Utility of shaking chills as a diagnostic sign for bacteremia in adults: a systematic review and meta-analysis.

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.

Role of inflammatory markers in the assessment of meningitis in adult patients with fever and headache.

BACKGROUND: Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar puncture, it is crucial to identify individuals who truly need it. The aim of this study was to assess the diagnostic role of inflammatory markers in distinguishing among patients without meningitis, those with aseptic meningitis, and those with bacterial meningitis. METHODS: This was a retrospective, diagnostic study at an acute care hospital, involving adult patients who presented to either ambulatory care or the emergency department with fever and headache, but without altered mental status or neurological deficits. Inflammatory markers (C-reactive protein [CRP], mean platelet volume, neutrophil-lymphocyte ratio, and red cell distribution width) were assessed as index tests. An expert panel classified patients into three groups: no meningitis, aseptic meningitis, and bacterial meningitis using predefined criteria. RESULTS: Of the 80 patients, 52 had no meningitis, 27 had aseptic meningitis, and 1 had bacterial meningitis. Of the inflammatory markers investigated, only CRP showed potential usefulness in differentiating these three diagnostic groups, with median values of 5.6 (interquartile range [IQR] 2.1, 11.3) mg/dL in those without meningitis, 0.2 (IQR 0.1, 1.2) mg/dL in those with aseptic meningitis, and notably elevated at 21.7 mg/dL in the patient with bacterial meningitis. CONCLUSION: In adult patients presenting with fever and headache in an emergency setting, CRP was the only marker that demonstrated potential diagnostic utility in distinguishing among those with no meningitis, aseptic meningitis, and bacterial meningitis.

Nonnegligible Seroprevalence and Predictors of Murine Typhus, Japan.

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.

Development and Initial Psychometric Validation of the COVID-19 Pandemic Burden Index for Healthcare Workers.

BACKGROUND: The burden of COVID-19 on healthcare workers (HCWs) is reported to be increasing, yet the psychometric scales now in use evaluate only single aspects; few measure the pandemic-specific burden on HCWs comprehensively. OBJECTIVE: To develop a scale to quantify the physical, mental, and socioeconomic burden of the COVID-19 pandemic on HCWs. DESIGN: Scale development and cross-sectional survey. PARTICIPANTS: Consenting HCWs aged ≥20. MAIN MEASURES: Development of an item-list based on literature reviews and HCW panel input, evaluation of content validity and item selection using the Delphi method, psychometric testing conducted on HCWs, validity assessment by factor analyses and hypothesis verification, internal consistency evaluation by Cronbach's alpha, test-retest analysis, and interpretability assessment. KEY RESULTS: Through the Delphi process, a 29-item pilot scale was generated. In psychometric testing, data from 863 HCWs contributed to the development of the final version of this scale, called Pandemic Burden Index twenty for HCWs (PBI-20), a 20-item scale to measure six domains: fatigue, fear of infection, inadequacy as a medical professional, mental health concerns, prejudice or discrimination, and anxiety about one's livelihood and daily life. Factor analysis showed each factor corresponded to the six domains of this scale. Hypothesis verification showed the PBI-20 total score to be moderately to highly correlated with the Short Form 36 vitality score and mental health score and with intention of turnover. The PBI-20 had good internal consistency (Cronbach's alpha 0.92). Test-retest analysis showed the intraclass correlation coefficient to be 0.70 and the minimal important change to be -7.0. CONCLUSIONS: The psychometrically sound questionnaire we developed to measure pandemic-specific burdens for HCWs provides an understanding of comprehensive burdens on HCWs and may serve to evaluate interventions to reduce the burdens.

Clinically defined aspiration pneumonia is an independent risk factor associated with long-term hospital stay: a prospective cohort study.

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 < 0.01), as were higher age, male sex, high CURB score, HCAP, low BMI, heart failure, cerebrovascular disease, and antipsychotics use. Sub-analysis revealed factors associated with long-term hospital stay in the aspiration pneumonia, which included male sex, and multi-lobar chest X-ray involvement. CONCLUSIONS: Clinically defined aspiration pneumonia itself was independently associated with long-term hospital stay. This result could potentially lead to specific rehabilitation strategies for pneumonia patients with underlying oropharyngeal dysfunction.

High prevalence of multiple serotypes of pneumococci in patients with pneumonia and their associated risk factors.

