[Optimal search conditions for identification of patients with chronic myeloid leukemia from Japanese National Health Insurance data].

This study investigated which conditions could be used to identify patients with chronic myeloid leukemia (CML) from a National Health Insurance claims dataset. During April 2012 and September 2018, 1,789,462 employees were enrolled in the dataset for Shizuoka Prefecture residents. The number of patients with the ICD-10 code for CML was 761. Among them, 246 who had been prescribed a tyrosine kinase inhibitor were considered as having true CML. The positive predictive value was calculated as 32.3% when CML was identified by ICD-10 code alone. Combination of ICD-10 code with prescribed drugs was required to accurately identify patients with CML from the insurance database.

Association of Eicosapentaenoic and Docosahexaenoic Acid Intake with Low Birth Weight in the Second Trimester: The Japan Pregnancy Eating and Activity Cohort Study.

This study examined the association of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during the second trimester with low birth weight (LBW) in pregnant Japanese women and was conducted in conjunction with the Japan Pregnancy Eating and Activity Cohort (J-PEACH) study. The study included 504 pregnant women from four Japanese sites. During the second trimester (14-27 weeks), the participants filled out a self-administered questionnaire assessing the frequency of DHA and EPA supplement intake in the past month, as well as a brief-type self-administered diet history questionnaire (BDHQ). The analysis involved data from two time points: responses to the BDHQ and infant data at birth. In total, 471 and 33 participants were classified into the normal birth weight and LBW groups, respectively. The participants were divided into high-, medium-, and low-intake groups based on their total dietary and EPA and DHA supplementary intakes. The Cochran-Armitage trend test was used to analyze the data; the prevalence of LBW was higher in the low-intake group (p = 0.04). There was no significant sex-based trend (p = 0.27 and p = 0.35). In Japanese women, low dietary and supplementary EPA and DHA intake until the second trimester were risk factors for LBW.

Distribution and Effects of Selenoneine by Ingestion of Extract from Mackerel Processing Residue in Mice.

Selenoneine is an organic selenium compound contained in blood and dark muscle of fish. It has a strong antioxidative capacity and is considered useful as a new functional food material. However, the distribution and effects of selenoneine in the mammalian body have not been thoroughly examined. In this study, a selenoneine-rich mackerel extract was developed and fed to mice at 0.07% in standard rodent chow (ME diet) for 32 days to examine its distribution in the body. Selenoneine was distributed in the liver, kidney, and spleen in mice fed with mackerel extract, but it was not distributed in the plasma or erythrocytes. Moreover, concentrations of the major selenium-containing protein were not affected by the mackerel extract. The results of this study suggest that selenoneine is absorbed in the body following ingestion of low doses in crude material and preferentially accumulates in organs and later distributes in erythrocytes. Biochemical analyses of plasma in male mice showed that the glucose level was significantly increased and LDL-cholesterol level was significantly decreased by ME diet feeding. The results indicate that male mice are sensitive to ME diet.

Nutrient Intake from Voluntary Fortified Foods and Dietary Supplements in Japanese Consumers: A Cross-Sectional Online Survey.

Consuming voluntary fortified foods (vFFs) and dietary supplements (DSs) is one method for addressing micronutrient inadequacy, but their efficacy is unclear. This study explored the use of vFFs and DSs, and the role of package labels. We conducted a nationwide online survey of 4933 Japanese adults in 2020. The use of vFFs and DSs was 23.3%. The reported vFFs were cereal products (n = 370), milk products/milk substitutes (n = 229), and one-shot drinks (n = 144). Vitamins, calcium, and iron were the main micronutrients added to the vFFs. Most users consumed vitamins C and B from vFFs and/or DSs, and females also consumed iron. The median intake of vitamins B6 and C, selenium, and zinc (plus vitamin B2 and copper in females) exceeded 50% of the respective estimated average requirement values. Approximately 60-70% of the users referred to nutrition labels. However, only a small percent of the respondents clearly understood the nutrient content. To address insufficient nutrient intake, the use of vFFs and DSs may be a good alternative; however, consumer education on the use of vFFs/DSs and package labels needs to be implemented before encouraging their use.

