Search

Background: Oral frailty is a concept that encompasses various aspects of impaired oral function in elderly people, leading to reduced food intake and less dietary diversity, which can result in sarcopenia and physical frailty. However, there have been no studies on the relationship between oral frailty and malnutrition, sarcopenia, and physical frailty in patients on hemodialysis (HD)., Methods: This prospective observational cohort study assessed the oral status of patients on HD. The patients were divided into an oral frailty group and non-oral frailty group using the Oral Frailty Index-8. Malnutrition was assessed using the Geriatric Nutritional Risk Index (GNRI), the Nutritional Risk Index for Japanese Hemodialysis Patients (NRI-JH), and the Short-Form Mini-Nutritional Assessment (MNA-SF). Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2019's criteria. Physical frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria. One year later, the changes in nutritional status, sarcopenia, and physical frailty risk categories were compared between the oral frailty and non-oral frailty groups., Results: The study enrolled 201 patients (non-oral frailty group, 123; oral frailty group, 78). After 1 year, the oral frailty group had a significantly higher proportion of patients with worsening nutrition status (GNRI, p = 0.0011; NRI-JH, p = 0.0019; MNA-SF, p < 0.001) and sarcopenia ( p = 0.0024). There was no significant between-group difference in the proportion of patients in a worse risk category for physical frailty after 1 year., Conclusions: Oral frailty predicts future malnutrition and the progression of sarcopenia in HD patients. In particular, our results strongly suggested that oral frailty was a strong determinant of worsening malnutrition and sarcopenia in HD patients aged ≥65 years.

Objective: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan., Methods: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022)., Results: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza., Conclusion: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults., Competing Interests: Declaration of competing interest The authors have no competing interests relevant to this article to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: This study utilized the World Health Organization Disability Assessment Schedule version 2 (WHODAS 2.0) to identify vulnerable students and explore the impact of mental and developmental disorders on disability., Participants: A total of 156 undergraduates who visited support service offices at large-scale universities in Japan between April 2018 and March 2020 were included., Methods: The 36-item WHODAS 2.0 was administered, and data were gathered regarding mental and developmental disabilities. Mann-Whitney and Kruskal-Wallis tests were conducted., Results: Parents/guardians typically initiated consultation with student support services. Students whose parents had initiated consultation did not have higher scores in any WHODAS domain except "Life Activities." In every WHODAS domain except "Cognition," the "Mental Disorder" group scored significantly higher than the "No Disorder" group. The addition of "Developmental Disorders" significantly increased WHODAS scores, except in "Mobility.", Conclusions: The WHODAS is a useful tool for identifying vulnerable students.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum β-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan., Competing Interests: Declaration of competing interest Koichiro Wada received speaker honoraria from Janssen Pharmaceuticals, Inc. Satoshi Takahashi received speaker honoraria from Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Shin Ito received research funding from Hologic, Inc., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: In therapeutic drug monitoring (TDM) of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to the clinical efficacy and toxicity. Therefore, herein, we examined the factors associated with achieving the target AUC at follow-up and developed a decision flowchart for achieving the target AUC in critically ill patients., Methods: This multicenter retrospective observational study was conducted at eight hospitals. We retrospectively analyzed data from patients who had received VCM in the intensive care unit from January 2020 to December 2022. Decision-tree (DT) analysis was performed using factors with p < 0.1 in univariate analysis as the independent variables. Case data were split up to two times, and four subgroups were included. The primary endpoint was achieving the target AUC at the follow-up TDM (AUC follow-up ) and target AUC follow-up achievement was defined as an AUC of 400-600 μg‧h/mL. The initial AUC values were calculated with the 2-point concentrations (peak and trough) using the Bayesian estimation software Practical AUC-guided TDM (PAT)., Results: Among 70 patients (median age [interquartile range], 66 [56, 79] years; 50 % women), the AUC follow-up was achieved in 70 % (49/70). Three factors were selected for the decision flow chart: predicted AUC follow-up of 400-600 μg‧h/mL, dosing at 12-h intervals, and CCr of 130 mL/min/1.73 m 2 or higher; the accuracy was adequate (92 %, R 2  0.52)., Conclusion: We successfully identified the factors associated with achieving the target AUC of VCM at follow-up TDM and developed a simple-to-use DT model. However, the validity of the findings needs to be evaluated., Competing Interests: Declaration of competing interest KM received grant support funding from Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd., and Shionogi & Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

In the western North Pacific, prominent granulomatous testes have been detected in many Brucella-infected common minke whales (Balaenoptera acutorostrata), but there have been no reports in toothed cetaceans. We found severe orchitis with granulomatous lesions in a rough-toothed dolphin (Steno bredanensis) stranded on the Pacific coast of Japan in 2011. Histopathological examination revealed leukocyte infiltration of the lesions. DNA from the lesion was analyzed by PCR and it showed molecular biological similarities with those of Brucella-infected common minke whales and Brucella ceti of sequence-type 27 (ST27). These results suggest that the type of Brucella ceti that infected the dolphin was ST27, which may have caused severe orchitis. This study adds to our understanding of Brucella infections in marine mammals.

