Prevalence and trends in persistent symptoms following COVID-19 in Japan: A nationwide cross-sectional survey.

INTRODUCTION: Even during the endemic phase of the COVID-19 pandemic, the impact of persistent symptoms on patients and healthcare systems remains significant. Thus, a more comprehensive understanding of these symptoms is essential. METHODS: Using data from the Japan Society and New Tobacco Internet Survey conducted in February 2023, this cross-sectional study investigated the prevalence of, and changes in, persistent COVID-19 symptoms. RESULTS: In total, 21,108 individuals responded to the survey. Of these, 29.1 % (6143) had a history of COVID-19. Our analysis found that arm/leg/joint pain (adjusted odds ratio [aOR]: 1.17; 95 % confidence interval [95 % CI]: 1.03-1.33), back pain (aOR: 1.13; 95 % CI: 1.01-1.27), chest pain (aOR: 1.53; 95 % CI: 1.20-1.96), malaise (aOR: 1.14; 95 % CI: 1.02-1.28), loss of taste (aOR: 2.55; 95 % CI: 1.75-3.72), loss of smell (aOR: 2.33; 95 % CI: 1.67-3.26), memory impairment (aOR: 1.27; 95 % CI: 1.04-1.56), and cough (aOR: 1.72; 95 % CI: 1.38-2.13) were independently associated with a history of COVID-19 contracted more than two months but less than six months previously. Further, back pain (aOR: 1.24; 95 % CI: 1.04-1.47) and loss of taste (aOR: 2.28; 95 % CI: 1.24-4.21) showed independent association with COVID-19 contracted more than 12 months previously. CONCLUSIONS: Various symptoms were independently associated with a history of COVID-19. While most patients tend to recover within a year after contracting COVID-19, certain symptoms, such as back pain and loss of taste, persist longer than a year, underscoring public health concerns and emphasizing the need for health care services to support patients suffering from persistent symptoms.

Nocardiosis in Japan: a Multicentric Retrospective Cohort Study.

Nocardia species cause a broad spectrum of infections, especially in immunocompromised patients. Given its relative rarity, data on the prognosis and distribution of nocardiosis from a large cohort are scarce. The present study aimed to scrutinize the clinical features and outcomes of nocardiosis in Japan, including 1-year mortality and microbiological data. The present multicentric, retrospective cohort study enrolled patients aged ≥18 years with nocardiosis diagnosed between January 2010 and December 2017 and recorded their clinical and microbiological characteristics. Factors associated with 1-year mortality were also determined using Cox proportional hazard analysis. In total, 317 patients were identified at 89 hospitals. Almost half (155/317, 48.9%) were receiving immunosuppressive agents, and 51 had disseminated nocardiosis (51/317, 16.1%). The 1-year all-cause mortality rate was 29.4% (80/272; lost to follow-up, n = 45). The most frequently isolated species was Nocardia farcinica (79/317, 24.9%) followed by the Nocardia nova complex (61/317, 19.2%). Selected antimicrobial agents were generally effective, with linezolid (100% susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. In Cox proportional hazard analysis, factors independently associated with 1-year mortality were a Charlson comorbidity index score of ≥5 (adjusted hazard ratio [aHR], 3.61; 95% confidence interval [CI], 1.95 to 6.71, P < 0.001) and disseminated nocardiosis (aHR, 1.79; 95%CI, 1.01 to 3.18, P = 0.047). The presence of advanced comorbidities and disseminated infection, rather than variations in antimicrobial therapy or Nocardia species, was independently associated with 1-year mortality.

How to use new antibiotics in the therapy of ventilator-associated pneumonia.

PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a common nosocomial infection in critically ill patients requiring endotracheal intubation and mechanical ventilation. Recently, the emergence of multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species, has complicated the selection of appropriate antimicrobials and contributed to treatment failure. Although novel antimicrobials are crucial to treating VAP caused by these multidrug-resistant organisms, knowledge of how to optimize their efficacy while minimizing the development of resistance should be a requirement for their use. RECENT FINDINGS: Several studies have assessed the efficacy of novel antimicrobials against multidrug-resistant organisms, but high-quality studies focusing on optimal dosing, infusion time and duration of therapy in patients with VAP are still lacking. Antimicrobial and diagnostic stewardship should be combined to optimize the use of these novel agents. SUMMARY: Improvements in diagnostic tests, stewardship practices and a better understanding of dosing, infusion time, duration of treatment and the effects of combining various antimicrobials should help optimize the use of novel antimicrobials for VAP and maximize clinical outcomes while minimizing the development of resistance.

