Improvement trend for individual health guidance intervention according to Japan clinical guidelines by public health nurses for type 2 diabetes mellitus who visited for medical checkups regularly: a case-control preliminary report.

We conducted a retrospective case-control study to assess the efficacy of personalized health guidance interventions on individuals with type 2 diabetes mellitus and obesity. A selection was made of individuals in regular visits to the Takagi Hospital for medical checkups between January 2017, and October 2021. Totally, 108 subjects (cases) with health guidance were divided into 2 groups: one group without pharmacotherapy for diabetes mellitus in medical institutions (n = 92) and another group with pharmacotherapy (n = 116). Cases were provided with personalized health guidance interventions by public health nurses for 30 min, in accordance with the Japanese clinical guidelines for the prevention of lifestyle-related diseases. Sex- and age-matched controls were chosen from individuals with diabetes mellitus without health guidance. The intervention without pharmacotherapy resulted in improvements in health indicators, including body weight, waist circumference, diastolic blood pressure, triglyceride levels, and γ-glutamyl trans-peptidase. These positive effects were not observed in the control group without health guidance. The therapeutic effects of health guidance were observed in cases where pharmacotherapy was administered. In conclusion, the implementation of individual health guidance interventions may prove to be effective for individuals with type 2 diabetes mellitus and obesity who regularly attend medical checkups.

Surveillance systems for healthcare-associated infection in high and upper-middle income countries: A scoping review.

BACKGROUND: Healthcare-associated infection (HAI) surveillance is useful for improved infection control. To understand the current HAI surveillance systems (HAISS) trend globally, a scoping review was performed. MATERIALS AND METHODS: The search strategy included academic literature review, Google search, and questionnaires by the Embassies of Japan (registration number: UMIN000036035). Eighty-two high and 56 upper-middle income countries defined by country income classification for the World Bank were targeted. The following information was reviewed: name of the system, official website, languages used in the official website, foundation year, operating body, survey type (prevalence or incidence), reporting periodicity, mode of participation (mandatory or voluntary), targeted medical facilities, targeted HAIs and definitions, targeted antimicrobial resistant pathogens, and parameters. Online accessibility of the official websites of the SS was assessed through Google search. RESULTS AND CONCLUSION: Forty-two (30.4%) countries (35 [42.7%] high and 7 [12.5%] upper-middle income countries) had national HAISS. Most systems operated on a voluntary basis, monitored HAI incidence, and used the Center for Disease Control and Prevention definitions. Methicillin-resistant Staphylococcus aureus, surgical site infection, and catheter-related blood stream infection were most commonly monitored. Surveillance for device-associated infections was implemented mainly in intensive care units. Thirty-five countries had at least one official website on their systems, while 7 (20.0%) were identified in the top 30 Google search hits, in English. Approximately half of the academic articles identified through PubMed were from three English-speaking countries. The feasibility and benefits of standardization of the HAI surveillance criteria and efficient feedback methods are future considerations.

A qualitative study on the stigma experienced by people with mental health problems and epilepsy in the Philippines.

BACKGROUND: Stigma towards people with mental health problems (PMHP) is known to have substantial negative impacts on their lives. More in-depth exploration of the stigma and discrimination experienced by PMHP in low- and middle-income countries is needed. Previous research suggests that negative attitudes towards PMHP are widespread among the Filipino general public. However, no study has investigated PMHP's own experiences of being stigmatised in the Philippines. METHODS: A qualitative study was conducted on the stigma experienced by PMHP (including people with epilepsy) and its related factors in the Philippines, employing the constructivist grounded theory approach. We analysed data on 39 PMHP collected through interviews with PMHP, their carers, and community health volunteers who know them well. RESULTS: The findings highlight the culturally and socio-economically specific contexts, consequences, and impact modifiers of experiences of stigma. Participants emphasised that PMHP face stigma because of the cultural traits such as the perception of mental health problem as a disease of the family and the tendency to be overly optimistic about the severity of the mental health problem and its impact on their life. Further, stigma was experienced under conditions where mental health care was not readily available and people in the local community could not resolve the PMHP's mental health crisis. Stigma experiences reduced social networks and opportunities for PMHP, threatened the economic survival of their entire family, and exacerbated their mental health problems. An individual's reaction to negative experiences can be fatalistic in nature (e.g. believing in it is God's will). This fatalism can help PMHP to remain hopeful. In addition, traditional communal unity alleviated some of the social exclusion associated with stigma. CONCLUSIONS: The study indicates that existing stigma-reduction strategies might have limitations in their effectiveness across cultural settings. Therefore, we propose context-specific practical implications (e.g. emphasis on environmental factors as a cause of mental health problems, messages to increase understanding not only of the possibility of recovery but also of challenges PMHP face) for the Philippines.

Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats.

The pathogenesis and therapeutics of depression are linked to the operation of the circadian system. Here, we studied the chronopharmacological action of a tricyclic antidepressant, imipramine. Male adult Wistar-Hannover rats were administered imipramine acutely or chronically in the morning or in the evening. The antidepressant action of imipramine was analyzed using the forced swim test (FST). A single dose of imipramine (30 mg/kg) in the morning, but not in the evening, reduced immobility and increased climbing in the FST. The plasma concentrations of imipramine and its metabolite, desipramine, were slightly higher in the morning than in the evening, which might explain the dosing time-dependent action of imipramine. Next, we analyzed the effect of chronic imipramine treatment. Rats received imipramine in the morning or in the evening for 2 weeks. The morning treatment resulted in larger effects in the FST than the evening treatment, and was effective at a dose that was ineffective when administered acutely. The levels of brain α-adrenergic receptors tended to decrease after chronic imipramine treatment. Imipramine might interact with noradrenergic neurons, and this interaction might chronically alter receptor expression. This alteration seemed greater in the morning than in the evening, which might explain the dosing time-dependent action of imipramine.

A novel anti-microtubule agent with carbazole and benzohydrazide structures suppresses tumor cell growth in vivo.

BACKGROUND: The mitotic spindles are among the most successful targets of anti-cancer chemotherapy, and they still hold promise as targets for novel drugs. The anti-mitotic drugs in current clinical use, including taxanes, epothilones, vinca alkaloids, and halichondrins, are all microtubule-targeting agents. Although these drugs are effective for cancer chemotherapy, they have some critical problems; e.g., neurotoxicity caused by damage to neuronal microtubules, as well as innate or acquired drug resistance. To overcome these problems, a great deal of effort has been expended on development of novel anti-mitotics. METHODS: We identified novel microtubule-targeting agents with carbazole and benzohydrazide structures: N'-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-methylbenzohydrazide (code number HND-007) and its related compounds. We investigated their activities against cancer cells using various methods including cell growth assay, immunofluorescence analysis, cell cycle analysis, tubulin polymerization assay, and tumor inhibition assay in nude mice. RESULTS: HND-007 inhibits tubulin polymerization in vitro and blocks microtubule formation and centrosome separation in cancer cells. Consequently, it suppresses the growth of various cancer cell lines, with IC50 values in the range 1.3-4.6µM. In addition, HND-007 can inhibit the growth of taxane-resistant cancer cells that overexpress P-glycoprotein. Finally, HND-007 can inhibit HeLa cell tumor growth in nude mice. CONCLUSIONS AND GENERAL SIGNIFICANCE: Taken together, these findings suggest that HND-007 is a promising lead compound for development of novel anti-mitotic, anti-microtubule chemotherapeutic agents.

[Single institution experience of HLA-haploidentical hematopoietic stem cell transplantation for children: current problems and perspective].