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from MSD K.K., Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Hiroyuki Nishiyama received research funding from Chugai Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Junichi Inokuchi received research funding from Chugai Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were β-lactamase-producing ampicillin resistant and β-lactamase-negative ampicillin resistant, respectively. Extended-spectrum β-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-β-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents., Competing Interests: Declaration of competing interest Issei Tokimatsu received research funding from Asahi Kasei Pharma Corporation, and scholarship donations from Shionogi & Co., Ltd., and Daiichi Sankyo Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., and Pfizer Japan Inc. Makoto Miki hold shares in Daiichi Sankyo Co., Ltd., and received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Tomotaro Wakamura is an employee of Sumitomo Pharma Co., Ltd. Daisuke Kurai received research funding from Daiichi Sankyo Co., Ltd., and scholarship donations from Shionogi & Co., Ltd. Hiroki Tsukada received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Nobuki Aoki received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Hiroshige Mikamo received speaker honoraria from Nippon Becton Dickinson Company, Ltd., Astellas Pharma Inc., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Pfizer Japan Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co., Ltd., Gilead Sciences K.K., Saraya Co., Ltd., Tsumura & Co., Meiji Seika Pharma Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd., Fukoku Co., Ltd., GlaxoSmithKline K.K., Kowa Company, Ltd., research funding from Fukoku Co., Ltd., Sekisui Medical Co., Ltd., Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., Saraya Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Roche Diagnostics K.K., ASKA Pharmaceutical Co., Ltd., Tosoh Corporation, Bruker Japan K.K., Abbott Diagnostics Medical Co., Ltd., Ortho Clinical Diagnostics K.K., Kyorin Pharmaceutical Co., Ltd., and scholarship donations from Asahi Kasei Pharma Co., Shionogi & Co., Ltd., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fukoku Co., Ltd., and Morii Co., Ltd. Atsushi Nakamura received speaker honoraria from Kyorin Pharmaceutical Co., Ltd., MSD K.K., Astellas Pharma Inc. Akira Ukimura received scholarship donations from Shionogi & Co., Ltd. Hiroshi Kakeya received speaker honoraria from MSD K.K., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Shionogi & Co., Ltd., Asahi Kasei Pharma Corporation., Astellas Pharma Inc., and Pfizer Japan Inc. Katsunori Yanagihara received speaker honoraria from Daiichi Sankyo Co., Ltd., MSD K.K., Astellas Pharma Inc., and Taisho Pharma Co., Ltd. (formerly Taisho Toyama Pharmaceutical Co., Ltd.), research funding from Fujifilm Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd., and scholarship donations from Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Kyorin Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: We describe the epidemiology of invasive Haemophilus influenzae disease (IHD) among adults in Japan., Methods: Data for 200 adult IHD patients in 2014-2018 were analyzed. The capsular type of H. influenzae was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable Haemophilus influenzae (NTHi) was identified by PCR., Results: The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15-64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5% were aged ≥ 65 years. About one-fourth of patients were associated with immunocompromising condition. The major presentations were pneumonia, followed by bacteremia, meningitis and other than pneumonia or meningitis (other diseases). The case fatality rate (CFR) was 21.2% for all cases, and was significantly higher in the ≥ 65-year group (26.1%) than in the 15-64-year group (7.5%) (p = 0.013). The percentage of cases with pneumonia was significantly higher in the ≥ 65-year group than in the 15-64-year group (p < 0.001). The percentage of cases with bacteremia was significantly higher in the 15-64-year group than in the ≥ 65-year group (p = 0.027). Of 200 isolates, 190 (95.0%) were NTHi strains, and the other strains were encapsulated strains. 71 (35.5%) were resistant to ampicillin, but all were susceptible to ceftriaxone., Conclusion: The clinical presentations of adult IHD patients varied widely; about three-fourths of patients were age ≥ 65 years and their CFR was high. Our findings support preventing strategies for IHD among older adults, including the development of NTHi vaccine., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: Following natural disasters, the number of motor vehicle crashes may increase as drivers are often forced to drive under stressful conditions. This study aims to analyze the changes in motor vehicle crashes that resulted in injury or death (injury crash) following the 2016 Kumamoto earthquake in Japan. An existing study reported that the increased crashes resulted in property damage following the earthquake; however, the effects on injury crashes remain unreported., Methods: Interrupted time series analysis is employed to investigate the changes in injury crashes following the earthquake. The results are compared based on several time series models, including negative binomial and autoregressive integrated moving average models. Monthly injury-crash data from 2011 to 2020 in Kumamoto and Fukuoka city is used., Results: The results reveal a 1,642-count or 20% increase (1.20-times increase, 95% confidence interval: 1.12, 1.27) in injury crashes due to the earthquake in Kumamoto city, where the earthquake damage was heavy. In contrast, statistically significant change is not detected in Fukuoka city, where the earthquake damage is negligible., Conclusion: The results indicate that the earthquake has increased the motor-vehicle-crash risk and that traffic crash alerts are important following disasters.

Oral health behaviors, risk aversion, and the health belief model are associated with health behaviors. However, there have been few studies that investigated the association between these factors and the willingness to undergo regular dental check-ups. The purpose of this cross-sectional study was to investigate the associations between the willingness of Japanese university students to undergo regular dental check-ups and oral health behaviors, the health belief model, and absolute risk aversion. An analysis was conducted with the cooperation of questionnaire respondents ( n = 748) who underwent dental check-ups at Okayama University. The students answered questionnaires on oral health behaviors, the health belief model, absolute risk aversion, and willingness to undergo regular dental check-ups. The logistic regression analysis showed significant positive associations ( p < 0.05) between oral health behaviors (use of the inter-dental brush and the dental floss) and the health belief model with the willingness to undergo regular dental check-ups. However, there was no significant association with absolute risk aversion ( p > 0.05). These results suggest that willingness to undergo regular dental check-ups was associated with oral health behaviors and the health belief model, but not with absolute risk aversion.

Self-rated oral health (SROH) is a valid, comprehensive indicator of oral health status. The purpose of this cross-sectional study was to analyze how oral health behaviors and clinical oral status were associated with SROH and how they had changed over the course of nine years in Japanese university students. Data were obtained from 17,996 students who underwent oral examinations and completed self-questionnaires from 2011 to 2019. Oral status was assessed using the decayed and filled teeth scores, bleeding on probing (BOP), probing pocket depth, the Oral Hygiene Index-Simplified (OHI-S), oral health behaviors, and related factors. SROH improved from 2011 to 2019. The logistic regression model showed that university students who were female and had a high daily frequency of tooth brushing, no BOP, no decayed teeth, no filled teeth, and a low OHI-S score and were significantly more likely to report very good, good, or fair SROH. An interaction effect was observed between survey year and regular dental check-ups (year × regular dental check-ups). The improvement trend in SROH might be associated with changes in oral health behaviors and oral health status.

