Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AIMS: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. APPROACH RESULTS: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000-2022 based on available data from countries. Trends in age-standardised mortality rates (ASRs) during 2013-2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% confidence interval: 2.5-3.1) in 2000, and 2.7 (2.3-3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8-6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3-2.9) and 2.2 (1.8-2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to GBC decreased by 45.5%, and those due to eCCA remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013-2022, with iCCA-associated ASRs showing increasing trends in many countries. CONCLUSIONS: Although internationally estimated BTC-associated ASRs showed a stable trend over the last two decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.

DOI： 10.1097/HEP.0000000000001200

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PURPOSE: Following the COVID-19 pandemic, group A Streptococcus (GAS) infection has been surging worldwide. We aimed to compare the disease burden between notified cases of streptococcal toxic shock syndrome (STSS) and unreported GAS infections. METHODS: This is a multicentral observational study, retrospectively performed at seven hospitals in Okayama prefecture in Japan from January 2022, to June 2024. Clinical and microbiological data of patients with positive cultures of GAS were collected from the medical records. Primary outcomes were defined as rates of surgical procedures, intensive care unit (ICU) admission, and in-hospital mortality, which were compared among patients with locally-defined STSS, invasive GAS (iGAS), and non-iGAS infection. RESULTS: GAS was detected in 181 patients, with 154 active cases of GAS infection. The number of patients with GAS infection surged in late 2023. The most common source of infection was skin and soft tissue infections, accounting for 83 cases, including 15 cases of necrotizing fasciitis, and 12 cases (7.8%) were notified to public health authorities as STSS. Among the 25 unreported iGAS cases, 9 (36.0%) underwent surgical intervention, and 4 patients (16.0%) required ICU admission. The mortality rates in the unreported iGAS cases were comparable to those observed in the notified STSS. CONCLUSIONS: We highlighted that the number of iGAS infections was twofold higher than that of notified STSS, with comparable mortality rate between these groups, indicating substantial underestimation of the true burden of iGAS. This epidemiological investigation has significant implications for enhancing infectious disease surveillance frameworks and public health policy development.

DOI： 10.1007/s10096-024-05015-2

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. METHODS: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including "Corynebacterium", "Daptomycin", and "Resistance", in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. RESULTS: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8%), and prosthetic device-associated infections accounted for 66.7% of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71% to 100%) within 24 hours of incubation, compared to other Corynebacterium strains CONCLUSION: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.

DOI： 10.1016/j.jiac.2024.12.004

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study aimed to clarify the epidemiology and clinical features of tick bites in a Japanese spotted fever (JSF)-endemic area. METHOD: The clinical records of patients with tick bites were retrospectively reviewed based on a survey conducted at Numakuma Hospital, Fukuyama City, Hiroshima, Japan, from 2016-2023. Data on basic characteristics, visit dates, residential address, exposure activities, tick-bite sites, and prophylactic antimicrobial prescriptions for each patient with tick bites were collected at the JSF hotspot hospital. RESULTS: A total of 443 patients with tick bites visited the hospital, of which data on 305 cases (68.8%) were reviewed. The median age of these patients was 71 years, with a higher proportion of women (63.0%). One-third of the patients had a preceding history of working in fields, whereas two-thirds had entered mountains or agricultural fields. Nearly 90% of the patients visited the hospital from April to August, and the most common bite sites were the lower extremities (45.1%). Most patients (76.1%) resided in the southern area of Numakuma Hospital. Nearly all patients were prescribed prophylactic antibiotics (minocycline in 87.8% of cases), and none subsequently developed JSF. CONCLUSION: Continued surveillance of patients with tick bites is warranted to better understand changes in the clinical impact of tick-borne diseases.

DOI： 10.1016/j.jiac.2024.11.020

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PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated. METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances. RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints. CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

DOI： 10.1080/0167482X.2024.2305899

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

A recent systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of prolonged versus intermittent β-lactam infusion in adult sepsis patients. The findings revealed a significant decrease in all-cause mortality and marked clinical success in the prolonged infusion group. Unfortunately, however, the manuscript lacked data and discussion for the specific regimens of prolonged β-lactam infusion defined in the included 15 RCT studies, which are herein additionally provided. Excluding one RCT, all protocols adopted a continuous infusion for the prolonged treatment. Except for three RCTs, dosages and timings of bolus injection were clearly defined. The total daily antibiotic dose for the continuous therapy was equivalent to those recommended for intermittent therapy. We believe this supplementary data aids clinicians in providing prolonged β-lactam infusions, contributing to enhanced treatment outcomes for patients suffering from severe sepsis or septic shock.

DOI： 10.1016/j.jiac.2024.07.003

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Language：Japanese   Publisher：(一社)日本臨床微生物学会  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The vaccination rate for HPV (Human Papillomavirus) has remained significantly low in Japan because of the administrative suspension of active recommendation. This study investigates the awareness and uptake of the HPV vaccine among healthcare students in Japan following the reinstatement of active recommendation for young women in April 2022. METHODS: A web-based survey was administered to 2567 healthcare students from Okayama and Shujitsu Universities in Japan in July 2023. The survey assessed participants' backgrounds, immunization status, awareness of vaccine recommendations, and knowledge of cervical cancer across various demographics, including sex, academic year, and department (Medicine, Health Science, Pharmaceutical, and Dentistry). RESULTS: The response rate was 36.3 % (933 students; 181 male, 739 female, and 13 unspecified gender). The overall immunization rate among female students was 55.6 %, with higher rates observed in medical (73.8 %) and dental (63.0 %) students. Awareness of the government's change in vaccine recommendation was notably high among female and senior male students. Over half of the female students (54.7 %) reported receiving vaccinations based on their parents' advice. Among those unvaccinated but interested in future immunization, concerns about adverse reactions (47.4 %) and challenges in scheduling vaccinations (29.1 %) were predominant. CONCLUSION: Healthcare students exhibited a higher HPV vaccination rate than the general population. Ongoing education to improve vaccine literacy is crucial for augmenting HPV vaccination rates in Japan.

DOI： 10.1016/j.jiac.2024.11.004

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Authorship：Lead author,　Last author,　Corresponding author   Language：English  

DOI： 10.1016/j.amjms.2024.07.002

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Authorship：Lead author,　Last author,　Corresponding author   Language：English  

DOI： 10.1007/s40121-024-01053-7

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.31662/jmaj.2024-0102

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control.

DOI： 10.18926/AMO/67657

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Authorship：Corresponding author   Language：English  

DOI： 10.1007/s15010-024-02382-y

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

We investigated the prevalence and characteristics of Cefazolin inoculum effect (CInE) among clinical MSSA isolates in Japan. Although 35.5 % (39 isolates) were positive for the blaZ gene, none met the phenotypic criteria for CInE. Our findings suggested a very low prevalence of CInE among MSSA isolates in our clinical setting.

DOI： 10.1016/j.diagmicrobio.2024.116399

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

52歳男性。COVID-19発症7日後に経皮的動脈血酸素飽和度94%(リザーバー10L/分投与下),右眼球共同偏倚と左半側空間無視,左上下肢完全麻痺をきたし搬送された。単純CTでは頭部で右中大脳動脈領域低吸収域を認め,胸部では両側広範囲の末梢優位のすりガラス影を認めた。造影CTでは右下肺動脈と左大腿静脈・膝窩静脈に血栓を認め,脳梗塞と肺塞栓症・深部静脈血栓症を合併した重症COVID-19と診断した。経過中に出血性脳梗塞を発症するも救命し得た。脳梗塞・肺塞栓を合併したCOVID-19では出血性脳梗塞の発症を念頭に慎重なフォローが必要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J05937&link_issn=&doc_id=20241218260009&doc_link_id=10.60227%2Fjhgmwabun.20.5_289&url=https%3A%2F%2Fdoi.org%2F10.60227%2Fjhgmwabun.20.5_289&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Healthcare-associated infections (HAIs) are a global concern in healthcare facilities, for which hand hygiene (HH) using alcohol-based hand rubs (ABHR) is fundamentally crucial for their prevention. While previous studies report improvements in HH compliance amid the COVID-19 pandemic, the real situation in Japanese medical settings remains unclear. METHODS: This observational study sought data from the Japanese national surveillance, focusing on ABHR use in hospitals before and after the COVID-19 pandemic. Data were retrieved from facilities certified to receive the Additional Healthcare Reimbursements for Infection Prevention and Control I. The study spanned five years (2019-2023), segmented quarterly, and employed Joinpoint regression analysis to assess the annual percentage change (APC). RESULTS: Overall, ABHR use per patient per day significantly increased both in critical care units and general wards amid the pandemic. However, the APC in the critical care units demonstrated a downward trend from Q4 of 2021 to Q1 of 2023, and ABHR use in general wards remained below the amount of WHO recommendations. CONCLUSION: This trend analysis highlighted recent patterns of ABHR use in Japanese hospitals by comparing pre- and post-COVID-19 periods. Although increases in ABHR use were observed over time, sustained efforts to promote HH compliance are necessary, particularly in general wards.

DOI： 10.1016/j.jhin.2024.08.007

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease.

DOI： 10.1016/j.jiac.2024.08.009

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11739-024-03731-3

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: We developed a virtual reality (VR) education system and evaluated its clinical utility for promoting hand hygiene practices. METHODS: This prospective, two-week, randomised controlled study conducted at Okayama University Hospital, Japan, from November 2023 to January 2024, involved 22 participants (18 medical students and four residents). A fully immersive 360° VR system (VIVE Pro Eye) using a head-mounted display and sensing gloves was used to develop three healthcare tasks in a virtual patient room-Environmental Cleaning, Gauze Exchange, and Urine Collection. After monitoring all participants' baseline usage data of portable hand-rubbing alcohol in the first week, we randomly assigned them into 1:1 groups (VR training and video lecture groups). The primary outcome was differences in hand-rubbed alcohol use before and after intervention. RESULTS: Before the intervention, alcohol use did not significantly differ between both groups. After the intervention, a significant increase in alcohol use was observed in the VR training group (median: 8.2 g vs. 16.2 g; p=0.019) but not in the video lecture group. CONCLUSION: Our immersive 360° VR education system enhanced hand hygiene practices. Infection prevention and control practitioners and digital technology experts must collaborate to advance the development of superior educational devices and content.

DOI： 10.1016/j.ajic.2024.08.003

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1016/j.chest.2024.03.021

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Language：English   Publishing type：Research paper (scientific journal)  

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

DOI： 10.3390/ijms25158370

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.

DOI： 10.3390/jcm13144199

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11739-024-03643-2

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Language：English   Publisher：日本細菌学会  

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijid.2024.107145

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Ureaplasma urealyticum is a rare pathogen associated with septic arthritis that predominantly affects patients with hypogammaglobulinemia. Bacterial identification of fastidious organisms is challenging because they are undetectable by routine culture testing. To the best of our knowledge, this is the first report of septic arthritis induced by U. urealyticum infection in Japan. CASE DESCRIPTION: We describe the case of a 23-year-old Japanese female with secondary hypogammaglobulinemia (serum immunoglobulin level < 500 mg/dL), identified 8 years after treatment with rituximab. The patient presented with persistent fever and polyarthritis that were unresponsive to ceftriaxone and prednisolone. Contrast-enhanced computed tomography and gallium-67 scintigraphy revealed effusion and inflammation in the left sternoclavicular, hip, wrist, knee, and ankle joints. Although Gram staining and bacterial culture of the drainage fluid from the left hip joint were negative, the condition exhibited characteristics of purulent bacterial infection. The patient underwent empirical treatment with doxycycline, and her symptoms promptly resolved. Subsequent 16S ribosomal RNA (rRNA) gene sequencing of the joint fluid confirmed the presence of U. urealyticum, leading to the diagnosis of septic arthritis. Combination therapy with doxycycline and azithromycin yielded a favorable recovery from the inflammatory status and severe arthritic pain. CONCLUSION: This case highlights U. urealyticum as a potential causative agent of disseminated septic arthritis, particularly in patients with hypogammaglobulinaemia. The 16S rRNA gene analysis proved beneficial for identifying pathogens in culture-negative specimens, such as synovial fluid, in suspected bacterial infections.

DOI： 10.1007/s15010-024-02301-1

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Language：Japanese   Publisher：日本細菌学会  

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

The global pandemic of COVID-19 has underscored the significance of establishing and sustaining a practical and efficient infection control system for the benefit and welfare of society. Infectious disease (ID) specialists are expected to take on leadership roles in enhancing organizational infrastructures for infection prevention and control (IPC) at the hospital, community, and national levels. However, due to an absolute shortage and an uneven distribution, many core hospitals currently lack the ID specialists. Given the escalating global risk of emerging and re-emerging infectious diseases as well as antimicrobial resistance pathogens, the education and training of ID specialists constitutes an imperative concern. As demonstrated by historical changes in the healthcare reimbursement system, the establishment and enhancement of IPC measures is pivotal to ensuring medical safety. The existing structure of academic society-driven certification and training initiatives for ID specialists, contingent upon the discretionary decisions of individual physicians, possesses both quantitative and qualitative shortcomings. In this article, I first address the present situations and challenges related to ID specialists and then introduce my idea of securing ID specialists based on the new concepts and platforms; (i) ID Specialists as National Credentials, (ii) Establishment of the Department of Infectious Diseases in Medical and Graduate Schools, (iii) Endowed ID Educative Courses Funded by Local Government and Pharmaceutical Companies, and (iv) Recruitment of Young Physicians Engaged in Healthcare Services in Remote Areas. As clarified by the COVID-19 pandemic, ID specialists play a crucial role in safeguarding public health. Hopefully, this article will advance the discussion and organizational reform for the education and training of ID specialists.

DOI： 10.18926/AMO/67195

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Authorship：Corresponding author   Language：Japanese   Publisher：The Japanese Association for Infectious Diseases  

The effectiveness of interventions by senior resident physicians to optimize blood culture examinations has rarely been reported. We compared the results of blood culture examinations performed before and after an intervention, which consisted of 1) holding a study session on blood culture, 2) informing the monthly contamination rate, 3) feeding back the blood culture results to the doctor who ordered the test, and 4) distributing the institutional manual. After the intervention, the contamination rate decreased from 7.7% to 2.4%, and the proportion of coagulase-negative staphylococci isolated decreased from 34.6% to 15.9%. Additional laboratory testing and antibiotic administration were ordered in 4 patients (30.8%) with suspected contamination. To reduce blood culture contamination, a multifaceted educational approach is essential. Our report highlights the fact that educational activities by senior residents could play a considerable role in promoting the optimization of blood culture examinations.

DOI： 10.11150/kansenshogakuzasshi.e23034

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. METHODS: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with >  600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. RESULTS: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. CONCLUSIONS: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators.

DOI： 10.1007/s15010-024-02284-z

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jpids/piae041

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase. METHODS: This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1,899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions. RESULTS: Compared with the <2,500 arbitrary unit (AU)/mL category, the 2,500-5,000, 5,000-10,000, and ≥10,000 AU/mL categories had adjusted RRs (95% CI) of 0.81 (0.61-1.08), 0.51 (0.36-0.72), and 0.41 (0.31-0.54), respectively. The spline function showed a non-linear relationship between antibody titer and risk. CONCLUSIONS: Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future vaccination.

DOI： 10.1093/infdis/jiae207

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Authorship：Corresponding author   Language：English  

DOI： 10.1016/j.ijantimicag.2024.107182

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Language：English   Publishing type：Research paper (scientific journal)  

Depressive disorders are among the leading causes of disability globally. However, information on the burden of depressive disorders in Vietnam is limited. We aimed to analyse the burden of depressive disorders in Vietnam from 1990 to 2019. Using data from the Global Burden of Disease Study 2019, prevalence and disability-adjusted life-years (DALYs) were used as indicators to analyse the burden of depressive disorders by age and sex. In 2019 in Vietnam, depressive disorders comprised 2629.1 thousand (95% uncertainty interval (UI): 2233.3-3155.9) estimated cases and 380.6 thousand (95% UI: 258.9-533.8) estimated DALYs. The crude prevalence rate of depressive disorders was higher among females than among males. The DALYs of depressive disorder accounted for a higher percentage of the total all-cause DALYs in the 10-64-year age group than in other age groups. Major depressive disorder was the largest contributor to the burden of depressive disorders. From 1990 to 2019, the crude prevalence and DALY rates per 100 000 population due to depressive disorders increased significantly, whereas age-standardised rates of prevalence and DALYs decreased significantly; the respective average annual percent changes were 0.88% (95% confidence interval: 0.87 to 0.89), 0.68% (0.66 to 0.70), -0.20% (-0.21 to -0.19), and -0.27% (-0.28 to -0.25). Although the age-standardised prevalence rate was lower than that seen globally, depressive disorders were considerable mental health issues in Vietnam. This study will help governments and policymakers to establish appropriate strategies to reduce the burden of these disorders by identifying the priority areas and individuals.