HLA-haploidentical 2 or 3-loci mismatched families are alternative donors for high-risk patients without HLA-matched donors. We retrospectively reviewed our case series of HLA-halpoidentical hematopoietic stem cell transplantations (haplo-HSCTs). Between Jul 2005 and Dec 2012, 25 patients (median age, 8 y; 13 ALL, 8 AML, 4 others) received haplo-HSCTs because of a worsening prognosis (i.e. induction failure, non-CR, or relapse after prior HSCT). Disease status was CR in 8 and non-CR in 17 patients. The 17 patients received myeloablative conditioning, while the 8 were given reduced-intensity conditioning because of their conditions (e.g. early relapse after prior HSCT). ATG was not administered in all but 3 patients. Tacrolimus and sMTX were used for prophylaxis GVHD and steroids were immediately given to prevent the onset of aGVHD. The 3-year OS and EFS were 35.6±10.0% and 31.3±10.1%, respectively (median follow-up, 49 mo); 14 patients died of their primary disease. Grade 3-4 aGVHD occurred in 7 patients, 2 of whom died of grade 4 aGVHD. Eleven patients had extensive cGVHD. While 4 of the 8 CR patients remained in CR, only 4 of the 17 non-CR patients achieved long-term CR (survival time, 6-89 mo). Haplo-HSCT was tolerable with strict control of infections and GVHD. However, further strategies for non-CR patients appear to be required.

Phase I study of bevacizumab plus irinotecan in pediatric patients with recurrent/refractory solid tumors.

OBJECTIVE: Studies have suggested that bevacizumab has shown activity against various pediatric solid tumors. We, therefore, conducted a Phase I study of bevacizumab plus irinotecan in Japanese children with recurrent, progressive or refractory solid tumors. METHODS: The starting dose was bevacizumab 10 mg/kg over 60-90 min and irinotecan 125 mg/m(2) over 90 min intravenously on Days 1, 15 and 29. The dose of irinotecan was 340 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs. Treatment was repeated every 6 weeks for up to three courses in the absence of disease progression or unacceptable toxicity. RESULTS: Of 11 patients, 9 (median age, 9 years) were fully assessable for toxicity and received 24 courses. Dose-limiting toxicities were Grade 2 diarrhea and Grade 4 neutropenia/thrombocytopenia in two of the five patients at dose level 1. No dose-limiting toxicities were observed in four patients at dose level -1 at bevacizumab 10 mg/kg and irinotecan 100 mg/m(2) (270 mg/m(2) for patients taking enzyme-inducing antiepileptic drugs). The maximum-tolerated dose was bevacizumab 10 mg/kg and irinotecan 100 mg/m(2). The most frequent non-dose-limiting toxicities were Grade 1 or 2 hypertension, bleeding and hematologic toxicity. One patient with optic nerve glioma had a partial response. Three patients with medulloblastoma, optic nerve glioma and diffuse intrinsic pontine glioma had stable disease. CONCLUSIONS: Combination chemotherapy of bevacizumab plus irinotecan was well tolerated in children. We plan Phase II pediatric studies at doses of bevacizumab 10 mg/kg and irinotecan 100 mg/m(2) every 2 weeks (270 mg/m(2) for patients taking enzyme-inducing antiepileptic drugs).

Relationship between Cognitive Decline and Daily Life Gait among Elderly People Living in the Community: A Preliminary Report.

Introduction: Early detection and intervention are important to prevent dementia. Gait parameters have been recognized as a potentially easy screening tool for mild cognitive impairment (MCI); however, differences in gait parameters between cognitive healthy individuals (CHI) and MCI are small. Daily life gait change may be used to detect cognitive decline earlier. In the present study, we aimed to clarify the relationship between cognitive decline and daily life gait. Methods: We performed 5-Cog function tests and daily life and laboratory-based gait assessments on 155 community-dwelling elderly people (75.5 ± 5.4 years old). Daily life gait was measured for 6 days using an iPod-touch with an accelerometer. Laboratory-based 10-m gait (fast pace) was measured using an electronic portable walkway. Results: The subjects consisted of 98 CHI (63.2%) and 57 cognitive decline individuals (CDI; 36.8%). Daily life maximum gait velocity in the CDI group (113.7 [97.0-128.5] cm/s) was significantly slower than that in the CHI group (121.2 [105.8-134.3] cm/s) (p = 0.032). In the laboratory-based gait, the stride length variability in the CDI group (2.6 [1.8-4.1]) was significantly higher than that in the CHI group (1.8 [1.2-2.7]) (p < 0.001). The maximum gait velocity in daily life gait was weakly but significantly correlated with stride length variability in laboratory-based gait (ρ = -0.260, p = 0.001). Conclusion: We found an association between cognitive decline and slower daily life gait velocity among community-dwelling elderly people.