Introduction: Seasonal influenza vaccination for the elderly is highly recommended during the COVID-19 pandemic. In Japan, the amount of subsidy for influenza differs among municipalities. Thus, we investigated the amount of and variation in subsidy for influenza vaccination for the elderly in 2020., Methods: This was an ecological study of 1,922 municipalities in Japan. The amount of subsidy for influenza vaccines for the elderly in each municipality was surveyed through websites or via telephone. Geographic and financial data for municipalities and prefectures were obtained from the open data. The amount of co-payment for the influenza vaccine and the geographical and financial status of each municipality were compared, according to the aging rate. Univariate logistic regression analysis was performed to explore factors related to the free influenza vaccine., Results: Municipalities with higher aging rates tended to have higher median co-payments for vaccines in 2020. (0 yen vs 1000 yen, p < 0.001) In addition, they tended to have worse financial conditions and lower per capita incomes. A similar trend was observed in the analysis by prefecture, i.e., a higher influenza mortality rate in prefectures with a higher aging rate. Despite having lower incomes, municipalities and prefectures with higher aging populations had higher mortality rates from influenza and higher co-payments for influenza vaccination., Conclusions: In Japan, there is a disparity among elderly people; areas with an aging population have higher co-payments for influenza vaccines despite lower incomes, suggesting that the government needs to implement corrective measures to reduce this disparity., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Influenza remains a clinically heavy burden worldwide. It is well known that some populations are at high risk of complications from influenza, whereas, even previously healthy people might suffer from severe influenza. The objective of this study was to clarify clinical manifestations of hospitalized patients without risk factors infected with influenza., Methods: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2020 (6 influenza seasons) using an internet-surveillance system. Among them, the patients who had no risk factors of complications from influenza were extracted., Results: Finally, a total of 91 patients (9.0% of all influenza-related hospitalizations) without risk factors were analyzed. The no risk group was younger than the risk group, though other significant differences of clinical characteristics were not recognized between the groups. Pneumonia was the most common cause of hospitalization in the no risk group, and primary influenza viral pneumonia was the most common pneumonia. Antiviral drugs were administered in 96.7% of the no-risk group, and artificial ventilation was performed in 18.7%. In-hospital death was recorded for 3 patients without risk factors., Conclusions: Severe complications of influenza which required hospitalization may occur in a certain degree of patients with no risk factors. Efforts are needed to diagnose and treat influenza appropriately even in previously healthy younger patients. Continuous nationwide surveillance will be required to clarify risk factors for severe influenza even in previously healthy younger patients. (UMIN000015989)., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Nationwide population-based surveillance for invasive pneumococcal disease (IPD) is being conducted in few Asian countries. We aimed to evaluate the clinical characteristics and serotype distribution among Japanese adult patients with IPD after introduction of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) in 2013. IPD surveillance was conducted among adults between 2013 and 2019, and 1,995 patients were analyzed by time period (early, 2013-2015; middle, 2016-2017; late, 2018-2019). We found that the period of 2018-2019 was independently associated with a lower risk of fatal outcome, compared with the period of 2013-2015. The proportion of those with serotype PCV13-nonPCV7 decreased significantly in patients aged 15-64 years and in those aged ≥ 65 years within 3 years after the introduction of pediatric PCV13. By contrast, the proportion of those with nonvaccine serotype increased significantly in those aged ≥ 65 years, but not in those aged 15-64 years. No significant change was found in the proportion of 23-valent polysaccharide pneumococcal vaccine (PPSV23)-nonPCV13 in both of adults aged 15-64 years and ≥ 65 years. The proportions of PCV15-, PCV20- and PCV24-covered serotypes were 38%, 56% and 58% in adult patients with IPD aged ≥ 65 years during the late period. Our data on the serotype distribution support an indirect effect from pediatric PCV13 use among adults, and afford a basis for estimates of protection against IPD by vaccination with newly developed PCVs in older adults in Japan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The enzyme-linked immunosorbent assay (ELISA) was applied to detect antibodies against Brucella abortus in serum samples from four seal species at nine coastal locations of Hokkaido, Japan. These antibodies were detected in 27% (32/118) of Western Pacific harbor seals (Phoca vitulina stejnegeri) at Cape Erimo. The antibodies were observed in spotted seals (P. largha) in one out of six at Nemuro, in two out of three at Rebun Island, in one out of two at Bakkai, and in examined one at Soya. They were also found in respective examined one ribbon seal (Histriophoca fasciata) and one ringed seal (Pusa hispida) at Akkeshi. Harbor seals that tested positive were mostly yearlings (35%, 20/57) and juveniles (45%, 10/22), while only one pup (1/13) and one subadult (1/5) tested positive with low titers of the antibody; no antibodies were observed in adults (n=21). These results suggest that Brucella mainly infected harbor seals from the environment while weaning, and the bacteria were cleared during the early life stage of the seals. In spotted seals, however, antibodies were also detected in adults, suggesting that spotted seals could become infected with Brucella even as adults. It is also possible that a different, more persistent strain of Brucella may have infected the spotted seals.

We aimed to define the burden and clinical features of invasive group B streptococcus (GBS) disease in infants younger than 1 year in Japan, to explore transmission route of late-onset disease (LOD), and to identify risk factors associated with recurrent GBS disease. We conducted a retrospective, questionnaire-based nationwide surveillance study between 2016 and 2020. A total of 875 GBS cases were identified, including 186 early-onset disease, 628 LOD, and 61 ultra-late-onset disease. Case fatality rate in each age category was 6.5%, 3.0%, and 3.3%, respectively. Patients with meningitis had neurodevelopmental sequelae in 21.5% (64/297). Annual incidence in infants younger than 1 year and in LOD significantly increased from 0.28 to 0.45/1000 livebirths (p = 0.021) and from 0.19 to 0.29/1000 livebirths (p = 0.046), respectively. Maternal colonization status at the LOD diagnosis was available for 148 mothers, of whom 21/58 (36.2%) had positive rectovaginal swabs and 42/117 (36.2%) had GBS in breastmilk culture. These two sites are potentially infectious routes in LOD. The four leading disease-causing serotypes III, Ia, Ib, and V represented 95% of the available serotypes. Thirty-one recurrent cases were identified, accounting for 3.7% of total patients. A multivariate regression analysis showed that prematurity (p = 0.029) and antepartum maternal GBS colonization (p = 0.032) were significantly associated with risk for the recurrence. Our findings indicated that GBS disease burden still remains with considerable mortality and morbidity in Japan, and provided important information for developing better strategies for the prevention of GBS disease, including maternal vaccination., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders., Methods: A total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public., Results: The survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) procedures on clinical trial information (Chapter 2.10, 5.7%). The top three sections identified as needing renovation were: (i) informed consent (Chapter 4.8, 27.6%), (ii) monitoring (Chapter 5.18, 22.9%), and (iii) composition, functions, and operations of the ethics committee (Chapter 3.2, 14.3%). Recommendations included clarification of ICH-GCP's scope, proportionality in various aspects of clinical trials, diversity and liquidity of ethics committee members, modernization of informed consent procedures, variations in monitoring, and regulatory grade when using real-world data., Conclusion: The recommendations from Japanese investigators and patients have been submitted to the ICH E6 Expert Working Group, which will strengthen the robustness of the GCP renovation., (© 2021. The Author(s).)

We assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014-2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016-2018 was 0.20-0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27-4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10-5.06) or 23A (aOR 3.91, 95% CI 2.47-6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44-0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51-5.65)., (© 2022. The Author(s).)

Under the Japanese health insurance system, medicines undergoing therapeutic drug monitoring (TDM) can be billed for medical fees if they meet the specified requirements. In Japan, TDM of vancomycin, teicoplanin, aminoglycosides, and voriconazole, which are used for the treatment of infectious diseases, is common practice. This means the levels of antibiotics are measured in-house using chromatography or other methods. In some facilities, the blood and/or tissue concentrations of other non-TDM drugs are measured by HPLC and are applied to treatment, which is necessary for personalized medicine. This review describes personalized medicine based on the use of chromatography as a result of the current situation in Japan.

Background: Previous studies have not estimated vaccine effectiveness (VE) against influenza in the working-age Japanese population. In this study, we determined VE in adult workers at a Japanese company., Methods: We estimated VE based on self-reported data regarding influenza infections and vaccinations in employees of an auto parts manufacturing company during three influenza seasons from 2017 to 2020. VE was estimated as 100% × [1 - odds ratio (the ratio of the odds of being diagnosed with influenza among enrollees with and without influenza vaccination)]. Odds ratios were estimated using logistic regression., Results: We included 11,347 worker records [3,592 (2017-18), 3,663 (2018-19), and 4,092 (2019-20)] from employees who had worked with the company throughout each influenza season. The adjusted VE was moderate and significant in the 2019-20 season (VE = 53%; 95% confidence interval [CI] = 30% to 69%) but low or negative and non-significant during the 2017-18 (VE = 28%; 95% CI = -5% to 50%) and 2018-19 (VE = -11%; 95% CI =  - 42% to 14%) seasons., Conclusions: Influenza vaccines were moderately effective during the 2019-20 season but showed low or negative effectiveness during the 2017-18 and 2018-19 seasons. Self-reports from worker records can successfully help determine VE against influenza., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: This study is aimed at clarifying the relationship between visit-to-visit variability of glycated hemoglobin (HbA1c) and the risk of diabetic kidney disease (DKD) and to identifying the most useful index of visit-to-visit variability of HbA1c., Methods: This clinic-based retrospective longitudinal study included 699 Japanese type 2 diabetes mellitus patients. Visit-to-visit variability of HbA1c was calculated as the internal standard deviation of HbA1c (HbA1c-SD), the coefficient of variation of HbA1c (HbA1c-CV), the HbA1c change score (HbA1c-HVS), and the area under the HbA1c curve (HbA1c-AUC) with 3-year serial HbA1c measurement data, and the associations between these indices and the development/progression of DKD were examined., Results: Cox proportional hazards models showed that the HbA1c-SD and HbA1c-AUC were associated with the incidence of microalbuminuria, independently of the HbA1c level. These results were verified and replicated in propensity score (PS) matching and bootstrap analyses. Moreover, the HbA1c-SD and HbA1c-AUC were also associated with oxidized human serum albumin (HSA), an oxidative stress marker., Conclusions: Visit-to-visit variability of HbA1c was an independent risk factor of microalbuminuria in association with oxidative stress among type 2 diabetes mellitus patients. HbA1c-AUC, a novel index of HbA1c variability, may be a potent prognostic indicator in predicting the risk of microalbuminuria., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Yunyi Yan et al.)

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC 90 ) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In order to investigate the relationship between the chemical composition of essential oils and haplotypes of the psbA-trnH intergenic spacer region of chloroplast DNA (psbA-trnH) in Valerianae Fauriei Radix (Japanese Valerian; JV), we analyzed the DNA sequence and GC-MS metabolome of JV from Japanese markets and of herbal specimens from related species. DNA analysis revealed that JV products from Japan consisted of three haplotypes, namely AH-1, -2 and -5 reported in our previous study. The GC-MS metabolome revealed five chemotypes (J 1 , J 2 , C, K and O), of which J 1 , J 2 and C were detected in the JV products from Japan. Chemotypes J 1 and J 2 , with kessyl glycol diacetate (KGD) as the main volatile component, were found in the products of Japanese origin whereas chemotype C, with 1-O-acetyl-2,10-bisaboladiene-1,6-diol (ABD), was found in the products of Chinese and Korean origin. The haplotypes were correlated with the chemotypes: haplotype AH-1 for chemotype J 1 , AH-2 for chemotype J 2 and AH-5 for chemotype C, suggesting that the chemical diversity of JV is not attributed to the environmental factors rather to the genetic factors. Since KGD and ABD were reported to have sedative effects and nerve growth factor (NGF)-potentiating effects, respectively, understanding the chemotypes and selecting an appropriate one would be important for the application of JV. The psbA-trnH haplotypes could be useful DNA markers for the quality control and standardization of JV.

Surgical site infection (SSI) is a serious complication following spine surgery and is correlated with significant morbidities, poor clinical outcomes, and increased healthcare costs. Accurately identifying risk factors can help develop strategies to reduce this devastating consequence; however, few multicentre studies have investigated risk factors for SSI following posterior cervical spine surgeries. Between July 2010 and June 2015, we performed an observational cohort study on deep SSI in adult patients who underwent posterior cervical spine surgery at 10 research hospitals. Detailed patient- and procedure-specific potential risk variables were prospectively recorded using a standardised data collection chart and were reviewed retrospectively. Among the 2184 consecutive adult patients enrolled, 28 (1.3%) developed postoperative deep SSI. Multivariable regression analysis revealed 2 statistically significant independent risk factors: occipitocervical surgery (P < 0.001) and male sex (P = 0.024). Subgroup analysis demonstrated that occipitocervical surgery (P = 0.001) was the sole independent risk factor for deep SSI in patients with instrumented fusion. Occipitocervical surgery is a relatively rare procedure; therefore, our findings were based on a large cohort acquired using a multicentre study. To the best of our knowledge, this is the first study to identify occipitocervical procedure as an independent risk variable for deep SSI after spinal surgery.

