Nationwide epidemiology and health resource use among children with COVID-19 in Japan.

BACKGROUND: The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited. METHODS: In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use. RESULTS: Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I-V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the case-hospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%). CONCLUSIONS: Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness.

Design of artificial molecular motor inheriting directionality and scalability.

Realizing artificial molecular motors with autonomous functionality and high performance is a major challenge in biophysics. Such motors not only provide new perspectives in biotechnology but also offer a novel approach for the bottom-up elucidation of biological molecular motors. Directionality and scalability are critical factors for practical applications. However, the simultaneous realization of both remains challenging. In this study, we propose a novel design for a rotary motor that can be fabricated using a currently available technology, DNA origami, and validate its functionality through simulations with practical parameters. We demonstrate that the motor rotates unidirectionally and processively in the direction defined by structural asymmetry, which induces kinetic asymmetry in motor motion. The motor also exhibits scalability, such that increasing the number of connections between the motor and stator allows for a larger speed, run length, and stall force.

Association of the predicted free blood concentration of teicoplanin with the development of renal dysfunction.

PURPOSE: In clinical practice, teicoplanin (TEIC) is typically administered at a trough concentration of 15-40 µg/mL. TEIC has a protein binding rate of approximately 90%, and its concentration rarely exceeds 40 µg/ml. Nevertheless, an increase in the free blood trough concentration may result in renal dysfunction. However, the relationship between the free blood trough concentration and the occurrence of renal dysfunction remains unclear. This study aimed to examine the impact of the predicted free blood concentration on the development of renal dysfunction. METHODS: This retrospective study included patients who underwent TEIC and had at least one trough concentration measurement. The association between the frequency of renal dysfunction occurrence and the predicted free blood concentration was evaluated using the following equation: free TEIC concentration = total TEIC concentration/(1 + 1.78 × serum albumin level). RESULTS: Of the 170 patients included in this study, 18% (31/170) developed renal dysfunction. The predicted free trough concentration was significantly higher in the renal dysfunction onset group than in the nononset group. However, the total trough concentration was not significantly associated with the development of renal dysfunction. The odds ratio for developing renal dysfunction was 4.5 (95% confidence interval, 1.9-10.5; P < 0.001) when the predicted free trough concentration was > 4.0 µg/mL. CONCLUSION: Elevated free trough concentrations of TEIC were associated with an increased risk of renal dysfunction. Controlling the increase in the predicted free blood concentration may effectively prevent the development of renal dysfunction.

Delayed formation and rupture of intracranial aneurysm following Abiotrophia defectiva endocarditis.

Abiotrophia defectiva is a type of Streptococci and is a rare cause of infectious endocarditis. The progression and outcomes of infectious intracranial aneurysms (IIAs) associated with this species are unknown due to a limited number of reported cases. A woman in her 20s with a sudden headache had a subarachnoid haemorrhage on a head CT scan. Cerebral angiography showed an aneurysm on the right middle cerebral artery. She was diagnosed with infectious endocarditis caused by A. defectiva and underwent parent artery occlusion. Despite initiating targeted antibiotic therapy, a new IIA developed and ruptured 14 days postadmission. A second parent artery occlusion was performed on the new IIA. Following 6 weeks of continued antibiotic therapy, she underwent mitral valve repair and was discharged with no neurological symptoms. Endocarditis caused by A. defectiva can lead to the delayed formation of an IIA. Endovascular treatment was effective for repeated ruptured IIAs.

Surgical antimicrobial prophylaxis in Japanese hospitals: Real status and challenges.

BACKGROUND: Information regarding the status of surgical antimicrobial prophylaxis (SAP) in Japanese hospitals is lacking. This study aimed to explore the status of SAP prescriptions for surgeries and adherence to Japanese SAP guidelines. METHODS: From February to July 2020, a 1-day multicentre point prevalent survey was conducted at 27 hospitals in Aichi Prefecture, Japan. Patients prescribed SAP were included in this study. The appropriateness of the SAP was evaluated based on the guidelines for selection of antimicrobials and their duration. Surgery was defined as appropriate when all the items were appropriate. RESULTS: A total of 728 patients (7.1 %; 728/10,199) received antimicrobials for SAP. Among them, 557 patients (76.5 %, 557/728) underwent the surgeries described in the guidelines. The overall appropriateness of all surgeries was 33.9 % (189/557). The appropriate selection of antimicrobial before/during and after surgery and their durations were 67.5 % (376/557), 67.5 % (376/557), and 43.3 % (241/557), respectively. The overall appropriateness ranged from 0 % (0/37, oral and maxillofacial surgery) to 58.7 % (88/150, orthopaedic surgery) and 27.7 % (36/130, community hospitals with 400-599 beds) to 47.2 % (17/36, specific hospitals). Cefazolin was the most prevalent antimicrobial prescribed before/during (55.5 %, 299/539), and after (45.1 %, 249/552) surgery. In total, 101 oral antimicrobials were prescribed postoperatively. CONCLUSIONS: SAP adherence by specific surgical fields and hospitals was shown in this study. Intensive intervention and repeated surveillance are necessary to improve SAP prescriptions in Japanese hospitals.