Pancreas transplantation improves the quality of life of Japanese type 1 diabetes patients with diabetic kidney disease.

Objectives: Type 1 diabetes mellitus (T1DM) patients with diabetic kidney disease-induced kidney failure have a significantly impaired quality of life (QOL), resulting in a high level of physical, mental, and social anxiety. In this study, we evaluated the QOL of T1DM patients on the list for pancreas transplantation (PTx) at their registration, and determined whether PTx improved their QOL. Methods: There were 58 patients (men/women, 22/36; mean age, 42.8±8.0 years) with T1DM and who were registered on the waiting list for PTx. Quantitative QOL assessment was performed using the Medical Health Survey Short Form (SF-36) version 2. Changes in the QOL before and after PTx were also examined in 24 of these patients. Results: The mean value of each endpoint and the summary score of the SF-36 physical (PCS), mental (MCS), and role (RCS) components were all below the national normal level at PTx registration. No significant difference in QOL scores was observed in the intergroup comparison of 35 patients on dialysis, 13 patients without dialysis, and ten patients after kidney transplantation. The 24 patients who underwent PTx showed improvement in PCS, MCS, and most SF-36 scores. Conclusion: T1DM patients waiting for PTx had a decreased QOL, regardless of dialysis, and PTx improved their QOL.

[Successful treatment for thrombotic microangiopathy with recombinant human soluble thrombomodulin after umbilical cord blood transplantation].

A 1-year-old girl with familial hemophagocytic lymphohistiocytosis underwent umbilical cord blood transplantation. On day 24, she developed renal failure, jaundice and hemolytic anemia, and we diagnosed transplantation-associated thrombotic microangiopathy (TMA). Despite discontinuation of tacrolimus, her condition became even worse. From day 25, we started to administer recombinant human soluble thrombomodulin (rTM). According to the recommendation of the pharmaceutical company, a dose reduction from 380 to 130 IU/kg/day in patients with renal failure, we administered rTM at the reduced dose during the first 2 days. Because the reduced dose was not effective, we administered rTM at the standard dose from day 27. Surprisingly, she began to recover from TMA on the next day, and we continued to administer rTM until day 109. She is alive without evidence of disease eighteen months after transplantation. Adverse events of rTM were severe gastrointestinal hemorrhage and hemorrhagic cystitis, and it was necessary to control hemorrhage by interruption of administration. This case report suggests that rTM may be effective for TMA. Moreover, alteration in the dosage schedule seems to be required according to the condition of patients. Further studies are needed to evaluate the effectiveness and an optimal dose of rTM as a treatment for TMA.

Synthesis of Tetra-Substituted Trifluoromethyl-3,1-Benzoxazines by Transition-Metal-Catalyzed Decarboxylative Cyclization of N-Benzoyl Benzoxazinones.

Invited for this month's cover are the group of Norio Shibata at Nagoya Institute of Technology (Japan). The cover picture is inspired by the diversity in the ocean also in cyberspace. In the present research, we can synthesize diverse heterocyclic molecules having a trifluoromethyl group in a single step by changing the N-substitution. You can see more variations of trifluoromethyl heterocycles in several papers by our group. Read the full text of their Communication at 10.1002/open.202000360.