Pneumococcal surface protein A (PspA) is a surface protein of Streptococcus pneumoniae that may be a candidate antigen for new pneumococcal vaccines. This study investigates the distribution of PspA clades of the causative strains of adult invasive pneumococcal disease (IPD) in Japan. Of the 1,939 strains isolated from cases of adult IPD during 2014-2019, the PspA clades of 1,932 (99.6%) strains were determined, and no pspA was detected in the remaining 7 strains (0.4%). PspA clades 1-6 were detected in 786 (40.5%), 291 (15.0%), 443 (22.8%), 369 (19.0%), 33 (1.7%), and 6 (0.3%) strains, respectively. New PspA clades (0.2%) were identified in two non-typeable and two serotype 35B pneumococci. The proportions of clade 1 and clade 2 showed significantly decreased and increased trends, respectively. Furthermore, the PspA clade of pneumococcal strains was partially serotype- and sequence type-dependent. The majority of strains belonging to serotypes contained in both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) belonged to PspA clades 1 or 3. In contrast, the distribution of clades in non-vaccine serotypes was wider than that of vaccine serotype pneumococci. Our findings demonstrate that almost all pneumococcal strains from adult IPD express PspA clades 1-4, especially for non-vaccine serotypes. These results may be useful for the development of a new pneumococcal vaccine with PspA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chang, Kinjo, Morita, Tamura, Watanabe, Tanabe, Kuronuma, Fujita, Oshima, Maruyama, Abe, Kasahara, Nishi, Kubota, Ohnishi, Suga and Oishi.)

Introduction: Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza., Methods: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system., Results: A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67-84), and the patients in the 2015-2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality., Conclusions: Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989)., Competing Interests: Declaration of competing interest Seki M received scholarship and honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Fujita J received honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Kadota J received scholarship from Daiichi Sankyo Co., Ltd. Izumikawa K received scholarship and honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Kakeya H received scholarship and honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Watanabe A received honorarium from Shionogi Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taisyo Phar, Co., Ltd., Tanabe Mitsubishi Pharmaceutical Co., Ltd., MSD Co., Ltd., FUJIFILM Toyama Chemical Co., Ltd., and Pfizer Co., Ltd. He received scholarship from Astellas Pharmaceutical Co., Ltd. and Daiicgi Sankyo Co., Ltd. Ishida T, Oishi K, Tateda K, Kawana A, Kikuchi T, Ohmagari N, Yamada M, Maruyama T, Takazono T, Miki M, Miyazaki Y, Yamazaki Y, Ogawa K, Nagai H have no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

As a new absolute quantitation method for low-molecular compounds, quantitative NMR (qNMR) has emerged. In the Japanese Pharmacopoeia (JP), 15 compounds evaluated by qNMR are listed as reagents used as the HPLC reference standards in the assay of crude drug section of the JP. In a previous study, we revealed that humidity affects purity values of hygroscopic reagents and that (i) humidity control before and during weighing is important for a reproducible preparation and (ii) indication of the absolute amount (not purity value), which is not affected by water content, is important for hygroscopic products determined by qNMR. In this study, typical and optimal conditions that affect the determination of the purity of ginsenoside Rb 1 (GRB1), saikosaponin a (SSA), and barbaloin (BB) (i.e., hygroscopic reagents) by qNMR were examined. First, the effect of humidity before and during weighing on the purity of commercial GRB1, with a purity value determined by qNMR, was examined. The results showed the importance afore-mentioned. The results of SSA, which is relatively unstable in the dissolved state, suggested that the standardization of humidity control before and during weighing for a specific time provides a practical approach for hygroscopic products. In regard to BB, its humidity control for a specific time, only before weighing, is enough for a reproducible purity determination.

Purpose: To clarify the subjective and objective impacts of a change in a 12-h shift schedule, involving a reduction in the number of crews, on workers at an electronic parts production company., Methods: Forty-two workers participated in this study. Subjective indicators (e.g. questionnaires) and objective indicators [e.g., psychomotor vigilance task (PVT)], as well as an activity monitor-based sleep assessment, were measured during a > 1-year period that encompassed the shift schedule change. The study outcome was a comparison of work-related injury rates measured 1 year before and after the change in shift schedule., Results: After the shift schedule change, questionnaire scores regarding work-related burdens and PVT performance parameters, including mean response time and number of lapses, increased significantly. However, we also observed divergences in the trends of the subjective and objective measures 1 year after the change. Despite these variations in both types of measures, we observed no significant differences in work-related injury rates measured before and after the shift schedule change., Conclusion: This study revealed that a reduction in the number of crews in a 12-h shift schedule has a negative impact on the subjective and objective indicator after the change in shift schedule; only indicators of alertness did not recover at 1 year after the change. Assessments of the workers' performances and the regular implementation of health and safety programs for more than 1 year are needed to maintain workers' health after the change in shift schedule.

Aims: This study aims to investigate the prognostic impact of mineralocorticoid receptor antagonists (MRAs) on cardiovascular events in patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF; defined as left ventricular ejection fraction ≥45%)., Methods and Results: A prospective multicentre cohort study was conducted in Nagano prefecture, Japan, between July 2014 and December 2018 that contained 518 consecutive HFpEF patients hospitalized for acute decompensated heart failure (HF). The primary outcome was a composite of cardiovascular death and HF readmission. We compared the incidence of cardiovascular events between patients who were prescribed with MRAs and those who were not in a propensity score matched cohort using a Cox proportional hazards regression model with a propensity score derived from 23 baseline variables. For sensitivity analysis, we conducted Cox proportional hazards regression models for the primary outcome adjusting for 16 clinically relevant variables in the crude cohort. The median age was 83 years, and 53% were female. The median left ventricular ejection fraction was 61%. During a median follow-up of 553 days, the primary outcome occurred in 192 (37%) patients. MRAs were used in 255 (49%) patients. After analysis, a matched cohort consisting of 370 patients was created. After propensity score matching, the baseline characteristics were well balanced between the two groups. The incidence of the primary outcome was significantly lower in MRA users than in non-users [32% (59/185) vs. 49% (90/185); hazard ratio (HR) 0.669, 95% confidence interval (CI) 0.482-0.929, P = 0.016]. The incidence of cardiovascular death was also significantly lower in the MRA users [11% (21/185) vs. 22% (41/185); HR, 0.563; 95% CI, 0.333-0.953; P = 0.032]. The risk of HF readmission tended to be lower in the MRA users [29% (54/185) vs. 41% (75/185); HR, 0.738; 95% CI, 0.520-1.048; P = 0.089]. MRA use was also associated with a lower risk of the primary outcome after Cox proportional hazards analysis adjusting for 16 clinically relevant variables in the crude cohort (HR, 0.710; 95% CI 0.507-0.995; P = 0.047)., Conclusions: Mineralocorticoid receptor antagonist use was significantly associated with a lower risk of the primary composite outcome of cardiovascular death and HF readmission in patients hospitalized for acute decompensated HFpEF. The incidence of cardiovascular mortality was also significantly lower in these patients., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

The decline in the proportion of pneumococcal conjugate vaccine (PCV)-covered serotypes among adult invasive pneumococcal disease (IPD) patients might change the overall effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) because its effectiveness differs according to serotype. Using the indirect cohort method, we calculated the effectiveness of PPSV23 against IPD among adults in Japan to assess the impact of the national pediatric PCV program. Clinical and epidemiologic information and pneumococcal isolates were collected from IPD patients >20 years of age through enhanced IPD surveillance during April 2013-December 2017. Adjusted effectiveness against PPSV23-serotype IPD was 42.2%. Despite a substantial decline in the proportion of 13-valent PCV serotypes during the study period (45% to 31%), the change in effectiveness for PPSV23-serotype IPD was limited (47.1% to 39.3%) and only marginal in the elderly population (39.9% to 39.4%). The pediatric PCV program had limited impact on PPSV23 effectiveness against IPD in adults.