Effects of probiotics in children with acute gastroenteritis: A systematic review and meta-analysis focusing on probiotics utilized in Japan.

BACKGROUND: Many randomized controlled trials and systematic reviews have evaluated the use of probiotics to treat acute infectious gastroenteritis. However, most probiotic species evaluated in previous large randomized controlled trials are unavailable in Japan. Our objective was to investigate the efficacy of probiotics utilized in Japan for acute gastroenteritis. METHODS: The inclusion criterion was a randomized controlled study that compared probiotics with a placebo to treat children younger than 18 years with acute infectious gastroenteritis. We excluded studies that did not contain the following species available in Japan: Bifidobacterium spp., Lactobacillus acidophilus, Enterococcus faecium, Clostridium butyricum, and Bacillus subtilis and studies in low- or lower-middle-income countries. We searched PubMed, CENTRAL, and Igaku Chuo Zasshi from their inception to November 27, 2022. After the risk of bias assessment, data on diarrhea duration, number of hospitalizations, length of hospital stay, and adverse effects were extracted. RESULTS: Fourteen studies were included in this meta-analysis. Diarrhea lasting longer than 48 h (7 articles, n = 878) was significantly lower in the probiotic group (risk ratio (RR) 0.70, 95 % confidence interval (CI) 0.59-0.83). The duration of diarrhea (14 articles; n = 1761) was 23.45 h (95 % CI 18.22-26.69) shorter in the probiotic group. Duration of hospitalization (6 articles; n = 971) was 17.73 h (95 % CI 6.9-28.56) shorter in the probiotic group. CONCLUSIONS: Although the certainty of evidence is very low, the use of probiotics for acute gastroenteritis in children may improve diarrhea approximately one day earlier. This study was registered with PROSPERO (CRD 42023405559).

Clinical Practice Patterns and Risk Factors for Severe Conditions in Pediatric Hospitalizations With Respiratory Syncytial Virus in Japan: A Nationwide Analyses (2018-2022).

BACKGROUND: Respiratory syncytial virus (RSV) represents a global health challenge, especially among younger children. While the disease burden in Japan has been preliminarily quantified, there remains a lack of comprehensive understanding regarding treatment patterns and the influence of known risk factors at a national scale. MATERIALS AND METHODS: We conducted a retrospective cohort study consisting of 50,482 children under 5 years hospitalized with RSV infections during 2018-2022 using the Medical Data Vision database. We investigated trends in patient characteristics, health resource use, treatment patterns, and laboratory data. Additionally, multivariable modified Poisson regression models were used to investigate the risk factors associated with severe conditions. RESULTS: We observed an increasing trend in the inpatient healthcare costs and decreasing trends in the use of antibiotics, bronchodilators, systemic corticosteroids and other symptomatic medications from 2018 to 2022. Risk factors associated with severe RSV infections were children less than 1 year (risk ratio, 2.90; 95% CI: 2.53-3.32) and the number of complex chronic diseases (risk ratio for 1 disease, 2.68; 95% CI: 2.34-3.06: risk ratio for 2 or more diseases, 6.91; 95% CI: 5.81-8.21). Annual inpatient healthcare costs for RSV infections were estimated at 11-14 billion Japanese Yen for younger children. CONCLUSIONS: Our study observed the changes in practice patterns and health resource use for children hospitalized with RSV infections and identified risk factors associated with severe conditions. These findings provide insights for policymakers and clinicians aiming to devise strategies for further improving clinical practices, including newly developed vaccines and single-dose long-acting monoclonal antibodies.

A randomized, double-blind, placebo-controlled pilot trial of low-intensity pulsed ultrasound therapy for refractory angina pectoris.