Synthesis of Tetra-Substituted Trifluoromethyl-3,1-Benzoxazines by Transition-Metal-Catalyzed Decarboxylative Cyclization of N-Benzoyl Benzoxazinones.

Efficient synthesis of N,O-heterocyclic tetra-substituted trifluoromethyl-3,1-benzoxazines via a transition-metal-catalyzed decarboxylative intramolecular cyclization was achieved. The decarboxylation of N-benzoyl trifluoromethyl-benzoxazinones generated the amide oxygen nucleophile, allowing a selective internal C1 -attack on Pd- or Cu-coordinated zwitterions, affording medicinally attractive tetra-substituted vinyl- or ethynyl-trifluoromethyl-3,1-benzoxazines. This protocol can be applied to the synthesis of perfluoroalkyl- and non-fluorinated 3,1-benzoxazines.

Clinical characteristics of central serous chorioretinopathy in patients by age.

PURPOSE: To investigate the clinical characteristics of central serous chorioretinopathy (CSC) with age. STUDY DESIGN: Retrospective, cross-sectional study. METHODS: One-hundred and forty-seven CSC patients were classified into three age groups (aged <50 years (younger group; n=53), 50-70 years (middle group; n=68), and >70 years (senior group; n=26)) and the characteristics were compared. Bilateral ophthalmic evaluation included the best corrected visual acuity (BCVA), spherical equivalents, fundus examination, fundus autofluorescence, optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography. RESULTS: The male/female ratio became lower at more advanced ages (P=0.011). Bilateral macular abnormalities were observed more frequently in the senior group than the other groups (p=0.018) and multiple drusen were characteristic in the senior group (p<0.0001). The more advanced age groups displayed a worse BCVA (P=0.002). The rate of eyes with flat retinal pigment epithelium (RPE) elevation on OCT was significantly higher in the middle group than the other groups (P=0.024). The mean subfoveal choroidal thickness (SCT) was thickest in the younger group (P<0.0001). Unifocal leakage on FA and choroidal vascular hyperpermeability were mostly found in eyes of the younger group (P<0.001,P=0.020). CONCLUSION: CSC cases in those aged >70 years were associated with an increased proportion of women and having bilateral macular abnormalities, multiple drusen, and multifocal leakage sites. The BCVA and the SCT decreased with age. Patients with CSC aged 50-70 years had the highest rate of flat RPE elevation on OCT. These characteristics need to be considered to make an accurate diagnosis, particularly in elderly patients.

Characteristics and limitations of national antimicrobial surveillance according to sales and claims data.

PURPOSE: Antimicrobial use (AMU) is estimated at the national level by using sales data (S-AMU) or insurance claims data (C-AMU). However, these data might be biased by generic drugs that are not sold through wholesalers (direct sales) and therefore not recorded in sales databases, or by claims that are not submitted electronically and therefore not stored in claims databases. We evaluated these effects by comparing S-AMU and C-AMU to ascertain the characteristics and limitations of each kind of data. We also evaluated the interchangeability of these data by assessing their relationship. METHODS: We calculated monthly defined daily doses per 1,000 inhabitants per day (DID) using sales and claims data from 2013 to 2017. To assess the effects of non-electronic claim submissions on C-AMU, we evaluated trends in the S-AMU/C-AMU ratio (SCR). To assess the effects of direct sales of S-AMU, we divided AMU into generic and branded drugs and evaluated each SCR in terms of oral versus parenteral drugs. To assess the relationship between S-AMU and C-AMU, we created a linear regression and evaluated its coefficient. RESULTS: Median annual SCRs from 2013 to 2017 were 1.046, 0.993, 0.980, 0.987, and 0.967, respectively. SCRs dropped from 2013 to 2015, and then stabilized. Differences in SCRs between branded and generic drugs were significant for oral drugs (0.820 vs 1.079) but not parenteral drugs (1.200 vs 1.165), suggesting that direct sales of oral generic drugs were omitted in S-AMU. Coefficients of DID between S-AMU and C-AMU were high (generic, 0.90; branded, 0.84) in oral drugs but relatively low (generic, 0.32; branded, 0.52) in parenteral drugs. CONCLUSIONS: The omission of direct sales information and non-electronically submitted claims have influenced S-AMU and C-AMU information, respectively. However, these data were well-correlated, and it is considered that both kinds of data are useful depending on the situation.

