that the feasibility of clinical trials that include pediatric patients, such as whether the countries in which the trial is to be conducted are suitable, must be considered prior to the trial.

Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with anticonvulsants in a Japanese population: Matched case-control and cohort studies.

BACKGROUND: Evidence for the risk and incidence of anticonvulsant-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Japan is scarce. METHODS: We conducted a matched case-control study using a large-scale Japanese claims database. SJS/TEN cases were identified using a claims-based algorithm developed in a previous study (sensitivity 76.9%, specificity 99.0%). Conditional logistic regression with Firth's bias correction to address an issue of rare events was used to estimate odds ratios (ORs) for SJS/TEN for each anticonvulsant use (90 days before the index date) versus non-use. 90-day cumulative incidence of SJS/TEN per 100,000 new users was calculated for 33 anticonvulsants. Causality between anticonvulsant use and SJS/TEN in each exposed case was assessed using the algorithm of drug causality for epidermal necrolysis (ALDEN) score. RESULTS: From 5,114,492 subjects, we selected 71 SJS/TEN cases and 284 controls. We observed significantly increased ORs for SJS/TEN among new users of carbamazepine (OR 68.00) and lamotrigine (OR 36.00) with ALDEN scores of "probable" or higher. Cumulative incidence of SJS/TEN was 93.83 for carbamazepine and 84.33 for lamotrigine. One case newly exposed to phenytoin which developed SJS/TEN was rated "unlikely" in ALDEN causality, resulting in cumulative incidence of 66.27. Cumulative incidence of SJS/TEN was 25.23 for levetiracetam, 7.52 for clonazepam, and 1.23 for diazepam, but their ALDEN scores were "very unlikely". CONCLUSIONS: This study is the first to document the differential risk of SJS/TEN for anticonvulsants in a real-world setting in Japan. Exposure to carbamazepine and lamotrigine was associated with an increased risk of SJS/TEN.

Determination of the Awareness about and Need for Health Support Pharmacies as the Provider of Consultation Service about Nutrition Education and Diet-Related Health Promotion by Health Professionals in Japan.

Health support pharmacies (HSPs) have been established as a new category of pharmacies in Japan. In addition to prescriptions, HSPs provide several health services, including consultations on diet/nutrition, health foods, and nursing care. Therefore, not only individuals receiving medications but also community residents should have access to HSPs. However, it is unclear whether people are aware of HSPs. Thus, the purpose of this study was to assess the awareness about HSPs and determine the need for their services. To this end, we conducted an online cross-sectional questionnaire survey in 10,000 Japanese adults. Approximately 60.2% of the participants were aware of family pharmacies/pharmacists, and 21.8% of these participants had a family pharmacy/pharmacist. Meanwhile, 2.6% of the participants were aware of HSPs, while 9.2% of the participants had only heard of HSPs. Awareness of HSPs was higher among men and younger individuals than among women and older generations. In addition, only 7.2% of the participants were aware of the location of the HSP in their area of residence. At the time at which this survey was conducted, only 3.5% of the participants were using HSP services, and half of them did not perceive the merits of using these services. However, 44.4% of the participants wished to avail themselves of HSP services in the future, and this desire increased with age. Half of the participants wished to use services that were associated with drugs, and the need for other services, such as consultations on diet/nutrition or health foods, was low. In conclusion, there was low awareness about HSPs among the survey participants. However, from our findings, we gathered that if individuals are aware of HSPs, they will wish to use HSP services. To improve healthy life expectancy, it is important to increase awareness about HSPs and their number.

Performance Index for Types of Clinical Research Support Service Providers for Academic Research Organizations in Japan: A Cross-Sectional Survey.

The purpose of this study was to conduct a factual survey to evaluate the type of clinical research support offered by service providers (supporters) in Japanese academic research organizations (AROs). From September to October 2018, we conducted an online questionnaire targeting researchers and supporters of AROs, including individuals supporting research and development (R&D) planning, as well as those involved in study management, biostatistics, coordination, data management, monitoring, and auditing. The number of responses was tabulated for each survey item. For items with written descriptions, we compiled summaries using the inductive regression method of qualitative research. Responses were obtained from 124 researchers, 258 supporters, and 40 AROs. None of the institutions responded that they had a performance index for all types of service providers, whereas 47% of institutions had an index for 1-3 types of service providers, and 40% of institutions had no index. Many institutions responded that they had a performance index for coordinators and data management, but few responded that there was a performance index for individuals engaged in R&D and study management. Furthermore, for all evaluations of AROs and researchers, the level of supporter satisfaction was low at only 20%. There was a discrepancy between the levels of researcher expectations and the actual contribution of R&D in the process of research planning. Our survey revealed that there is currently no performance index for services supporting clinical research. In future studies, we need to examine a performance index that accurately reflects the researcher attitudes revealed in this study.

