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Abstract Background A number of antibody test kits for detecting prior SARS-CoV-2 infection and post-immunization status have been commercialized. Indirect immunoperoxidase assay (IIP) is a conventional method to test antibodies. We evaluated the diagnostic accuracy and antibody titer profile of the IIP in COVID-19 and pre- and post-vaccination. Methods We conducted a hospital-based observational study in Fukushima prefecture, Japan. We enrolled COVID-19 inpatients who tested positive by PCR. We used serum samples collected > 10 years before the pandemic as the negative control. We also included volunteers vaccinated at the hospital. All participants were tested using an IIP with whole-cell antigen of the six SARS-CoV-2 variants isolated in Japan during the epidemic and an IgG ELISA kit. Negative controls and vaccinated volunteers were also tested using a lateral flow assay (LFA) kit. We conducted receiver operating characteristic (ROC) analysis to evaluate diagnostic accuracy and performed logistic regression analysis to explore factors associated with antibody titer. Results We included 146 COVID-19 inpatients, 38 negative controls, and 36 vaccinated volunteers. Most participants had the highest titer for IgG and IgM in the wild type-A antigen among the six variants. The sensitivity, specificity, and accuracy of the IgG ELISA kit were 60.3%, 100%, and 68.5%; of the IIP for IgG with the cutoff titer at 1:80, 82.2%, 94.7%, and 84.8%, respectively. The ROC curves of the ELISA and IIP for IgG were almost identical. In the IgG tests of the 36 volunteers, 35 were positive for ELISA and IIP and 34 for LFA after two vaccinations. IgM titers in the IIP were = 7 days after the second vaccination, and immunosuppressants for comorbidity were associated with IgG titer of > = 1:640 in the IIP. Conclusions The diagnostic accuracy of the IIP for detecting IgG antibodies in COVID-19 or after two vaccinations is equivalent to that of an ELISA. Further investigations are required to address the association between antibody titers in the IIP and their protective or harmful effects against COVID-19.

Abstract Background Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients. Methods We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively. Results We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain. Conclusions Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.

Abstract Background Long-term hospital stay is associated with functional decline in patients with pneumonia, especially in the elderly. Among elderly patients with pneumonia, aspiration pneumonia is a major category. Clinical definition is usually used because it can occur without apparent aspiration episodes. It is still not clear whether a long-term hospital stay is due to aspiration pneumonia itself caused by underlying oropharyngeal dysfunction or simply due to functional decline in elderly patients with multiple comorbidities during acute infection. The aim of this study is to identify whether clinically defined aspiration pneumonia itself was associated with a long-term hospital stay. Methods A prospective observational study on community-acquired (CAP) or healthcare-associated pneumonia (HCAP) was conducted from January 2012 through January 2014. Aspiration pneumonia was clinically defined as pneumonia not only occurring in patients after documented aspiration episodes, but also occurring in those with underlying oropharyngeal dysfunction: chronic disturbances of consciousness and/or chronic neuromuscular diseases. We defined thirty-day hospital stay as a long-term hospital stay and compared it with logistic regression analysis. Potential confounders included age, sex, HCAP, body mass index (BMI), long-term bed-ridden state, heart failure, cerebrovascular disorders, dementia, antipsychotics use, hypnotics use, and CURB score which is a clinical prediction tool used to assess the severity, standing for; C (presence of Confusion), U (high blood Urea nitrogen level), R (high Respiratory rate), and B (low Blood pressure). In a sub-analysis, we also explored factors associated with long-term hospital stay in patients with aspiration pneumonia. Results Of 2,795 patients, 878 (31.4%) had aspiration pneumonia. After adjusting potential confounders, the aspiration pneumonia itself was significantly associated with long-term hospital stay (adjusted odds ratio 1.44; 95% confidence interval 1.09—1.89, p

To elucidate the epidemiology of murine typhus, which is infrequently reported in Japan, we conducted a cross-sectional study involving 2,382 residents of rickettsiosis-endemic areas in Honshu Island during August–November 2020. Rickettsia typhi seroprevalence rate was higher than that of Orientia tsutsugamushi, indicating that murine typhus is a neglected disease.

