Associations of COVID-19 symptoms with omicron subvariants BA.2 and BA.5, host status, and clinical outcomes in Japan: a registry-based observational study.

BACKGROUND: Previous SARS-CoV-2 infection and vaccination, coupled with the rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We aimed to characterise the clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. METHODS: In this registry-based observational study, individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Eligibility criteria included symptomatic individuals who tested positive for SARS-CoV-2 (PCR or antigen test), and individuals who were not tested for SARS-CoV-2 but developed new symptoms after a household member tested positive for SARS-CoV-2. Symptom prevalence, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. FINDINGS: Data were collected and analysed between April 25 and Sept 25, 2022. For 157 861 omicron-infected symptomatic individuals, cough was the most common symptom (99 032 [62·7%] patients), followed by sore throat (95 838 [60·7%] patients), nasal discharge (69 968 [44·3%] patients), and fever (61 218 [38·8%] patients). Omicron BA.5 infection was associated with a higher prevalence of systemic symptoms than BA.2 in vaccinated and unvaccinated individuals (adjusted odds ratio [OR] for fever: 2·18 [95% CI 2·12-2·25]). Omicron breakthrough-infected individuals with three or more vaccinations or previous infection were less likely to exhibit systemic symptoms (fever 0·50 [0·49-0·51]), but more likely to exhibit upper respiratory symptoms (sore throat 1·33 [1·29-1·36]; nasal discharge 1·84 [1·80-1·89]). Infected older individuals (≥65 years) had lower odds for all symptoms. However, when symptoms were manifest, systemic symptoms were associated with increased odds for severe disease (dyspnoea 3·01 [1·84-4·91]; fever 2·93 [1·89-4·52]), whereas upper respiratory symptoms were associated with decreased odds (sore throat 0·38 [0·24-0·63]; nasal discharge 0·48 [0·28-0·81]). INTERPRETATION: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a higher systemic symptom prevalence than BA.2. Vaccination and previous infection reduced systemic symptom prevalence and improved outcomes but increased upper respiratory tract symptom prevalence. Systemic, but not upper respiratory, symptoms in older people heralded severe disease. Our findings could serve as a practical guide to use COVID-19 symptoms to appropriately modify health-care strategies and predict clinical outcomes for older patients with omicron infections. FUNDING: Japan Agency for Medical Research and Development.

Associations of COVID-19 Symptoms with Omicron Subvariants BA.2 and BA.5, Host Status, and Clinical Outcomes: A Registry-Based Observational Study in Sapporo, Japan.

Background: Previous SARS-CoV-2 infection and vaccination, coupled to rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We characterized clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. Methods: Individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Symptom frequencies, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. Results: For all omicron-infected individuals, cough was the most common symptom (62.7%), followed by sore throat (60.7%), nasal discharge (44.3%), and fever (38.8%). Omicron BA.5 infection was associated with a higher symptom burden than BA.2 in vaccinated and unvaccinated individuals. Omicron breakthrough-infected individuals with ≥ 3 vaccinations or previous infection were less likely to exhibit systemic symptoms, but more likely to exhibit upper respiratory symptoms. Infected elderly individuals had lower odds for all symptoms, but, when symptoms were manifest, systemic symptoms were associated with an increased risk, whereas upper respiratory symptoms with a decreased risk, of severe disease. Conclusion: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a greater symptom burden than BA.2. Vaccination and prior infection mitigated systemic symptoms and improved outcomes, but increased upper respiratory tract symptom burden. Systemic, but not upper respiratory, symptoms in the elderly heralded severe disease.

Listeria monocytogenes bacteremia mimicking the systemic metastasis of adrenal cancer: a case report.

BACKGROUND: Listeria monocytogenes is a causative agent of food poisoning and is also known to cause invasive diseases, such as bacteremia, meningitis, and encephalitis, in neonates, elderly and immunocompromised patients. However, the clinical course of a multi-organ disseminated disease secondary to bacteremia has been rarely reported. CASE PRESENTATION: A 76-year-old woman undergoing immunosuppressive therapy for rheumatoid arthritis presented to our outpatient clinic with a chief complaint of weight loss. Computed tomography showed a left adrenal mass, enlarged lymph nodes, and multiple intrahepatic nodules. Positron emission tomography demonstrated accumulation of fluorodeoxyglucose F18 in the adrenal mass, lymph nodes, hepatic nodules, and bones, leading to the suspicion of systemic metastasis of adrenal cancer. She subsequently developed a fever. Blood culture results led to the diagnosis of Listeria monocytogenes bacteremia. Percutaneous needle biopsy of the adrenal lesion revealed no malignant findings. After extended treatment with antimicrobial agents, the fever resolved, along with the disappearance of the systemic lesions. CONCLUSIONS: This case shows that listeriosis can lead to lesions in the adrenal gland, which can exhibit clinical presentation that is difficult to differentiate from malignancy on imaging studies.