Data Resource Profile of Shizuoka Kokuho Database (SKDB) Using Integrated Health- and Care-insurance Claims and Health Checkups: The Shizuoka Study.

BACKGROUND: Analyzing real-world data, including health insurance claims, may help provide insights into preventing and treating various diseases. We developed a database covering Shizuoka Prefecture (Shizuoka Kokuho Database [SKDB]) in Japan, which included individual-level linked data on health- and care-insurance claims and health checkup results. METHODS: Anonymized claims data on health insurance (National Health Insurance [age <75 years] and Latter-Stage Elderly Medical Care System [age ≥75 years]), care insurance, subscriber lists, annual health checkups, and all dates of death were collected from 35 municipalities in Shizuoka Prefecture. To efficiently link claims and health checkups, unique individual IDs were assigned using a novel procedure. RESULTS: From April 2012 to September 2018, the SKDB included 2,230,848 individuals (men, 1,019,687; 45.7%). The median age (min-max) of men and women was 60 (0-106) and 62 (0-111) years, respectively. During the study period, the median subscription time was 4.4 years; 40.8% of individuals continuously subscribed for the 6.5 years; 213,566 individuals died. Health checkup data were available for 654,035 individuals, amounting to 2,469,648 records. Care-service recipient data were available for 283,537 individuals; they used care insurance to pay for care costs. CONCLUSION: SKDB, a population-based longitudinal cohort, provides a comprehensive dataset covering health checkups, disorders, medication, and care service. This database may provide a robust platform to identify epidemiological problems and generate hypotheses for preventing and treating disorders in the elderly.

Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro.

Natto, a traditional Japanese fermented soybean food, is well known to be nutritious and beneficial for health. In this study, we examined whether natto impairs infection by viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as bovine herpesvirus 1 (BHV-1). Interestingly, our results show that both SARS-CoV-2 and BHV-1 treated with a natto extract were fully inhibited infection to the cells. We also found that the glycoprotein D of BHV-1 was shown to be degraded by Western blot analysis and that a recombinant SARS-CoV-2 receptor-binding domain (RBD) was proteolytically degraded when incubated with the natto extract. In addition, RBD protein carrying a point mutation (UK variant N501Y) was also degraded by the natto extract. When the natto extract was heated at 100 °C for 10 min, the ability of both SARS-CoV-2 and BHV-1 to infect to the cells was restored. Consistent with the results of the heat inactivation, a serine protease inhibitor inhibited anti-BHV-1 activity caused by the natto extract. Thus, our findings provide the first evidence that the natto extract contains a protease(s) that inhibits viral infection through the proteolysis of the viral proteins.

Structural changes in cell wall of Japanese radish accompanied by release of rhamnogalacturonan during pressure cooker heating.

Changes in the cell wall of Japanese radish due to heating at 100 °C or 117 °C for 3 h were examined. Signals in 13C cross polarization magic angle spinning solid-state NMR (which detects rigid components) showed no differences between heating temperatures. 13C pulse saturation transfer magic angle spinning NMR (which detects flexible components) showed clear temperature-dependent changes in the rhamnose side chains of rhamnogalacturonan. Alcohol-insoluble solids isolated from raw samples were heated in water at 100 °C or 117 °C for 3 h. The concentrations of dissolved sugars and metal ions measured after heating in water at 117 °C were greater than in samples heated at 100 °C, indicating that loosening of cell wall structures increased with temperature, likely via degradation and elution of rhamnogalacturonan followed by ß-elimination of homogalacturonan, and fewer interactions between cell wall components, including divalent metal ions. Vegetable shape was retained despite fewer interactions.

Bioshell calcium oxide (BiSCaO) for cleansing and healing Pseudomonas aeruginosa-infected wounds in hairless rats.