Objectives In older patients, the diagnosis of acute pyelonephritis (APN) is challenging. The aim was to evaluate the added value of CT to history, physical examination and urinalysis for the diagnosis of APN in older patients with suspected infection with an unknown focus.Design Retrospective diagnostic study.Setting Department of General Medicine in an acute care hospital in Japan.Participants Patients aged ≥65 years who underwent blood cultures, a urine culture, and chest and abdominal CT to detect the focus of infection were included.Primary outcome measures Two radiologists independently reviewed four non-contrast CT signs: perirenal fat stranding, pelvicalyceal wall thickening, enlargement of the kidney and thickening of Gerota’s fascia. Findings on contrast-enhanced CT could not be evaluated due to an insufficient number of patients in whom contrast-enhanced CT was performed. An expert panel was used as the reference standard for APN. The added value of CT findings was quantified by comparing the diagnostic performance between a model based on 10 predictors available before CT and an extended model including the CT findings.Results Of 473 patients, 61 (14.8%) were diagnosed with APN. When the laterality of the CT findings was taken into account, the model fit was not improved by adding them. In the laterality-insensitive analysis, the model performance was significantly improved by adding the CT signs (likelihood-ratio test p=0.03; c-index 0.89 vs 0.91, p=0.03). However, their clinical utility was only to improve the classification of 11.5% of patients with APN.Conclusions The added value of non-contrast CT findings to history, physical examination and urinalysis was limited for the diagnosis of APN in older patients with a suspected infection with an unknown focus.

Objectives: We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae using antibody endpoint titers. Methods: Patients’ immunoglobulin (Ig)M and IgG titers against Rickettsia japonica and Rickettsia typhi in two phases were measured using an indirect immunoperoxidase assay at two reference centers for rickettsiosis in Japan. Cross-reaction was defined as a higher titer against R. typhi in convalescent sera than in acute sera among patients fulfilling the criteria for JSF diagnosis. The frequencies of IgM and IgG were also evaluated. Results: Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases. Conclusion: Cross-reactions of 20% in serodiagnosis may lead to the misclassification of rickettsial diseases. However, with the exception of some cases, we were able to successfully differentiate JSF from murine typhus using each endpoint titer.

Abstract Advance care planning (ACP) is essential for end-of-life care, especially during the novel coronavirus disease 2019 (COVID-19) pandemic, and resilience is critical to deal with pandemic-related stressors. Therefore, we investigated the association between resilience ability and ACP discussions during the COVID-19 pandemic. A nationwide web-based survey was conducted in July 2021 in Japan. We analyzed the respondents’ ability to bounce back from stress (bouncing-back ability), positive stress coping (e.g., “seeking social support”, “planning”), and negative stress coping (e.g., “avoidance”, “alcohol and drug use”) in relation to ACP discussions using multivariable logistic regression models. In total, 2000 responses (86% participation rate) were received (mean age: 51.8 ± 16.7). Normal and high bouncing-back ability (adjusted odds ratio [AOR]: 1.69, 95% CI: 1.03–2.79; AOR: 2.07, 95% CI: 1.18–3.65, respectively) were significantly associated with the occurrence of ACP discussions. Seeking social support and planning were significantly associated with ACP discussions, whereas avoidance and alcohol and drug use were not. Both bouncing-back ability and positive stress coping were significantly associated with the occurrence of ACP discussions during the COVID-19 pandemic in Japan. These findings could be useful for aiding health-care providers involved in ACP discussions during the COVID-19 pandemic.

Abstract Background Laboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis. Methods We conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA). Results Total number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31–58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2–14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1–212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0–882) was associated with tubercular meningitis. Conclusions Addition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.

BackgroundEosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear.Methodology/principal findingsAdult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia.ConclusionsThe etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF.

Abstract Background Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction. Methods Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age ≥ 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed. Results In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28–14.99), recent hospitalization (2.21; 1.36–3.60), age ≥ 85 years (2.15; 1.08–4.28), low body mass index (1.99, 1.25–3.16), neoplastic disease (1.82; 1.17–2.85), and male gender (1.78; 1.16–2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0–10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 ≥ 3) (risk ratio: 7.24, 95%CI: 3.08–25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94–2.50). Conclusions Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion.

