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Background: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan., Methods: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping., Results: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found., Conclusion: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R 2  = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A 23-year-old Japanese woman, previously a commercial sex worker, presented with a 2-day history of right upper quadrant (RUQ) abdominal pain, worse on deep inspiration. She had noticed increased vaginal discharge 2 months earlier and had developed dull, lower abdominal pain 3 weeks prior to presentation. Although pelvic examination and transvaginal ultrasonography revealed neither a tubal nor ovarian pathology, abdominal CT scan with contrast demonstrated early enhancement of the hepatic capsule, a finding pathognomonic for Fitz-Hugh-Curtis syndrome (FHCS). Cervical discharge PCR assay confirmed Chlamydia trachomatis infection. This case highlights that normal gynaecological evaluation may be insufficient to rule out FHCS, for which physicians should have a high index of suspicion when seeing any woman of reproductive age with RUQ pain., (2016 BMJ Publishing Group Ltd.)

Background: The Multiple Mini-Interview (MMI) mostly uses 'Situational' Questions (SQs) as an interview format within a station, rather than 'Past-Behavioural' Questions (PBQs), which are most frequently adopted in traditional single-station personal interviews (SSPIs) for non-medical and medical selection. This study investigated reliability and acceptability of the postgraduate admissions MMI with PBQ and SQ interview formats within MMI stations., Methods: Twenty-six Japanese medical graduates, first completed the two-year national obligatory initial postgraduate clinical training programme and then applied to three specialty training programmes - internal medicine, general surgery, and emergency medicine - in a Japanese teaching hospital, where they underwent the Accreditation Council for Graduate Medical Education (ACGME)-competency-based MMI. This MMI contained five stations, with two examiners per station. In each station, a PBQ, and then an SQ were asked consecutively. PBQ and SQ interview formats were not separated into two different stations, or the order of questioning of PBQs and SQs in individual stations was not changed due to lack of space and experienced examiners. Reliability was analysed for the scores of these two MMI question types. Candidates and examiners were surveyed on this experience., Results: The PBQ and SQ formats had generalisability coefficients of 0.822 and 0.821, respectively. With one examiner per station, seven stations could produce a reliability of more than 0.80 in both PBQ and SQ formats. More than 60% of both candidates and examiners felt positive about the overall candidates' ability. All participants liked the fairness of this MMI when compared with the previously experienced SSPI. SQs were perceived more favourable by candidates; in contrast, PBQs were perceived more relevant by examiners., Conclusions: Both PBQs and SQs are equally reliable and acceptable as station interview formats in the postgraduate admissions MMI. However, the use of the two formats within the same station, and with a fixed order, is not the best to maximise its utility as an admission test. Future studies are required to evaluate how best the SQs and PBQs should be combined as station interview formats to enhance reliability, feasibility, acceptability and predictive validity of the MMI.

Introduction: Acinetobacter baumannii can cause serious infection in susceptible patients, but little has been published regarding risk factors for infection and outcomes in solid organ transplant (SOT) recipients., Methods: We identified A. baumannii infection among adult SOT recipients that occurred between January 2001 and March 31, 2008 at a Chicago transplant center and evaluated characteristics of these infections and outcomes., Results: Thirty-three individuals developed A. baumannii infection during the study period. Seventy-nine percent had healthcare-associated infection with respiratory tract as the most common site of infection (64%). Eighty-two percent of patients had received antibiotics within two wk prior to A. baumannii infection and multidrug resistance (MDR) or extensive resistance (XDR) occurred in 85%. The median time to onset of infection was five months after transplant. The 30-d mortality was 24% and was associated with XDR. Administration of an appropriate antibiotic within three d was associated with lower 30-d mortality (OR 0.16, p = 0.047). All isolates tested against colistin were susceptible., Conclusion: SOT recipients with A. baumannii infection had high mortality associated with delay in appropriate antibiotic therapy and XDR organisms. The use of colistin-containing treatment regimens should be considered in these patients when A. baumannii infection is suspected or identified in patients who have received prior antibiotics., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The absence of meningeal signs and symptoms is rare in patients with bacterial meningitis and may lead to a delay in diagnosis and treatment. Furthermore, the onset of bacterial meningitis associated with pneumocephalus is a rare complication of ear infections. We herein report a rare case of otogenic meningitis complicated by pneumocephalus that was initially missed due to the absence of typical meningeal signs and symptoms and later diagnosed correctly based on a thorough review of the patient's systems.