BACKGROUND: Scallop shell powder is called bioshell calcium oxide (BiSCaO), which is known to possess deodorizing properties and broad antimicrobial activity against various pathogenic microbes, including viruses, bacteria, spores, and fungi. OBJECTIVE: This study aims to investigate the applications of BiSCaO suspension cleansing in clinical situations, for instance for the prevention and treatment of infections in chronic wounds in healing-impaired patients, without delaying wound healing. METHODS: The bactericidal activities of 1000 ppm BiSCaO suspension; 500 ppm hypochlorous acid; 1000 ppm povidone iodine; and saline were compared to evaluate in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. RESULTS: Cleansing of the infected wounds with BiSCaO suspension daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts, in comparison to hypochlorous acid, povidone iodine, and saline. Furthermore, histological examinations showed significantly advanced granulation tissue and capillary formation in the wounds cleansed with BiSCaO suspension than in those cleansed with the other solutions. CONCLUSIONS: This study suggested that the possibility of using BiSCaO suspension as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects on wound repair.

Coleus forskohlii Extract Attenuated the Beneficial Effect of Diet-Treatment on NASH in Mouse Model.

Obesity is one of the main causes of non-alcoholic steatohepatitis (NASH), which is associated with impaired liver functions including drug metabolism. Coleus forskohlii extract (CFE) is a popular ingredient of weight loss dietary supplements in Japan. In this study, we examined the effect of CFE on the treatment of NASH. C57BL/6 mice (male, 10-wk-old) were fed a NASH diet (high-fat, low-methionine, and choline-deficient diet) for 12 wk to establish NASH. Then, we examined the effect of 0.5% (w/w) CFE in diet during diet-treatment (change to control diet) and/or treadmill-exercise (45 min at 20 m/min, 5 d/wk) to improve NASH for 3 wk. After experimental period, lipids profiles and liver functional markers in the blood, and hepatic lipid content and major CYP subtype mRNA expression and activity in liver were measured. Diet-treatment, but not exercise decreased liver weight and hepatic lipid contents in NASH induced mice. CFE attenuated the effects of diet-treatment which reduced liver weight, even though body weight and adipose tissue weight were reduced. Further, CFE significantly increased liver microsomal CYP1A1, CYP1A2, CYP2C, and CYP3A activities in each condition, and CYP inductions were greater in diet-treatment group compared to those in exercise group. These results suggest that taking CFE should be avoided during diet-treatment of NASH, especially in patients under medication.

[Consulting Pharmacists Who Have Advisory Staff License Regarding the Use of Medicines and Health Foods].

The widespread use of health foods, including supplements, is now common among patients. This is because many health foods are being claimed to be beneficial. If patients use medicines and health foods concurrently, the interaction between the two might lead to adverse events. Additionally, it is reported that pharmacists do not generally care about health food use in their patients, because they also lack sufficient knowledge about health foods. On the contrary, there are some licenses to be a health food advisor in Japan, and the generic name of these licenses is "advisory staff". Pharmacists who have this license are specialists in both medicines and health foods, and thus, they might pay more attention to the concurrent use of medicines and health foods compared to those who do not have the advisory staff license. To address this issue, we conducted a study with an online questionnaire about health food consultation, and 87 pharmacists with advisory staff license participated. Only 36.8% of participants were found to always ask their patients about health food use. However, 92.0% of them had experience of consultation about the simultaneous use of medicines and health foods, and 17.2% of them recognized adverse events by knowing about the concurrent use. Patients who experienced adverse events have used either eicosapentaenoic acid/docosahexaenoic acid supplement with epadel or Ginkgo biloba extract with warfarin. Therefore, an active interview with pharmacists is important to avoid such adverse events in patients.

Concomitant Use of Dietary Supplements and Medicines among Preschool and School-Aged Children in Japan.

Dietary supplement use is widespread amongst the general population including in children and adolescents. The ingredients in dietary supplements can interact with medicines when patients take them concomitantly. However, the prevalence of the concomitant use of dietary supplements and medicines in Japan among children remains unclear. To clarify this issue, a nationwide internet survey was administered to 55,038 mothers (25 to 60 years old) of preschool- or school-aged children in Japan. Among them, 7.6% currently provide dietary supplements and 3.2% concomitantly provide dietary supplements and prescription or over-the-counter medicines to their children. The prevalence of concomitant use increased with the children's grade. Among 1057 mothers with 1154 children who were concomitantly using dietary supplements and medicines, 69.1% provided dietary supplements without physician consultation because they considered dietary supplements as only foods and therefore safe. Although the purpose of the use and types of dietary supplement differed between boys and girls, the most popular product was probiotics in both boys and girls. Among concomitant users, 8.3% of mothers gave dietary supplements for treatment of diseases and 4.9% mothers recognized the adverse events of dietary supplements in their child. The findings of this study suggest that mothers' knowledge about the risk of using dietary supplement with medicines is insufficient. Parental education about the safety of dietary supplements and potential risk of drug-supplement interaction is needed.