DOI： 10.1016/j.jpsychires.2024.02.041

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Escherichia coli-associated native-valve infective endocarditis is a rare disease that affects elderly patients with underlying risk factors such as diabetes mellitus, malignancy, and renal failure. Long-term use of calcium polystyrene sulfonate is a potential risk factor for gastrointestinal mucosal damage or even colorectal ulcers. Herein, we describe a fatal case of a 66-year-old Japanese man with diabetes mellitus and renal failure who was prescribed calcium polystyrene sulfonate (CPS) for 11 years and developed a CPS-induced rectal ulcer, leading to E. coli native-valve infective endocarditis. The patient was admitted to our hospital due to acute-onset impaired consciousness. As a result of the systemic investigation, he was diagnosed with E. coli bacteremia accompanied by multiple cerebral infarctions and an acute hemorrhagic rectal ulcer. Transesophageal echocardiography revealed a 20-mm vegetative structure on the mitral valve, resulting in a final diagnosis of E. coli-associated infective endocarditis. After rectal resection, mitral valve replacement surgery was performed; however, the patient died shortly after surgery. Pathological findings of the resected rectum showed deposition of a basophilic crystalline material suggesting the presence of CPS. Our case highlights the potential risk of colorectal ulcers in a long-term CPS user, which can trigger bacterial translocation and endocarditis as fatal complications.

DOI： 10.1007/s12328-024-01949-4

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INTRODUCTION: Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19. METHODS: The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 μg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders. RESULTS: Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors. CONCLUSIONS: Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

DOI： 10.1016/j.jiac.2024.03.007

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Language：English   Publishing type：Research paper (scientific journal)  

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

DOI： 10.1038/s41598-024-55526-3

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Key Clinical Message

We present a patient catheterized for prostatic lesions who developed sepsis of urinary origin with a penile cavernosal abscess due to urethral injury caused by catheter ballooning. Urethral injury might lead to a life‐threatening penile abscess.

DOI： 10.1002/ccr3.8534

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Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index ≥ 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology.

DOI： 10.3390/jcm13030889

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jtm/taae011

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. METHODS: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). RESULTS: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] - 5.4-27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI - 15.5-10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI - 1.5-8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. CONCLUSION: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required.

DOI： 10.1007/s11046-023-00814-1

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.teln.2023.08.004

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

In this age of antimicrobial resistance (AMR), improving treatment using existing antibiotics is desirable. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are high priority AMR pathogens according to the World Health Organization. Cephamycin-class beta- lactams are tolerant to hydrolysis by ESBL activity and have bactericidal effects on ESBL-E. The aim of the present study was to compare the in vitro minimum inhibitory concentration (MIC) of cefmetazole (CMZ) and flomoxef (FMOX) among ESBL-E strains. This was a retrospective study using microbiology laboratory data from Okayama University Hospital (Japan) from January 2014 to June 2022. The MIC was determined by broth microdilution method and the ESBL phenotypes were determined by double-disk method. Antimicrobial use density (AUD) data for CMZ and FMOX were also gathered. Annual proportions of ESBL-producing organisms in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex were 20.4-30.6%, 3.5-13.7%, and 0-3.1%, respectively. The ESBL-producing bacteria with MIC levels ≤1 μg/mL for CMZ and FMOX ranged from 57 to 84% and 97 to 100%, respectively, for E. coli, and from 50 to 92% and 80 to 100%, respectively, for K. pneumoniae. E. cloacae strains showed MIC levels ≥32 μg/mL for both agents. The AUD ratio for CMZ to FMOX ranged from 5.31 to 12.27, with no apparent upward or downward trend. Proportions of ESBL-producing E. coli and K. pneumoniae strains with MIC ≤1 μg/mL were greater in FMOX than in CMZ. To corroborate the clinical superiority of FMOX in treating ESBL-E infections, a randomized controlled study, as well as pharmacokinetic/pharmacodynamic analysis, is required.

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BACKGROUND: In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan. METHODS: This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death. RESULTS: After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0-19 age group, while hospital deaths decreased in the 20-64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by -4.0% (95% CI: -4.9 to -3.1) in 2019-2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively. CONCLUSION: PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age.

DOI： 10.1371/journal.pone.0299700

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Language：English   Publishing type：Research paper (scientific journal)  

Methicillin-resistant Staphylococcus spp. present challenges in clinical and veterinary settings because effective antimicrobial agents are limited. Phage-encoded peptidoglycan-degrading enzyme, endolysin, is expected to be a novel antimicrobial agent. The enzymatic activity has recently been shown to be influenced by the linker between functional domains in the enzyme. S6_ORF93 (ORF93) is one of the endolysins derived from previously isolated Staphylococcus giant phage S6. The ORF93 was speculated to have a catalytic and peptidoglycan-binding domain with a long linker. In this study, we examined the influence of linker shortening on the characteristics of ORF93. We produce wild-type ORF93 and the linker deletion mutants using an Escherichia coli expression system. These mutants were designated as ORF93-Δ05, ORF93-Δ10, ORF93-Δ15, and ORF93-Δ20, from which 5, 10, 15, and 20 amino acids were removed from the linker, respectively. Except for the ORF93-Δ20, ORF93 and its mutants were expressed as soluble proteins. Moreover, ORF93-Δ15 showed the highest yield and bacteriolytic activity, while the antimicrobial spectrum was homologous. The cold storage experiment showed a slight effect by the linker deletion. According to our results and other studies, linker investigations are crucial in endolysin development.

DOI： 10.1371/journal.pone.0310962

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6-8, 9-11, and 12-14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%-4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%-4.0%) and 9- to 11-year (0.9%-2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%-8.9%) and girls of many age groups (2.6%-8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary.

DOI： 10.1111/cob.12636

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND OBJECTIVE: Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level. METHODS: This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates. RESULTS: The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92-3.18) in 2001 to 6.86 (95% confidence interval 5.76-7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20-50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019. CONCLUSIONS: The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally.

DOI： 10.1007/s40264-023-01387-0

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Language：English   Publishing type：Research paper (scientific journal)  

This paper presents the results of a series of surveys conducted from July 2021 to March 2023 to investigate the post-vaccination adverse reactions to the mRNA-1273 (Moderna) vaccine among faculty, staff, and students at Okayama University. These studies complement the official surveys conducted by the Ministry of Health, Labour and Welfare (MHLW) and provide a more representative picture of adverse reactions in the general population including large numbers of healthy young people. Pain, swelling, redness at the injection site, fever, headache, and malaise were the main adverse reactions reported. The proportion of adverse reactions was generally higher after the second vaccination and decreased with each additional vaccination. No statistically significant differences in the adverse reactions were found for males and females and those with/without a history of allergy, but a lower proportion of fever was observed in older participants and those with underlying medical conditions. We also evaluated the association between adverse reactions and antibody titers after the third vaccination and found no significant differences in antibody levels one month after vaccination. This series of studies highlights the importance of conducting surveys in diverse populations to provide a more representative picture of post-vaccination adverse reactions during a pandemic.

DOI： 10.18926/AMO/66148

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Language：Japanese   Publisher：(一社)日本臨床微生物学会  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Simulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties.

Methods

This study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents’ medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups.

Results

A total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation.

Conclusion

Simulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties.

DOI： 10.1186/s12909-023-04798-w

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Other Link： https://link.springer.com/article/10.1186/s12909-023-04798-w/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31–64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment.

DOI： 10.3390/vaccines11111661

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50). METHODS: This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors. RESULTS: Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66). CONCLUSIONS: High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.

DOI： 10.1016/j.jiac.2023.10.016

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy. METHODS: According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022. RESULTS: Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed. CONCLUSION: In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.

DOI： 10.1016/j.pupt.2023.102233

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Language：English   Publishing type：Research paper (scientific journal)  

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

DOI： 10.18926/AMO/65975

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

During this age of climate change, the incidence of tropical diseases may change. This study compared the epidemiological characteristics and trends of leptospirosis in Japan between the endemic region, Okinawa, and the rest of the country. Infectious Diseases Weekly Reports were used to determine the numbers and crude incidence rates of leptospirosis. Data were stratified by sex, age, the estimated location of the infection, the notified regions, and the reporting month. A joinpoint regression analysis was performed to estimate the annual percentage change (APC). During the 16-year study period (2006-2021), 543 leptospirosis cases were reported, with male dominance (86.2%). Approximately half of these cases were reported from Okinawa (47.1%). The patients were relatively younger in Okinawa (20-29 years, 23.4%; 30-39 years, 20.7%) than outside Okinawa. The frequency of imported cases was significantly higher outside Okinawa (0.4% versus 14.3%). The incidences of leptospirosis in and outside Okinawa were apparently higher during the summer and typhoon seasons. The annual crude incidence ratios were 20-200 times higher in Okinawa than in the rest of the country. The average APCs for the entire study period in Okinawa and the rest of Japan were 1.6% (95% CI: -5.9 to 9.6) and -1.8% (95% CI: -7.8 to 4.6), respectively, without any particular trends. Collectively, the patient profile of leptospirosis differed between Okinawa (younger men) and outside Okinawa (middle- or older-aged men with a history of traveling abroad). The disease remains a neglected tropical disease; continuous surveillance with close monitoring is required.

DOI： 10.4269/ajtmh.23-0131

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Authorship：Corresponding author   Language：English  

Leptospirosis is a zoonotic disease that primarily affects people in tropical and subtropical areas worldwide. Owing to the temperate climate of Japan, leptospirosis is not endemic across the country. Domestic cases of leptospirosis have been mainly reported in Okinawa and the southwestern subtropical islands, but not in the other regions. Here, we describe a case of leptospirosis that developed and was diagnosed outside the domestically endemic region. Notably, disease onset occurred shortly after the patient experienced a flood after a typhoon disaster. With global warming, the international prevalence of leptospirosis may change. Physicians outside currently endemic areas must be aware of this tropical disease.

DOI： 10.4269/ajtmh.23-0133

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Authorship：Corresponding author   Language：English  

Intravesical Bacillus Calmette-Guérin (BCG) instillation is an established immunotherapy for superficial bladder cancer. Herein, we describe a case of disseminated BCG infection that developed immediately after the first BCG injection. A 76-year-old man diagnosed with non-invasive bladder cancer underwent intravesical BCG instillation; he developed high fever and systemic arthralgia later that night. General examination did not reveal any infectious sources, and a combination therapy of isoniazid, rifabutin, and ethambutol was initiated after collecting his blood, urine, bone marrow, and liver biopsy samples for mycobacterial cultures. Three weeks later, Mycobacterium bovis was detected in the urine and bone marrow samples, and pathological investigation of liver biopsy revealed multiple small epithelial granulomas with focal multinucleated giant cells, leading to a diagnosis of disseminated BCG infection. The patient recovered after long-term antimycobacterial therapy without remarkable sequelae. Most cases of disseminated BCG infection occur after several doses of BCG injections, and its onset reportedly varies among cases, ranging from a few days to several months. The present case was notable as disease onset was observed only a few hours after the first BCG injection. Although rare, development of disseminated BCG infection should be considered as a differential diagnosis in patients at any time after intravesical BCG instillation therapy.

DOI： 10.1016/j.jiac.2023.05.017

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Language：English   Publishing type：Research paper (scientific journal)  

To reduce physician burden, task shifting of clerical work from physicians to medical assistants is being promoted; however, it depends on hospitals. A questionnaire survey was conducted among 40 general physicians at Okayama University Hospital in December 2022 to investigate physicians' preferences toward task shifting. Compared to other tasks, most physicians thought that ordering examinations (14, 47%), replying to referral letters (19, 63%), and prescriptions (21, 70%) and medical record entries (22, 73%) should not be task shifted. Physicians' controversial opinions on task shifting maybe the reason behind the slow progress in task shifting.

DOI： 10.1002/jgf2.641

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

INTRODUCTION: Extended-spectrum β-lactamases-producing Enterobacteriaceae (ESBL-E) is a critical antimicrobial resistance pathogen, to which we need to pay the greatest attention. This study was aimed at uncovering the present evidence for the preventive effectiveness of contact precautions for patients colonized or infected with ESBL-E. METHODS: According to the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews, we searched MEDLINE for articles with relevant keywords from the beginning of 2010 to October 18, 2022. RESULTS: Of the 355 articles found, 9, including 8 observational studies and 1 randomized controlled trial, were selected. Safety of discontinuing contact precautions was evaluated mainly in acute-care and long-term care hospitals. Consistently, all authors concluded that contact precautions can be safely discontinued in patients colonized or infected with ESBL-E. CONCLUSION: The clinical impact of discontinuing contact precautions for patients with ESBL-E is minimal and can be safely withdrawn at acute, noncritical, adult care wards. Relevant data from pediatric and geriatric wards, as well as intensive care units, were insufficient and should be investigated in future research.

DOI： 10.1016/j.ajic.2023.01.018

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1111/ene.16019

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Language：English  

Octreotide is used in patients with insulinomas to treat hypoglycemia, and somatostatin receptor (SSTR) 2 expression is important for its efficacy. We report a case of insulinoma in a 50-year-old woman that responded to an octreotide test, showed accumulation in somatostatin scintigraphy, and was positive for SSTR2A on immunostaining.

DOI： 10.1002/ccr3.7771

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

DOI： 10.3390/cancers15153786

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. METHODS: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. RESULTS: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8-353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4-251.5) and no-fatigue group (86.7 μg/L, 37.5-209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05). CONCLUSIONS: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients.

DOI： 10.3390/jcm12144737

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Typhoid fever is one of the representative febrile diseases in tropical and subtropical countries with poor hygiene. Among the anaemic conditions involving patients with typhoid fever, autoimmune hemolytic anaemia would be one of the potential causes in the absence of G6PD deficiency or intestinal haemorrhage

DOI： 10.1093/jtm/taad092

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11739-023-03368-8

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19). METHODS: In this exploratory multicenter randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6. RESULTS: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; p=0.022). Serious adverse events were not observed in either group. Phlebitis occurred in approximately 50% of patients treated with nafamostat. CONCLUSIONS: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

DOI： 10.1016/j.ijantimicag.2023.106922

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Language：Japanese  

J-GLOBAL

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Authorship：Lead author   Language：English  

DOI： 10.1016/j.jinf.2023.06.011

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama.

DOI： 10.18926/AMO/65490

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Language：English   Publishing type：Research paper (scientific journal)  

Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID.

DOI： 10.3390/jcm12103533

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Parvimonas micra commonly present in the oral cavity and intestinal tract of humans. P. micra indicating a high virulence, has the potential of forming abscess. The infection of P. micra may require surgical excision.

DOI： 10.1002/rcr2.1161

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Language：English   Publishing type：Research paper (scientific journal)  

The clinical impact of Strongyloides stercoralis hyperinfection secondary to immunosuppressive therapy for coronavirus disease 2019 (COVID-19) has been an emerging topic of interest, although characteristics of Strongyloides infection in COVID-19 patients are not yet well characterized. This study summarizes the existing evidence of Strongyloides infection in COVID-19 patients and recommends future areas of research. According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including "Strongyloides," "Strongyloidiasis," and "COVID-19" from the inception of these databases to June 5, 2022. A total of 104 articles were found. After excluding duplication and thorough reviews, 11 articles, including two observational studies, one conference abstract, and nine case reports or series, were included. Two observational studies focused on revealing the prevalence of Strongyloides screening in COVID-19 patients and clinical follow-up. Among the included cases, patients were mostly from low- or middle-income countries and suffered from severe or critical COVID-19. Strongyloides hyperinfection and disseminated infection were reported in 60% and 20%, respectively. Interestingly, 40% did not have eosinophilia, a hallmark of parasitic infection, potentially leading to delay in diagnosis of strongyloidiasis. This systematic review summarizes the clinical characteristics of strongyloidiasis in COVID-19 infection. Although further studies to identify risks and precipitants associated with the onset of strongyloidiasis are crucial, increased awareness of the critical condition is warranted.

DOI： 10.4269/ajtmh.22-0671

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

J-GLOBAL

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Authorship：Last author   Language：English  

A 22-year-old Vietnamese woman presented with anterior chest swelling. Computed tomography revealed an osteolytic lesion in the manubrium, whereas MRI showed an extra-osseous expansion. A needle biopsy showed granuloma formation, whereas a 3-week mycobacterial culture indicated Mycobacterium tuberculosis infection. Manubrium/sternum involvement in tuberculosis is extremely rare but should be considered.

DOI： 10.1002/ccr3.7119

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Ceftolozane (CTLZ) is a novel cephalosporin antibiotic that exhibits broad-spectrum activity against gram-negative pathogens, including Pseudomonas aeruginosa, especially when combined with tazobactam (TAZ). We examined the minimum inhibitory concentration (MIC) of CTLZ/TAZ for 21 multidrug-resistant P. aeruginosa (MDRP) and eight carbapenem-resistant P. aeruginosa (CRPA) strains isolated at Okayama University Hospital, Japan. Consequently, 81% (17/21) of the MDRP strains and 25% (2/8) of the CRPA strains were resistant to CTLZ/TAZ (MIC >8 μg/mL). All 18 blaIMP-positive strains showed resistance to CTLZ/TAZ, whereas the drug retained in vitro susceptibility in 54.5% (6/11 strains) of blaIMP-negative strains.