The Japanese government developed a strategy for plastics and laid out ambitious targets including the reduction of 25% for single-use plastic waste and the reuse/recycling of 60% for plastic containers and packaging by 2030. However, the current usage situation of single-use plastics including containers and packaging, which should be a basis of the strategy, is unclear. Here, we identify the nationwide material flow of plastics in Japan based on input-output tables. Of the domestic plastic demand of 8.4 Mt in 2015, 1.6 and 2.5 Mt were estimated to be for containers and packaging comprising household and industry inflows, respectively, through the purchase/procurement of products, services, and raw materials. Considering the current amount of recycling collected from households (1.0 Mt) and industries (0.3 to 0.4 Mt), the reuse/recycling target has already been achieved if the goal is limited to household container and packaging waste, as is the focus of Japan's recycling law. Conversely, the results indicate that it will be extremely difficult to reach the target collectively with industries. Therefore, it is essential that efforts be made throughout the entire supply chain. Food containers and packaging that flowed into the food-processing and food service sectors accounted for 15% of the inflow of containers and packaging into industries. Thus, the key to achieving the reuse/recycling target will comprise the collection of plastic food packaging from not only households but also the food industry. Furthermore, the collection of flexible plastic films used between industry sectors will put the target within reach., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

The prognostic significance of resting heart rate (HR) in atrial fibrillation (AF) patients with heart failure with reduced ejection fraction (HFrEF) is unclear, and there are no recommendations about the optimal HR in patients with HF in the current guidelines. Thus, we aimed to identify the relationship between resting HR and mortality in AF patients with HFrEF. A prospective multicenter cohort study was conducted between July 2014 and December 2018. We enrolled consecutive 144 AF patients with HFrEF (mean age 75 years, 34% female). The primary endpoint was all-cause death. We compared the outcomes between the high HR group (HR > 81 beats per minute [bpm], interquartile range [IQR] of HR ≥ 67%, n = 50), and the low HR group (HR ≤ 81 bpm, IQR of HR < 67%, n = 94). During a median follow-up of 538 days, the primary endpoint occurred in 41 (28.5%) patients. In Kaplan-Meier analysis, high HR was associated with a progressively increased risk of mortality (log-rank test, p = 0.034). After multivariate Cox regression analysis, high HR predicted all-cause death after adjusting for age, sex, hemoglobin, estimated glomerular filtration rate, LVEF, use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, digoxin, amiodarone, and calcium channel blockers (hazard ratio, 1.979; 95% confidence interval, 1.005-3.898; p = 0.048). Resting HR > 81 bpm at discharge had a significantly higher risk of death compared with HR ≤ 81 bpm in AF patients with HFrEF.

Background: Amniotic fluid embolism (AFE), also known as anaphylactoid syndrome of pregnancy (ASP), typically occurs during labor and may result in cardiorespiratory collapse and disseminated intravascular coagulation (DIC). There are reports describing less typical presentations of AFE/ASP in which patients do not necessarily have the classic triad of hypoxia, hypotension, and coagulopathy. AFE/ASP rarely occurs in the absence of labor, but such cases may involve medical or surgical abortion, spontaneous miscarriage, or obstetrical procedures including amniocentesis and amnioinfusion. There are, however, no previously reported cases of AFE/ASP with sudden loss of consciousness and disseminated intravascular coagulation occurring during early pregnancy, in the absence of any intervention or obstetric event., Case Presentation: A 32-year-old G3P2 Japanese woman had sudden-onset syncope at 14 weeks' gestation. On arrival at our hospital, her level of consciousness was severely disturbed as determined by the Glasgow Coma Scale. Although her vital signs were initially stable, blood samples collected intravenously and by femoral artery puncture did not coagulate. A subchorionic hematoma with active extravasation of blood was apparent on contrast-enhanced computed tomography. Two hours after her arrival, she developed hypovolemic shock with progression of DIC, presumably due to intrauterine and retroperitoneal bleeding. After transfusion of blood products; treatments for DIC including the use of recombinant human soluble thrombomodulin, ulinastatin, and corticosteroids; and hysterectomy, her level of consciousness and physical condition improved remarkably. Later investigation of preoperative blood samples revealed that serum levels of AFE/ASP-associated markers were elevated. Immunohistochemical studies on the excised, unruptured uterus showed that amniotic fluid components were present inside a uterine blood vessel., Conclusions: This is the first reported patient with sudden-onset syncope and DIC, but without apparent cardiorespiratory collapse, with the highly likely etiology of AFE/ASP occurring at the beginning of the second trimester of pregnancy and in the absence of intervention or delivery. Maternal collapse with DIC during any stage of pregnancy should be considered an AFE/ASP-associated event, even in the absence of labor or obstetric procedures. This event may occur in the presence of subchorionic hematoma alone.

Prediction of short-term mortality in elderly patients with heart failure (HF) would be useful for clinicians when discussing HF management or palliative care.A prospective multicenter cohort study was conducted between July 2014 and July 2018. A total of 504 consecutive elderly patients (age ≥ 75 years) with HF (mean age 85 years, 50% women) were enrolled. We used a multiple logistic regression analysis with stepwise variable selection to select predictive variables and to determine weighted point scores. After analysis, the following variables predicted short-term mortality and comprised the risk score: previous HF admission (3 points), New York Heart Association III or IV (2 points), body mass index < 17.7 kg/m 2 (4 points), serum albumin < 3.5 g/dL (9 points), and left ventricular ejection fraction < 50% (2 points). The c-statistic was 0.820. We compared mortality in low-risk (0-6 points, n = 188), intermediate-risk (7-13 points, n = 241), and high-risk (14-20 points, n = 75) groups. A total of 43 (8.5%) patients died within 6 months after discharge. Mortality was significantly higher in groups with higher scores (low-risk group, 0.5%; intermediate-risk group, 9.1%; high-risk group, 26.7%; P < 0.001).We developed a predictive model for 6-month mortality in elderly patients with HF. This risk score could be useful when discussing advanced HF therapies, palliative care, or hospice referral with patients.