To examine the impact of the plasma homocysteine level on the anti-atherosclerotic effects of pitavastatin treatment, we retrospectively examined 59 patients who had a history of stroke and had been prescribed pitavastatin for the treatment of dyslipidemia at the Neurology department of Toho University Ohashi Medical Center Hospital. The patients were classified into two groups according to their homocysteine levels. Carotid artery plaque progression was determined before and after pitavastatin treatment. Plasma levels of high-sensitivity C-reactive protein, platelet molecular markers, and von Willebrand factor were measured. Pitavastatin treatment had beneficial effects on the lipid profiles of these patients and slowed atherosclerosis progression. These effects were observed in both the high and low homocysteine groups. Proactive lipid intervention using pitavastatin may inhibit the progression of atherosclerosis and contribute to secondary prevention of stroke in high-risk patients. We conclude that this statin could inhibit progression at any stage of disease and should therefore be proactively administered to these patient groups, regardless of disease severity.

Background: The study of communication skills of Asian medical students during structured Problem-based Learning (PBL) seminars represented a unique opportunity to assess their critical thinking development. This study reports the first application of the health education technology, content analysis (CA), to a Japanese web-based seminar (webinar)., Methods: The authors assigned twelve randomly selected medical students from two universities and two clinical instructors to two virtual classrooms for four PBL structured tutoring sessions that were audio-video captured for CA. Both of the instructors were US-trained physicians. This analysis consisted of coding the students' verbal comments into seven types, ranging from trivial to advanced knowledge integration comments that served as a proxy for clinical thinking., Results: The most basic level of verbal simple responses accounted for a majority (85%) of the total students' verbal comments. Only 15% of the students' comments represented more advanced types of critical thinking. The male students responded more than the female students; male students attending University 2 responded more than male students from University 1. The total mean students' verbal response time for the four sessions with the male instructor was 6.9%; total mean students' verbal response time for the four sessions with the female instructor was 19% (p < 0.05)., Conclusions: This report is the first to describe the application of CA to a multi-university real time audio and video PBL medical student clinical training webinar in two Japanese medical schools. These results are preliminary, mostly limited by a small sample size (n = 12) and limited time frame (four sessions). CA technology has the potential to improve clinical thinking for medical students. This report may stimulate improvements for implementation.

We report herein on a case of Plasmodium malariae malaria with more than a 4-month incubation period. A 35-year-old Japanese man who first presented to our clinic with fever and history of travel to Papua New Guinea was suspected of having Plasmodium vivax malaria based on peripheral smear results. We admitted him and initiated treatment with mefloquine. After two days of therapy, he became afebrile. We discharged him, and P. vivax was later confirmed with PCR. We started mefloquine prophylaxis for a planned trip to Papua New Guinea. After his return, a standard dose of primaquine (15 mg x 14 days) was prescribed for a radical cure of P. vivax. About 4 months after his last visit to Papua New Guinea, he returned to our clinic with fever. We suspected a relapse of P. vivax malaria and admitted him for a second time. After two days of mefloquine therapy, his symptoms improved. We discharged him and restarted a higher dose of primaquine (30 mg x 14 days) therapy for a radical cure of P. vivax. Subsequently, the PCR test revealed the parasite was P. malariae and not P. vivax. Only 13 cases of Plasmodium malariae malaria have been reported in Japan during the past 10 years. Blood-stage schizonticides such as mefloquine is not active against the liver stage. Therefore, the use of these drugs for prophylaxis will not be effective for prevention of malaria if its liver stage is longer than the duration of effective chemoprophylaxis. Although the incubation period of P. malariae is typically 13 to 28 days, it occasionally lasts for months or even years. Careful attention should be given to the possibility that P. malariae occasionally has a long incubation period even in the absence of the hypnozoite stage.

We report a 71-year-old man with legionellosis, who presented with abducens nerve palsy, singultus, confusion, memory impairment, ataxia, and hyporeflexia. Legionella pneumonia was diagnosed on the basis of detection of Legionella pneumophila antigen in the urine. The cerebrospinal fluid was negative for the antigen and antibody, but an oligoclonal band was detected, and the IgG index was elevated. It was speculated that an undetermined immune-mediated mechanism had contributed to the development of the neurological manifestations.

