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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. 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. 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). 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.

Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.

Methicillin-resistant Staphylococcus aureus (MRSA) has a high mortality and requires effective treatment with anti-MRSA agents such as vancomycin (VCM). Management of the efficacy and safety of VCM has been implemented with the assignment of pharmacists in hospital wards and the establishment of teams related to infectious diseases. However, there are no reports evaluating the association between these factors and the efficacy and safety of VCM in large populations. This study used the Japanese administrative claims database accumulated from 2010 to 2019. The population was divided into two groups, therapeutic drug monitoring (TDM) group and non-TDM group, and adjusted by propensity score matching. We performed multivariate logistic regression analysis to determine the influence of pharmacists and infection control teams or antimicrobial stewardship teams on acute kidney injury (AKI) and 30-day mortality. The total number of patients was 73 478 (TDM group, n = 55 269; non-TDM group, n = 18 209). After propensity score matching, 18 196 patients were matched in each group. Multivariate logistic regression analysis showed that pharmacological management for each patient contributed to the reduction of AKI (odds ratio [OR]: 0.812, 95% confidence interval [CI]: 0.723-0.912) and 30-day mortality (OR: 0.538, 95% CI: 0.503-0.575). However, the establishment of infectious disease associated team in facilities and the assignment of pharmacists in the hospital wards had no effect on AKI and 30-day mortality. In addition, TDM did not affect the reduction in AKI (OR: 1.061, 95% CI: 0.948-1.187), but reduced 30-day mortality (OR: 0.873, 95% CI: 0.821-0.929). Pharmacologic management for individual patients, rather than assignment systems at facilities, is effective to reduce AKI and 30-day mortality with VCM administration.

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) has a high mortality and requires effective treatment with anti-MRSA agents such as vancomycin (VCM). Management of the efficacy and safety of VCM has been implemented with the assignment of pharmacists in hospital wards and the establishment of teams related to infectious diseases. However, there are no reports evaluating the association between these factors and the efficacy and safety of VCM in large populations.MethodsThis study used the Japanese administrative claims database accumulated from 2010 to 2019. The population was divided into two groups, therapeutic drug monitoring (TDM) group and non-TDM group, and adjusted by propensity score matching. We performed multivariate logistic regression analysis to determine the influence of pharmacists and infection control teams or antimicrobial stewardship teams on acute kidney injury (AKI) and 30-day mortality.ResultsThe total number of patients was 73 478 (TDM group, n = 55 269; non-TDM group, n = 18 209). After propensity score matching, 18 196 patients were matched in each group. Multivariate logistic regression analysis showed that pharmacological management for each patient contributed to the reduction of AKI (odds ratio [OR]: 0.812, 95% confidence interval [CI]: 0.723‒0.912) and 30-day mortality (OR: 0.538, 95% CI: 0.503‒0.575). However, the establishment of infectious disease associated team in facilities and the assignment of pharmacists in the hospital wards had no effect on AKI and 30-day mortality. In addition, TDM did not affect the reduction in AKI (OR: 1.061, 95% CI: 0.948‒1.187), but reduced 30-day mortality (OR: 0.873, 95% CI: 0.821‒0.929).ConclusionPharmacologic management for individual patients, rather than assignment systems at facilities, is effective to reduce AKI and 30-day mortality with VCM administration.