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Authorship：Corresponding author   Language：English  

Granulicatella species are rare, nutritionally variant streptococci that cause infective endocarditis. Their clinical and microbiological characteristics remain unknown. We reviewed five years of Granulicatella cases in our hospital database (Jan 2017-Jun 2022), finding 6 Granulicatella adiacens cases and 1 Granulicatella elegans case. Clinical backgrounds and bacteremia sources were diverse; 3 cases developed polymicrobial bacteremia. Antimicrobial testing showed non-susceptibility to penicillin G in 4 of 7 cases (57.1%), and high susceptibility to carbapenems and vancomycin in all cases. Determining optimal antibiotic therapy for Granulicatella infections is vital in this era of antimicrobial resistance.

DOI： 10.18926/AMO/65151

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.3346/jkms.2023.38.e84

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Authorship：Corresponding author   Language：Japanese   Publisher：(一社)日本感染症学会  

症例は30歳代ネパール人男性で、下痢と嘔気を主訴とした。ハンセン病(LL型)と新型コロナウイルス感染症の既往があり、らい反応に対して長期間のステロイド製剤内服による免疫抑制療法を行っていた。各種検査所見より、糞線虫の過剰感染状態による播種性糞線虫症と診断した。栄養状態は不良で、寄生虫の消化管内過剰増殖に伴う腸管浮腫を認め、イベルメクチンは吸収不良で血中濃度が不十分であった。多臓器不全を併発したため集学的治療を行ったが第36病日に死亡した。日本では糞線虫症は稀であるが、インバウンドの増加に伴い播種性糞線虫症のリスクが増加する可能性があり、ステロイドの長期内服などで免疫抑制状態の可能性がある場合は寄生虫スクリーニングを行う必要があると考えられた。

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Authorship：Corresponding author   Language：English  

Buruli ulcer is the third most common mycobacterial infection worldwide and is mainly diagnosed in tropical regions. Globally, this progressive disease is caused by Mycobacterium ulcerans; however, Mycobacterium ulcerans subsp. shinshuense, an Asian variant, has been exclusively identified in Japan. Because of insufficient clinical cases, the clinical features of M. ulcerans subsp. shinshuense-associated Buruli ulcer remain unclear. A 70-year-old Japanese woman presented with erythema on her left backhand. The skin lesion deteriorated without an apparent etiology of inflammation, and she was referred to our hospital 3 months after disease onset. A biopsy specimen was incubated in 2% Ogawa medium at 30 °C. After 66 days, we detected small yellow-pigmented colonies, suggesting scotochromogens. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI Biotyper; Bruker Daltonics, Billerica, MA, USA) indicated that the organism was Mycobacterium pseudoshottsii or Mycobacterium marinum. However, additional PCR testing for the insertion sequence 2404 (IS2404) was positive, suggesting that the pathogen was either M. ulcerans or M. ulcerans subsp. shinshuense. Further examination by 16S rRNA sequencing analysis, focusing on nucleotide positions 492, 1247, 1288, and 1449-1451, we finally identified the organism as M. ulcerans subsp. shinshuense. The patient was successfully treated with 12 weeks of clarithromycin and levofloxacin treatment. Mass spectrometry is the latest microbial diagnostic method; however, it cannot be used to identify M. ulcerans subsp. shinshuense. To accurately detect this enigmatic pathogen and uncover its epidemiology and clinical characteristics in Japan, more accumulation of clinical cases with accurate identification of the causative pathogen is essential.

DOI： 10.1016/j.jiac.2023.02.009

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

The worldwide spread of tick-borne diseases (TBDs) has become a public health concern. Therefore, this study aimed to clarify trends in the incidence of Japanese spotted fever (JSF), one of Japan's most prevalent TBDs. Weekly infectious disease reports were used to calculate the annual incidence rates (AIRs) of JSF. Data were stratified by age and sex, and joinpoint regression analysis was performed to estimate the annual percentage change (APC). AIR and APC were geographically compared among the 47 prefectures. A total of 3,453 JSF cases were observed from 2001 to 2020. The AIR per 100,000 population was 0.03 in 2001, which increased approximately 10-fold to 0.33 in 2020. The average APC (AAPC) during the study period was 12.3% (95% CI: 10.7-13.9). By age group, the incidence of JSF increased more rapidly among the older population: 11.5% (95% CI: 10.1-12.9) in those aged ≥ 65 years and 8.9% (95% CI: 6.4-11.5) in those aged < 50 years. Although the AIR over the past two decades was higher in climatically warm regions located in southwestern Japan and on the Pacific coast, increases in the AAPC were notable in colder regions located in eastern Japan. The incidence of JSF continues to increase in Japan, especially among older populations and in eastern prefectures, where the disease has not been previously diagnosed.

DOI： 10.4269/ajtmh.22-0487

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Inducible resistance to the macrolide, lincosamide, and streptogramin B (iMLSB) antibiotic family is a latent mechanism for antimicrobial resistance in Staphylococcus aureus. We here investigated the frequency and genotypic profiles of iMLSB resistance in clindamycin (CLDM)-susceptible S. aureus isolated in Okayama University Hospital from June 2020 to June 2021. We phenotypically screened the iMLSB resistance via D-zone test and performed PCR testing for the erythromycin ribosomal methylase (erm) genes: ermA and ermC. Among 432 CLDM-susceptible S. aureus isolates, 138 (31.9%) exhibited an iMLSB-resistance phenotype, with methicillinresistant S. aureus isolates (MRSA; 61 isolates: 58.6%) exhibiting higher positivity than methicillin-sensitive S. aureus isolates (MSSA; 77 isolates: 23.5%) (p<0.001). Male patients had a higher frequency of iMLSB resistance than females (OR [95%CI]: 1.8 [1.2-2.8]; p=0.007). Genotypically, ermA predominated in both MSSA (70.1%) and MRSA (86.9%) compared to ermC (14.3% in MSSA and 11.5% in MRSA). A single strain of MRSA possessed both ermA and ermC, while 12 (15.6%) MSSA isolates were negative for both ermA and ermC, suggesting the presence of other genetic mechanisms. Collectively, these results show that approximately 33% of CLDM-susceptible S. aureus isolates at our university hospital exhibited iMLSB resistance, predominantly caused by ermA in both MSSA and MRSA.

DOI： 10.18926/AMO/64355

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.

DOI： 10.3390/medicina59020261

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Tuberculous meningitis is possibly complicated with multiple cerebral infarctions and basal meningitis, and the mortality and neurological prognosis is reportedly poor. This case suggested that clinicians should consider tuberculous meningitis as a differential diagnosis of patients with disturbed consciousness in an aging country Japan.

DOI： 10.1002/ccr3.6865

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.6865

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Campylobacter species are the pathogens of the intestinal tract, which infrequently cause bacteremia. To reveal the clinical characteristics of Campylobacter bacteremia, we performed a retrospective, multicenter study. Patients diagnosed with Campylobacter bacteremia in three general hospitals in western Japan between 2011 and 2021 were included in the study. Clinical, microbiological, and prognostic data of the patients were obtained from medical records. We stratified the cases into the gastroenteritis (GE) and fever predominant (FP) types by focusing on the presence of gastrointestinal symptoms. Thirty-nine patients (24 men and 15 women) were included, with a median age of 57 years and bimodal distribution between those in their 20 s and the elderly. The proportion of GE and FP types were 21 (53.8%) and 18 (46.2%), respectively. Comparing these two groups, there was no significant difference in patient backgrounds in terms of sex, age, and underlying diseases. Campylobacter jejuni was exclusively identified in the GE type (19 cases, 90.5%), although other species such as Campylobacter fetus and Campylobacter coli were isolated in the FP type as well. Patients with the FP type underwent intravenous antibiotic therapy more frequently (47.6% vs. 88.9%), and their treatment (median: 5 days vs. 13 days) and hospitalization (median: 7 days vs. 21 days) periods were significantly longer. None of the patients died during the hospitalization. In summary, we found that nearly half of the patients with Campylobacter bacteremia presented with fever as a predominant manifestation without gastroenteritis symptoms.

DOI： 10.1038/s41598-022-27330-4

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.idcr.2023.e01733

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

Cryptococcal meningitis is a critical disease that occasionally involves immunosuppressed patients. We herein report a 79-year-old Japanese man who received low-dose prednisolone therapy for neurosarcoidosis and panhypopituitarism. He presented a 10-day history of a fever and altered mental status. The FilmArray® Meningitis/Encephalitis Panel and serum cryptococcal antigen tests were both negative, but the cerebrospinal fluid sample became positive for Cryptococcus neoformans after seven-day incubation. After the diagnosis of cryptococcal meningitis, we successfully treated the patient with a recommended treatment regimen. When an immunocompromised patient presents with a subacute fever accompanying any central nervous symptoms, cryptococcal meningitis should be screened for.

DOI： 10.2169/internalmedicine.0879-22

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: This study aimed to assess the distribution of board-certified infectious disease (ID) specialists at medical schools and Designated Medical Institutions (DMIs) in Japan. METHODS: Data on the number of board-certified ID specialists was extracted by gender, prefecture, and hospital from the Japanese Association for Infectious Diseases database. The numbers and types of Japanese university hospitals that have a Faculty of Medicine, as well as the DMIs legally determined by the Infectious Diseases Control Law, were collected from the database of the Ministry of Health, Labour, and Welfare of Japan. RESULTS: As of November 2022, there were 1,688 board-certified ID specialists in Japan, with 510 employed at 82 university hospitals. Two medical schools had no ID specialists, and six had only one ID specialist. There was no ID specialists in 14.3% of Class I DMIs and 66.7% of Class II DMIs. Additionally, 14.9% of prefectures had no ID specialists at all in their Class II DMIs. The percentage of female doctors among ID specialists was 12.7%, approximately half of the overall male-to-female ratio of medical doctors in Japan. CONCLUSION: The allocation of Japanese ID specialists to medical schools and legally designated healthcare institutes is inadequate and skewed. Female physicians are expected to play a more active role in this increasing demand.

DOI： 10.1371/journal.pone.0291677

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. METHODS: This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or no-teprenone groups in a 1:1 ratio. We stratified patients by sex, age < and ≥ 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. RESULTS: One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). CONCLUSION: Teprenone afforded no clinical benefit. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs061200002 (registered on 20/May/2020).

DOI： 10.1371/journal.pone.0287501

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The objective of this study was to determine the clinical and endocrinological features of sleep disturbance in patients with long COVID. METHODS: This study was a single-center retrospective observational study for patients who visited the COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital in Japan during the period from 15 February 2021 to 29 July 2022. The long COVID patients were divided into two groups based on the presence or absence of sleep disturbance, and the clinical and laboratory characteristics of the patients were analyzed. RESULTS: Out of 363 patients with long COVID, after excluding 6 patients, 60 patients (16.5%) (55% males, median age of 38 years) complaining of sleep disturbance were compared with 303 patients (83.5%) (43% males, median age of 40 years) without sleep-related symptoms. Although there were no significant differences in clinical backgrounds and severities of COVID-19 between the two groups by the multivariate analysis, the percentage of long COVID patients with sleep disturbance was significantly increased among patients infected in the Omicron-dominant phase. In addition, the prevalence rate of sleep disturbance in patients when infected in the Omicron phase (24.8%) was two-times higher than that in patients infected in the Delta phase (12.8%). Of note, the percentages of patients with sleep disturbance who also complained of general fatigue, headache, concentration loss, anxiety, low-grade fever, and brain fog symptoms were higher than the percentages of patients without sleep disturbance who had the same complaints. Among the types of sleep disturbance, the percentage of patients who complained of loss of sleep induction (75%) was much higher than the percentage of patients with early-awakening sleep disturbance (6.7%), and many of the patients with mid-awakening types of insomnia had brain fog symptoms. Endocrine examinations revealed that long COVID patients with sleep disturbance had significantly higher levels of plasma adrenocorticotropin and lower levels of serum growth hormone, suggesting the presence of hypothalamic-pituitary stress. CONCLUSION: The prevalence of sleep disturbance has been increasing in long COVID patients infected in the Omicron phase with a certain clinical and endocrine trend.

DOI： 10.3390/jcm11247332

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/CCM.0000000000005646

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Amidst the global spread of antimicrobial resistance, New Delhi metallo-β-lactamase (NDM)-type carbapenemase-producing Enterobacterales (CPE) remain uncommon in Japan, and the detection of such highly drug-resistant organisms is limited to inbound cases. There is little evidence regarding the prevalence of NDM β-lactamase gene (blaNDM)-harboring CPE in the domestic community, especially in the provincial cities of Japan. Herein, we report the isolation of a blaNDM-1-harboring plasmid in Enterobacter cloacae complex strain isolated from an elderly woman without a history of traveling abroad who had resided in a long-term care facility in Okayama, Japan. The multidrug-resistant blaNDM-harboring CPE isolate was detected in a stool sample of the patient during routine screening at admission. We performed whole-genome sequencing analysis of the isolate using MiSeq (Illumina) and MinION (Oxford Nanopore Technologies) platforms. The isolate was identified as sequence type 171, which has predominantly been reported in the United States and China. The blaNDM-1 gene was encoded on the 46,161 bp IncX3 plasmid, with sequence similarity to plasmids of similar size isolated from individuals in China. Collectively, the genomic data suggest that an imported CPE isolate may have spread among healthy individuals in the regional area of Japan.

DOI： 10.1016/j.jiac.2022.08.019

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Language：English  

A patient complained of acute right vision loss and headache. A computed tomography scan revealed ethmoidal sinus mucocele in the right ethmoid sinus that was compressing the optic nerve and emergency endoscopic sinus surgery was performed.

DOI： 10.1002/ccr3.6696

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM &amp; IgG Quantum Dot immunoassay (Mokobio Biotechnology R&amp;D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (&gt; 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p &lt; 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

DOI： 10.1038/s41598-022-24464-3

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Other Link： https://www.nature.com/articles/s41598-022-24464-3

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

The reduced use of antimicrobial drugs has been recommended worldwide, according to the global action for antimicrobial resistance published in 2015 by the World Health Organization. In this study, we retrospectively reviewed the incidence of surgical site infection in consecutive patients with cataract surgeries at a single hospital in the 6-year process when prophylactic systemic antibiotics were reduced in a step-by-step manner. The entire study period from 2016 to 2022 was divided into five stages, based on the use of systemic antibiotics. In stage 1 with 649 cataract surgeries, an intravenous drip infusion of cefazolin 1 g was given at surgery, followed by oral cefdinir 100 mg in the evening on surgery day and three times for two postoperative days. In stage 2 with 541 cataract surgeries, oral cefdinir 100 mg was given in the late morning before surgery, in the evening, and three times (300 mg in total) for two postoperative days. In stage 3 with 103 cataract surgeries, oral levofloxacin 500 mg was given in the late morning before surgery and once in the morning for two postoperative days. In stage 4 with 545 cataract surgeries, oral levofloxacin 500 mg was given only in the late morning before surgery. In stage 5 with 311 cataract surgeries, no systemic antibiotics were given. As common procedures in all stages, moxifloxacin eye drops were given four times daily as topical antibiotics in the 3 days before surgery and about 2 weeks after surgery. At surgery, the ocular surface was frequently irrigated with saline-diluted povidone iodine at 0.5% working concentration. No postoperative infection was recorded in any stage. This study showed neither harm nor risk in reduced use and, consequently, no use of prophylactic systemic antibiotics in cataract surgery as far as local precautionary measures were secured.

DOI： 10.3390/ijerph192315796

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Long-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic. METHODS: We performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers. RESULTS: Stool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The blaCTX-M-9 group was the most common (38.5%), followed by the blaTEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different. CONCLUSION: Our active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather.

DOI： 10.1016/j.jiac.2022.07.014

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Language：Japanese   Publisher：(一社)日本小児感染症学会  

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BACKGROUND: Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including 'cefepime', 'neurotoxicity', 'encephalopathy' and 'seizure', from their inception to 20 January 2022. RESULTS: We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction.Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4 days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of >20 mg/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3 days. No CIN-associated deaths were reported. CONCLUSIONS: This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.

DOI： 10.1093/jac/dkac271

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Objective Amid the global spread of antimicrobial resistance, antimicrobial stewardship should be further promoted in the clinical setting. Our previous study suggested an intra-week disproportion of discontinuation of broad-spectrum antibiotics. We therefore explored the generalization of this prescription trend by investigating the use of all intravenous antibiotics. Methods A retrospective, observational study. Patients Between January 1, 2018, and December 31, 2020, we collected data on the initiation and discontinuation of intravenous antimicrobials on each day of the week and on days after holidays at Okayama University Hospital, Japan. We compared the monthly antimicrobial prescription initiation and discontinuation using the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction as a post-hoc procedure. Results Data from 15,293 hospitalized cases were analyzed. The initiation of antimicrobials differed slightly among days of the week, although this trend was clinically insignificant. Compared with the initiations, antimicrobial discontinuations were disproportionately biased among the weekdays, tending to occur on Mondays (p <0.001) about twice as often as on other days. Similarly, antimicrobials were unevenly discontinued on the day after holidays compared to other days (p <0.001), with an approximately 2-fold difference. The use of antimicrobials in the hospital was thus unequally terminated on weekdays. Conclusion To further promote antimicrobial stewardship, clinicians should be aware of the influence of behavioral, environmental, and social factors on antimicrobial prescription, which is seemingly beyond medical indications.