BACKGROUND: Despite the advances in the treatment of cardiovascular diseases, effective treatment remains to be established to improve the quality of life and prognosis of patients with chronic coronary syndromes. This study was aimed to evaluate the effectiveness and safety of the low-intensity pulsed ultrasound (LIPUS) therapy, which we have developed as a novel non-invasive angiogenic therapy through upregulation of endothelial nitric oxide synthase (eNOS). METHODS AND FINDINGS: We conducted a randomized, double-blind, placebo-controlled (RCT) pilot trial of the LIPUS therapy for patients with refractory angina pectoris. The patients who received optimal medical therapy without indication of PCI or CABG due to the lack of graftability or complexity of coronary lesions were enrolled. They were randomly divided into the LIPUS treatment group (N = 31) and the placebo group (N = 25) in a 1:1 fashion. The LIPUS therapy was performed in a transthoracic manner for 20 min for 3 sections each (mitral, papillary muscle, and apex levels) under the conditions that we identified; frequency 1.875 MHz, intensity 0.25 MPa, and 32 cycles. The primary endpoint was weekly use of nitroglycerin. Secondary endpoints included stress myocardial perfusion imaging and others. The average weekly nitroglycerin use (times/week) was decreased from 5.50 to 2.44 in the LIPUS group and from 5.94 to 2.83 in the placebo group. The changes in the average weekly nitroglycerin use were comparable; -3.06 (95% CI: -4.481 to -1.648) in the LIPUS group (P<0.01) and -3.10 (95% CI: -4.848 to -1.356) in the placebo group (P<0.01). No adverse effects were noted. CONCLUSIONS: In the present study, the LIPUS therapy did not further ameliorate chest pain as compared with optimal medications alone in patients with refractory angina pectoris. The present findings need to be confirmed in another trial with a large number of patients. (Registration ID: UMIN000012369).

A case of Robinsoniella peoriensis bacteremia during using piperacillin-tazobactam.

Infections caused by Robinsoniella peoriensis, particularly bacteremia, are rare, of which only six cases were reported R. peoriensis bloodstream infections. This case report describes an instance of R. peoriensis bacteremia arising while we treated the patient with piperacillin-tazobactam. We treated an 84-year-old female patient with peritoneal carcinoma and febrile neutropenia using piperacillin-tazobactam. The patient's fever subsided. However, she developed a fever again on the fourth day of treatment with piperacillin-tazobactam. Blood cultures taken at this time were positive for R. peoriensis. We substituted meropenem and vancomycin for piperacillin-tazobactam, after which the patient improved. We administered meropenem and vancomycin for 17 days. There is currently no appropriate established treatment for R. peoriensis. In this case, we isolated R. peoriensis from blood cultures using piperacillin-tazobactam, although it was susceptible to piperacillin-tazobactam in vitro. Therefore, monotherapy with penicillins, especially piperacillin-tazobactam, may not be sufficient for R. peoriensis infections, although it was susceptible in vitro. Carbapenem may be effective in the treatment of R. peoriensis bloodstream infections.

A case of bloodstream co-infection of Saccharomyces cerevisiae and Candida glabrata while using micafungin.

BACKGROUND: Saccharomyces cerevisiae is ubiquitous in the gastrointestinal tract and known as brewer's or baker's yeast. We experienced a case of S. cerevisiae and Candida glabrata co-infectious bloodstream infection. It is rare to detect both S. cerevisiae and Candida species in blood cultures together. CASE: We treated a 73-year-old man who developed a pancreaticoduodenal fistula infection after pancreaticoduodenectomy. The patient had a fever on postoperative day 59. We took blood cultures and detected C. glabrata. Thus, we started micafungin. On postoperative day 62, we retested blood cultures, and detected S cerevisiae and C. glabrata. We changed micafungin to liposomal amphotericin B. Blood cultures became negative on postoperative day 68. We changed liposomal amphotericin B to fosfluconazole and micafungin because of hypokalemia. He got well, and we terminated antifungal drugs 18 days after the blood cultures became negative. CONCLUSION: Co-infection with S. cerevisiae and Candida species is rare. In addition, in this case, S. cerevisiae developed from blood cultures during micafungin administration. Thus, micafungin may not be effective enough to treat S. cerevisiae fungemia, although echinocandin is considered one of the alternative therapy for Saccharomyces infections.

The first case of deep neck abscess due to Filifactor alocis co-infected with Eggerthia catenaformis, Parvimonas micra, and Streptococcusconstellatus.