Background The inappropriate use of antimicrobials for acute infectious diarrhea is widespread and leads to the problem of antimicrobial resistance. To improve the use of antimicrobials, it is first necessary to understand the actual situation of diarrheal disease and to identify potential targets for intervention. This study aimed to investigate the recent epidemiological characteristics of and antimicrobial prescriptions for acute infectious diarrhea in Japan. Methods This was a retrospective observational study of outpatients aged 0–65 years, separated into children (age 0–17 years) and adults (age 18–65 years), diagnosed with acute infectious diarrhea, using the administrative claims database of the Japan Medical Data Center from 2013 to 2018. We evaluated the number of eligible visits/number of database registrants (defined as the visit rate). The analysis of the antimicrobial prescription rate was restricted to otherwise healthy individuals diagnosed with acute infectious diarrhea alone by excluding patients with multiple disease diagnoses and with medical backgrounds of chronic bowel diseases or immunocompromised conditions. We further classified them by diagnosis of bacterial or nonbacterial acute infectious diarrhea. Results The total number of eligible visits for acute infectious diarrhea was 2,600,065. The visit rate, calculated based on the number of eligible visits by database registrants, was higher in children (boys, 0.264; girls, 0.229) than in adults (men, 0.070; women, 0.079), with peaks in early summer and winter. The peaks for visits in adults lagged those of children. In total, 482,484 visits were analyzed to determine the antimicrobial prescription rate; 456,655 (94.6%) were diagnosed with nonbacterial acute infectious diarrhea. Compared with children (boys, 0.305; girls, 0.304), the antimicrobial prescription rate was higher in adults, and there were differences between sexes in adults (men, 0.465; women, 0.408). Fosfomycin and fluoroquinolone were most frequently used for nonbacterial acute infectious diarrhea in children (44.1%) and adults (50.3%), respectively. Conclusions These results revealed overprescription of antimicrobials for acute infectious diarrhea in this administrative claims database in Japan and contribute to the development of antimicrobial stewardship strategies and the identification of targets for efficiently reducing inappropriate antimicrobial use.

PurposeChemotherapy-induced nausea and vomiting (CINV) affects quality of life for patients with cancer undergoing chemotherapy. We aimed to assess the effect of lorazepam with granisetron on CINV in children with acute lymphoblastic leukemia (ALL).MethodsWe reviewed the records of 71 consecutive patients with newly diagnosed ALL who received chemotherapy including vincristine, anthracycline, and systemic steroids between January 2011 and December 2016 in our hospital. The number of chemotherapy cycles reviewed was 164. All patients received granisetron as CINV prophylaxis.ResultsNausea was observed in 51/71 patients (72%) and 93/164 cycles (57%). Vomiting was observed in 47/71 patients (66%) and 79/164 cycles (48%). Age and gender distribution were not significantly different between patients who received lorazepam at the initiation of the chemotherapy cycle (LZP group, n = 30) and those who did not receive lorazepam (non-LZP group, n = 134). There were no significant differences in the incidence of CIN and CIV between the LZP group and non-LZP group (CIN, 67% vs. 57%, P = 0.31; CIV, 53% vs. 47%, P = 0.98). In multivariate logistic regression, female gender and older age (> 5 years) were significant risk factors for CIV (female, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.3–5.0, P = 0.007; older age, OR 2.5, CI 1.3–4.8, P = 0.008).ConclusionsWe found no beneficial effect of providing lorazepam as adjuvant antiemetic for prevention of CINV in children with ALL.

Advancements in large-scale analysis of metabolites in human peripheral blood samples revealed the links between metabolite concentrations and genetic variations. This field is known as metabolome-genome-wide association study (MGWAS). Although MGWAS is a powerful tool, it has some limitations, particularly in terms of the number of metabolites that can be measured. Whether the observed associations are directly due to genetic variation or indirectly due to changes in unmeasured metabolites is unclear. To address this, we used simulations of metabolic pathway models to investigate the influence of genetic variants on metabolite concentrations and enhance the interpretation of MGWAS results. By systematically adjusting the enzyme reaction rates to simulate genetic variants, we observed changes in the metabolite levels. Our simulations accurately represented most of the variant-metabolite pairs identified by MGWAS with significant p -values, thereby demonstrating the potential of our approach. Furthermore, our simulations revealed additional marked fluctuations in metabolite levels that the MGWAS did not detect, suggesting that some variant-metabolite pairs might become more significant with larger sample sizes. We also categorized the enzymes into three types based on their impact on metabolite concentrations, highlighting enzymes with minimal impact. This indicated that genetic variations in these enzymes may have limited biological significance. Our study not only validates key MGWAS findings, but also provides a systematic framework for understanding enzyme-metabolite relationships. This approach offers valuable insights for future experimental studies and potential therapeutic interventions.

Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.