Background: It is known that patients on hemodialysis (HD) are prone to developing zinc deficiency due to removal of zinc by HD, inadequate dietary intake, and reduced gastrointestinal zinc absorption. However, the prevalence of zinc deficiency in patients on peritoneal dialysis (PD) has not been well established., Methods: Serum zinc levels were compared between 47 patients on PD and 47 patients on HD matched for age, sex, and duration of dialysis. A serum zinc level < 60 μg/dL was defined as clinical zinc deficiency and a level of 60-80 μg/dL as subclinical zinc deficiency. The prevalence of zinc deficiency and associated clinical factors were determined in both groups., Results: Clinical zinc deficiency was found in 59.6% of the PD group and 70.2% of the HD group ( p = 0.391). Subclinical zinc deficiency was found in 40.4% of the PD group and 29.8% of the HD group. Age, body mass index, and serum albumin level were identified as independent predictors of zinc deficiency in the PD group by multivariate analysis., Conclusions: A higher prevalence of clinical and subclinical zinc deficiency was found in patients on PD. The rates were comparable between patients on PD and those on HD after adjustment for confounding factors.

A serologic investigation of Brucella infection was performed in 7 species of cetaceans inhabiting along the coast of Japan. A total of 32 serum samples were examined by enzyme-linked immunosorbent assay (ELISA) using Brucella abortus and B. canis antigens. One serum sample from five melon-headed whales (Peponocephala electra) was positive for B. abortus. No serum sample showed positive for B. canis. The ELISA-positive melon-headed whale serum demonstrated a strong band appearance only against B. abortus antigens in Western blot analysis. Many detected bands were discrete, while some of them had a smeared appearance. The present results indicate that Brucella infection occurred in melon-headed whale population and the bacterial antigenicity is more similar to that of B. abortus than B. canis.

Quantitative NMR (qNMR) has been developed as an absolute quantitation method to determine the purity or content of organic compounds including marker compounds in crude drugs. The "qNMR test" has been introduced into the crude-drug section of the Japanese Pharmacopoeia (JP) for determining the purity of reagents used for the assay in the JP. In Supplement II to the JP 17th edition published in June 2019, fifteen compounds adopted qNMR test were listed as the reagents for the assay. To establish the "qNMR test" in the crude drug section of the JP, there were several problems to be solved. Previously, we reported that the handling impurity signals from reference substances and targeted marker compounds, chemical shifts of reference substances, and peak unity of signals of targeted marker compounds are important factors to conduct qNMR measurements with intended accuracy. In this study, we investigated that the hygroscopicity of reagents could cause the changes in the compounds' purity depending on increasing their water content. Twenty-one standard products used for the crude-drug test in JP were examined by water sorption-desorption analysis, and ginsenosides and saikosaponins were found to be hygroscopic. To prepare a sample solution of saikosaponin b 2 for qNMR analysis, samples need to be maintained for 18 h at 25°C and 76% relative humidity; further, samples need to be weighed at the same humidity for the qNMR analysis.

Introduction: Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis., Methods: Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years., Results: Early (within 2 years after primary surgery) and non-early (> 2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (≤ 6 months) and slow ( > 6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD, IDH1-mutant DA, and IDH wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection ≥ 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG., Conclusions: Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development.

Objective: Acetaldehyde, associated with consumption of alcoholic beverages, is known to be a carcinogen and to be related to the tongue dorsum. The aim of this study was to investigate the relationship between acetaldehyde concentration in mouth air and bacterial characteristics on the tongue dorsum., Methodology: Thirty-nine healthy volunteers participated in the study. Acetaldehyde concentrations in mouth air were evaluated by a high-sensitivity semiconductor gas sensor. A 16S rRNA gene sequencing technique was used to compare microbiomes between two groups, focusing on the six samples with the highest acetaldehyde concentrations (HG) and the six samples with lowest acetaldehyde concentrations (LG)., Results: Acetaldehyde concentration increased in correlation with the increase in bacterial count (p=0.048). The number of species observed in the oral microbiome of the HG was higher than that in the oral microbiome of the LG (p=0.011). The relative abundances of Gemella sanguinis, Veillonella parvula and Neisseria flavescens in the oral microbiome of the HG were higher than those in the oral microbiome of the LG (p<0.05)., Conclusion: Acetaldehyde concentration in mouth air was associated with bacterial count, diversity of microbiome, and relative abundance of G. sanguinis, V. parvula, and N. flavescens.

Six years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the third revised edition was published in 2017. The 2017 Guidelines includes 10 additional clinical questions (CQ), which brings the total to 95 CQ (12 on infectious disease, 28 on oncology and benign tumors, 27 on endocrinology and infertility and 28 on healthcare for women). Currently a consensus has been reached on the Guidelines and therefore the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding recommendation level (A, B, C) is indicated., (© 2019 Japan Society of Obstetrics and Gynecology.)

Enhanced surveillance of invasive pneumococcal disease (IPD) in adults was conducted during April 2013-March 2018 in 10 of 47 prefectures in Japan, and a total of 1277 IPD patients were enrolled. An emergence of IPD caused by serotype 12F was identified during May 2015-March 2018 through this surveillance. 12F isolates were composed of four related sequence types. In total, 120 patients with 12F IPD were reported during this period. To characterize the clinical features of 12F IPD, the disease characteristics of these patients were compared with those of 1157 patients with non-12F IPD. Compared with the non-12F IPD patients, a significantly lower proportion of 12F IPD patients was aged 65 years or older (55% vs. 70%), vaccinated with 23-valent pneumococcal polysaccharide (4% vs. 14%), had comorbid illness (65% vs. 77%), or were immunocompromised (19% vs. 30%; all P < 0.05). No significant difference in the proportion of case fatalities was found between the two groups. The proportions of those aged 65 years or older (53% vs. 69%) and with bacteremic pneumonia (35% vs. 69%) were significantly lower in 17 patients who died from 12F IPD than in 205 patients who died from non-12F IPD (all P < 0.05). Differences in clinical features were similarly found between 12F IPD patients and patients in low- or intermediate-level invasive potential serogroups. Our data demonstrated that serotype 12F was associated with IPD in younger adults and a lower proportion of comorbid illness, including immunocompromised conditions, in adult IPD, suggesting the high invasive potential of the serotype 12F. In addition, patients who died from 12F IPD were younger and had proportionately more bacteremia without focus. These findings may provide new insight into the pathogenesis of IPD in adults caused by 12F serotype with a high invasive potential., Competing Interests: The authors have declared that no competing interests exist.