DOI： 10.2169/internalmedicine.0707-22

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

AIM: An increasing number of older adults in Japan are at an increased risk of road traffic crashes. This study aimed to investigate the prevalence of potential underlying medical factors that increase the risk of road traffic crashes among older people. METHODS: This cross-sectional observational study was conducted in 11 medical institutions in Japan using self-administered questionnaires and physical examination from January to May 2021. The background and social data, data on the use of nursing care insurance, and clinical data suggestive of polypharmacy, sarcopenia, cognitive impairment, and frailty/oral frailty were obtained. The prevalence of these factors was compared between everyday and occasional drivers. RESULTS: Data of 127 patients were collected; their median (interquartile range) age was 73 (70-78) years. Of the total participants, 82 were men (64.6%) and 45 were women (35.4%). There were 77 everyday drivers and 50 occasional drivers. Of these, 121 (95.3%) had not applied for nursing care insurance, but the numbers of those who required help 1 and 2 were 1 (0.8%) and 3 (2.4%), respectively. Prevalence of medical factors was as follows: polypharmacy, 27.6%; sarcopenia, 8.7%; dementia, 16.4%; frailty, 15.0%; and oral frailty, 54.3%; it was not significantly different between every day and occasional drivers. Intention to return the car license was significantly higher among the occasional drivers (2.6% vs. 14.0%; odds ratio: 6.7, 95% confidence interval: 1.2-70.6, p = 0.024). CONCLUSION: We uncovered the prevalence of medical factors that can be associated with road traffic crashes among Japanese older people aged ≥ 65 years in our community.

DOI： 10.1186/s12877-022-03490-w

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Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p &lt; 0.01), dysgeusia (14% vs. 40%, ** p &lt; 0.01) and hair loss (7% vs. 28%, ** p &lt; 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p &lt; 0.05), insomnia (26% vs. 13%, * p &lt; 0.05) and cough (20% vs. 7%, ** p &lt; 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized.

DOI： 10.3390/medicina58101393

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Candida dubliniensis phenotypically mimics Candida albicans in its microbiological features; thus, its clinical characteristics have yet to be fully elucidated. Here we report the case of a 68-year-old Japanese man who developed C. dubliniensis fungemia during treatment for severe coronavirus disease 2019 (COVID-19). The patient was intubated and received a combination of immunosuppressants, including high-dose methylprednisolone and two doses of tocilizumab, as well as remdesivir, intravenous heparin, and ceftriaxone. A blood culture on admission day 11 revealed Candida species, which was confirmed as C. dubliniensis by mass spectrometry. An additional sequencing analysis of the 26S rDNA and ITS regions confirmed that the organism was 100% identical to the reference strain of C. dubliniensis (ATCC MYA-646). Considering the simultaneous isolation of C. dubliniensis from a sputum sample, the lower respiratory tract could be an entry point for candidemia. Although treatment with micafungin successfully eradicated the C. dubliniensis fungemia, the patient died of COVID-19 progression. In this case, aggressive immunosuppressive therapy could have caused the C. dubliniensis fungemia. Due to insufficient clinical reports on C. dubliniensis infection based on definitive diagnosis, the whole picture of the cryptic organism is still unknown. Further accumulation of clinical and microbiological data of the pathogen is needed to elucidate their clinical significance.

DOI： 10.1016/j.jiac.2022.07.007

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To clarify the clinical and microbial characteristics of polymicrobial bacteremia (PMB) to contribute to improvements in clinical diagnosis and effective early treatment. METHODS: This retrospective multicenter study used data from three acute-care hospitals in Okayama Prefecture, Japan, collected between January 2014 and March 2019. We reviewed the demographics, comorbidities, organisms isolated, infectious focus, and 30-day mortality of patients with PMB. RESULTS: Of the 7233 positive blood cultures, 808 (11.2%) were positive for more than one organism. Of the patients with bacteremia, 507 (7.0%) had PMB, of whom 65.3% were male. Infectious foci were identified in 78.3% of the cases, of which intra-abdominal infections accounted for 47.1%. A combination of Gram-positive cocci (GPC) (chain form) and Gram-negative rods (GNR) accounted for 32.9% of the cases, and GPC/GNR and GNR/GNR patterns were significantly associated with intra-abdominal infections. The 30-day mortality rate of patients with PMB was 18.1%, with a median of 7.5 days from diagnosis to death. The mortality in patients with an infectious focus identified was significantly lower than that in patients with an unknown focus (16.3% vs. 24.5%; p = 0.031). CONCLUSIONS: Intra-abdominal infections were the most common source of PMB, and were strongly associated with a Gram-staining combination pattern of GPC (chain form)/GNR. PMB cases with an unknown focus had a poorer prognosis, highlighting the importance of early diagnosis and appropriate treatment.

DOI： 10.1007/s15010-022-01799-7

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Physicians should keep in mind that Kikuchi-Fujimoto disease can show bilateral lymphadenopathy like the present case.

DOI： 10.1002/ccr3.6494

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/qjmed/hcac150

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Other Link： https://academic.oup.com/qjmed/article-pdf/115/9/615/45973068/hcac150.pdf

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

The immunization and screening rates for human papillomavirus in Japan are lower than those in other countries. We aimed to evaluate the impact of cervical cancer awareness months on public attention using Google Trends analysis. Between 2012 and 2021, we analyzed the trends in relative search volumes (RSVs) for "Shikyuu-keigan" (cervical cancer in English) in Japan, during the cervical cancer awareness month (CCAM) in January and cervical cancer prevention awareness enhancement month (CCPAEM) in November. We performed a joinpoint regression analysis to identify a statistically significant trend change point. Additionally, we compared the mean RSVs of each awareness month with the rest of the year. Significant trend change points were observed, but none were found in CCAM and CCPAEM periods. Comparison of mean RSVs among CCAM, CCPAEM, and the rest of the months did not suggest any significant increases in RSVs during these awareness periods. In conclusion, CAM and CCPAEM did not raise public interest in cervical cancer in Japan. Although the results are based on internet users, the findings might suggest a need to develop a more effective and attractive approach to achieve the 90-70-90 targets of cervical cancer prevention by 2030.

DOI： 10.1038/s41598-022-19798-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

BACKGROUND: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. METHODS: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3-13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. RESULTS: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). CONCLUSION: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.

DOI： 10.1016/j.jiac.2022.09.012

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Authorship：Lead author,　Corresponding author   Language：Japanese  

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has prevailed worldwide since early 2020 and has caused the global coronavirus disease 2019(COVID-19)pandemic. A considerable number of patients suffer from various sequela after SARS-CoV-2 infection, which is known as post COVID-19 condition(PCC). Amid the COVID-19 pandemic, we opened a COVID-19 aftercare clinic in February 2021 in Okayama University Hospital, where we specifically consult PCC patients. While examining such patients, three Cs are essential: complexity, continuity, and collaboration. Neurological and psychiatric manifestations are particularly important from the wide range of PCC symptoms. Indeed, a recent meta-analysis demonstrated that PCC patients suffer from brain fog(32%), memory loss(27%), attention disorder(22%), dyssomnia(31%), anxiety(23%), and depression(12%). The pathophysiology and treatment strategies for these conditions are yet to be developed, and further research is required. We have corroborated that endocrinological impairments may underlie the onset and deterioration of PCC. Through our continuous consultation at the COVID-19 aftercare clinic, we intend to conduct research on the pathophysiology of and treatment strategies for PCC.

DOI： 10.11477/mf.1436204667

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01228&link_issn=&doc_id=20220928260020&doc_link_id=10.11477%2Fmf.1436204667&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204667&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Hand hygiene (HH) compliance among health-care workers has not satisfactorily improved despite multiple educative approaches. Between October 2019 and February 2020, we performed a self-evaluation test and a direct observation for the compliance of the 5 Moments for Hand Hygiene program advocated by the World Health Organization at two Japanese hospitals. Average percentages of self-evaluated HH compliance were as follows: (i) 76.9% for "Before touching a patient," (ii) 85.8% for "Before clean/aseptic procedures," (iii) 95.9% for "After body fluid exposure/risk," (iv) 84.0% for "After touching a patient," and (v) 69.2% for "After touching patient surroundings." On the other hand, actual HH compliance was 11.7% for "Before touching a patient" and 18.0% for "After touching a patient or patient surroundings." The present study demonstrated a big gap between self-evaluation and actual HH compliance among nurses working at hospitals, indicating the need of further providing the education in infection prevention.

DOI： 10.1177/17571774221094160

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/qjmed/hcac142

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/qjmed/hcac189

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BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

DOI： 10.1186/s12889-022-13899-y

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/qjmed/hcac167

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/qjmed/hcac172

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2169/internalmedicine.9498-22

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic has led to increased burnout among frontline healthcare workers (HCWs), little research has been done regarding the potential psychological burden among public health officials who have worked tirelessly to tackle the pandemic from an administrative perspective. This study aimed to determine the prevalence of burnout, depression, and job-related stress in Japanese public health officers amid the COVID-19 pandemic. METHODS: We conducted an anonymous, self-administered web-based cross-sectional survey including basic demographics, work-related questions, the Maslach Burnout Inventory, Patient Health Questionnaire-9, Utrecht Work Engagement Scale-3, and Brief Job Stress Questionnaire. 100 public health officers working in the public health centers (PHCs) in Okayama, Japan, answered the survey in December 2021 when the 5th surge in the number of COVID-19 was over. RESULTS: The prevalence of burnout, depression, and job-related stress was 27%, 43%, and 62%, respectively. The multivariate logistic analysis demonstrated that females, public health nurses, and those who suffered from a lack of support from their workplaces were significantly associated with psychological distress. CONCLUSIONS: While we tend to focus on mitigation plans to help alleviate burnout of frontline HCWs, more focus is needed to help public health officers, and public health nurses, in particular, to alleviate their psychological distress and job-related stress to prevent further staff shortages and secure sustainable health systems.

DOI： 10.1016/j.ajp.2022.103160

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial and community infections, and vancomycin (VCM) is widely recommended as a first-line therapeutic drug. Minimum inhibitory concentrations (MICs) of VCM ≤2 μg/mL are defined as susceptible, but increases in these levels, known as "VCM MIC creep" have been reported. The aim of this study was to investigate VCM MIC creep during the promotion of a national antimicrobial stewardship campaign. METHODS: We collected data from 2013 to 2020 on S. aureus isolated at the clinical microbiology laboratory at Okayama University Hospital, Japan. We calculated the annual proportions of MRSA isolation rates by MIC levels for nosocomial and community samples and estimated annual percentage changes in the antimicrobial use density of the VCM. RESULTS: Of the 1,716 MRSA isolates, no strains showed intermediate or resistant ranges of VCM MIC levels. By 2020, the proportion of MRSA with an MIC of ≤0.5 μg/mL decreased to 35.4%, while that with an MIC of 1 μg/mL increased to 64.1% over time. The annual percentage changes of the VCM antimicrobial use density significantly increased without any trend change point (average 8.1%, p = 0.035). There was no clear correlation between the VCM AUD and annual proportion of nosocomial MRSA with MIC 1 μg/mL (correlation coefficient 0.48; p value = 0.24). CONCLUSION: We demonstrated a deteriorating situation of VCM MIC creep among MRSA strains isolated at our university hospital during the national antimicrobial stewardship campaign.

DOI： 10.1016/j.jiac.2022.03.017

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Netherton's syndrome, a rare congenital disorder, is clinically characterized by chronic dermatologic disorders such as ichthyosiform erythroderma and ichthyosis linearis circumflexa. Curable treatment is yet to be established, and corticosteroid ointment is required to maintain good dermatological condition. Because of the permanent skin barrier impairment, patients with Netherton's syndrome are considered to be vulnerable to cutaneous infections. However, its clinical characteristics are yet to be elucidated due to the limited number of reported cases. Herein, we describe the clinical course of a patient who developed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A 19-year-old Japanese woman who had been diagnosed with Netherton's syndrome in her infancy and had been applying topical corticosteroid agents all over her body since her then, was referred to our hospital because of persistent MRSA bacteremia and secondary adrenal insufficiency. The patient was diagnosed with a central line-associated bloodstream infection and was appropriately treated with antibiotics and corticosteroid therapies. We assume that the damaged skin barrier due to the congenital dermatological disorder causes a disruption in the normal bacterial flora of the skin, leading to the invasion of harmful bacteria, such as S. aureus. In addition, internal (humoral immunodeficiency by decreased antibody against bacterial polysaccharide antigens) and external (prolonged and systemic use of corticosteroid ointment) factors bring about an immunodeficiency state in such patients. We highlight that in the absence of radical treatment, clinicians need to recognize that patients with Netherton's syndrome are vulnerable to bacterial infections owing to the mixture of immunosuppressive factors.

DOI： 10.1016/j.jiac.2022.02.021

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jinf.2022.07.007

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Language：English   Publishing type：Research paper (scientific journal)  

We aimed to compare the differences in testing performance of extraction-based polymerase chain reaction (PCR) assays, elution-based direct PCR assay, and rapid antigen detection tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used nasopharyngeal swab samples of patients with coronavirus disease 2019 (COVID-19). We used the MagNA Pure 24 System (Roche Diagnostics K.K.) or magLEAD 12gC (Precision System Science Co., Ltd.) for RNA extraction, mixed the concentrates with either the LightMix Modular SARS-CoV PCR mixture (Roche Diagnostics K.K.) or Takara SARS-CoV-2 direct PCR detection kit (Takara Bio Inc.), and amplified it using COBAS® z480 (Roche Diagnostics K.K.). For elution-based PCR, we directly applied clinical samples to the Takara SARS-CoV-2 direct PCR detection kit before the same amplification step. Additionally, we performed Espline SARS-CoV-2 (Fuji Rebio Co., Ltd.) for rapid diagnostic test (RDT), and used Lumipulse SARS-CoV-2 antigen (Fuji Rebio Co., Ltd.) and Elecsys SARS-CoV-2 antigen (Roche Diagnostics K.K.) for automated antigen tests (ATs). Extraction-based and elution-based PCR tests detected the virus up to 214-216 and 210 times dilution, respectively. ATs remained positive up to 24-26 times dilution, while RDT became negative after 22 dilutions. For 153 positive samples, positivity rates of the extraction-based PCR assay were 85.6% to 98.0%, while that of the elution-based PCR assay was 73.2%. Based on the RNA concentration process, extraction-based PCR assays were superior to elution-based direct PCR assays for detecting SARS-CoV-2.

DOI： 10.1002/jmv.27709

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Language：English   Publishing type：Research paper (scientific journal)  

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

DOI： 10.3390/medicina58070850

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

AIM: Amid the global aging, an establishment of healthcare policies for the aged population is a common issue to be addressed. However, few studies on centenarians have reported place and cause of death (PoD and CoD, respectively) as indicators of end-of-life care quality. This study aimed to analyze trends in PoD and CoD among centenarians in Japan. METHODS: Data from death certificates from Japanese vital statistics were analyzed; 205 513 deaths occurred among centenarians (aged ≥100 years) in Japan during the period from 2006 to 2016. PoD prevalence was calculated for each CoD. Trends in PoD prevalence were analyzed using the Joinpoint regression model. Changing points, annual percentage changes, and average annual percentage changes (AAPCs) were calculated to examine trends. RESULTS: The number of deaths more than doubled from 10 340 in 2006 to 26 427 in 2016. PoDs were composed of hospitals (52.7%), nursing homes (31.4%), own homes (13.6%) and others (2.2%). Dementia and old age increased rapidly as CoD. Proportions of hospital and home deaths decreased, with AAPCs of -2.3% (95% confidence interval [CI], -2.6 to -1.9) and -2.3% (95% CI, -3.2 to -1.4), respectively. Conversely, the proportion of deaths in nursing homes rapidly increased, with an AAPC of 6.8% (95% CI, 6.0-7.7). CONCLUSIONS: The results revealed changes in PoD among centenarians in Japan. Understanding these transitions is indispensable for health policy in aging societies. Geriatr Gerontol Int 2022; ••: ••-••.

DOI： 10.1111/ggi.14416

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Evidence regarding treatment for the acute phase of COVID-19 has been accumulating, but specific treatment for long COVID/post-COVID-19 condition has not yet been established. Treatment with herbal medicine might be one treatment option for long COVID, but there has been little research on the effectiveness of herbal medicine for long COVID. The aim of this study was to clarify the prescription patterns of Kampo medicines, which are herbal medicines that originated in China and were developed in Japan, for the treatment of general fatigue due to long COVID. A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period from Feb 2021 to Dec 2021 with a focus on symptoms accompanying general fatigue and prescriptions of Kampo medicine. Among the clinical data obtained from medical records of 195 patients, clinical data for 102 patients with general fatigue and accompanying symptoms were analyzed. The patients had various symptoms, and the most frequent symptoms accompanying general fatigue were dysosmia, dysgeusia, headache, insomnia, dyspnea, and hair loss. Prescriptions of Kampo medicine accounted for 24.1% of the total prescriptions (n = 609). The most frequently prescribed Kampo medicine was hochuekkito (71.6%) and other prescribed Kampo medicines were tokishakuyakusan, ryokeijutsukanto, juzentaihoto, hangekobokuto, kakkonto, ninjin'yoeito, goreisan, rikkunshito, and keishibukuryogan. Since the pathophysiology of general fatigue after an infectious disease is, in general, considered a qi deficiency in Kampo medicine, treatments with such compensation agents can be the major prescription as a complement for the qi. In conclusion, Kampo medicine can be one of the main pharmacological treatments for long COVID accompanying general fatigue.