Filifactor alocis, an anaerobic Gram-positive rod, has garnered interest from its association with periodontal disease. Extraoral infections by F. alocis are rare; only seven cases have been reported. We report the first case in which we identified F. alocis as one of the causative organisms of a deep neck abscess. A 71-year-old male on hemodialysis came to our hospital with a fever and left buccal pain. The patient's left neck was swollen, and contrast-enhanced computed tomography showed an abscess with gas extending from the left cheek to the deep neck. We diagnosed the patient with a deep neck abscess and performed an urgent neck drainage. We isolated F. alocis, Eggerthia catenaformis, Parvimonas micra, and Streptococcus constellatus in the abscess and identified them using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Blood cultures were negative. We initiated treatment with piperacillin-tazobactam and vancomycin. The patient improved but developed a hemorrhagic duodenal ulcer on the third day of admission. We attempted endoscopic hemostasis, but the patient's bleeding continued. Ultimately, he died of the duodenal ulcer hemorrhage on the sixth day of admission. This is the first case of F. alocis detected in a deep neck abscess.

The Incidence of Serious/Invasive Bacterial Diseases in Infants 90 Days Old or Younger at an Emergency Hospital in Japan.

Background The incidence of severe bacterial infections (SBIs) in infants aged ≤90 days is thought to have decreased because of widespread vaccination programs. However, relevant epidemiological data in Japan are scarce. Materials and methods This observational, single-center study investigated the epidemiology of fever in infants aged ≤90 days. SBI was defined as the presence of meningitis, urinary tract infections (UTIs), or bacteremia. Invasive bacterial infection (IBI) was defined as the presence of meningitis, bacteremic UTI, or bacteremia. We determined the incidence of UTIs, bacteremia, meningitis, SBIs, and IBIs in the following three age groups: 0-28, 29-60, and 61-90 days. We subsequently calculated the relative incidence for the groups aged 29-60 and 61-90 days, using the group aged 0-28 days as the reference group.  Results Herein, 58, 124, and 166 infants were included in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. Of the total number of patients, 15.5%, 8.9%, and 16.9% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with SBI. The relative incidences were 1 for the 0-28 days group (reference group), 0.67 for the 29-60 days group (95% confidence interval [CI], 0.39-1.15), and 1.08 for the 61-90 days group (95% CI, 0.58-2.00). Of the total number of patients, 10.3%, 3.2%, and 0.6% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with IBI. Relative incidences were 1 (reference group), 0.50 (95% CI, 0.29-0.88), and 0.28 (95% CI, 0.19-0.41) for the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. All cases of IBI were caused by Group B streptococcus (GBS), except for two cases of bacteremia, which were caused by Haemophilus influenzae.  Conclusion The incidence of SBI was similar in the 0-28 days and 61-90 days age groups. However, the incidence of IBI decreased with increasing age. The incidence of UTIs was highest in the 61-90 days age group, and that of meningitis and bacteremia decreased with increasing age.

Beneficial Effects of Low-Intensity Pulsed Ultrasound Therapy on Right Ventricular Dysfunction in Animal Models.

Right ventricular failure (RVF) is a leading cause of death in patients with pulmonary hypertension; however, effective treatment remains to be developed. We have developed low-intensity pulsed ultrasound therapy for cardiovascular diseases. In this study, we demonstrated that the expression of endothelial nitric oxide synthase (eNOS) in RVF patients was downregulated and that eNOS expression and its downstream pathway were ameliorated through eNOS activation in 2 animal models of RVF. These results indicate that eNOS is an important therapeutic target of RVF, for which low-intensity pulsed ultrasound therapy is a promising therapy for patients with RVF.

Risk Factors for Septic Shock After Irinotecan-Containing Chemotherapy: An Exploratory Case-Control Study.

BACKGROUND AND OBJECTIVES: Irinotecan sometimes causes lethal septic shock but the risk factors remain unclear. This retrospective case-control study explored the potential risk factors for septic shock following irinotecan treatment. METHODS: All women who received irinotecan-containing chemotherapy for gynecologic malignancies at Shizuoka General Hospital from October 2014 to September 2020 were investigated. The clinical backgrounds and blood test results of those who developed septic shock after irinotecan-containing chemotherapy were compared with those who did not. Odds ratios (ORs) for developing septic shock after receiving irinotecan were calculated with 95% confidence intervals (CIs), using univariable logistic regression analysis. RESULTS: During the study period, 147 women received irinotecan-containing chemotherapy. Three women developed septic shock due to neutropenic enterocolitis after irinotecan treatment, and 144 did not. The three patients with septic shock had recurrent cervical cancer, heterozygous variants in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene (two patients had *1/*6, one had *1/*28 variants), a history of concurrent chemoradiation therapy, 50-60 Gy of pelvic irradiation, and platinum-combined chemotherapy. A history of pelvic irradiation was identified as a possible risk factor for developing septic shock after irinotecan-containing chemotherapy (OR 63.0, 95% CI 5.71-8635; p < 0.001). The OR of UGT1A1 polymorphism for septic shock was 9.09 (95% CI 0.86-1233; p = 0.070) in the complete case analysis. CONCLUSION: Medical personnel involved in cancer therapy should consider the possible risk of septic shock developing due to neutropenic enterocolitis when administering irinotecan-containing chemotherapy in patients with a history of pelvic irradiation.