Poor Walking Speed Is Associated With Higher Segment-Specific Arterial Stiffness in Older Adult Japanese Community Dwellers: A Cross-Sectional Study.

Walking speed as one index of gait ability is an important component of physical fitness among older adults. Walking speed-arterial stiffness relationships have been studied, but whether poor walking speed is associated with higher segment-specific arterial stiffness in older adults is unclear. We thus aimed to examine the relationship between walking speed and segmental arterial stiffness among older community dwellers. This study was a cross-sectional study of 492 older Japanese community dwellers (age range, 65 to 96 years). Heart-brachial PWV (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and cardio-ankle vascular index (CAVI) were used as arterial stiffness indices. Walking speed, strength, flexibility, and cognitive function were also assessed. The participants were categorized into low (Slow), middle (Middle), and high (Fast) tertiles according to walking speed. The CAVI and baPWV were significantly lower in Fast than in Slow. Significant decreasing trends in CAVI and baPWV and a tendency toward decreasing trend in haPWV were observed from Slow to Fast, whereas hbPWV did not significantly differ among tertiles and no trend was evident. The results remained significant after normalizing CAVI and PWVs for multicollinearity of arterial stiffness indices and major confounding factors, such as age, gender, body mass index, blood pressure, cognitive function, and each physical fitness. Therefore, these findings suggest that poor walking speed is associated with higher segment-specific arterial stiffness of the central and lower limbs, but not of upper, in older adult community dwellers.

Negative Mood States Are Related to the Characteristics of Facial Expression Drawing: A Cross-Sectional Study.

An assessment of mood or emotion is important in developing mental health measures, and facial expressions are strongly related to mood or emotion. This study thus aimed to examine the relationship between levels of negative mood and characteristics of mouth parts when moods are drawn as facial expressions on a common platform. A cross-sectional study of Japanese college freshmen was conducted, and 1,068 valid responses were analyzed. The questionnaire survey consisted of participants' characteristics, the Profile of Mood States (POMS), and a sheet of facial expression drawing (FACED), and the sheet was digitized and analyzed using an image-analysis software. Based on the total POMS score as an index of negative mood, the participants were divided into four groups: low (L), normal (N), high (H), and very high (VH). Lengths of drawn lines and between both mouth corners were significantly longer, and circularity and roundness were significantly higher in the L group. With increasing levels of negative mood, significant decreasing trends were observed in these lengths. Convex downward and enclosed figures were significantly predominant in the L group, while convex upward figures were significantly predominant and a tendency toward predominance of no drawn mouths or line figures was found in the H and VH groups. Our results suggest that mood states can be significantly related to the size and figure characteristics of drawn mouths of FACED on a non-verbal common platform. That is, these findings mean that subjects with low negative mood may draw a greater and rounder mouth and figures that may be enclosed and downward convex, while subjects with a high negative mood may not draw the line, or if any, may draw the line shorter and upward convex.

Epidemiology of Antimicrobial Use among Nursing Homes in Japan, 2016: a Pilot Study.