DOI： 10.3390/medicina58060730

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1016/j.jns.2022.120232

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BACKGROUND: The sarcoidosis mortality rate has increased over the years, which contributes to the health care burden. Although epidemiological studies of sarcoidosis mortality in aging societies are essential, none have been published since 1989 in Japan. METHODS: We aimed to investigate the trends in crude and age-adjusted sarcoidosis-associated mortality rates per 1,000,000 population in Japan from 2001 to 2020 using national death certificate data among older adults aged over 50 years. The data were analysed using the joinpoint regression models to estimate long-term trends and average annual percentage changes (AAPCs). RESULTS: A total of 3094 sarcoidosis-associated deaths were recorded from 2001 to 2020 in Japan; women constituted 65.3% of these, with a female:male ratio of 1.89. Nearly 80% of deaths were over the age of 65 years, of which 32% were over the age of 80 years. The trend in crude mortality of those aged ≥80 years markedly increased from 0.81 to 9.68 per 1,000,000 population in men and from 2.38 to 12.87 in women, respectively. The overall age-adjusted sarcoidosis mortality rate increased 2.46-fold during the study period, with an AAPC of 5.1%. CONCLUSIONS: This study revealed that sarcoidosis-associated deaths in Japan have significantly increased over the past two decades, especially among the older population with a female predominance. Given the rising mortality rate and susceptibility of the older population, sarcoidosis will require more attention from health care providers in terms of a multidisciplinary approach to address the specific needs of the older population.

DOI： 10.1016/j.rmed.2022.106828

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Language：English   Publishing type：Research paper (scientific journal)  

To investigate adverse reactions and attitudes toward the vaccine during the first month after mRNA- 1273 vaccination in a larger sample including younger men and women in Japan, we distributed a 1-month post-vaccination questionnaire using a Google form to 8,566 people who received a second dose of mRNA-1273 at Okayama University. The response rate was about 40.2% (3,447 responses), the sex ratio was about the same, and 73.3 % (2,528 respondents) were students in their twenties or younger. Poisson regression with robust variance was performed to calculate the prevalence ratio of each symptom by different attributes. The most common adverse reactions after the second vaccine dose were local pain (80.4%), fever (85.1%), malaise (82.0%), headache (64.0%), and chills (57.4%). Approximately 99% of respondents reported that their adverse reactions resolved within 1 week. Over 80% of respondents were satisfied with their vaccination (87.2%), expressed interest in receiving the third vaccination (83.3%), and would recommend vaccination to their loved ones (80.2%). However, among them, 22.0% (757 respondents) would recommend and 28.4% (980 respondents) also stated that they would consider the type of vaccine in these decisions.

DOI： 10.35772/ghm.2021.01125

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Language：English   Publishing type：Research paper (scientific journal)  

Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.

DOI： 10.1507/endocrj.EJ22-0093

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Language：English  

After the acute phase of COVID-19, some patients have been reported to have persistent symptoms including general fatigue. We have established a COVID-19 aftercare clinic (CAC) to provide care for an increasing number of these patients. Here, we report the case of a 36-year-old man who developed post-COVID fatigue after acute infection with SARS-CoV-2. In the acute phase of COVID-19, the patient's fever resolved within four days; however, general fatigue persisted for three months, and he visited our CAC 99 days after the initial infection. Examination revealed a high Aging Male's Symptoms (AMS) score of 44 and low free testosterone (FT) level of 5.5 pg/mL, which meet the Japanese criteria of late-onset hypogonadism (LOH) syndrome. Imaging studies revealed an atrophic pituitary in addition to fatty liver and low bone mineral density. Anterior pituitary function tests showed a low follicle-stimulating hormonelevel and delayed reaction of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation, indicating the possibility of hypothalamic hypogonadism in addition to primary hypogonadism seen in patients with post-COVID-19 conditions. After the initiation of Japanese traditional medicine (Kampo medicine: hochuekkito followed by juzentaihoto), the patient's symptoms as well as his AMS score and serum FT level were noticeably improved. Furthermore, follow-up tests of GnRH stimulation revealed improvements in LH responsiveness. Although many patients have been reported to meet the criteria of ME/CFS such as our case, we emphasize the possibility of other underlying pathologies including LOH syndrome. In conclusion, LOH syndrome should be considered a cause of general fatigue in patients with post-COVID-19 conditions and herbal treatment might be effective for long COVID symptoms due to LOH (264 words).

DOI： 10.3390/medicina58040536

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

To promote antimicrobial stewardship, we studied antimicrobial prescription rates for uncomplicated cystitis, a common outpatient disease requiring antibiotic treatment. This multicenter retrospective study was performed from January 1, 2018, to December 31, 2020, in Japan, targeting outpatients aged ≥ 20 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting uncomplicated cystitis (N300). The data of 1445 patients were collected and that of 902 patients were analyzed. The overall median patient age was 71 years and a proportion of those aged less than 50 years was 18.8% with a female dominance (82.6%). Antimicrobials were prescribed for 884 patients (98.0%) and a total of 623 patients (69.1%) were treated with broad-spectrum drugs, including fluoroquinolones (36.0%), third-generation cephalosporins (29.9%) and faropenem (3.1%). A logistic regression model revealed that the broad-spectrum agents were significantly prescribed for the older patients, male patients, and those who visited internists. Recurrence was observed in 37 (4.1%) cases, and the multivariate analysis suggested any of age, sex, or antimicrobial types were not associated with the recurrence. Collectively, approximately two-thirds of antimicrobials prescribed for uncomplicated cystitis were broad-spectrum agents. The present data would be an indicator for antimicrobial prescriptions in uncomplicated cystitis in Japan.

DOI： 10.1038/s41598-022-09946-8

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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A patient complaining of swelling and tenderness in her left axilla was diagnosed with cat scratch disease despite no apparent history of cat exposure. Zoonosis can occur even in the absence of cat exposure because cat flea Ctenocephalides felis is also the vector of the pathogen through the flea feces.

DOI： 10.1002/ccr3.4816

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that "general fatigue" mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients' backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT &lt; 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = -0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID.

DOI： 10.3390/jcm11071955

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AIM: Despite the increasing attention that has been paid to amyloidosis in recent years, there have been few reports on amyloidosis mortality and its trends worldwide. This study aimed to evaluate the trends in crude and age-adjusted amyloidosis-associated mortality rates in Japan from 1998 to 2019. METHODS: We used national Vital Statistics data among older adults aged over 50 years. The data were analyzed using the joinpoint regression program to estimate the long-term trends and average annual percentage changes (AAPCs). RESULTS: A total of 9158 amyloidosis-associated deaths were recorded from 1998 to 2019, of which 56.1% were in men. The crude mortality rate per 1 000 000 older adults aged over 80 years increased from 9.65 to 54.3 among men and from 7.02 to 22.1 among women during the study period. Overall, the AAPCs of age-adjusted amyloidosis-associated mortality rates increased significantly over the study period (1.8%, 95% confidence interval [CI], 1.0-2.7%). While the annual percentage change (APC) of age-adjusted mortality rates in women showed no significant change over the study period, the APC in men markedly increased in the 2013-2019 period (8.2%, 95% CI: 6.0-10.4%). CONCLUSIONS: This study revealed an increasing trend in mortality associated with amyloidosis, and in particular a marked increase in mortality among men over the past 6 years. Considering its high mortality rate and susceptibility to the effects of an increasing population of older adults, amyloidosis deserves more attention from healthcare providers to improve the understanding of diagnosis, clinical treatment, and healthcare planning. Geriatr Gerontol Int 2022; 22: 246-250.

DOI： 10.1111/ggi.14348

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(一社)日本感染症学会  

初期研修医の卒後ローテーションにおける「感染症研修の必須化」に関する意識などを明らかにすることを目的に、岡山県内で初期研修プログラムを有する16の研修病院に所属する初期研修医(卒後1・2年)、および専攻医(卒後3・4・5年)を対象にウェブ・アンケートを行い、127名(男性64名、女性60名、無回答3名)より回答を得た。その結果、初期研修医制度における「感染症研修の必須化」(例:最低1ヵ月ローテーションするなど)について84名(66.1%)が賛成すると回答した。一方、18名(14.2%)は必須化に反対しており、その理由として、「ローテーション選択の自由度を損なうため」(15名)などが挙げられた。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00276&link_issn=&doc_id=20220406400006&doc_link_id=1390010292792199424&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390010292792199424&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Various symptoms persist even after the acute symptoms in about one third of patients with COVID-19. In February 2021, we established an outpatient clinic in a university hospital for patients with long COVID and started medical treatment for sequelae that persisted one month or more after infection. METHODS: To determine the key factors that affect the onset and clinical course of sequelae, a retrospective analysis was performed at Okayama University Hospital (Japan) between February and July 2021. We focused on changes in the numbers of symptoms and the background of the patients during a three-month period from the first outpatient visit. We also examined the relationship with SARS-CoV-2 antibody titers. RESULTS: Information was obtained from medical records for 65 patients. The symptoms of sequelae were diverse, with more than 20 types. The most frequent symptoms were general malaise, dysosmia, dysgeusia, sleeplessness, and headache. These symptoms improved in about 60% of the patients after 3 months. Patients who required hospitalization and had a poor condition in the acute phase and patients who received oxygen/dexamethasone therapy had higher antibody titers at the time of consultation. Patients with antibody titers ≥200 U/mL showed significantly fewer improvements in long COVID symptoms in 1 month, but they showed improvements at 3 months after the first visit. CONCLUSION: Long COVID symptoms were improved at 3 months after the initial visit in more than half of the patients. Serum antibody titers were higher in patients who experienced a severe acute phase, but the serum antibody titers did not seem to be directly related to the long-term persistence of long COVID symptoms.

DOI： 10.3390/jcm11051309

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DOI： 10.2169/internalmedicine.8950-21

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BACKGROUND: We analyzed data from COVID-19 patients in Japan to assess the utility of the 4C mortality score as compared with conventional scorings. METHODS: In this multicenter study, COVID-19 patients hospitalized between March 2020 and June 2021, over 16 years old, were recruited. The superiority for correctly predicting mortality and severity by applying the receiver operating characteristic (ROC) curve was compared. A Cox regression model was used to compare the length of hospitalization for each risk group of 4C mortality score. RESULTS: Among 206 patients, 21 patients died. The area under the curve (AUC) (95% confidential interval (CI)) of the ROC curve for mortality and severity, respectively, of 4C mortality scores (0.84 (95% CI 0.76-0.92) and 0.85 (95% CI 0.80-0.91)) were higher than those of qSOFA (0.66 (95% CI 0.53-0.78) and 0.67 (95% CI 0.59-0.75)), SOFA (0.70 (95% CI 0.55-0.84) and 0.81 (95% CI 0.74-0.89)), A-DROP (0.78 (95% CI 0.69-0.88) and 0.81 (95% CI 0.74-0.88)), and CURB-65 (0.82 (95% CI 0.74-0.90) and 0.82 (95% CI 0.76-0.88)). For length of hospitalization among survivors, the intermediate- and high- or very high-risk groups had significantly lower hazard ratios, i.e., 0.48 (95% CI 0.30-0.76)) and 0.23 (95% CI 0.13-0.43) for discharge. CONCLUSIONS: The 4C mortality score is better for estimating mortality and severity in COVID-19 Japanese patients than other scoring systems.

DOI： 10.3390/jcm11030821

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Coronavirus disease 2019 (COVID-19) has been spreading worldwide with unprecedented rapidity. Staphylococcus aureus is reported to frequently cause bacterial complications in patients with COVID-19. We herein present two additional cases of S. aureus pneumonia involving such patients. The first case was an obese 48-year-old man without any particular underlying diseases. The second case was another patient, a 72-year-old man, with hypertension, dyslipidemia, and steatohepatitis. Both patients developed methicillin-susceptible S. aureus pneumonia in the clinical course of COVID-19, to which antibiotic therapy with cefazolin was effectively administered. Through these cases, we emphasize that S. aureus secondary infections should be well cared with a high degree of caution in a case of critically ill COVID-19 patients.

DOI： 10.7759/cureus.22486

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Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH.

DOI： 10.18926/AMO/63203

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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DOI： 10.31662/jmaj.2021-0129

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DOI： 10.31662/jmaj.2021-0134

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Herein, we report a remarkable case of post-coronavirus disease 2019 (COVID-19) diffuse alopecia that gradually improved and recovered, and the hair volume returned approximately to the pre-infection level, seven months after the patient's first diagnosis of COVID-19. Approximately 20% of patients with COVID-19 develop alopecia a few months after the acute infection phase. Telogen effluvium is the major type of COVID-19 sequela secondary to physical or psychological distress. It is reversible and is expected to improve without any treatment, and it can be addressed by explaining to the patients their conditions, sharing medical information, and eliminating psychophysical stress by managing systemic complications.

DOI： 10.7759/cureus.21160

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis.

DOI： 10.1177/23247096221086450

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/23247096221086450

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, and the United States and European authorities established criteria for the release of COVID-19 patients from isolation in October 2020. However, a huge discrepancy exists between the hospital-discharge protocol for COVID-19 patients and the release of patients from in-hospital isolation. Our initially proposed criteria for in-hospital release from isolation was not adhered to by healthcare workers (HCWs) due to prevailing concerns regarding disease infectivity. Herein, we report difficulties encountered in attempting to establish a common understanding of the management of emerging infections. METHODS: We performed a Google Form-based questionnaire survey targeting HCWs from Okayama University Hospital, Japan, via e-mail on January 21-28, 2021. The anonymous investigation required respondents to provide information regarding their background as well as perceptions regarding the requirement, level of understanding, and readiness for developing release criteria. RESULTS: We obtained 150 eligible responses, including 57 (38.0%) from medical doctors and 53 (35.3%) from nurses. Most HCWs managing COVID-19 patients advocated for the implementation of the criteria, whereas those not working in that capacity did not (p<0.001). Over half of the HCWs indicated discomfort at seeing COVID-19 patients transitioning to general management even after meeting the criteria. CONCLUSIONS: It was challenging to establish a common understanding regarding the ideal criteria for in-hospital release of COVID-19 patients from isolation in our hospital. The dissemination of our experiences and multifaceted discussions with HCWs would be of great value as a countermeasure against the emergent pandemic.

DOI： 10.1371/journal.pone.0266853

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INTRODUCTION: The emergence of the novel coronavirus disease of 2019 (COVID-19) has led to huge disruptions in the medical field and society. The significance of training and education for experts has been increasingly acknowledged in Japan, where the number of infectious disease (ID) specialists is reportedly insufficient. In this paper, we report the results of a web-based survey that was conducted to reveal the ways in which the COVID-19 pandemic has influenced medical students' awareness of ID specialists and future career choices. METHOD: This cross-sectional descriptive study was conducted in March 2021 and targeted 717 medical students belonging to Medical School of Okayama University, Japan. The questionnaire consisted of four questions meant to assess students' knowledge and future intentions of becoming ID specialists. RESULTS: We obtained 328 eligible questionnaires (response rate: 45.7%). Of 227 (69.2%) students who were aware of ID specialists, 99 (43.6%) answered that they came to know about them only after the pandemic, 12 (3.7%) answered that their interest in being an ID specialist arose during the pandemic, while 36 (11.0%) responded that they would rather not become ID specialists. At the time of the survey, 5 students (1.5%) were aiming to become ID specialists. CONCLUSION: We observed a very low rate of interest to be an ID specialist among medical students. The experience of the pandemic does not seem to have influenced Japanese medical students to choose ID as a specialty for their careers. Continuous efforts to increase the number of ID specialists are necessary in Japan as a countermeasure against the coming pandemic.

DOI： 10.1371/journal.pone.0267587

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Background: Mild encephalitis/encephalopathy and a reversible splenial lesion (MERS) is a clinicoradiological syndrome with an unknown pathogenic mechanism, which usually involves children. Thus, adult-onset MERS is quite rare. Case presentation: A 71-year-old man, undergoing haemodialysis due to diabetes-induced chronic kidney disease, manifested a persistent fever and disorientation. Blood culture detected methicillin-resistant Staphylococcus aureus (MRSA), while echocardiography revealed vegetation in the aortic and mitral valves. Magnetic resonance imaging of the head revealed a fluid-attenuated inversion recovery-high, diffusion-weighted image-high lesion in the splenium of the corpus callosum, with a number of emboli. Accordingly, the patient was diagnosed with MERS induced by MRSA endocarditis. Discussion: Neurological impairment by MERS can be reversible. However, the differential diagnosis of the disease includes ischaemic lesions, multiple sclerosis, malignant lymphoma, acute disseminated encephalomyelitis, and posterior reversible encephalopathy. Clinicians should consider these diseases when MERS is suspected. LEARNING POINTS: Adult-onset mild encephalitis/encephalopathy and a reversible splenial lesion (MERS) is quite rare, and physicians should be aware of it as a differential diagnosis of a diffusion-weighted image-high lesion in the splenium of the corpus callosum.Methicillin-resistant Staphylococcus aureus (MRSA) has rarely been reported as a triggering factor for MERS.