BACKGROUND: Multiple serotypes of pneumococci have epidemiological and clinical implications, such as the emergence of non-vaccine serotypes and the acquisition of antimicrobial resistance. Prevalence of multiple serotypes of pneumococci in adults and their risk factors are not known. METHODS: We enrolled adult patients from age ≥15 years with radiologically confirmed pneumonia in four hospitals across Japan. Pneumococcal pneumonia was defined with a pneumococcal bacterial density of ≥104/mL in sputum by lytA quantitative PCR, and serotypes were determined. Pneumonias with a single serotype were categorised as single-serotype pneumococcal pneumonia and with two or more serotypes as multiple-serotype pneumococcal pneumonia. Multivariable logistic regression was used to assess the risk factors. RESULTS: 3470 patients (median age 77 years, IQR 65-85) were enrolled. Pneumococcal pneumonia was identified in 476 (18.3%, n=2605) patients. Multiple serotypes were detected in 42% of them. Risk of having multiple serotypes was low among patients who had received 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccines (adjusted OR 0.51 (95% CI 0.27 to 0.94)). Proportion of non-PCV7 PPSV23 serotypes in overall distribution of multiple serotypes was 67.4% (n=324/481) compared with 46.4% (n=128/276) in that of single serotypes (p=0.001). Serotypes 5, 9N/9L, 10A, 12/22/46, 17F and 35F were associated with multiple-serotype pneumonia, and serotypes 6A/6B, 23F, 11 and 6C/6D were associated with single-serotype pneumonia. Proportion of more invasive serotypes (serotypes 1, 5, 7F, 8) was significantly higher in multiple-serotype pneumonia (p=0.001). CONCLUSIONS: Multiple serotypes of pneumococci are common in sputum of adult patients with pneumonia. The risk of multiple-serotype pneumococcal pneumonia is lower than that of single-serotype pneumococcal pneumonia among PPSV23-vaccinated patients. TRIAL REGISTRATION NUMBER: UMIN000006909.

Significance of Overactive Bladder as a Predictor of Falls in Community Dwelling Older Adults: 1-Year Followup of the Sukagawa Study.

PURPOSE: Little is known about the fall risk of older adults with overactive bladder, especially in the absence of urgency incontinence. We evaluated the impacts of overactive bladder with and without urgency incontinence (overactive bladder wet and overactive bladder dry) on the fall risk in older adults, and investigated the importance of overactive bladder as a predictor of falls by using tree based models. MATERIALS AND METHODS: This prospective cohort study included 630 community dwelling, independent older adults 75 years old or older who attended a health checkup in 2017 with a 1-year followup. The associations of overactive bladder dry and overactive bladder wet with a fall history, and future fall risk compared to no overactive bladder were assessed using logistic regression models. The contribution of overactive bladder as a predictor of falls was examined using a random forest and decision tree approach. RESULTS: Of the 577 analyzed participants (median age 79 years), 273 (47%) were men. The prevalence of overactive bladder dry and overactive bladder wet at baseline was 15% and 14%, respectively. Multivariable logistic regression analysis revealed that both overactive bladder dry and overactive bladder wet were associated with a higher likelihood of prior falls (adjusted ORs vs no overactive bladder 2.03 and 2.21, respectively; 95% CI 1.23-3.37 and 1.29-3.78, respectively). Among the 363 participants without a fall history, the adjusted ORs (95% CIs) of overactive bladder dry and overactive bladder wet for the occurrence of falls during the 1-year followup were 2.74 (1.19-6.29) and 1.35 (0.47-3.87), respectively. The tree based approach used for all participants showed that overactive bladder was an important predictor of falls in adults without a fall history, and the model had 83.6% accuracy and 81.8% AUC. CONCLUSIONS: Overactive bladder, even in the absence of urgency incontinence, is an important predictor of falls in older adults with a low absolute fall risk.

Six underlying health conditions strongly influence mortality based on pneumonia severity in an ageing population of Japan: a prospective cohort study.

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.

Virtual patients to explore and develop clinical case summary statement skills amongst Japanese resident physicians: a mixed methods study.

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.

Hypothyroidism Due to Seaweed Overconsumption.

Hypothyroidism presents various symptoms, ranging from commonly observed signs, such as fatigue, cold sensation, and constipation, to rare features, such as rash and pancytopenia, resembling certain rheumatological and hematological diseases. Chronic, excessive iodine consumption causes primary hypothyroidism. However, when iodine overconsumption becomes a regular part of daily dietary habits, it becomes difficult for patients to associate their symptoms with daily iodine consumption. Therefore, clinicians cannot obtain information on excessive iodine intake from the patient. Here, we present a case of hypothyroidism that was subsequently identified as caused by excessive dairy seaweed consumption for health purposes. This case report highlights the importance of a detailed dietary history in patients diagnosed with primary hypothyroidism without thyroid autoantibodies.

Fatal Myocarditis in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Without Mortality-Related Risk Factors: A Case Report and Literature Review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction characterized by skin rash, organ involvement, lymph node swelling, eosinophilia, and atypical lymphocytosis, with myocarditis being a rare but potentially fatal complication. It has been reported that in patients with cardiac involvement due to DRESS, older age and shorter periods between offending drug exposure and symptom onset are associated with mortality. We report a case of fatal DRESS-associated myocarditis in a young woman, occurring one month after drug exposure, despite intensive immunosuppressive therapy. This case report highlights the risk of mortality from DRESS-associated myocarditis even in patients lacking known risk factors.

Added value of non-contrast CT for the diagnosis of acute pyelonephritis in older patients with suspected infection with an unknown focus: a retrospective diagnostic study.

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.

Association between resilience and advance care planning during the COVID-19 pandemic in Japan: a nationwide cross-sectional study.