Infectious Aneurysms Caused by Streptococcus Pyogenes in Children.

We describe the detailed clinical course of rapidly enlarging infective aneurysms during the treatment of endocarditis and purulent pericarditis caused by Streptococcus pyogenes . We show that S. pyogenes aneurysms can enlarge rapidly within 1-2 days. Moreover, we highlight the benefit of transporting patients to a facility offering multidisciplinary treatment, even if vital signs stabilize to the point.

A case of recurrent acute cholecystitis caused by Actinomyces odontolyticus, rare actinomycosis.

BACKGROUNDS: Actinomyces species are gram-positive, obligate anaerobic rods and are rare causes of cholecystitis. Because Actinomyces species are anaerobic bacteria, it is difficult for Actinomyces to survive in bile apart from A. naeslundii. We experienced a case of recurrent acute cholecystitis caused by A. odontolyticus. CASE PRESENTATION: A patient had been diagnosed with acute cholecystitis and treated one month before and after that, admitted to our hospital because of recurrent cholecystitis. Gram stain of the bile revealed gram-positive rods and gram-positive cocci. We found A. odontolyticus and MRSA in bile culture and MRSA in blood culture. We administered piperacillin-tazobactam and then changed it to ampicillin-sulbactam and vancomycin. The patient underwent laparoscopic cholecystectomy and was discharged safely. CONCLUSIONS: To our knowledge, this is the first case of cholecystitis caused by A. odontolyticus. Cholecystitis caused by Actinomyces species is rare. In addition, we may overlook it with the low positivity of bile cultures of Actinomyces. Whenever the cholecystitis recurs without any obstruction of the biliary tract, we should search for the gram-positive rods hidden in the bile, such as A. odontolyticus, as the causative organism, even if the bile culture is negative.

Shared genetic components between metabolic syndrome and schizophrenia: Genetic correlation using multipopulation data sets.

AIM: The genetic relationship between schizophrenia (SCZ) and other nonpsychiatric disorders remains largely unknown. We examined the shared genetic components between these disorders based on multipopulation data sets. METHODS: We used two data sets for East Asian (EAS) and European (EUR) samples. SCZ data was based on the Psychiatric Genomics Consortium Asia with our own genome-wide association study for EAS and Psychiatric Genomics Consortium for EUR. Nonpsychiatric data (20 binary traits [mainly nonpsychiatric complex disorders] and 34 quantitative traits [mainly laboratory examinations and physical characteristics]) were obtained from Biobank Japan and UK Biobank for EAS and EUR samples, respectively. To evaluate genetic correlation, linkage disequilibrium score regression analysis was utilized with further meta-analysis for each result from EAS and EUR samples to obtain robust evidence. Subsequent mendelian randomization analysis was also included to examine the causal effect. RESULTS: A significant genetic correlation between SCZ and several metabolic syndrome (MetS) traits was detected in the combined samples (meta-analysis between EAS and EUR data) (body mass index [rg  = -0.10, q-value = 1.0 × 10-9 ], high-density-lipoprotein cholesterol [rg  = 0.072, q-value = 2.9 × 10-3 ], blood sugar [rg  = -0.068, q-value = 1.4 × 10-2 ], triglycerides [rg  = -0.052, q-value = 2.4 × 10-2 ], systolic blood pressure [rg  = -0.054, q-value = 3.5 × 10-2 ], and C-reactive protein [rg  = -0.076, q-value = 7.8 × 10-5 ]. However, no causal relationship on SCZ susceptibility was detected for these traits based on the mendelian randomization analysis. CONCLUSION: Our results indicate shared genetic components between SCZ and MetS traits and C-reactive protein. Specifically, we found it interesting that the correlation between MetS traits and SCZ was the opposite of that expected from clinical studies: this genetic study suggests that SCZ susceptibility was associated with reduced MetS. This implied that MetS in patients with SCZ was not associated with genetic components but with environmental factors, including antipsychotics, lifestyle changes, poor diet, lack of exercise, and living conditions.