We report an extremely rare case of urosepsis caused by Globicatella sanguinis and Corynebacterium riegelii coinfection in a 94-year-old Japanese man with nephrolithiasis. Prompt identification of this coinfection is important so that effective antimicrobial coverage can be initiated.

Limb-girdle muscular dystrophy 2B and Miyoshi myopathy are characterized by muscle fiber necrosis caused by a defect in dysferlin and inflammatory changes. SJL/J mice are deficient in dysferlin and display severe inflammatory changes, most notably the presence of cytokines, which may be related to destruction of the sarcolemma. We tested the hypothesis that tumor necrosis factor (TNF) contributes to myofibril necrosis. Administration of etanercept, an agent that blocks TNF, resulted in dose-dependent reductions in inflammatory change, necrosis, and fatty/fibrous change. These findings indicate that TNF does indeed play a role in the damage to muscle in SJL/J mice and that etanercept has the potential to reduce such damage., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We report on the case of a 32-year-old woman with tuberculous meningitis (TBM) with electroencephalogram (EEG) output displaying triphasic waves (TWs). The EEG on day 8 revealed generalized slowing, frontal bilateral TWs, a background of 2Hz delta waves, and no epileptiform activity. The patient's condition improved slowly with antituberculosis chemotherapy treatment. A follow-up EEG on day 34 showed marked improvement, with no TWs, background activity improved to a 12Hz symmetric alpha wave pattern, and no epileptiform activity, as before. To our knowledge, this is the first report of TWs observed in a TBM case., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Previous studies suggest that Asians may be less likely to develop venous thromboembolism (VTE) than Caucasians. While inherited thrombophilias occur infrequently among Asians, the distribution of other VTE risk factors in these populations remains unclear., Objective: To identify VTE risk factors in a Japanese population., Patients and Methods: We evaluated 131,060 patients admitted to Okinawa Chubu Hospital in Japan (January 1987-December 1999). Patients with VTE were identified through discharge diagnoses using the hospital database. Medical records were reviewed for information on demographics, potential VTE risk factors, and diagnostic modalities. Controls were randomly selected from the same database, matched 1:1 to cases on age, sex, year of hospital admission, and nearest medical record number We used conditional logistic regression to examine potential VTE risk factors., Results: We identified 141 cases of newly diagnosed VTE (128 with deep vein thrombosis, 41 with pulmonary embolism). In multivariable analyses adjusting for all measured potential risk factors, statistically significant VTE risk factors included lower extremity paralysis [odds ratio (OR), 3.07; 95% CI, 1.01-9.33], immobilization >7 days (OR, 4.96; 95% CI, 2.26-10.9), diagnosis of an acquired hypercoagulable state (OR, 19.1; 95% CI, 1.75-209.2), body mass index > or = 25.0 kg/nm2 (OR, 2.35; 95% CI, 1.13-4.89), and prior VTE (OR, 22.37; 95% CI, 2.35-213.4)., Conclusion: The VTE risk factors identified in this Japanese population are similar to those previously described among Caucasians. Further study is needed to define how the distribution of VTE risk factors in Asian populations may influence appropriate preventive strategies.

Limited data suggest that Asian Americans may have a lower risk of venous thromboembolism (VTE) than Caucasians. However, the actual prevalence of VTE among Asians remains controversial, and has not been described in Japan. We studied all 131,060 patients hospitalized at a single medical centre in Japan (January 1987 - December 1999). Patients with VTE were identified through discharge diagnoses. Hospital records were reviewed for information on patient demographics, risk factors, and diagnostic modalities. VTE occurred in 0.11% of admissions (n=141, 95%CI 0.09-0.13%). Mean age (+/-SD) was 64+/-17 years, 70% were women, 91% had deep vein thrombosis, and 29% pulmonary embolism. Among hospitalized patients 50-69 years old, VTE was significantly more common among women than men (0.31% vs. 0.08%; OR 3.88; 95%CI 1.45-6.31). We found a low prevalence of VTE in Japan compared to that reported in the US. Future studies are needed to clarify the reasons for our findings.