Real World Survey of Patient Engagement Status in Clinical Research: The First Input from Japan.

BACKGROUND: The updated international draft guidelines, the "General Considerations for Clinical Studies, ICH E8 (R1)", state that patient engagement ensures that all perspectives are captured in the research process; however, this is not well understood, specifically in Japan. OBJECTIVE: This study examined the current status and perceptions of patient engagement in clinical research from the perspectives of patient groups, pharmaceutical corporations, and researchers in Japan, using anonymous self-administered questionnaires. METHODS: Three online surveys were conducted with patient groups (n = 100), pharmaceutical corporations (n = 66), and researchers (n = 300) in May and June 2019. The main variables were the current status and the current perception of patient engagement in clinical research. RESULTS: The response rate was 71% for patient groups and 85% for pharmaceutical corporations, and there were 300 valid responses (emergence rate: 4.9%) from researchers. Experiences with clinical research involving patient engagement were reported by 76.5% of the patients, 21.4% of the pharmaceutical corporations, and 51.7% of the researchers. Patient groups reported three major factors that negatively impacted their relationship with pharmaceutical corporations and researchers: (1) 'lack of understanding of the benefits of partnering'; (2) 'lack of transparency or openness'; and (3) 'unclear or ill-defined processes'. CONCLUSIONS: Pharmaceutical corporations in Japan have less experience with patient engagement in clinical research than other stakeholders. A neutral connecting system among the stakeholders with a constructive co-learning system will allow effective involvement/engagement of patient groups for enhancing the effectiveness of clinical research.

Utility of a Specific Health Checkup Database Containing Lifestyle Behaviors and Lifestyle Diseases for Employee Health Insurance in Japan.

BACKGROUND: The Japanese Ministry of Health, Labour and Welfare introduced Specific Health Checkups (SHC) to identify individuals at risk of metabolic syndrome (MS). This study aimed to describe the SHC database developed by the Japan Medical Data Center Co., Ltd. (JMDC) as a means of exploring lifestyle behaviors and lifestyle diseases among working generations. METHODS: We conducted a retrospective, cross-sectional study of employees and their families using the JMDC-SHC database to describe the prevalence of lifestyle behaviors (smoking, exercise, dietary habits, drinking habits, and sleeping) and lifestyle diseases (MS, hypertension, dyslipidemia, and diabetes mellitus). Results were compared with data from the 2015 National Health and Nutrition Survey (NHNS) in Japan as a benchmark. RESULTS: All 646,869 enrollees in the JMDC-SHC database were included, of whom 66.5% were men. Age ranged from 40-74 years. Compared with the results of the NHNS, the JMDC-SHC subjects were younger and had fewer MS components and a lower prevalence of diabetes and hypertension. Subjects in their 40s were most likely to have unhealthy lifestyle behaviors in all age groups (eg, smoking: 41.0% in men and 10.2% in women). The SHC group had more favorable behaviors overall, but underweight was more prevalent in the SHC females. CONCLUSIONS: The JMDC-SHC population showed different lifestyle and lifestyle disease profiles to the NHNS population, probably due to its different age, gender, and employment distributions. Development of healthcare policies and plans for working generations would benefit from the selection of an age- and employment-appropriate database.

Differences in efficacy evaluation endpoints in clinical trials for claiming reduction of post-prandial glycemic response between Japan and the European Union.

When evaluating the efficacy of foods with health claims (FHC), each country sets different standards for efficacy evaluation endpoints in clinical trials, which may result in a barrier, namely the case that the claim that is allowed in Japan cannot be used on the label in another region and vice versa. We aimed to investigate the efficacy evaluation endpoints used in clinical trials of FFCs containing ID and submitted in Japan, in reference to the EU requirements for substantiating the claim, namely "reduction of post-prandial glycemic responses". We detected only one difference in efficacy evaluation endpoints, which was insulin levels. We found 67 such clinical trials cited in systematic literature reviews on finished products or functional substance(s). Of these, 43 (64%) trials lacked insulin assessment. Particularly, for foods that were claimed to reduce post-prandial glycemic responses, the EU does not consider a claim to be substantiated unless insulin levels have been evaluated. Our findings suggest the need for standardization of requirements for FHC between Japan and the EU. This consideration will strengthen the evidence for clinical significance of ID and allow products labeled with this health claim to be more widely distributed.