BACKGROUND:Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS:We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case). CONCLUSIONS/SIGNIFICANCE:Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential.

The article focuses on the potential reemergence of murine typhus in Japan, challenging the conclusion drawn from a study indicating a high seroprevalence rate for Rickettsia typhi in residents on Honshu Island. It author suggests that the study's cross-sectional nature and the absence of consideration for historical cases might lead to premature conclusions about the reemergence of murine typhus in Japan.

The reformation of medical training in Japan is essential to maintain pace with international standards in medical education ; central to this is embracing outcome-based education in medical colleges nationwide. At Fukushima Medical University, the bedside training period was extended from 50 to 72 weeks in 2018, offering a window for targeted improvement to promote student-centered, active learning. In order to enrich the clinical learning experience, three key interventions were initiated. First, the establishment of clear objectives for teaching staff and students were set to maximize the effectiveness of bedside training. Secondly, we revised our student evaluation strategy and adapted more stringent methods promoting peer evaluation, simulated patients, and tutor feedback. Finally, we introduced information and communication technology (ICT) to create a dynamic and interactive learning environment, designed to facilitate constructive peer feedback and deep reflection. We hope that these three approaches will lead to the promotion of outcome-based education within our college. [ABSTRACT FROM AUTHOR]

Zoonotic potential of a rat-derived hepatitis E virus (HEV), designated as HEV-C1, remains unknown. To evaluate the risk for HEV-C1 infection in humans, paired sera of 208 hospitalized febrile patients collected from 2001 to 2003 in Hanoi, Vietnam, were examined for IgG antibodies to HEV-C1 and genotype 1 HEV (HEV-1), which is common in humans. IgG antibodies to virus-like particles (VLPs) of HEV-C1 and/or HEV-1 were detected from 99 of the 208 convalescent sera in enzyme-linked immunosorbent assay (ELISA). IgG antibody titers to HEV-C1 antigen in 3 of the 99 sera were more than 8-fold higher than those to HEV-1 antigen. IgM antibodies to HEV-C1 antigen were detected in acute sera from 2 of the 3 patients in ELISA and Western blotting. However, no HEV genome was detected. Clinical information was available for 1 of the 2 patients. Hepatic enzymes, aspartate aminotransferase and alanine aminotransferase, were mildly elevated (156 IU/l and 68 IU/l, respectively), and hepatomegaly was detected by ultrasonography. The patient recovered from the illness after 17 days. These results indicated that HEV-C1 or its variants infect humans in Vietnam and may cause acute febrile illness with mild liver dysfunction. [ABSTRACT FROM AUTHOR]

Background: In Western clinical training, formulation of a summary statement (SS) is a core exercise for articulation, evaluation, and improvement of clinical reasoning (CR). In Japanese clinical training, structured guidance in developing CR, including opportunity for SS practice, is uncommon, and the present status of case summarization skills is unclear. We used Virtual Patients (VPs) to explore Japanese junior residents' SS styles and the effectiveness of VPs on improving SS quality. Methods: All first-year junior resident physicians at 4 residency programs (n = 54) were assigned randomized sequences of 5 VP modules, rolled out at 6 day intervals. During each module, participants free-texted a case summary and then reviewed a model summary. Thematic analysis was used to identify SS styles and each SS was categorized accordingly. Frequency of SS styles, and SS CR quality determined by 1) an internally developed Key Feature rubric and 2) demonstration of semantic qualification, were compared across modules. Results: Four SS styles were identified: numbered features matched to differential diagnoses, differential diagnoses with supportive comments, feature listing, and narrative summarization. From module #1 to #5, significant increases in the narrative summarization SS style (p = 0.016), SS CR quality score (p = 0.021) and percentage of semantically driven SS (p = 0.003) were observed. Conclusions: Our study of Japanese junior residents identified distinct clinical case summary statement styles, and observed adoption of the narrative summarization style and improvement in the CR quality of summary statements during a series of VP cases. [ABSTRACT FROM AUTHOR]