Are There Adverse Events after the Use of Sexual Enhancement Nutrition Supplements? A Nationwide Online Survey from Japan.

Dozens of safety alerts for sexual enhancement and weight loss dietary supplements have been launched from the government not only in Japan but also overseas. However, adverse events have been reported only for the use of weight loss supplements, and the prevalence of use and adverse events in sexual enhancement supplements is not known in Japan. To address this issue, we assessed the situation of sexual enhancement supplement use through a nationwide online survey. The prevalence of sexual enhancement supplement use among males was 23.0%. Use of these supplements was higher among younger people than among older people (p < 0.001). In total, 17.6% of users had experienced adverse events, but 58.3% of them did not consult about the events with anybody because of the temporality of their symptoms and their sense of shame. In addition, eight supplement products were found to be possible adulterated supplements in this survey. It is necessary to inform the public about the risk of sexual enhancement supplement use and also prepare a place for consultation on media channels that younger people are more familiar with, in order to monitor adverse events while also preserving their privacy.

[Systematic Review of Case Reports on the Adverse Events Due to Health Food Intake by Cancer Patients].

Cancer patients use health foods (HFs) as complementary and alternative medicine, although the details of their adverse events (AEs) are unclear. We searched three databases [PubMed, "Igaku Chuo Zasshi", and Information System on Safety and Effectiveness for Health Foods website (https://hfnet.nibiohn.go.jp/)] for case reports on AEs related to HF intake in cancer patients published before October 2018. Of the matched reports, 76 studies and 92 patients (31 in Japan, 61 overseas) that met the selection criteria were included in this review. Thus, the severity of AEs and outcomes were not related to either the concomitant use of HF with cancer chemotherapy or cancer stages of patients. AEs caused by HF intake itself accounted for 87%, while drug-HF interaction accounted for 11%. According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, 70% of patients whose grades were identified had severe cases (grades 3 to 5). In Japanese patients, hepatic and respiratory disorders accounted for 52% of the severe cases. Cases were predominantly developed as a result of an allergic mechanism, and mushroom products were mostly used. Overseas, serious cases were induced by products that were already indicated for safety problems. Moreover, notable AEs were recognized, such as hypercalcemia, which were caused by intake of HF containing calcium, vitamin D, and shark cartilage, and bacterial infection caused by probiotic products. Analyzing the details of AEs related to HF intake can help health professionals and cancer patients prevent health hazards.

[Evaluation of Safety Information of the Foods with Function Claims Based on Adverse Event Reports in Information System on Safety and Effectiveness for Health Foods Database].

Foods with Function Claims are allowed to label health claims based on scientific evidence evaluated by the manufacturers. To prevent health problems caused by inadequate use, the manufacturers should label proper safety information. To evaluate whether safety information is sufficiently provided, we conducted the adverse event review focused on popular functional ingredients using the database; Information system on safety and effectiveness for health food. The data suggested that causal factor of adverse events related to products containing soy isoflavone, ginkgo biloba extract and docosahexaenoic acid/eicosapentaenoic acid were overdose intake, concomitant use with certain medicines, and use by whom with an allergic predisposition. However, the safety information on the label was insufficient to prevent adverse events on each products' label. It is important not only to encourage food manufacturers to provide sufficient information based on safety review, but also to inform consumers about adverse events.

A Nationwide Survey of the Attitudes toward the Use of Dietary Supplements among Japanese High-School Students.