Development of an electronic medical record-based algorithm to identify patients with Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), severe drug reactions, are often misdiagnosed due to their rarity and lack of information on differential diagnosis. The objective of the study was to develop an electronic medical record (EMR)-based algorithm to identify patients with SJS/TEN for future application in database studies. From the EMRs of a university hospital, two dermatologists identified all 13 patients with SJS/TEN seen at the Department of Dermatology as the case group. Another 1472 patients who visited the Department of Dermatology were identified using the ICD-10 codes for diseases requiring differentiation from SJS/TEN. One hundred of these patients were then randomly sampled as controls. Based on clinical guidelines for SJS/TEN and the experience of the dermatologists, we tested 128 algorithms based on the use of ICD-10 codes, clinical courses for SJS/TEN, medical encounters for mucocutaneous lesions from SJS/TEN, and items to exclude paraneoplastic pemphigus. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) of each algorithm were calculated, and the optimal algorithm was defined as that with high PPV and maximal sensitivity and specificity. One algorithm, consisting of a combination of clinical course for SJS/TEN, medical encounters for mucocutaneous lesions from SJS/TEN, and items to exclude paraneoplastic pemphigus, but not ICD-10 codes, showed a sensitivity of 76.9%, specificity of 99.0%, PPV of 40.5%, NPV of 99.8%, and DOR of 330.00. We developed a potentially optimized algorithm for identifying SJS/TEN based on clinical practice records. The almost perfect specificity of this algorithm will prevent bias in estimating relative risks of SJS/TEN in database studies. Considering the small sample size, this algorithm should be further tested in different settings.

Pediatric off-label use of psychotropic drugs approved for adult use in Japan in the light of approval information regarding pediatric patients in the United States: a study of a pharmacy prescription database.

BACKGROUND: Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan. This study sought to clarify pediatric patients' off-label use of psychotropics approved only for adults in Japan. METHODS: This retrospective study on psychotropic utilization employed a pharmaceutical health insurance claims database supplied by a pharmacy for the fiscal year 2016. Seven psychotropic drugs were examined. For each drug, we calculated the proportion of patients aged < 16 years or who were under the approved age limit set in the United States out of all patients. The maximum daily dose of each drug within the study period was plotted by age. RESULTS: Data of 45,715 patients (female: 26,799, male: 18,916) with 331,920 prescriptions were examined in this study. For each drug, the proportion of pediatric patients aged < 16 years ranged from 0.15 to 1.1%, while the proportion of those under the approved age limit in the United States ranged from 0 to 0.27%. Olanzapine had the highest reported proportion. No drugs other than olanzapine were taken under the approved age limit in the United States. CONCLUSIONS: We identified the pediatric off-label use of psychotropics that were limited to adult use in Japan. The results indicated the possibility of referring to international guidelines or evidence in clinical practice, but these factors do not discount the existing problems with off-label use. More clinical trials within the pediatric population in Japan are needed to address the issue of off-label use and obtain useful and reliable information in the package inserts for rational use in future pediatric patients.

Comparison of Drug Use Between Clinical Practice and Regulatory Approval: Results in Older Japanese Patients With Rheumatoid Arthritis, Diabetes, High Blood Pressure, or Depression.

BACKGROUND: In this study, differences in older patients between drug use as reported in clinical practice and in clinical trials for regulatory approval were examined. METHODS: Electronic medical record (EMR) data such as patient background (age, sex), concomitant drugs, data on laboratory tests, and prescribed doses of drugs from outpatients with rheumatoid arthritis, diabetes, high blood pressure, or depression at Chiba University Hospital were obtained for the period from January 2003 to December 2012. These data were compared with data from relevant clinical trials for regulatory approval in order to examine differences in drug use. RESULTS: There were 5134 eligible patients. The prescribed doses of drugs were lower than the standard approved doses for depression and rheumatoid arthritis but were generally within the approved dose range for type 2 diabetes mellitus and hypertension. When comparing the characteristics of older patients taking tacrolimus, 5.6% to 17.0% of those would not be able to participate in clinical trials because of liver or renal abnormality, and the incidence rates of some adverse drug events (ADEs) differed significantly between clinical practice and clinical trials. CONCLUSIONS: Appropriate doses of drugs for older patients may differ from approved doses in certain diseases. Complex situations such as a lot of polypharmacy, comorbidity, and functional impairment in older patients in clinical practice make it difficult to evaluate safety based on data from clinical trials. In the future, utilization of a database created from the EMR of older patients should be considered for assessment of drug safety in older patients in clinical practice.