Accelerating reductions in antimicrobial resistance: Evaluating the effectiveness of an intervention program implemented by an infectious disease consultant.

OBJECTIVES: Very few infectious disease physicians exist in Japan. A concerted infection control intervention program involving an antimicrobial stewardship team and multiple components was designed and implemented in multiple hospitals from 2010. Here, we aimed to retrospectively evaluate the intervention program's effectiveness. METHODS: The frequencies of methicillin resistant Staphylococcus aureus (MRSA) and drug-resistant Pseudomonas aeruginosa were monitored in four acute-care hospitals. The primary goal of the program was to accelerate the speed of decline of such resistance. A quasi-experimental study design was used to detect accelerated rates of increases in drug susceptibility, comparing time before and after the intervention. RESULTS: Both MRSA and drug-resistant P. aeruginosa exhibited decreasing trends (p < 0.01 for all four hospitals and all bacterial cultures). Compared with the whole of Japan, the decreasing trends for MRSA and drug-resistant P. aeruginosa in the four hospitals accelerated after the intervention program was established; notably, the rate of MRSA decrease increased by 50%-150% of its original value. CONCLUSIONS: The intervention program successfully reduced the proportion of drug resistance in the four hospitals. Centering on systematic education, decision-making support, and implementation and oversight by an infectious disease consultant, this program was shown to be effective where specialist physicians are scarce.

Demographic supply-demand imbalance in industrial structure in the super-aged nation Japan.

BACKGROUND: Japan has a rapidly decreasing population, with ultra-low fertility and extremely fast aging. The rapid dynamics constitute a warning that change in the industrial structure may be unable to meet the changing pace of age-dependent demand. METHODS: The present study estimated the supply-demand imbalance by industrial sector, and we investigated the effectiveness of possible countermeasures. To quantify the demographic burden of different industry experts, we employed the dependency ratio to calculate the supply and demand of each industrial sector and occupation. RESULTS: We identified an expected excess of demand in the health-care sector; the growth in that deficiency is likely to continue until 2045, when the elderly population is likely to reach a peak. By contrast, oversupply is expected in the education and construction sectors. An overall shortage of full-time workers is likely to continue until 2050, when we predict that Japan will lack 3.1-9.3 million full-time workers to satisfy the baseline demand level. CONCLUSIONS: Considering that the imbalance is evident over different sectors, interministerial regulation of occupational choice may need to be imposed, e.g., by drastically changing student sizes in different area of higher education. Japan may have to decide to downgrade its social services and potentially consider increasing immigrant workers.

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.

Functional pancreatic acinar cell carcinoma extending into the main pancreatic duct and splenic vein.

INTRODUCTION: Pancreatic acinar cell carcinoma (ACC) has several unique characteristics, such as its progression pattern, spreading into the pancreatic duct and large blood vessels, and its secretion of pancreatic exocrine enzymes, which induces a paraneoplastic syndrome. CASE REPORT: A 79-year-old Japanese man, with medical history of chronic renal failure, was referred to our institution for the examination of his abdominal pain and hyperglycemia. Plain computed tomography demonstrated a mass lesion, 4 cm in diameter, in the body of pancreas. Abdominal ultrasonogram demonstrated a bulky, hypoechoic mass extending into the splenic vein. Multiple hepatic nodules were detected on suspicion of metastasis. Positron emission tomography using 18F-fluorodeoxyglucoase revealed the tumor extended towards the pancreatic head through the main pancreatic duct. We obtained the tumor tissues from the pancreatic body using endoscopic ultrasound-guided fine-needle aspiration biopsy. Pathological diagnosis, supported by immunohistochemistry, was that of an ACC. In the follow-up period, he complained of subcutaneous nodules and arthralgia on his lower legs. Serum and intra-articular lipase levels were elevated, 6,420 I/U and 594 I/U, respectively. Histology of the skin lesion at the knee joint showed necrotizing panniculitis with eosinophilic infiltration. The patient was treated with weekly gemcitabine, but succumbed to acute respiratory distress unexpectedly 2 months after the initial diagnosis.