We previously studied the prevalence of dietary supplement use in Japanese high-school students by conducting a study on mothers. However, there is often a discrepancy between mothers' understanding and children's attitudes. Thus, we conducted an internet survey of high-school students to clarify their attitudes toward the use of dietary supplements. An invitation to the internet survey was e-mailed to registrants of a research company aged 15 to 18 years. A total of 1031 students (276 male, 755 female) answered the questionnaire on a first come, first served basis. The participants were classified according to the purchasers of their supplements: students who purchased supplements themselves were defined as active users, and others were defined as passive users. The prevalence of dietary supplement use was 30.8% in males and 26.7% in females. Among the users, 42.4% of males and 43.8% of females were active users. Males used supplements for health regardless of active or passive use. However, in females, more active users (40.9%) used supplements for weight loss than passive users (20.4%); the corresponding prevalence was 2.3% in our previous report on mothers' understanding of their daughters. The most frequently used source of information for active users was the internet, whereas for passive users it was family. The frequency of adverse events was 9.4% in males and 14.4% in females, with gastrointestinal symptoms being the most commonly experienced events. Our results suggest that dietary education, including healthy eating and the appropriate use of dietary supplements, should be provided to high-school students.

Characteristics of Moyamoya Disease Based on National Registry Data in Japan.

Background and Purpose- A public registration system for intractable diseases was started in Japan in 1972 to investigate the etiology and pathogenesis of intractable diseases while reducing out-of-pocket medical expenses on patients. The goal of this study was to investigate the epidemiology and clinical characteristics of Moyamoya disease using data from applications submitted to this system between 2004 and 2008. Methods- In addition to demographic factors such as onset age and family history, we evaluated clinical presentation type, imaging findings, clinical symptoms, and functioning in activities of daily living (ADL). Results- Of 3859 cases for which applications were submitted, 2545 were confirmed to meet the diagnostic criteria after data cleansing. Onset age showed a bimodal distribution, and Moyamoya disease had a higher incidence in women than in men. The presence of occlusion and infarction in the proximal region of the anterior cerebral artery was more frequent in pediatric cases than adult cases. Our findings also indicated that 23% of patients required assistance with ADL. Cerebral infarction (odds ratio [OR], 12.5; 95% CI, 3.55-44.66), seizure (OR, 7.44; 95% CI, 1.29-42.96), and sensory disorders (OR, 5.23; 95% CI, 1.15-23.75) were identified as significant predictors of impaired ADL in pediatric cases 3 years after the initial application. Moderate ADL function (OR, 11.59; 95% CI, 5.29-25.39) and intellectual disabilities (OR, 4.38; 95% CI, 1.58-12.17) at the time of the application were identified as significant prognostic factors in adults. Conclusions- The results of this study indicated that characteristics of Moyamoya disease such as onset type, symptoms, and imaging abnormalities differ with onset age. Prognostic analyses suggested that pediatric cases with good ADL but with infarct type onset, seizure, or sensory disorders might have a subsequent decline in ADL.

Nationwide Online Survey Enables the Reevaluation of the Safety of Coleus forskohlii Extract Intake Based on the Adverse Event Frequencies.

The formulations of the functional ingredients of dietary supplements was studied with a small number of subjects, with a particular focus on their effectiveness, but not enough to evaluate their safety. In this regard, the reevaluation and estimation of the safe use of marketed products, with regards to their adverse event (AE) frequencies, are important. To address this issue, a post-marketing nationwide online survey was conducted for the herbal ingredient Coleus forskohlii extract (CFE), a popular weight-loss ingredient. The questionnaire included product names, adherence to the claimed amount, and AE experiences. The safe intake amount was estimated by the relationship between the claimed amount of CFE and the frequencies of AEs of each product. The number of users who experienced AEs was 75 (10.5% of all users). Gastrointestinal symptoms accounted for 92.0% (n = 69) of all AEs, and diarrhea alone accounted for 81.3% (n = 61). The amount of CFE was significantly associated with the occurrence of diarrhea (p = 0.005). The fitted curve showed that the safe intake amount of CFE was less than 250 mg/day; however, considering its effectiveness, 500 mg/day of CFE might be acceptable. In conclusion, nationwide online surveys of users enable us to confirm and reevaluate the safety of herbal supplements.

Nationwide Online Survey to Complement the Current Voluntary Reporting System for Adverse Events Associated with Dietary Supplements: Application to the Case of Skin Manifestations.