Experience of 101 patients with coronavirus infectious disease 2019 (COVID-19) at a tertiary care center in Japan.

INTRODUCTION: Clusters of novel coronavirus infectious disease of 2019 (COVID-19) have spread to become a global pandemic imposing a significant burden on healthcare systems. The lack of an effective treatment and the emergence of varied and complicated clinical courses in certain populations have rendered treatment of patients hospitalized for COVID-19 difficult. METHODS: Tokyo Metropolitan Tama Medical Center, a public tertiary acute care center located in Tokyo, the epicenter of COVID-19 in Japan, has been admitting patients with COVID-19 since February 2020. The present, retrospective, case-series study aimed to investigate the clinical course and outcomes of patients with COVID-19 hospitalized at the study institution. RESULTS: In total, 101 patients with COVID-19 were admitted to our hospital to receive inpatient care. Eleven patients (10.9%) received ECMO, and nine patients (8.9%) died during hospitalization after COVID-19 was diagnosed. A history of smoking and obesity were most commonly encountered among patients with a complicated clinical course. Most patients who died requested to be transferred to advanced palliative care in the early course of their hospitalization. CONCLUSIONS: Our experience of caring for these patients demonstrated a relatively lower mortality rate and higher survival rate in those with extracorporeal membrane oxygenation placement than previous reports from other countries and underscored the importance of proactive, advanced care planning in the early course of hospitalization.

Critical National Shortage of Cefazolin in Japan: Management Strategies.

The shortage of antimicrobials poses a global health threat. In Japan, for instance, the current, critical shortage of cefazolin, a first-line agent for the treatment of common infectious diseases and surgical antimicrobial prophylaxis, has had a substantial impact on inpatient care. A shortage of essential antimicrobial agents like cefazolin leads to increased consumption of alternative antimicrobial agents with broad-spectrum activity, with the unintended consequence of militating against antimicrobial stewardship efforts in inpatient settings and potentially promoting antimicrobial resistance. Although there is global awareness of the shortage of crucial antimicrobials, action to resolve this problem, especially with a view to preventing antimicrobial resistance and promoting antimicrobial stewardship, has been slow, possibly due to the failure to appreciate the urgency of the dilemma. A comprehensive plan for stabilizing antimicrobial access and international collaboration to secure a continuous supply of essential antimicrobials are urgently needed.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

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.

Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

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 (R2 = 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.

Inadequate empiric antimicrobial therapy and mortality in geriatric patients with bloodstream infection: A target for antimicrobial stewardship.

BACKGROUND: Bloodstream infections are responsible for a large proportion of deaths among geriatric patients. Japan is a rapidly aging society; however, little is known about the epidemiology of bloodstream infections in geriatric patients in Japanese institutions. METHODS: We conducted a retrospective cohort study of patients aged ≥65 years old with a bloodstream infection in a Japanese tertiary care hospital in 2013. We defined inadequate empiric antimicrobial therapy as either antimicrobial treatment that was ineffective against subsequently isolated organisms or treatment initiated after notification of a positive culture. Predictors of inadequate antimicrobial therapy and 30-day mortality among geriatric patients with bloodstream infections were evaluated. RESULTS: We identified 275 patients with a bloodstream infection, of which 42.2% of cases (116/275) were healthcare-associated, hospital-onset. The most common source of bloodstream infection was hepatobiliary (28.0%). Inadequate empiric antimicrobial therapy occurred in 29.8% of the patients. Factors associated with inadequate empiric therapy included a history of surgery prior to bloodstream infection during index hospitalization (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.18-9.12). In 275 patients, 38 (13.8%) died within 30 days after the first positive blood culture. Predictors of 30-day mortality was Pitt bacteremia score >6 (aOR 9.80; 95% CI 4.72-20.36). CONCLUSION: Inadequate empiric antimicrobial therapy occurred in approximately one-third of episodes of bloodstream infection in geriatric patients. Severity at the time of bloodstream infection was likely to have contributed to mortality. The initiation of adequate empiric antimicrobial therapy may have important implications for antimicrobial stewardship even in the elderly population.