DOI： 10.12890/2022_003185

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

DOI： 10.2188/jea.je20220210

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

AIM: Sexually transmitted infections remain a neglected area of research in geriatrics. However, in the global aging societies, sexual health among the middle-aged and older adults is an emerging public concern. High-income countries are facing a resurgence of syphilis cases among young generations, but little is known about its prevalence in older populations. We aimed to investigate the national trend of syphilis cases in Japan. METHODS: This nationwide observational study used the publicly-available database (2009-2019) to calculate crude and age-adjusted incidence rates of syphilis per 100 000 population by age, sex and clinical stage. We collected data from patients aged ≥50 years and performed joinpoint regression analysis to estimate long-term trends and average annual percentage changes (AAPCs). RESULTS: The total number of patients with syphilis increased about 8-fold from 165 in 2009 to 1280 in 2019. AAPCs of crude incidence rates significantly increased in every age category; 33.2% in 50-59 years, 23.8% in 60-69 years and 20.9% in ≥70 years. Age-adjusted incidence rates have surged at AAPCs of 28.7% in men and 23.1% in women, reaching 4.09 in men and 0.71 in women in 2019. By clinical stage, marked increases were observed in primary (AAPCs, 42.3% in men and 41.6% in women) and secondary syphilis (AAPCs, 24.9% in men and 24.2% in women). CONCLUSIONS: An up-toward trend of syphilis among people aged ≥50 years was observed. The importance of sexual health among older people should be highlighted in this aging Japanese society. Geriatr Gerontol Int 2022; 22: 1019-1024.

DOI： 10.1111/ggi.14500

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ggi.14500

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DOI： 10.1093/jac/dkab464

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DOI： 10.1093/cid/ciab1011

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Objective: To describe a case of anti-glomerular basement membrane (GBM) nephritis that occurred shortly after initiation of nebulized tobramycin (TOB) therapy using intravenous solution, suggesting an association with the inhalation therapy and the disease onset. Background: With the emergence of antimicrobial resistance, clinical importance of aminoglycosides that usually remain susceptibility against gram-negative organisms is increasingly acknowledged. Despite the growing number of evidence supporting the effectiveness of aminoglycoside inhalation therapy for respiratory tract infections, its clinical application has yet to be widely approved by Japanese health insurance. Case Presentation: A 79-year-old Japanese woman had developed amyotrophic lateral sclerosis and experienced recurrent pneumonia mainly caused by Pseudomonas aeruginosa, which required monthly treatments with broad-spectrum antibiotics. Owing to the limited approval, we had no choice but to use intravenous TOB solution for inhalation therapy as an off-label use under an endorsement of the Institutional Review Board of the hospital. Although the repeated pneumonia subsided, the patient subsequently needed immunosuppressive therapy along with plasma exchanges for the treatment of anti-GBM nephritis. Conclusion: Although this off-label use of intravenous solutions is common in both clinical and research purposes, our case raised an issue that its safety needs to be re-evaluated.

DOI： 10.1089/jamp.2021.0053

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to the modern healthcare system and led to increased burnout among healthcare workers (HCWs). We previously reported that HCWs who engaged in COVID-19 patient care had a significantly higher prevalence of burnout (50.0%) than those who did not in November 2020 (period 1). We performed follow-up surveys in HCWs in a Japanese national university hospital, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks, and the Maslach Burnout Inventory in February 2021 (period 2) and May 2021 (period 3). Periods 1 and 3 were amid the surges of COVID-19 cases, and period 2 was a post-surge period with a comparatively small number of COVID-19 patients requiring hospitalization. Response rates to the surveys were 33/130 (25.4%) in period 1, 36/130 (27.7%) in period 2, and 56/162 (34.6%) in period 3, respectively. While no consistent tendency in the prevalence of burnout based on variables was observed throughout the periods, the prevalence of burnout tends to be higher in periods 1 and 3 in those who engaged in COVID-19 patient care in the last 2 weeks (50.0%, 30.8%, 43.1% in period 1, 2, and 3, respectively). Given the prolonged pandemic causing stigmatization and hatred against HCWs leading to increased prevalence of burnout, high-level interventions and supports are warranted.

DOI： 10.3390/ijerph182111581

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Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

DOI： 10.1507/endocrj.EJ21-0488

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DOI： 10.1080/1120009X.2021.1994689

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An 89-year-old woman who had type 2 diabetes mellitus suddenly presented with abdominal pain. Abdominal computed tomography showed thickening of the wall and intramural gas in the gastric hilum, suggesting emphysematous gastritis. The patient underwent treatment with a proton-pump inhibitor and broad-spectrum antibacterial agents.

DOI： 10.1002/ccr3.5094

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Language：Japanese  

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新型コロナウイルス感染症(COVID-19)が最初に報告されてからおよそ1年半が経過したが、いまだ収束の兆しの見えない世界的流行のなかで「Long-COVID」ないし「post-acute sequelae of COVID-19(PASC)」と定義され、一般には「コロナ後遺症」として知られる、急性期以降に残存する症状に悩まされる患者が多く存在している。そのなかでも「倦怠感」は、最も多い症状として報告され、COVID-19罹患後に4割程度の患者が自覚すると言われている。倦怠感は視認できず検査での客観的評価も難しい症状である一方で、さまざまな要因が複雑に絡みあって生じており病態メカニズムも未解明なところが多く、診療に難渋する。われわれは2021年2月にLong-COVID/PASCを専門的に診療する「コロナ・アフターケア(COVID-19 aftercare:CAC)外来」を大学病院内にいち早く設立し、倦怠感などの症状に悩む患者の診療と研究・教育に取り組んできた。本稿ではそうしたわれわれの診療経験も踏まえ、診断や治療を行ううえでの対面診療の必要性や総合診療的アプローチの重要性についても触れながら、Long-COVID/PASCにおける倦怠感について概説する。(著者抄録)

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BACKGROUND: Scientific evidence suggest that hand hygiene as one of the most effective measures to control infection. To promote good hand hygiene practices, the World Health Organization introduced May 5 as World Hand Hygiene Day (WHHD), and international stakeholders established Global Handwashing Day (GHD) on October 15. However, its contributions to raising public awareness of hand hygiene is unclear. METHODS: This study evaluates the impact of the WHHD and GHD on the public awareness of hand hygiene in Japan, the United Kingdom, the United States, and worldwide from 2016 to 2020, using the relative search volume of "Hand hygiene" in Google Trends as a surrogate. To identify a statistically significant timepoint of a trend change, we performed Joinpoint regression analysis. RESULTS: Upticks of the relative search volumes as well as joinpoints were noted worldwide around the WHHD and GHD from 2016 to 2019, but no joinpoints were identified around the WHHD and GHD in 2020. No such changes were observed in Japan, the United Kingdom, and the United States during these periods. CONCLUSIONS: While the WHHD was originally established to raise awareness of hand hygiene in healthcare facilities, our result suggests that the WHHD and GHD may not have effectively disseminated the importance of hand hygiene to the general public at a country level. Additional policy measures to advocate hand hygiene to the public are necessary to communicate its benefits.

DOI： 10.1016/j.ajic.2021.08.033

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DOI： 10.2196/32856

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The emergence of high-level daptomycin (DAP)-resistant (HLDR) Corynebacterium striatum has been reported as a result of loss-of-function point mutations or premature stop codon mutations in a responsible gene, pgsA2. We herein describe the novel detection of an HLDR C. striatum clinical isolate, in which IS30-insertion was corroborated to cause destruction of pgsA2 gene. We isolated an HLDR C. striatum from a critically ill patient with underlying mycosis fungoides who had been treated with DAP for 10 days. With a sequence investigation, IS30-insertion was discovered to split pgsA2 in the HLDR C. striatum strain, which may cause disrupted phospholipid phosphatidylglycerol (PG) production. Future studies should survey the prevalence of IS-mediated gene inactivation among HLDR C. striatum clinical isolates.

DOI： 10.1007/s10096-021-04369-1

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To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future.

DOI： 10.1038/s41598-021-00206-9

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DOI： 10.1093/qjmed/hcab260

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OBJECTIVES: To evaluate the impact of the World Antimicrobial Awareness Week (WAAW) on public awareness of antimicrobial resistance using Google Trends analysis. METHODS: The impact of WAAW on public awareness of 'antimicrobial resistance' (AMR), 'antibacterial', and 'antibiotics' in Japan, the UK, the United States, and worldwide from 2015 to 2020 was analyzed, using the relative search volume (RSV) of Google Trends as a surrogate. A joinpoint regression analysis was performed to identify a statistically significant time point of a change in trend. RESULTS: No joinpoints around WAAW were identified in Japan, the United Kingdom, or the United States from 2015 to 2020 with RSVs of 'AMR', whereas increasing RSVs were noted worldwide in 2017 and 2020. Further, there were decreasing RSVs of 'antibiotics' in the first half of 2020, which could be due to the COVID-19 pandemic. The study results suggest that WAAW did little to improve public awareness of AMR in the selected countries despite its contribution worldwide. CONCLUSIONS: This study implies that we need to develop a more effective method to improve public awareness to fight against AMR.

DOI： 10.1016/j.ijid.2021.08.018

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The options available for treating infections with carbapenemase-producing Enterobacteriaceae (CPE) are limited; with the increasing threat of these infections, new treatments are urgently needed. Biapenem (BIPM) is a carbapenem, and limited data confirming its in vitro killing effect against CPE are available. In this study, we examined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of BIPM for 14 IMP-1-producing Enterobacteriaceae strains isolated from the Okayama region in Japan. The MICs against almost all the isolates were lower than 0.5 µg ml-1, indicating susceptibility to BIPM, while approximately half of the isolates were confirmed to be bacteriostatic to BIPM. However, initial killing to a 99.9 % reduction was observed in seven out of eight strains in a time-kill assay. Despite the small data set, we concluded that the in vitro efficacy of BIPM suggests that the drug could be a new therapeutic option against infection with IMP-producing CPE.

DOI： 10.1099/jmm.0.001430

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Introduction The long-term clinical course, prognosis, and optimal management of symptoms and conditions after the acute phase of coronavirus disease 2019 (COVID-19) remain to be elucidated. The purpose of this study was to clarify the characteristics of patients referred to a COVID-19 aftercare (CAC) clinic established at a tertiary academic hospital in Japan. Methods This study was a descriptive case series study. All patients who visited the CAC clinic between February 15 and September 17 in 2021 were included. Patients' background, chief complaints, and clinical courses after the onset of COVID-19 were described. Results A total of 87 Japanese patients (median age, 40.0 years; interquartile range [IQR], 26.5-53.0 years; 52.9% women) were referred to the CAC clinic. The median interval between the onset of COVID-19 and the visit to the clinic was 79.0 (IQR, 52.5-112.0) days. Referral sources were hospitals (36 patients), clinics (47 patients), a local healthcare center (3 patients), and other (1 patient). The most common chief complaint was general fatigue (50.4%) followed by dysosmia (28.7%), dysgeusia (26.4%), hair loss (18.4%), headache (17.2%), dyspnea (16.1%), and dyssomnia (13.1%). Respiratory symptoms were common in the early stages of the disease but were less common as the chief complaints when visiting the clinic. On the other hand, neurological, psychiatric, and extremity symptoms were predominant one month after the onset of COVID-19. Conclusions Regardless of the severity in the acute phase, patients visiting our CAC clinic suffered from a variety of symptoms. General physicians skilled in using a comprehensive approach would be optimal to see patients with such complex symptoms.

DOI： 10.7759/cureus.18568

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Language：Japanese   Publisher：(公社)日本医師会  

国際化を背景に、在日外国人も新型コロナウイルス感染症(COVID-19)に罹患しているが、本邦でその診療上の課題に関する文献はない。2020年2月からの1年間に岡山大学病院総合内科・総合診療科に入院した、外国人COVID-19患者全5人を対象として、患者背景や言語状況、入院中のトラブルや解決策について診療録から抽出した。全員が日本語の書字・読字が全く不能であり、うち1人は日常会話も困難で電話医療通訳サービスを要したが、担当医や看護師に加えて、国際診療支援センターや臨床栄養部、精神科などと連携することで隔離解除まで入院継続が可能であった。COVID-19では本人の希望に沿わない入院や予定外入院のため、通常の外国人診療に比して負担・課題が大きい。特に言語面での制約は、隔離管理下での意思疎通や同意書の取得などの面で障壁となることが明らかとなった。院内組織の連携と、病院を超えた情報共有による病軟な対応が重要である。(著者抄録)

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Objectives Vitamin D deficiency, which is common worldwide, increases the risks of falls and fractures and can lead to increased morbidity and mortality. However, the clinical utility and relevance of vitamin D activation remain unknown. The aim of the present study was to clarify the clinical usefulness of serum 1,25-dihydroxyvitamin D (1,25D)/25-hydroxyvitamin D (25D) ratio for assessment of the extent of bone metabolism. Methods We retrospectively screened data for 87 patients whose serum 1,25D and 25D levels were measured. Eight patients who were taking vitamin D preparations were excluded, and data for 79 patients (33 males and 46 females) were analyzed. Since menopausal status can be associated with serum vitamin D level, we divided the patients by gender and divided the female patients into two groups at the age of 50 years. Results The median serum 1,25D/25D ratio was significantly lower in males than in females, with the most considerable difference in all males [4.1 (interquartile range: 2.3-5.8) × 10-3] versus elderly females (aged ≧50 years) [7.9 (3.3-10.1) × 10-3). Main disorders were endocrine (30.6%), inflammatory (18.5%), and bone-related (16.7%) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual-energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between the 1,25D/25D ratio and serum levels of inorganic phosphate (iP), parathyroid hormone, and alkaline phosphatase (ALP). The 1,25D/25D ratio had gender-specific characteristics: the ratio was significantly correlated with age in males (R=-0.49), while it was significantly correlated with BMI in females (R=0.34). Conclusions The results of this study suggested that vitamin D activity is negatively correlated with bone mineral density, being reduced in aged males but enhanced in obese females.

DOI： 10.7759/cureus.18070

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COVID-19 patients treated with anti-inflammatory drugs are rarely complicated by candidemia. Since immunosuppressive therapy can blunt inflammatory reactions, clinicians should actively survey latent candidemia during severe COVID-19 treatment.

DOI： 10.1002/ccr3.4858

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Pregnancy was reported to be a risk factor for coronavirus disease 2019 (COVID-19), with an increased risk for premature birth. Corticosteroids and remdesivir are used for patients with COVID-19; however, there is no established treatment for these patients. In particular, the effective management of pregnant, critically ill patients with COVID-19 remains unknown. We describe a 34-year-old, critically ill woman at 30 weeks of gestation with COVID-19, who was successfully treated with remdesivir and combined high-dose betamethasone (12 mg/day for two days) and methylprednisolone (125 mg/day for three days) followed by steroid tapering. During treatment, fetal biophysical profile scores on obstetric ultrasound were normal; her pregnancy course progressed well. Since high-dose corticosteroids improve fetal lung maturation and as well as cytokine storm due to COVID-19, this case provides an insight into the management of pregnant COVID-19 patients.

DOI： 10.7759/cureus.17398

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INTRODUCTION: The global spread of emerging infections has increased the demand for infectious disease (ID) experts. There is no established method to evaluate the sufficiency of professionals on a regional basis. We aimed to determine the correlation of the number of ID doctors and certified nurses in infection control (CNIC) with the prevalence of representative antimicrobial-resistant (AMR) pathogens across the 47 prefectures in Japan using publicly available databases. METHODS: We determined the number of ID doctors and CNIC registered in each prefecture based on the Japanese Association for Infectious Diseases and the Japanese Nursing Association websites and calculated their numbers per 100,000 population. Data on representative AMR pathogens were extracted from the Japan Nosocomial Infections Surveillance database. Spearman's correlation coefficient was used to measure statistical associations. RESULTS: There was no epidemiologically applicable correlation between the deployment of ID doctors and CNIC and the isolation rates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime- or levofloxacin-resistant Escherichia coli and Klebsiella pneumoinae, and meropenem-resistant Pseudomonas aeruginosa. Solely, the isolation rate of levofloxacin-resistant K. pneumoinae and the number of CNIC were statistically correlated (correlation coefficient = -0.33; p = 0.02), while the isolation rate of cefotaxime-resistant E. coli was paradoxically correlated with the number of ID doctors (correlation coefficient = 0.33; p = 0.02). Conclusions: Our macroscopic analysis using the open database was not a reliable method to evaluate the sufficiency of ID experts across the prefectures in Japan. A scheme to assess the appropriate distribution of ID experts should be developed.

DOI： 10.7759/cureus.16918

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Primary Sjögren's syndrome (SS) is an autoimmune disease that usually affects the exocrine glands in mid-dle-aged women. Fifteen percent of SS patients experience severe systemic extraglandular complications, and pleuritis is one of the rare complications of SS. We report the case of an elderly Japanese man who initially pre-sented with a prolonged fever and chest pain and was finally diagnosed with primary SS-associated pleuritis. Of the nine reported cases of primary SS that initially presented with pleuritis, up to six cases were elderly males. This case highlights the complication of pleuritis among elderly males with primary SS.