Collectivism is an important factor for coping with stress in one's social life. To date, no imaging studies have revealed a direct association between collectivism and white matter structure. Collectivism is positively related to independence, harm avoidance, rejection sensitivity, cooperativeness, external locus of control, and self-monitoring and negatively related to need for uniqueness. Accordingly, we hypothesised that the neural structures underpinning collectivism are those that are also involved with its relationship using magnetic resonance imaging (MRI). This study aimed to identify the brain structures associated with collectivism in healthy young adults (n = 797), using regional grey and white matter volume, fractional anisotropy, and mean diffusivity (MD) analyses of MRI data. Scores on the collectivism scale were positively associated with MD values in the bilateral dorsolateral prefrontal cortex, left orbitofrontal cortex, inferior frontal gyrus, right superior temporal gyrus, ventral posterior cingulate cortex, globus pallidus, and calcarine cortex using the threshold-free cluster enhancement method with family-wise errors corrected to P < 0.05 at the whole-brain level. No significant associations between were found collectivism and other measures. Thus, the present findings supported our hypothesis that the neural correlates of collectivism are situated in regions involved in its related factors.

Background: Carnitine deficiency is common in patients on hemodialysis. However, the efficacy of L-carnitine supplementation for improving lean body mass (LBM) and physical function has not yet been evaluated., Methods: In this multicenter, prospective, parallel, randomized, controlled trial, 91 patients on hemodialysis who developed carnitine deficiency were randomly assigned to receive injections of 1,000 mg L-carnitine 3 times per week after each hemodialysis session (L-carnitine group) or no injections (control group) with monitoring for 12 months., Results: The data for 84 of the 91 patients were available for analysis (L-carnitine group, n = 42; control group, n = 42). Dry weight and body mass index did not significantly change in the L-carnitine group, but significantly decreased in the control group. Arm muscle area (AMA) did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean AMA between the groups was 6.22% (95% confidence interval [CI] 1.90-10.5; P = 0.037). Hand grip strength did not change significantly in the L-carnitine group, but decreased significantly in the control group. The difference in change in hand grip strength between the groups was 4.27% (95% CI 0.42-8.12; P = 0.030). Furthermore, LBM did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean LBM between the groups was 2.92 % (95% CI 1.28-4.61; P = 0.0007)., Conclusions: L-carnitine supplementation is useful in patients who develop carnitine deficiency on hemodialysis because it maintains physical function and LBM.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. Disulfide bond-forming oxidoreductase A-like protein (DsbA-L) is known to be a key molecule in protection against obesity and obesity-induced inflammation. In the present study, we used a modeling and simulation approach in an attempt to develop body mass index (BMI) and BMI-based NAFLD prediction models incorporating the DsbA-L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A nonlinear mixed-effect model best represented the sigmoidal relationship between the BMI and the logit function of the probability of NAFLD prevalence. The final models for BMI and NAFLD showed that DsbA-L rs1917760 polymorphism, age, and gender were associated with the BMI, whereas gender, patatin-like phospholipase 3 rs738409 polymorphism, HbA1c, and high-density and low-density lipoprotein cholesterol levels were associated with the risk of NAFLD. This information may aid in the genetic-based prevention of obesity and NAFLD in the general elderly population., (© 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: We evaluated the 1-year outcomes of percutaneous coronary intervention (PCI) for elderly patients (aged ≥ 80 years) in the second-generation drug-eluting stent (DES) era., Methods and Results: Between August 2012 and July 2013, 1923 consecutive patients (mean age, 71 ± 11 years; ≥80 years, 23%; men, 77%) who underwent 2250 elective/urgent PCI procedures were enrolled in the Shinshu Prospective Multicenter Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention registry. The primary end point was major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, and stroke) at 1 year. The 1-year incidence of MACEs, cardiac death, and stroke was significantly higher in elderly patients than in nonelderly patients (12.4% vs 5.3%, P < .0001; 7.8% vs 2.2%, P < .0001; and 2.8% vs 1.3%, P = .033, respectively). However, no significant difference in elective PCI procedures was detected. In elderly patients, the incidence of cardiac death and target lesion revascularization was significantly lower for DES than for non-DES (2.7% vs 10.5%, P = .0001 and 4.1% vs 8.6%, P = .029, respectively)., Conclusion: Although elderly patients had a significantly poorer prognosis than younger patients, the adverse events rate was comparable in those patients who underwent elective PCI in the second-generation DES era.

Background: In Japan, the routine use of early antiviral therapy for patients with influenza is standard., Methods: This multicenter prospective cohort evaluation of hospitalized patients with laboratory-confirmed influenza identified prognostic factors among the patients receiving antiviral therapy., Results: Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding those aged < 1 year (who are not approved for antiviral therapy), 97.7% (1,224 of 1,253) received antiviral therapy. Among the adult patients, 24 (4.1%) died within 30 days, whereas none of the pediatric patients died. Five hundred twenty-eight (91.2%) adult patients had influenza A, 509 (87.9%) had a chronic underlying illness, and 211 (36.4%) had radiographically confirmed pneumonia. Twenty of the 24 patients who died had pneumonia of the following etiologies: Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as having community-acquired pneumonia (CAP) and 60 as having health-care-associated pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more common (21.7% vs 2.6%, P < .001) in patients with HCAP, particularly MRSA (10% vs 0.7%, P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional hazards modeling with prescribed independent variables, male sex, severity score, serum albumin levels (malnutrition), and pneumonia were associated with survival 30 days from the onset of influenza., Conclusions: Among the prognostic factors, malnutrition and pneumonia are amenable to medical intervention. An opportunity exists to improve empirical therapy for patients with HCAP and influenza., Trial Registry: Japan Medical Association Center for Clinical Trials; No.: JMA-IIA00123; URL: http://www.jmacct.med.or.jp/en/., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone., (Copyright © 2016 Elsevier Inc. All rights reserved.)