Antimicrobial Stewardship in Inpatient Settings in the Asia Pacific Region: A Systematic Review and Meta-analysis.

BACKGROUND: An antimicrobial stewardship program (ASP) is one of the core elements needed to optimize antimicrobial use. Although collaboration at the national level to address the importance of ASPs and antimicrobial resistance has occurred in the Asia Pacific region, hospital-level ASP implementation in this region has not been comprehensively evaluated. METHODS: We conducted a systematic review and meta-analysis to assess the efficacy of ASPs in inpatient settings in the Asia Pacific region from January 2005 through March 2016. The impact of ASPs on various outcomes, including patient clinical outcomes, antimicrobial prescription outcomes, microbiological outcomes, and expenditure were assessed. RESULTS: Forty-six studies were included for a systematic review and meta-analysis. The pooled risk ratio for mortality from ASP before-after trials and 2-group comparative studies were 1.03 (95% confidence interval [CI], .88-1.19) and 0.69 (95% CI, .56-.86), respectively. The pooled effect size for change in overall antimicrobial and carbapenem consumption (% difference) was -9.74% (95% CI, -18.93% to -.99%) and -10.56% (95% CI, -19.99% to -3.03%), respectively. Trends toward decreases in the incidence of multidrug-resistant organisms and antimicrobial expenditure (range, 9.7%-58.1% reduction in cost in the intervention period/arm) were also observed. CONCLUSIONS: ASPs in inpatient settings in the Asia Pacific region appear to be safe and effective to reduce antimicrobial consumption and improve outcomes. However, given the significant variations in assessing the efficacy of ASPs, high-quality studies using standardized surveillance methodology for antimicrobial consumption and similar metrics for outcome measurement are needed to further promote antimicrobial stewardship in this region.

Personal protective equipment and improving compliance among healthcare workers in high-risk settings.

PURPOSE OF REVIEW: Personal protective equipment (PPE) protects healthcare workers (HCWs) from infection by highly virulent pathogens via exposure to body fluids and respiratory droplets. Given the recent outbreaks of contagious infectious diseases worldwide, including Ebola virus and Middle Eastern respiratory syndrome, there is urgent need for further research to determine optimal PPE use in high-risk settings. This review intends to provide a general understanding of PPE and to provide guidelines for appropriate use based on current evidence. RECENT FINDINGS: Although previous studies have focused on the efficacy of PPE in preventing transmission of pathogens, recent studies have examined the dangers to HCWs during removal of PPE when risk of contamination is highest. Access to adequate PPE supplies is crucial to preventing transmission of pathogens, especially in resource-limited settings. Adherence to appropriate PPE use is a challenge due to inadequate education on its usage, technical difficulties, and tolerability of PPE in the workplace. Future projects aim at ameliorating this situation, including redesigning PPE which is crucial to improving the safety of HCWs. SUMMARY: PPE remains the most important strategy for protecting HCW from potentially fatal pathogens. Further research into optimal PPE design and use to improve the safety of HCWs is urgently needed.

Clostridium difficile infection in solid organ transplant recipients.

PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections, and the threat associated with CDI continues to grow in all patient populations. There is increasing evidence that CDI has a substantial impact on the morbidity and mortality in solid organ transplant (SOT) recipients. Furthermore, new diagnostic and treatment options and strategies for CDI have emerged over the last decade. The purpose of this review is to provide a general understanding of CDI and its evidence-based diagnosis and management strategies, with a focus on SOT recipients. RECENT FINDINGS: The incidence and severity of CDI have significantly increased since the year 2000. Studies have identified novel risk factors for CDI, and a new epidemic strain, the NAP1/BI/027, has emerged. Despite the development of newer testing methods and approaches, including nucleic acid amplification tests and testing algorithms, the optimal method for diagnosing CDI is an area of controversy. New agents for treating CDI are being developed, and the use of fecal microbiota transplantation to treat recurrent CDI in SOT recipients is also evolving. SUMMARY: CDI is a significant problem for SOT recipients. Further studies on diagnostic and therapeutic strategies with a focus on SOT recipients are needed to further improve patient outcomes.