DOI： 10.18926/AMO/62409

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DOI： 10.1007/s11739-021-02766-0

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DOI： 10.1016/j.clinthera.2021.07.007

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Granulocyte colony-stimulating factor (G-CSF) is a relatively new drug that is used for recovery of chemotherapy-associated neutropenia. It is known to cause bone pain, headache and fatigue as side-effects; however, large-vessel vasculitis is extremely rare and its relation with G-CSF remains unknown. We describe a 49-year-old woman in whom arteritis developed after chemotherapy and subsequent G-CSF administration. She had experienced pinealoma 3 months ago and received surgery and chemotherapy, leading to neutropenia. After administration of lenograstim at 100 μg/day for 1 week, high fever and neck pain appeared. White blood cell count and serum levels of C-reactive protein and interleukin-6 were increased to 37,930/μL, 23.71 mg/dL, and 241 pg/mL, respectively. Contrast-enhanced computed tomography revealed thickened walls of large vessels including the bilateral common carotid artery (CCA), right brachiocephalic artery, and ascending aorta. Ultrasonography showed wall thickening of the CCA (maximum of intima media thickness: right, 2.9 mm; left, 3.2 mm). As differential diagnoses, infection, chemotherapy, autoimmune diseases, and cancer were considered other than G-CSF. Blood culture tests, lumbar puncture, β-D-glucan tests, and tests for viral antibodies indicated no active infection, and autoantibodies were negative. Empirical antibiotic therapy was ineffective. The score of Naranjo's algorithm to lenograstim was 6, indicating "probable" causality. Considering the clinical course and test results, we made a diagnosis of G-CSF-associated arteritis and commenced glucocorticoid therapy, which drastically improved the symptoms and inflammation. Clinicians should be aware of this uncommon but significant complication of GCS-F administration, for which glucocorticoid treatment can be a useful therapeutic option.

DOI： 10.1080/24725625.2020.1857022

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Objective During the ongoing global pandemic of novel coronavirus disease 2019 (COVID-19), an emerging infectious disease, the implementation and execution of infection prevention and control (IPC) is of paramount importance. In this study, we aimed to assess the current deployment of infection control medical personnel in Okayama prefecture, who are supposed to play an essential role to prevent the outbreak of infectious diseases, and the current prevalence of antimicrobial-resistant (AMR) bacteria isolated in Okayama. Materials and methods This was a descriptive study using publicly available data. The numbers of infectious disease (ID)-doctors and the certified nurses in infection control (CNIC) per 100,000 population in 47 prefectures in Japan were calculated. We then compared the detected proportions of AMR pathogens among the prefectures in 2019 to be employed as a comparative parameter, which was obtained from Japan Nosocomial Infections Surveillance (JANIS) data. Results The number of ID-doctors was the 11th highest in Japan; however, they were unevenly distributed in southern Okayama, particularly at three tertiary hospitals. While the deployment of CNIC was geographically less uneven in the prefecture, their number was lower than the domestic average. According to the JANIS data, isolation rates of AMR pathogens were high in Okayama compared to other prefectures in Japan: vancomycin-resistant Enterococcus faecium (the third-worst); cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae (the third-worst and the second-worst, respectively); and meropenem-resistant Pseudomonas aeruginosa (the worst). Conclusions Our assessment provides underlying data and reinforces the need for educating multi-professional experts in the field of infectious diseases to prevent future public health threats in Okayama.

DOI： 10.7759/cureus.16643

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The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect™ 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.

DOI： 10.1016/j.jiac.2021.05.001

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We have presented a case of barium appendicitis, which is a rare complication of barium enema studies. Barium sulfate is used widely for gastrointestinal radiographic studies and is associated with few complications. Clinicians need to be fully aware of this complication.

DOI： 10.1002/ccr3.4583

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Background: Carbapenemase-producing Enterobacterales (CPE) are spreading in hospitals, environment and retail foods in Yangon, Myanmar. Objectives: To investigate whether CPE colonize healthy individuals living in Yangon and whether clinical-related strains are spreading in the community. Methods: CPE was isolated from faecal samples obtained from healthy Japanese residents of Yangon with no history of hospitalization. Isolates were subjected to WGS using short- and long-read sequencers and compared with those previously isolated in Yangon. Results: Six Escherichia coli strains harbouring blaNDM-1 or blaNDM-5 belonging to five different STs - ST10, ST38, ST48, ST410 and ST8453 - were isolated from 69 volunteers. The ST38 isolates were related to those previously isolated from retail food in Yangon. The ST410 and ST8453 isolates were highly related to previous Yangon isolates including those of clinical and food origins. Conclusions: The analysis suggested the acquisition of blaNDM-positive E. coli, which are disseminating in a clinical setting and through retail foods, by healthy residents in Yangon.

DOI： 10.1093/jac/dkab070

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho = 0.62), soluble interleukin-2 receptor (sIL-2R; rho = 0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho = -0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

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Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho=0.62), soluble interleukin-2 receptor (sIL-2R; rho=0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho=-0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

DOI： 10.18926/AMO/62221

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DOI： 10.2169/internalmedicine.5314-20

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INTRODUCTION: Adverse drug events (ADEs) are a major cause of mortality. OBJECTIVE: We examined long-term trends for ADE-related deaths in Japan. METHODS: This observational study was conducted using the Japanese Vital Statistics from 1999 to 2016. Data for all ADE-related deaths were extracted using International Classification of Diseases, Tenth Revision codes. We analysed ADE-related deaths by age and sex and calculated crude and age-standardised mortality rates (ASMR) per 100,000 people. We used Joinpoint regression analysis to identify significant changing points in mortality trends and to estimate annual percentage change (APC). RESULTS: In total, 16,417 ADE-related deaths were identified. The crude mortality rate for individuals aged ≥ 65 years was higher than that of young individuals. The ASMR per 100,000 people increased from 0.44 in 1999 to 0.64 in 2016. The crude mortality rate increased from 0.44 in 1999 to 1.01 in 2016. The APC of ASMR increased at a rate of 2.8% (95% confidence interval [CI] 1.4-4.2) throughout the study period. In addition, crude mortality increased at a rate of 5.7% (95% CI 4.2-7.3) annually from 1999 to 2016. The ADE-related mortality rate was higher for men than for women during the study period. CONCLUSIONS: The number of and trend in ADE-related deaths increased in Japan from 1999 to 2016, particularly in the older population.

DOI： 10.1007/s40264-020-01037-9

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DOI： 10.1111/ggi.14159

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DOI： 10.1136/postgradmedj-2020-138416

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BACKGROUND: We evaluated the effect of the two-dose vaccination strategy, which has been a widely adopted as childhood routine schedule worldwide to acquire herd immunity, on healthcare workers (HCWs) in Japan. METHODS: Between 2010 and 2019, antibody titers for measles and rubella were measured annually among newly employed HCWs at Osaka University Hospital, Japan, using Enzygnost® assays (Siemens Healthcare Diagnostics Co. Ltd., Marburg, Germany). The data were categorized by age to compare the antibody positivity rates and antibody titers among no-vaccine, single-dose, and two-dose groups. RESULTS: Over the 10-year period, the annual antibody positivity rates for measles and rubella were 84.0%-95.3% and 90.0%-94.5%, respectively, without any particular trend. The antibody titers for measles (median [interquartile range]: 8.4 [3.9, 20] vs. 6.1 [3.5, 12]) and rubella (11 [5.5, 20] vs. 6 [3.7, 11]) were statistically lower (p < 0.001) in the two-dose generation than in the single-dose generation. DISCUSSION: A shift from single-dose to two-dose vaccination did not yield an increase in antibody positivity rates for both measles and rubella among HCWs. Notably, antibody titers were significantly lower in the two-dose generation. CONCLUSION: Despite several limitations, our data suggests a paradoxical vulnerability in young HCWs who received the two-dose vaccination in a view of sero-positivity rates.

DOI： 10.1016/j.jiac.2021.04.006

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BACKGROUND AND AIM: The current prevalence of hepatitis C virus infection and hepatitis C virus-associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus-associated mortality in Japan. METHODS: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus-associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age-standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. RESULTS: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age-standardized mortality rate was higher in women than in men. The average annual percentage change was -3.8% (95% confidence interval: -5.0 to -2.5). The declining trend was more rapid in men (-4.5%, 95% confidence interval: -5.3 to -3.6) than in women (-2.7%, 95% confidence interval: -3.8 to -1.6). CONCLUSIONS: Trends in hepatitis C virus-associated mortality rates have declined in an accelerating manner in Japan, especially among men.

DOI： 10.1111/jgh.15517

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RATIONALE: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. PATIENT CONCERNS: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. DIAGNOSIS: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. INTERVENTIONS: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. OUTCOMES: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. LESSONS: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.

DOI： 10.1097/MD.0000000000025265

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This study examined temporal trend, seasonality, and geographical variations of legionellosis incidence and mortality in Japan. This nationwide observational study used the Japanese Vital Statistics and Infectious Diseases Weekly Report (1999-2017) data to calculate legionellosis crude and age-adjusted incidence and mortality rates per 100,000 population by age and sex. Incidence was compared among the 4 seasons and regional incidence among 47 prefectures. Of 13,613 (11,194 men) people with legionellosis in Japan, 725 (569 men) were fatal. Increasing incidence trend occurred from 0.0004 (1999) to 1.37 (2017) per 100,000 population. People aged ≥ 70 years accounted for 43.1% overall; men's age-adjusted incidence rate was consistently approximately five times higher than for women. Significantly higher incidence occurred in summer than in winter (p = 0.013). Geographically, highest incidence (≥ 2.0 per 100,000 population) occurred in Hokuriku District, with increasing trends in Hokkaido and middle-part of Japan. Estimated fatality rates decreased consistently at 5.9% (95% confidence interval: - 8.1, - 3.5) annually, from 1999 to 2017, with no trend change point. Increasing legionellosis incidence occurred in Japan during 1999-2017, with declining estimated fatality rates. In this aging society and warming world, disease clinical burden may further deteriorate in future due to increasing incidence trends.

DOI： 10.1038/s41598-021-86431-8

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The coronavirus disease 2019 (COVID-19) global pandemic has drastically changed how we live and work. Amid the prolonged pandemic, burnout of the frontline healthcare professionals has become a significant concern. We conducted a cross-sectional survey study to provide data about the relationship between the COVID-19 pandemic and the prevalence of burnout in healthcare professionals in Japan. Healthcare workers in a single Japanese national university hospital participated in the survey, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks and the Maslach Burnout Inventory. Of those, 25.4% fully answered the survey; 33.3% were doctors and 63.6% were nurses, and 36.3% engaged in care of COVID-19 patients in the past 2 weeks. Compared to those belonging to General Medicine, those in Emergency Intensive Care Unit were at higher risk of burnout (odds ratio (OR), 6.7; 95% CI, 1.1-42.1; p = 0.031). Of those who engaged in care of COVID-19 patients, 50% reported burnout while 6.1% did not (OR 8.5, 95% CI; 1.3-54.1; p = 0.014). The burnout of healthcare workers is a significant concern amid the pandemic, which needs to be addressed for sustainable healthcare delivery.

DOI： 10.3390/ijerph18052434

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The global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a major concern in public health. Due to the existence of the diversity of carbapenemases, development of an easily available, cost-effective multiplex detection assay for CPE is required worldwide. Using clinically available and reliable equipment, COBAS® z480 (Roche Diagnostics K.K., Tokyo, Japan), we developed a multiplex real-time PCR assay for the detection of two combinations of carbapenemases; first, blaNDM, blaKPC, and blaIMP (Set 1), and second, blaGES, blaOXA-48, and blaVIM (Set 2). We constructed standard curves for each carbapenemase gene using serial dilutions of DNA standards, then applied reference or clinical isolates with each carbapenemase gene to this assay. The multiplex assay showed satisfactory accuracy to detect CPE genes, with the correlation coefficients of greater than 0.99 for all genotypes. The assay appropriately differentiated the reference or clinical strains harboring each carbapenemase gene without cross reactivity. Lastly, the assay successfully detected multiple genes without false-positive reactions by applying six clinical isolates carrying both NDM and OXA-48-like carbapenemase genes. Major advantages of our assay include multiplicity, simple operation, robustness, and speed (1 h). We believe that the multiplex assay potentially contributes to early diagnosis of CPE with a diverse genetic background.

DOI： 10.3390/pathogens10030276

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BACKGROUND: The COVID-19 pandemic has negatively affected medical education. However, little data are available about medical students' distress during the pandemic. OBJECTIVE: This study aimed to provide details on how medical students have been affected by the pandemic. METHODS: A cross-sectional study was conducted. A total of 717 medical students participated in the web-based survey. The survey included questions about how the participants' mental status had changed from before to after the Japanese nationwide state of emergency (SOE). RESULTS: Out of 717 medical students, 473 (66.0%) participated in the study. In total, 29.8% (141/473) of the students reported concerns about the shift toward online education, mostly because they thought online education would be ineffective compared with in-person learning. The participants' subjective mental health status significantly worsened after the SOE was lifted (P<.001). Those who had concerns about a shift toward online education had higher odds of having generalized anxiety and being depressed (odds ratio [OR] 1.97, 95% CI 1.19-3.28) as did those who said they would request food aid (OR 1.99, 95% CI 1.16-3.44) and mental health care resources (OR 3.56, 95% CI 2.07-6.15). CONCLUSIONS: Given our findings, the sudden shift to online education might have overwhelmed medical students. Thus, we recommend that educators inform learners that online learning is not inferior to in-person learning, which could attenuate potential depression and anxiety.

DOI： 10.2196/25232

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DOI： 10.1136/bcr-2021-241640

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 +/- 1.5 years old), decreases in serum FT levels to <8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The percentages of patients with low FT levels were high in the >= 50 years age group (83%), the HbA1c <7% group (67%), and the 25 <= BMI < 30 kg/m(2) group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R= 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = -0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R= 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males.

DOI： 10.18926/AMO/61424

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The genus Tsukamurella is a fastidious, environmental organism that potentially causes various infections in humans. Due to the morphological and biochemical similarities to others pathogens, such as Gordona, Rhodococcus, Corynebacterium, Nocardia, and Mycobacterium, a molecular-based approach is indispensable to correctly identify them. Herein, we describe a case of Tsukamurella inchonensis bacteremia complicated with septic pulmonary emboli (SPE), which is the first in the literature. A 44-year-old Japanese woman diagnosed with tongue cancer had undergone partial tongue resection. While receiving chemotherapy and radiotherapy, she developed high fever. Chest computed tomography suggested multiple emboli at the bilateral, peripheral lungs, indicating SPE. Blood culture detected Gram-positive rods, to which matrix-assisted laser desorption/ionization-time of flight mass spectrometry failed to identify. Then, we attempted to characterize it by 16S rRNA sequence, which suggested the organism to be Tsukamurella species but resulted in low resonance of the species-level identification. Additionally, we employed a confidence gene targeting groEL, leading to 100% matching (753/753 bps) with T. inchonensis NCTC 10741 (GenBank accession no. LR131273.1), which has been incorrectly registered as wrong species name Tsukamurella paurometabola in the database. Under the diagnosis of T. inchonensis-associated SPE, we successfully treated the patient with imipenem/cilastatin administration for 4 weeks. Sequencing analysis of groEL was of great use in identifying the organism in this case. More clinical cases based on molecular diagnosis of the fastidious pathogens need to be accumulated to further understand the characteristics and appropriate treatment regimen.

DOI： 10.1016/j.jiac.2020.09.024

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DOI： 10.1136/postgradmedj-2020-139562

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Primary effusion lymphoma (PEL) is a kind of malignant lymphoma that develops without a tumor mass. A fluid smear is of no use for the diagnosis of miscellaneous condition. Repeated cell-block smear with immunostaining is useful for the diagnosis of PEL.

DOI： 10.1002/ccr3.3469

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Fifteen Klebsiella pneumoniae isolates harbouring blaNDM genes were identified from blood and sputum specimens of patients at a tertiary-care facility (Yangon General Hospital, Yangon, Myanmar) in 2018. Two of the isolates belonged to sequence type (ST) 11, an international high-risk clone. Whole-genome sequencing and phylogenetic analyses revealed that these two isolates were clustered together with other ST11 isolates originating from other countries. The isolates harboured the blaNDM-5 gene on an IncFII-type plasmid that is prevalent among carbapenemase-producing Enterobacteriaceae in Yangon but has rarely been found in other ST11 isolates. Our data suggests the regional presence of the ST11 international high-risk clone and its acquisition of an endemic blaNDM-5-carrying plasmid.

DOI： 10.1099/JMM.0.001348

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Influenza potentially has a high mortality rate when it affects the elderly. We aimed to examine the differences in clinical manifestations in patients with influenza according to their age. This multicenter prospective study was performed in six medical institutions in Okayama and Kagawa prefectures (Japan). Between December 1, 2019 and March 31, 2020, we collected data on adult patients diagnosed with influenza type A, who were strat-ified into younger (20-49 years), middle-aged (50-64 years), and older groups (≥ 65 years). We compared the presence or absence of fever, respiratory symptoms, and extrapulmonary symptoms according to age group. In total, 203 patients (113, younger; 51, middle-aged; and 39, older) were eligible for the analysis. The maxi-mum body temperature and temperature at first physician visit in the older group were significantly lower than those in the younger group. The incidence of respiratory symptoms was not different among the three groups. Chills, muscle pain, and arthralgia as systemic symptoms were noted significantly more frequently in the younger (80.9%) and middle-aged (75.5%) groups than in the older group (51.3%) (p = 0.002). Fever and sys-temic symptoms were less likely to appear in older patients, possibly resulting in the delaying of hospital visits among older adults.