Antimicrobial resistance is an emerging problem in both acute care hospitals and nursing homes. From January to December 2016, we conducted a pilot, descriptive epidemiological study to examine antimicrobial use (AMU) among 6 nursing homes in Tokyo, Japan. AMU was extracted from prescription data of a pharmacy that received all prescriptions from the 6 nursing homes. To standardize the comparison of drug usage, AMU was measured using the defined daily dose (DDD) and estimated as DDDs/1,000 resident-days. The overall AMU was 15.3/1,000 resident-days, including oral antimicrobials (15.2/1,000 resident-days [99.3%]). The most frequently prescribed oral-antimicrobials was macrolides (5.8/1,000 resident-days [38.2%]) and quinolones (4.2/1,000 resident-days [27.6%]). Oral macrolides and quinolones were thought to be a convenience in prescription among nursing homes with resource limiting due to smaller defined the number of daily doses compared to penicillins and cephalosporins. In addition, multicenter studies that include resident-specific data (demographics and diagnosis) and focus on the purpose of antimicrobials (treatment or prevention) are needed to evaluate the appropriateness of antimicrobials.

The first national survey of antimicrobial use among dentists in Japan from 2015 to 2017 based on the national database of health insurance claims and specific health checkups of Japan.

PURPOSE: To counter the global health threat of antimicrobial resistance, effective antimicrobial stewardship programs are needed to improve antimicrobial use (AMU) among dentists in addition to physicians. This study aimed to investigate the nationwide epidemiology of AMU among Japanese dentists to facilitate the development of dentist-centered programs. METHODS: We conducted a retrospective population-based study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan to analyze the AMU among Japanese dentists between 2015 and 2017. AMU was quantified as the defined daily doses per 1,000 inhabitants per day (DID). The trends in dentist-prescribed AMU were examined according to antimicrobial category and administration route. We also compared outpatient oral AMU between dentists and physicians as well as between on-site and off-site dispensing. RESULTS: The DID values of dentist-prescribed AMU were 1.23 in 2015, 1.22 in 2016, and 1.21 in 2017. During this study period, outpatient oral antimicrobials comprised the majority (approximately 99%) of dentist-prescribed AMU, and cephalosporins were the most frequently prescribed antimicrobials (>60% of all antimicrobials). The DID values of outpatient oral AMU were 1.21 for dentists and 12.11 for physicians. The DID value for on-site dispensing was 0.89 in 2017, in which cephalosporins were the predominantly used antimicrobials (DID: 0.60). CONCLUSIONS: Interventions that target dentists in Japan should focus on on-site dispensing of oral antimicrobials (especially cephalosporins) for outpatients. Further studies are needed to ascertain the underlying factors of oral cephalosporin prescriptions to guide the development of effective antimicrobial stewardship programs.

Regional Variation of Antimicrobial Use in Japan from 2013-2016, as Estimated by the Sales Data.

The National Action Plan on Antimicrobial Resistance in Japan aims to achieve a 50% reduction in the use of broad-spectrum oral antimicrobials (cephalosporins, macrolides, and quinolones) from 2013 to 2020. Based on the national sales data for antimicrobials, we estimated the regional antimicrobial use (AMU) from 2013-2016 and evaluated the differences in the use of broad-spectrum oral antimicrobials among three regions in which differences had been identified previously. The AMU was standardized based on the defined daily dose (DDD) and described as the DDDs/1,000 inhabitants/day (DID). Annual combined total oral and parenteral AMU during 2013-2016 was 14.9, 14.5, 14.7, and 14.6 DID, respectively. The change in mean ± standard deviation in the total AMU at the prefectural level was - 0.2 ± 0.8 DID. Among the 47 prefectures, decreasing trends were observed in 34, while in the remaining 13 prefectures increasing trends were recorded. In 2016, no significant differences in the mean usage of oral cephalosporins among the three regions were observed. The mean usage of oral macrolides in the eastern (4.1 DID) was significantly lower than that in the central region (4.7 DID) (p = 0.009) and the western (4.8 DID) (p = 0.002). The mean usage of oral quinolones in the western (3.2 DID) was significantly higher than that in the eastern (2.3 DID) (p ＜ 0.001) and central (2.7 DID) (p = 0.001) regions. To determine appropriate targets for the implementation of antimicrobial stewardship for reducting the use of broad-spectrum oral antimicrobials, further studies are required to identify the reasons underlying these differences.