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.

Serological cross-reactivity between spotted fever and typhus groups of rickettsia infection in Japan.

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.

Predictive Performance of MRI for Antibiotic Treatment Failure of Pyogenic Vertebral Osteomyelitis: A Validation Study.

INTRODUCTION: Intravenous antibiotics are the primary treatment of choice for pyogenic vertebral osteomyelitis (PVO). Surgical intervention is required when the initial antibiotic treatment fails but is often difficult to perform, especially in older adults with multiple comorbidities, because of the reduced physical activity. The size of the infection signal in the spinal bone on magnetic resonance imaging (MRI) at the time of diagnosis was reported to have a high predictive accuracy for antibiotic treatment failure. However, the sample size was too small for this result to be adopted in clinical practice. Thus, we conducted a validation study of the previous research using a larger sample size. METHODS: We conducted a retrospective review of electronic medical records of patients admitted to the orthopedic department of a university hospital with a diagnosis of PVO between 2006 and 2021, and consecutively included patients without planned PVO surgery on admission and with a sagittal view of T1-weighted spinal MRI at the time of diagnosis. The index test was the percentage involvement of the affected areas in one motion segment on sagittal MRI. We also evaluated other MRI findings, such as bone destruction, segmental instability, epidural abscesses, and multiple sites for their predictive accuracy for antibiotic treatment failure. RESULTS: A total of 82 participants were eligible for the analysis. The presence of ≥90% affected area of one motion segment had a sensitivity of 16.7% and a specificity of 70.3% for future antibiotic treatment failure, resulting in poor predictive performance, with positive (LR+) and negative likelihood ratios of 0.56 and 1.19, respectively. The area under the receiver operating characteristic curve for a 10% increase in the affected area was 0.48. Among the other MRI findings, the presence of bone destruction had a significantly higher predictive accuracy (LR+ 3.11, 95% confidence interval 1.30-7.42). CONCLUSION: An infection signal ≥90% on a T1-weighted MRI of one spinal motion segment did not show sufficient predictive performance for antibiotic treatment failure. Spinal bone destruction had a mild-to-moderate predictive accuracy.

Poor Sleep Quality as a Risk Factor for Constipation Among Community-Dwelling Older Adults in Japan.

Background Older adults commonly experience both sleep disturbances and constipation. Pathophysiological mechanisms such as inhibition of colonic peristalsis due to sympathetic activation associated with sleep disturbances have been postulated. Here, we aimed to assess the temporal association between the degree of sleep quality and the incidence of constipation. Methods We conducted a prospective cohort study of independent community-dwelling older adults aged ≥75 years (the Sukagawa Study). Using a self-administered questionnaire inquiring about awareness of own constipation or the use of laxatives in 2019 and 2020, we determined the onset of constipation. The Japanese version of the Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality in 2019. The global PSQI score was divided into quartiles. We analyzed the association between the degree of sleep quality and the incidence of constipation using logistic regression models. Results Overall, 1,696 participants without constipation at baseline were analyzed after 1 year, of whom 823 (48.5%) were male. The mean age of participants was 79.9 years. In total, 191 participants (11.3%) developed constipation. The median (interquartile range; IQR) global PSQI score was 4 (2, 6). According to the quartiles of the global PSQI scores (0-2, 3-4, 5-6, and ≥7), 35 (7.8%), 55 (11.3%), 48 (12.8%), and 53 (13.8%), respectively, developed constipation. Compared to those with global PSQI scores of 0-2, the odds ratios, adjusted by age, sex, smoking status, alcohol status, educational level, working status, exercise, and medical history were 1.57, 1.78, and 2.02 for participants with global PSQI scores of 3-4, 5-6, and ≥7, respectively (p = 0.003 for trend). Conclusions We identified poor sleep quality as a new risk factor for developing constipation in independent, community-dwelling, older adults aged ≥75 years.

Antiviral medications for mild-to-moderate COVID-19 in Japan: a gap of timing between clinical trials and real-world scenarios in a fast-changing pandemic.

The rapid spread of a novel type of coronavirus infection, coronavirus disease 2019 (COVID-19) has made it difficult to implement the results of clinical trials in real-world situations. After the emergence of the Omicron variant and messenger RNA vaccine, a combination of less virulent but more contagious viruses and more people with protective immunity has resulted in a larger number of patients with less severe, mild-to-moderate COVID-19. Many patients with severe conditions did not have extensive viral pneumonia frequently seen in the "pre-Omicron" era but had serious complications due to aggravation of underlying comorbidities or secondary bacterial infections. Most clinical trials for new antiviral drugs were conducted in the "pre-Omicron" period based on a different set of background patient characteristics than the ones seen in the Omicron period. Understanding situational differences due to the gap in the timing between clinical trials and the practical use of drugs for COVID-19 will assist in developing an effective treatment strategy in real-world practice. In this seminar, we reviewed antiviral treatments for mild-to-moderate COVID-19 from the viewpoint of the difference in patient backgrounds between clinical trials and real-world studies, focusing on drugs currently used in Japan.