The changing epidemiology of Clostridium difficile infection.

PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a growing concern and has a substantial impact on morbidity and mortality. Epidemiology of CDI has dramatically changed over the last decade. Diagnostic and treatment strategies are even more complicated given the wide variety of available diagnostic methods and the emergence of refractory or recurrent CDI. This review is intended to provide information on current CDI epidemiology and guidance for evidence-based diagnosis and management strategies. RECENT FINDINGS: Various studies from the United States, Europe, and Canada revealed increased incidence of CDI since 2000. Although CDI has long been associated with healthcare settings, recent studies indicate it is more common in the community than previously recognized. For diagnostic strategies, newer testing methods, including nucleic acid amplification tests, have enhanced sensitivity compared with toxin testing, but at the expense of decreased specificity. New agents for treating CDI are being developed and higher quality data to support fecal microbiota transplantation for treating recurrent CDI are emerging. SUMMARY: CDI epidemiology continues to evolve. Prompt recognition and an evidence-based treatment approach is the key to successfully manage CDI. Further, studies on diagnostic and therapeutic strategies are needed to further improve patient outcomes.

Cerebrospinal fluid/blood glucose ratio as an indicator for bacterial meningitis.

BACKGROUND: Bacterial meningitis is an emergent disease requiring prompt diagnosis and treatment with appropriate antimicrobials. Although the lumbar puncture is widely used as a diagnostic tool for bacterial meningitis, it remains unclear which value in cerebrospinal fluid (CSF) analysis in emergency laboratory tests precisely predicts the presence of bacterial meningitis. METHODS: This is a single-center, retrospective review of medical records to determine which emergency laboratory CSF test results are useful for predicting bacterial meningitis. The diagnosis of meningitis is made when the white blood cell count in CSF exceeds 5 cells/µL, while the diagnosis of bacterial meningitis additionally requires the growth of a pathogen from a CSF culture or the identification of a pathogen in Gram staining of CSF specimen. RESULTS: We identified 15 patients with bacterial meningitis and 129 patients with aseptic meningitis. While neutrophil-predominant pleocytosis and a decreased glucose level in CSF can predict the presence of bacterial meningitis, the CSF/blood glucose ratio is more precise (optimal cut-off=0.36, sensitivity=92.9%, specificity=92.9%, area under the curve=.97) even after administration of antimicrobials prior to examination in the emergency department. CONCLUSION: This study suggests that the CSF/blood glucose ratio may be a better single indicator for bacterial meningitis. Since the CSF glucose and blood glucose values are promptly and easily obtained from a lumbar puncture, the CSF/blood glucose ratio should be considered as a timely diagnostic indicator of bacterial meningitis. It may also help exclude the diagnosis of bacterial meningitis especially in cases in which no microorganisms can be cultured.

Incidence and mortality associated with Clostridium difficile infection at a Japanese tertiary care center.

BACKGROUND: Although increases in Clostridium difficile infection (CDI) incidence and severity have been observed in numerous countries, the incidence of CDI in Japan remains unclear. The goal of this study was to determine the incidence and outcomes of CDI at a Japanese tertiary care center. MATERIALS AND METHODS: Retrospective cohort study in patients with CDI was conducted at a 550-bed, tertiary care, academic center in Sapporo, Japan from September 2010 through August 2012. CDI cases diagnosed by enzyme immunoassays were categorized per internationally recognized surveillance definitions. Data on demographic characteristics, medication exposures, CDI presentation, and CDI treatment were collected on all CDI cases. Factors associated with 30-day all-cause mortality after the completion of CDI treatment were also investigated. RESULTS: There were 32,296 admissions and 350,074 patient-days from 22,863 patients during the study period; 126 patients were diagnosed with CDI. The median age of CDI case patients was 78 years. Healthcare facility-onset (HO) CDI accounted for 86.5% of CDI cases, with a HO-CDI incidence of 3.11 cases per 10,000 patient-days. Three patients underwent surgery for CDI (2.4%) and 19 patients (15%) died within a 30 days of completing CDI treatment. Factors independently associated with mortality were diabetes mellitus and shock at time of CDI diagnosis. CONCLUSIONS: The CDI incidence was lower than that typically reported from North American hospitals, but the proportion of patients requiring surgical therapy and dying within 30 days of CDI in non-outbreak settings was higher. More study is needed to determine why CDI incidence is low relative to CDI-associated outcomes in Japan.