DOI： 10.18926/AMO/62769

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Antimicrobial stewardship for outpatients with acute respiratory tract infections (ARTIs) should be urgently promoted in this era of antimicrobial resistance. Previous large-sample studies were based on administrative data and had limited reliability. We aimed to identify current antimicrobial prescription practices for ARTIs by directly basing on medical records. This multicenter retrospective study was performed from January to December in 2018, at five medical institutes in Japan. We targeted outpatients aged ≥18 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting ARTIs. We divided the eligible cases into three age groups (18-64 years, 65-74 years, and ≥75 years). We defined broad-spectrum antimicrobials as third-generation cephalosporins, macrolides, fluoroquinolones, and faropenem. Primary and secondary outcomes were defined as the proportion of antimicrobial prescriptions for the common cold and other respiratory tract infections, respectively. Totally, data of 3,940 patients were collected. Of 2,914 patients with the common cold, 369 (12.7%) were prescribed antimicrobials. Overall, compared to patients aged ≥75 years (8.5%), those aged 18-64 years (16.6%) and those aged 65-74 years (12.1%) were frequently prescribed antimicrobials for the common cold (odds ratio [95% confidential interval]; 2.15 [1.64-2.82] and 1.49 [1.06-2.09], respectively). However, when limited to cases with a valid diagnosis of the common cold by incorporating clinical data, no statistical difference was observed among the age groups. Broad-spectrum antimicrobials accounted for 90.2% of the antimicrobials used for the common cold. Of 1,026 patients with other respiratory infections, 1,018 (99.2%) were bronchitis, of which antimicrobials were prescribed in 49.9% of the cases. Broad-spectrum antimicrobials were the main agents prescribed, accounting for nearly 90% of prescriptions in all age groups. Our data suggested a favorable practice of antimicrobial prescription for outpatients with ARTIs in terms of prescribing proportions, or quantitative aspect. However, the prescriptions were biased towards broad-spectrum antimicrobials, highlighting the need for further antimicrobial stewardship in the outpatient setting from a qualitative perspective.

DOI： 10.1371/journal.pone.0259633

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DOI： 10.1136/bcr-2020-240075

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DOI： 10.2169/internalmedicine.5374-20

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We have presented a case of Salmonella-induced infective aortic aneurysm in which the presence of peri-aortic gas was a clue for diagnosis. The disease is clinically infrequent but potentially has a high mortality rate. Clinicians should consider this fatal disease from any trivial findings.

DOI： 10.1002/ccr3.3367

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Alkaline phosphatase (ALP) is an enzyme that is expressed in a variety of tissues. Among the isoforms of ALP, bone-specific alkaline phosphatase (BAP) is used as a marker for evaluating bone metabolism. We investigated the clinical usefulness of the ratio of serum BAP to total ALP for the diagnosis of various disorders in general practice. We retrospectively analyzed the cases of 107 Japanese patients whose serum BAP levels were exam-ined, focusing on clinical characteristics. We observed that the BAP/ALP ratios of the patients with fever and those with inflammatory diseases were significantly lower than the ratios of other patient groups. The BAP/ALP ratios of the patients with osteoporosis and those with metabolic bone diseases were higher than those of the patients with other conditions. The BAP/ALP ratio was found to be negatively correlated with age, a cor-relation that has not been found in other ethnicities. The serum BAP/ALP ratio was inversely correlated with serum CRP levels but was positively correlated with serum albumin levels and hemoglobin concentrations. Collectively, our results suggest that the BAP/ALP ratio could be a useful predictor for important geriatric con-ditions seen in general practice.

DOI： 10.18926/AMO/61205

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Septic pulmonary embolism (SPE) is a rare yet serious infectious disorder with nonspecific clinical findings due to microorganism-containing emboli disseminating from extrapulmonary infectious foci. It is unknown whether a positive blood culture correlates with a worse clinical outcome. We compared the clinical and microbiologic characteristics of patients with SPE divided into the culture-positive group and the culture-negative one. This study was a retrospective observational study of the patients diagnosed with SPE and treated in an academic hospital from April 2010 to May 2020. We identified six culture-positive and four culture-negative patients with SPE during the study period. The culture-positive group had significantly longer periods of hospitalization (median: 75 days, range: 45-125 days) than the culture-negative group (median: 14.5 days, range: 3-43 days) (p < 0.05), as well as significantly elevated serum C-reactive protein and procalcitonin. Patients with culture-negative SPE more commonly had odontogenic infections as the primary infectious foci. Our study highlights the importance of giving extra attention to SPE patients who have a positive blood culture, as they may have worse clinical outcomes. Physicians need to collaborate with dentists when faced with patients with culture-negative SPE, since they may have primary odontogenic infections.

DOI： 10.3390/pathogens9120995

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Complications of pheochromocytoma, such as hypertensive emergency, can be critical. Clinicians should recognize that pheochromocytoma is not uncommon in patients with large adrenal tumors, and screening should be undertaken prior to any intervention.

DOI： 10.1002/ccr3.3124

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Shewanella sp., the progenitors of blaOXA-48 -like genes are increasingly reported with the possession of different blaOXA-48 -like variants. This study aims to characterize blaOXA-731 , a new variant of a blaOXA-48 -like gene identified in Shewanella sp. isolated from the aquatic environment in Myanmar. Phylogenetic analysis of the blaOXA-731 sequence with other blaOXA-48 -like variants showed that it has the highest nucleotide identity of 86.09% with blaOXA-48 . However, the active site motifs in OXA-731 were 100% identical to that in OXA-48. Whole-genome sequencing analysis showed that blaOXA-731 is not surrounded by any mobile genetic elements. The genetic context of blaOXA-731 was found as similar to other blaOXA-48 -like genes previously identified in Shewanella sp. S1 nuclease pulsed-field gel electrophoresis followed by Southern blotting confirmed the location of blaOXA-731 in the chromosome of the Shewanella genome. Cloning and expression studies showed that OXA-731 has β-lactamase activity similar to OXA-48 and OXA-181, but it has no significant carbapenemase activity. Our results showed the significance of blaOXA-48 -like-carrying Shewanella sp. in the spreading of blaOXA-48 -like genes in the community.

DOI： 10.1111/1758-2229.12875

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TAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.

DOI： 10.1016/j.jiac.2020.06.020

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INTRODUCTION: Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy). METHODS: The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients' baseline hospital admittance status, as intensive care unit or general wards. RESULTS: We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02). CONCLUSION: VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.

DOI： 10.1016/j.jiac.2020.05.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (>= 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=-0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.

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To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (≥ 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=-0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.

DOI： 10.18926/AMO/60797

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER  

Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2020.06.021

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Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship.

DOI： 10.1016/j.jiac.2020.06.021

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In the era of hyper-ageing, Creutzfeldt-Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005-2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4-5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7-8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.

DOI： 10.1038/s41598-020-72519-0

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DOI： 10.1136/postgradmedj-2019-137328

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Odontogenic infections, generally caused by dental caries and periodontal disease, can result in fatal illness. We herein report a 71-year-old Japanese woman with type 2 diabetes and hemodialysis who suffered from multiple dentofacial abscesses mainly caused by multidrug-resistant Streptococcus oralis. She complained of pain and swelling of her face, with an extraoral fistula from the left cheek. Following 3 surgical debridement procedures and partial mandibulectomy, in addition to 12 weeks of antimicrobial therapy, the multiple dentofacial abscesses were ameliorated. A combination of surgical and antimicrobial treatments following an early diagnosis is essential for reducing further complications.

DOI： 10.2169/internalmedicine.4283-20

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Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BAC-TECT (TM) FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2020.03.004

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Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BACTEC™ FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient.

DOI： 10.1016/j.jiac.2020.03.004

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BACKGROUND: The widespread administration of the Haemophilus influenzae type b vaccine has led to the predominance of non-typable H. influenzae (NTHi). However, the occurrence of invasive NTHi infection based on gynecologic diseases is still rare. CASE PRESENTATION: A 51-year-old Japanese woman with a history of adenomyoma presented with fever. Blood cultures and a vaginal discharge culture were positive with NTHi. With the high uptake in the uterus with 67Ga scintigraphy, she was diagnosed with invasive NTHi infection. In addition to antibiotic administrations, a total hysterectomy was performed. The pathological analysis found microabscess formations in adenomyosis. CONCLUSIONS: Although NTHi bacteremia consequent to a microabscess in adenomyosis is rare, this case emphasizes the need to consider the uterus as a potential source of infection in patients with underlying gynecological diseases, including an invasive NTHi infection with no known primary focus.

DOI： 10.1186/s12879-020-05193-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

BACKGROUND: Cytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated. AIM: This study aimed to assess the risk of CMV infection among HCWs through daily medical practices. METHODS: Serum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids. FINDINGS: We analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different. CONCLUSION: Our study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding.

DOI： 10.1016/j.jiac.2020.02.011

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BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) infections has been increasing worldwide, becoming a significant healthcare burden especially among elderly people. This study aimed to evaluate the trends in NTM-associated mortality in Japan. METHODS: This study used vital statistics data and data on all NTM-associated deaths (N=18,814) among individuals aged ≥40 years in Japan from 1997 to 2016. We calculated the crude and age-adjusted mortality rates by age and sex and used joinpoint regression to analyze trends and estimate the average annual percentage change (AAPC). We compared crude NTM- and tuberculosis (TB)-associated mortality rates by sex. RESULTS: The overall crude annual mortality rate increased from 0.63/100,000/year in 1997 to 1.93/100,000/year in 2016 and was the highest among individuals aged 80-84 years. The AAPC of the crude mortality rates among males of all ages and females aged 40-59 years were stable but increased among females aged 60-79 years (3.5%, 95% confidence interval [CI]: 2.8-4.3%) and ≥80 years (4.3%, 95% CI: 3.7-4.9%). Among males, the age-adjusted mortality rates did not show a significant trend, while among females, the rates increased over the study period (AAPC: 4.6%, 95% CI: 2.7-6.6%). In females, the crude NTM-associated mortality rate exceeded the TB mortality rate in 2014, 2015, and 2016. CONCLUSIONS:  NTM mortality increased in Japan between 1997 and 2016, especially among the elderly female population. Given the increasing NTM-associated mortality and susceptible aging population, public health authorities in Japan should pay greater attention to NTM infections.

DOI： 10.1093/cid/ciaa810

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OBJECTIVES: Appropriate antibiotic prescriptions for outpatients with acute respiratory tract infections (ARTIs) are urgently needed in Japan. However, the empirical proof of this need is under-documented. Therefore, we aimed to determine antibiotic prescription rates, and the proportions of antibiotic classes prescribed for Japanese patients with ARTIs. METHODS: We analysed health insurance claims data over 2013-2015 among Japanese patients aged <75 years and determined the following indicators: 1) visit rates for patients with ARTIs and antibiotic prescription rates per 1000 person-years, and 2) proportion of visits by antibiotic-prescribed patients with ARTIs. We defined broad-spectrum antibiotics using the WHO Anatomical Therapeutic Chemical classification 4 level codes. RESULTS: Among 8.65 million visits due to ARTIs at 6859 hospitals and 62,024 physicians' offices, the visit rate and antibiotic prescription rate per 1000 person-years were 990.6 (99% confidence interval [CI], 989.4-991.7) and 532.4 (99% CI, 531.6-533.3), respectively. The visit rates for patients aged 0-17, 18-59, and 60-74 years were 2410.0 (99% CI, 2407.2-2412.9), 683.6 (99% CI, 682.7-684.6), and 682.1 (99% CI, 678.2-686.0), and antibiotic prescription rates were 1093.3 (99% CI, 1091.4-1095.2), 434.1 (99% CI, 433.4-434.9), and 353.4 (99% CI, 350.7-356.1), respectively. The overall proportion of antibiotic prescriptions for ARTI visits was 52.7% and 91.3% of the antibiotics prescribed were broad-spectrum. CONCLUSIONS: Both the visit rates and antibiotic prescription rates for ARTIs were high in this Japanese cohort. The proportion of antibiotic prescriptions exceeded that recommended in the clinical guidelines. Thus, there might be a scope for reducing the current antibiotic prescription rate in Japan.

DOI： 10.1016/j.jiac.2020.02.001

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DOI： 10.2169/internalmedicine.3507-19

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Language：Japanese  

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A 69-year-old Japanese man with a 10-year history of hemodialysis for end-stage renal disease presented with painful necrosis of the fingers of his right hand. A plain radiograph of the right hand revealed severely calcified arteries, particularly in the ring finger, suggesting the diagnosis of calciphylaxis of the fingers.

DOI： 10.1002/jgf2.296

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Background:
Globally, the number of deaths is estimated to increase to 74 million per year by 2030. Place of death (PoD) is increasingly being recognized as an important aspect of end-of-life care. However, recent trends in PoD in Japan, one of the super-aged societies, are unknown.
Objective:
To analyze trends in PoD in Japan over two decades.
Design:
Population-based retrospective observational study.
Setting:
All deaths reported in Japan, 1998-2017. PoD was defined as hospital, nursing home, or own home.
Results:
All Japanese decedents (∼22.6 million) over the past 20 years were analyzed. The proportion of hospital deaths was consistently high (>80%), with a significant decreasing trend from the mid-2000s. Although the proportion of deaths at home decreased in the first half of the study period, they later increased. There was a low proportion of deaths in nursing homes compared to other places of death; however, the proportion increased continually throughout the study period, particularly among women. In 2015, more women died in nursing homes than at home. Although the proportion of hospital deaths declined in the second half of the study period, their overall number continued to increase, reflecting an increase in total deaths in Japan.
Conclusions:
This study highlighted rapid changes in trends in PoD in Japan, and the need to consider affordable end-of-life care in Japan as well as other countries with aging populations. The findings from this long-term epidemiological study provide important insights on this issue.

DOI： 10.1089/jpm.2019.0445

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DOI： 10.2169/internalmedicine.3121-19

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A relationship between diabetes and depression is apparent. To clarify the clinical relevance of diabetic patients' gastroesophageal symptoms to their psychological status, we retrospectively analyzed the data from a Selfrating Depression Scale (SDS) and a Frequency Scale for Symptoms of Gastroesophageal reflux disease (FSSG) among 143 type 2 diabetic patients who visited a general medicine department. Among the 45 Japanese patients enrolled, the group with relatively high SDS scores (≥ 36) showed higher (FSSG) dysmotility symptom scores versus the low-SDS (< 36) group, although the 2 groups' characteristics and laboratory data were not significantly different. Positive correlations of postprandial plasma glucose (PPG) levels with FSSG scores (R=0.321, p<0.05), particularly with reflux scores (R=0.455, p<0.01) were revealed. PPG and HbA1c levels were not correlated with SDS scores. The patients' SDS scores were significantly correlated with their FSSG scores (R=0.41, p<0.01), suggesting that depressive status is linked to GERD-related manifestations. Considering that the patients' PPG levels were correlated with GERD-related symptoms, diabetic patients' blood glucose levels are associated with depressive status. Collectively, key symptoms related to GERD and glucose level values would be helpful.

DOI： 10.18926/AMO/57950

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BACKGROUND: Limited treatment options complicate management of infections with New Delhi metallo-β-lactamase (NDM)-producing organisms. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against NDM-producing Enterobacteriaceae. MATERIALS AND METHODS: Twelve E. coli clinical isolates harbouring blaNDM-1 along with a positive control E. coli BAA-2469 harbouring blaNDM-1 were studied. Minimum inhibitory concentrations (MICs) of MEM, ertapenem (ERT), and CMZ were determined by broth microdilution. Checkerboard and time-kill assays were performed to confirm the in vitro efficacy of the MEM/CMZ combination. Scanning electron microscopy, kinetic studies, and whole genome sequence analysis were used to determine the antimicrobial resistant mechanisms. RESULTS: MICs of MEM, ERT, and CMZ in monotherapy ranged from 8 to 32, 16 to 128, and 32 to 512 μg/mL, respectively. In checkerboard, MEM/ERT resulted in no synergy, whereas MEM/CMZ showed a synergistic effect in all the tested isolates. Furthermore, the MIC of MEM in combination decreased by 2- to 8-fold compared to that of MEM alone. The time-kill study revealed a bactericidal effect in 4 out of 13 isolates at 24 hours. Scanning electron microscopy showed spheroidisation of the bacterial cell in the MEM/CMZ combination, which was not observed in single antibiotic conditions. The kinetic studies indicated a better activity of CMZ to ERT as an antagonist for NDM-1. Whole genome sequence analysis did not reveal any explainable differences between isolates susceptible to the combination therapy and those not susceptible to combination therapy. CONCLUSION: In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.

DOI： 10.1016/j.ijantimicag.2020.105905

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Language：Japanese  

DOI： 10.6009/jjrt.2020_JSRT_76.9.965

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01192&link_issn=&doc_id=20200930490009&doc_link_id=130007906098&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007906098&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

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Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

DOI： 10.1038/s41598-019-56388-w

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OBJECTIVES: Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. DESIGN: We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. RESULTS: The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. CONCLUSIONS: Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.

DOI： 10.1136/bmjopen-2019-033462

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