Serological and pathogenic characterization of Erysipelothrix rhusiopathiae isolates from two human cases of endocarditis in Japan.

We characterized the serological and pathogenic properties of two Erysipelothrix rhusiopathiae isolates from human cases of infective endocarditis in Japan. One isolate was recovered from a fisherman, and was identified as serovar 3, which is known to be prevalent among fish isolates. This strain exhibited high virulence in mice but was avirulent in swine. Another was untypable, and avirulent in both mice and swine. Our results suggest that various serological and athogenical types of E. rhusiopathiae can induce human endocarditis. This is the first report to characterize the pathogenicity of E. rhusiopathiae isolates from human endocarditis.

Cognitive error as the most frequent contributory factor in cases of medical injury: a study on verdict's judgment among closed claims in Japan.

BACKGROUND: Cognitive errors in the course of clinical decision-making are prevalent in many cases of medical injury. We used information on verdict's judgment from closed claims files to determine the important cognitive factors associated with cases of medical injury. METHODS: Data were collected from claims closed between 2001 to 2005 at district courts in Tokyo and Osaka, Japan. In each case, we recorded all the contributory cognitive, systemic, and patient-related factors judged in the verdicts to be causally related to the medical injury. We also analyzed the association between cognitive factors and cases involving paid compensation using a multivariable logistic regression model. RESULTS: Among 274 cases (mean age 49 years old; 45% women), there were 122 (45%) deaths and 67 (24%) major injuries (incomplete recovery within a year). In 103 cases (38%), the verdicts ordered hospitals to pay compensation (median; 8,000,000 Japanese Yen). An error in judgment (199/274, 73%) and failure of vigilance (177/274, 65%) were the most prevalent causative cognitive factors, and error in judgment was also significantly associated with paid compensation (odds ratio, 1.9; 95% confidence interval [CI], 1.0-3.4). Systemic causative factors including poor teamwork (11/274, 4%) and technology failure (5/274, 2%) were less common. CONCLUSIONS: The closed claims analysis based on verdict's judgment showed that cognitive errors were common in cases of medical injury, with an error in judgment being most prevalent and closely associated with compensation payment. Reduction of this type of error is required to produce safer healthcare.

[Two cases of bacteremic pneumonia caused by Pseudomonas aeruginosa in solid-organ cancer patients].

Pseudomonas aeruginosa, the leading nosocomial pneumonia pathogen in immunocompromised patients, has Recently become typically presented as slowly progressive ventilator-associated pneumonia. We report two cases of bacteremic pneumonia due to Pseudomonas aeruginosa in non-neutropenic solid-organ cancer. Both subjects had sudden sepsis or septic shock but few respiratory symptoms. Chest radiography showed a diffuse unilateral decrease in permeability, becoming necrotizing pneumonia and lung abscess in 7-10 days. Conventional literature describe fulminant pseudomonas bacteremic pneumonia in non-neutropenic immunocompromised hosts as the initial presentation with septic shock and interstitial lung opacity, leading lung abscess.

[Non disseminated pulmonary cryptococcosis with very marked eosinophilia in solid-organ cancer].

Cryptococcal lung disease is usually diagnosed by chest X-ray abnormalities. Although no treatment exists for asymptomatically immunocompetent patients, a case with central nervous system (CNS) involvement as cryptococcus dissemination had a new chest X-ray abnormality during marked eosinophilia diagnosed as pulmonary cryptococcosis by lung biopsy. Eosinophilia may thus be associated with pulmonary cryptococcosis. We had seen reports of disseminated cryptococcosis with eosinophilia, so we conducted lumbar puncture and blood culture, but found no disseminated lesion or CNS involvement. Eosinophilia association with disseminated cryptococcosis has been reported, but not pulmonary cryptococcosis with solitary localized lung lesion with marked eosinophilia, making our case the first, in so far as we know reported of pulmonary cryptococcosis with a solitary localized lung lesion with marked eosinophilia.