Faculty Profiles - HAGIYA Hideharu

Papers - HAGIYA Hideharu

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Trends in the incidence and mortality of legionellosis in Japan: a nationwide observational study, 1999-2017. International journal

Shinnosuke Fukushima, Hideharu Hagiya, Yuki Otsuka, Toshihiro Koyama, Fumio Otsuka

Scientific reports 11 ( 1 ) 7246 - 7246 2021.3

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

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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Burnout of Healthcare Workers amid the COVID-19 Pandemic: A Japanese Cross-Sectional Survey. International journal

Yoshito Nishimura, Tomoko Miyoshi, Hideharu Hagiya, Yoshinori Kosaki, Fumio Otsuka

International journal of environmental research and public health 18 ( 5 ) 2021.3

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

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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Multiplex Real-Time PCR Assay for Six Major Carbapenemase Genes. International journal

Nori Yoshioka, Hideharu Hagiya, Matsuo Deguchi, Shigeto Hamaguchi, Masanori Kagita, Isao Nishi, Yukihiro Akeda, Kazunori Tomono

Pathogens (Basel, Switzerland) 10 ( 3 ) 2021.3

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

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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Impact of the COVID-19 Pandemic on the Psychological Distress of Medical Students in Japan: Cross-sectional Survey Study. International journal

Yoshito Nishimura, Kanako Ochi, Kazuki Tokumasu, Mikako Obika, Hideharu Hagiya, Hitomi Kataoka, Fumio Otsuka

Journal of medical Internet research 23 ( 2 ) e25232 2021.2

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

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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Positron emission tomography for the diagnosis of prosthetic heart valve endocarditis. International journal

Yuki Otsuka, Hideharu Hagiya, Kosuke Oka, Fumio Otsuka

BMJ case reports 14 ( 2 ) 2021.2

Clinical Characteristics of Low Androgen Status in Males with Type 2 Diabetes Mellitus

Jun Hamahara, Hiroyuki Honda, Koichiro Yamamoto, Kazuki Tokumasu, Yoshihisa Hanayama, Hideharu Hagiya, Mikako Obika, Keigo Ueda, Masayuki Kishida, Fumio Otsuka

ACTA MEDICA OKAYAMA 75 ( 1 ) 1 - 8 2021.2

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

Web of Science

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Septic pulmonary emboli caused by Tsukamurella inchonensis: A case report International journal

Kazuyoshi Gotoh, I. Putu Bayu Mayura, Hideharu Hagiya, Kyoichi Obata, Tatsuo Ogawa, Koji Iio, Takumi Fujimori, Fumio Otsuka, Osamu Matsushita

Journal of Infection and Chemotherapy 27 ( 2 ) 369 - 372 2021.2

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

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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De-escalation concept and MIC literacy among medical students and clinical residents. International journal

Hideharu Hagiya, Kazuki Tokumasu, Mikako Obika, Fumio Otsuka

Postgraduate medical journal 98 ( e3 ) e183-e184 2021.1

Without a silhouette. International journal

Yosuke Sazumi, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 9 ( 1 ) 574 - 575 2021.1

Characterization of bla<inf>NDM-5</inf>-harbouring Klebsiella pneumoniae sequence type 11 international high-risk clones isolated from clinical samples in Yangon General Hospital, a tertiary-care hospital in Myanmar International journal

Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Khwar Nyo Zin, Mya Mya Aye, Dan Takeuchi, Yuki Matsumoto, Daisuke Motooka, Isao Nishi, Kazunori Tomono, Shigeyuki Hamada

Journal of Medical Microbiology 70 ( 5 ) 2021

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

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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Clinical Manifestations of Patients with Influenza Differ by Age : A Prospective, Multi-centered Study in the Setouchi Marine Area.

Ryosuke Takase, Hideharu Hagiya, Hiroyuki Honda, Yasuhiro Nakano, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Yoshihisa Hanayama, Fumio Otsuka

Acta medica Okayama 75 ( 5 ) 567 - 574 2021

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

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 prescription practices for outpatients with acute respiratory tract infections: A retrospective, multicenter, medical record-based study. International journal

Tomoharu Ishida, Hideharu Hagiya, Hiroyuki Honda, Yasuhiro Nakano, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Yoshihisa Hanayama, Fumio Otsuka

PloS one 16 ( 11 ) e0259633 2021

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

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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Acute encephalopathy associated with severe fever with thrombocytopaenia syndrome. International journal

Manami Fujita, Yasuhiro Nakano, Hiroyuki Honda, Hideharu Hagiya

BMJ case reports 13 ( 12 ) 2020.12

Rheumatoid Meningoencephalitis.

Chie Inoue, Hideharu Hagiya, Yoshito Nishimura, Osamu Sui

Internal medicine (Tokyo, Japan) 59 ( 24 ) 3255 - 3256 2020.12

Intra-arterial gas, a clue for diagnosis of peri-aortic inflammation due to infection. International journal

Daisuke Omura, Masatoshi Ogata, Yoshio Sakane, Ryuichi Matsuo, Harushige Nakatsukasa, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 8 ( 12 ) 3619 - 3620 2020.12

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

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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Clinical Application of the Ratio of Serum Bone Isoform to Total Alkaline Phosphatase in General Practice.

Yuya Yokota, Yoshito Nishimura, Akemi Ando, Yoshihisa Hanayama, Kou Hasegawa, Hideharu Hagiya, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Fumio Otsuka

Acta medica Okayama 74 ( 6 ) 467 - 474 2020.12

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

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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Comparison of the Clinico-Microbiological Characteristics of Culture-Positive and Culture-Negative Septic Pulmonary Embolism: A 10-Year Retrospective Study. International journal

Yoshito Nishimura, Hideharu Hagiya, Mikako Obika, Fumio Otsuka

Pathogens (Basel, Switzerland) 9 ( 12 ) 2020.11

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

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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Massive pheochromocytoma. International journal

Terumitsu Anai, Kosuke Oka, Yuya Yokota, Yoshito Nishimura, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 8 ( 11 ) 2308 - 2309 2020.11

blaOXA -731 , a new chromosome-encoded blaOXA -48 -like variant in Shewanella sp. from the aquatic environment in Myanmar. International journal

Rathina Kumar Shanmugakani, Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Noriko Sakamoto, Mya Mya Aye, Thuzar Myint, Shigeyuki Hamada, Kazunori Tomono

Environmental microbiology reports 12 ( 5 ) 548 - 554 2020.10

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

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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Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome. International journal

Kosuke Oka, Mai Yamane, Yuya Yokota, Miho Yasuda, Kou Hasegawa, Takumi Fujimori, Koji Iio, Hideharu Hagiya, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 26 ( 10 ) 1095 - 1099 2020.10

Language：English

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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Papers - HAGIYA Hideharu