The current adverse event reporting system for dietary supplements lacks the ability to collect and analyze ongoing case reports in sufficient numbers to detect health issues. We conducted an online survey to collect data on skin manifestations due to supplement use in consumers and to identify the suspected products and ingredients. An online survey was conducted among 63,737 dietary supplement users in 2016. Those who self-reported experiences of skin anthema or itching caused by supplement use and recognized a causal relationship as almost certain (0.8%) were invited to provide further details of symptoms and products. Most of the users experienced mild symptoms with "itching and/or rash of body part." After the onset of skin manifestations, 69.3% ceased supplement use, while 26.6% continued supplement use, including those who reduced the amount or frequency of use. Respondents who visited the hospital in response to symptoms accounted for 26.0%, while 53.3% did not seek treatment. The products used were identified in 155 of 300 eligible respondents. Although those products were composed of multiple ingredients, the accumulated data suggested that cutaneous symptoms were related to the following constituents: "Peptides or animal by-products" (31.0%), "Herbal/Botanical" (23.2%) and "Fats and lipid" (13.5%). Conducting an online survey to elicit information directly from consumers identified components of supplements that are involved in skin manifestations that could lead to serious damage, and may fill a void in the current adverse event reporting system.

The Prevalence of Dietary Supplement Use Among Elementary, Junior High, and High School Students: A Nationwide Survey in Japan.

The prevalence of dietary supplement use, such as vitamins, minerals, or fish oil, has increased among children in Japan; however, whether children are using dietary supplements appropriately remains unclear. This study aimed to determine dietary supplement use among children. In August 2017, a nationwide internet preliminary survey of 265,629 mothers aged from 25 to 59 years old was undertaken. Of these, 19,041 mothers of children attending either elementary school, junior high school, or high school were selected. Among them, 16.4% were currently providing their children with dietary supplements and 5.2% had previously given dietary supplements to their children. The prevalence of dietary supplement use was higher in boys than in girls, and the prevalence increased according to their grade. A total of 2439 participants were eligible to undertake a targeted survey on dietary supplement use. Dietary supplements were being taken to maintain health, supplement nutrients, and enhance growth in both boys and girls, and many children (37.5%) were provided with vitamin and mineral supplements. Mothers mainly obtained information concerning dietary supplements via the internet, and supplements were purchased in drug stores or via the internet. The prevalence of dietary supplement use in mothers was 65.4% and may be associated with the prevalence rates in children. Some mothers reported adverse events (3.6%) in their children, such as stomachache, diarrhea, nausea and vomiting, and constipation. The cause-and-effect relationships for adverse events were not clear, but some children were given products for adults. Children are more influenced by dietary supplements compared to adults. To prevent adverse events due to inappropriate use, parental education concerning dietary supplements is essential.

[Nationwide Online Survey Method to Estimate Ongoing Adverse Events Caused by Supplement Use: Application to Diarrhea].

The current adverse event reporting systems are inadequate to prevent potential health damage caused by dietary supplement use, and a better case-collecting system is needed. The aim of this study was to examine whether online surveys would be a useful methodology for estimating ongoing adverse events, focusing on diarrhea as a model symptom. We used four online survey companies and requested that they administer the same questionnaire to their registrants regarding experiences of adverse events associated with supplement use and details of diarrhea symptoms, as well as the product and ingredient names of suspected supplements. Of 78,220 dietary supplement users, 9% to 25% reported experiencing adverse events in the previous year. A total of 723 participants who answered affirmatively about a putative causal relationship between supplement use and the onset of diarrhea and who clearly identified the product and/or ingredient were eligible for final analysis. Comparisons among the survey companies showed differences in the proportions of reported symptoms; however, the rank orders were consistent in the preliminary survey. Also, when analysis was limited to specific participants from a full-scale survey, even the numerical values of the proportions were consistent among the four companies. Herbal/botanical ingredients, specifically Coleus forskohlii, were the ingredients most frequently reported to be associated with diarrhea. These results indicate that online survey can be a useful method to complement the current system for estimating ongoing adverse events and identifying the responsible supplements.