Difference between days of therapy and days of antibiotic spectrum coverage in an inpatient antimicrobial stewardship program: Vector autoregressive models for time-series analysis.

OBJECTIVE: The days of therapy (DOT) metric, used to estimate antimicrobial consumption, has some limitations. Days of antibiotic spectrum coverage (DASC), a novel metric, overcomes these limitations. We examined the difference between these 2 metrics of inpatient intravenous antimicrobial consumption in assessing antimicrobial stewardship efficacy and antimicrobial resistance using vector autoregressive (VAR) models with time-series analysis. METHODS: Differences between DOT and DASC were investigated at a tertiary-care center over 8 years using VAR models with 3 variables in the following order: (1) the monthly proportion of prospective audit and feedback (PAF) acceptance as an index of antimicrobial stewardship efficacy; (2) monthly DOT and DASC adjusted by 1,000 days present as indices of antimicrobial consumption; and (3) the monthly incidence of 5 organisms as an index of antimicrobial resistance. RESULTS: The Granger causality test, which evaluates whether incorporating lagged variables can help predict other variables, showed that PAF activity contributed to DOT and DASC, which, in turn, contributed to the incidence of drug-resistant P. aeruginosa. Notably, only DASC helped predict the incidence of drug-resistant Enterobacterales. Another VAR analysis demonstrated that a high proportion of PAF acceptance was accompanied by decreased DASC in a given month, whereas increased DASC was accompanied by an increased incidence of drug-resistant Enterobacterales, unlike with DOT. CONCLUSIONS: The VAR models of PAF activity, antimicrobial consumption, and antimicrobial resistance suggested that DASC may more accurately reflect the impact of PAF on antimicrobial consumption and be superior to DOT for predicting the incidence of drug-resistant Enterobacterales.

Differences in the incidence of nosocomial-onset COVID-19 among hospitalized patients with exposure to SARS-CoV-2.

We evaluated the secondary COVID-19 incidence among uninfected hospitalized patients after nosocomial COVID-19 exposure. An exposure source of SARS-CoV-2 was hospitalized patients or healthcare personnel (HCP) newly diagnosed as having COVID-19. Patients exposed to a COVID-19-infected patient in a shared room more frequently developed COVID-19 than those exposed to an infected HCP.

Association of Individual Behaviors With Infection Prevention Measures and COVID-19 Development: A Japanese Cross-Sectional Study.

During the COVID-19 pandemic, people often modified their behaviors and performed individual infection control practices despite the uncertain effectiveness of these in preventing COVID-19. A cross-sectional study using a nationwide internet survey (Japan COVID-19 Society Internet Survey) was conducted from September 2022 through October 2022. The questionnaire consisted of individual-level social distancing behaviors and infection prevention measures, and COVID-19 vaccination status. A multivariate logistic regression was performed to determine factors associated with the diagnosis of COVID-19 in the last two months of the survey date. In total, 19,296 respondents were selected for the primary analysis. Of 19,296 respondents, those with COVID-19 diagnosed in the last two months were 1,909 (9.9%). Factors independently associated with a recent history of COVID-19 were meeting colleagues in person ≧ 1 per week (adjusted odds ratio [aOR] 1.72). The response of "never or rarely" to the question of taking out (i.e., dining in) foods was marginally associated with a recent history of COVID-19 (aOR 1.27). Most individual, infection prevention practices and behavioral modifications during the omicron variant phase of the pandemic did not substantially impact COVID-19 prevention in the community.

Content analysis of medical students' seminars: a unique method of analyzing clinical thinking.

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.