Transmission of COVID-19 in Nightlife, Household, and Health Care Settings in Tokyo, Japan, in 2020.

Importance: There have been few studies on the heterogeneous interconnection of COVID-19 outbreaks occurring in different social settings using robust, surveillance epidemiological data. Objectives: To describe the characteristics of COVID-19 transmission within different social settings and to evaluate settings associated with onward transmission to other settings. Design, Setting, and Participants: This is a case series study of laboratory-confirmed COVID-19 cases in Tokyo between January 23 and December 5, 2020, when vaccination was not yet implemented. Using epidemiological investigation data collected by public health centers, epidemiological links were identified and classified into 7 transmission settings: imported, nightlife, dining, workplace, household, health care, and other. Main Outcomes and Measures: The number of cases per setting and the likelihood of generating onward transmissions were compared between different transmission settings. Results: Of the 44 054 confirmed COVID-19 cases in this study, 25 241 (57.3%) were among male patients, and the median (IQR) age of patients was 36 (26-52) years. Transmission settings were identified in 13 122 cases, including 6768 household, 2733 health care, and 1174 nightlife cases. More than 6600 transmission settings were detected, and nightlife (72 of 380 [18.9%]; P < .001) and health care (119 [36.2%]; P < .001) settings were more likely to involve 5 or more cases than dining, workplace, household, and other settings. Nightlife cases appeared in the earlier phase of the epidemic, while household and health care cases appeared later. After adjustment for transmission setting, sex, age group, presence of symptoms, and wave, household and health care cases were less likely to generate onward transmission compared with nightlife cases (household: adjusted odds ratio, 0.03; 95% CI, 0.02-0.05; health care: adjusted odds ratio, 0.57; 95% CI, 0.41-0.79). Household settings were associated with intergenerational transmission, while nonhousehold settings mainly comprised transmission between the same age group. Among 30 932 cases without identified transmission settings, cases with a history of visiting nightlife establishments were more likely to generate onward transmission to nonhousehold settings (adjusted odds ratio, 5.30 [95% CI, 4.64-6.05]; P < .001) than those without such history. Conclusions and Relevance: In this case series study, COVID-19 cases identified in nightlife settings were associated with a higher likelihood of spreading COVID-19 than household and health care cases. Surveillance and interventions targeting nightlife settings should be prioritized to disrupt COVID-19 transmission, especially in the early stage of an epidemic.

Bowel frequency (night) and urgent defecation are improved by budesonide foam in patients with ulcerative colitis: a retrospective observational study.

INTRODUCTION: Patients with ulcerative colitis (UC) are known to have a significantly poor quality of life due to bowel frequency (night) and urgent defecation. Budesonide foam is a topical medication that was approved in Japan in 2017 for the treatment of UC. However, its efficacy in the treatment of bowel frequency (night) or urgent defecation is unknown. This study aimed to explore the efficacy of budesonide foam for the alleviation of these symptoms. METHODS: UC patients who received budesonide foam between December 2017 and January 2020 at the Jikei University School of Medicine in Tokyo were enrolled. The simple clinical colitis activity index (SCCAI) was evaluated at the start of budesonide foam treatment and 2 and 6 weeks later in patients who initially scored ≥ 1 for bowel frequency (night) and urgent defecation, respectively. We also studied the effect of budesonide foam on remaining symptoms in patients who had used 5-aminosalicylic acid (5-ASA) topical treatment, those with SCCAI ≥ 3, and those in remission with residual symptoms (SCCAI 1 or 2). RESULTS: Of the 233 enrolled patients, 102 were eligible for the study. In 36 patients with bowel frequency (night) treated with budesonide foam were significantly effective, score in SCCAI decreased from 1.17 ± 0.45 at baseline to 0.53 ± 0.61 at week 2 (p < 0.0001) and 0.17 ± 0.38 at week 6 (p < 0.0001). In 45 patients with urgent defecation score in SCCAI decreased significantly from 1.33 ± 0.52 at baseline to 0.44 ± 0.59 at week 2 (p < 0.0001) and 0.22 ± 0.40 at week 6 (p < 0.0001). Of 22 patients who switched from topical 5-ASA administration to budesonide foam, nine at week 2 (41%) and 11 (50%) at week 6 were improved with no symptoms, and there were no cases of worsened symptoms. No severe side effects associated with budesonide foam were observed. CONCLUSION: Budesonide foam administration significantly improves both bowel frequency (night) and urgent defecation-related UC activity and is also effective for the patients who were refractory to topical 5-ASA administration.

Characteristics and Endoscopic Classification of Ulcerative Lesions Affecting the Ileocecal Valve.

OBJECTIVES: The aim of this study was to propose an endoscopic classification system for ulcerative lesions on the ileocecal valve and investigate its relevance to the underlying etiology. METHODS: Among the 60,325 patients who underwent colonoscopy at our hospital from January 2006 to December 2018, patients with ulcerative lesions on the ileocecal valve were included. The following data were obtained using the hospital's medical records: sex, age, clinical diagnosis, laboratory data, and endoscopic and histological findings. Patients who have ulcerative colitis and who were not evaluated by histological examination were excluded. Ulcerative lesions on the ileocecal valve were classified into 3 groups according to their endoscopic appearance: small shallow ulcerative lesions without edematous change (group A), lateral spreading shallow ulcerative lesions with edematous change (group B), and deep deformed ulcerative lesions (group C). The association between this endoscopic classification and its clinical diagnosis, clinical course, and the interobserver reliability were evaluated. RESULTS: Of 72 patients who were eligible for analysis, 18 were assigned to group A, 9 to group B, and 45 to group C. Infectious enteritis was mainly assigned to group A (group A, 12; group B, none; and group C, 6; p < 0.0001), inflammatory bowel disease was mainly assigned to group C (group A, none; group B, 5; and group C, 35; p < 0.0001), and malignant tumor was assigned to group C only. Interobserver reliability was extremely high among the 3 examining doctors (kappa value 0.7-0.8). CONCLUSION: Endoscopic classification was divided into 3 groups for ulcerative lesions on the ileocecal valve, and this system could be beneficial for presuming their clinical diagnoses.

An Analysis of Medication Adherence and Patient Preference in Long-term Stable Maintenance Hemodialysis Patients in Japan.

Objective This follow-up survey report describes medication adherence and patient preferences, beliefs, and expectations of maintenance hemodialysis treatment in Japan. Methods This patient-reported questionnaire-based survey was conducted in six regions in Japan from September 2016 to November 2016. Patients The questionnaire was provided to 700 patients (50-79 years old) on maintenance hemodialysis for >3 years who were members of the Japan Association of Kidney Disease Patients. Patients were randomly selected by a stratified sampling method based on patient distribution observed from the Japanese Society for Dialysis Therapy Renal Data Registry. Results A total of 524 (74.9%) complete patient questionnaires were evaluated; the mean (SD) age was 66.6 (7.2) years (men, 63.4%) with a dialysis vintage of 16.9 (9.1) years. Adherence was high for all types of medications: between 76.7% for phosphate binders and 95.7% for antidiabetic medications. The most common reason for a missed dose was forgetting to take medication [52.5% (117/223)]. Patient preference for oral medication was as low as 0.9% (1/110), 9% (31/345), and 2.9% (2/69) for patients who felt mental burden, felt no mental burden, and neither, respectively, with their current treatment regimen. In addition, 37.8% (198/524) of patients responded that the elimination of 1 medication (1 tablet) would reduce their mental burden. Conclusion The results of this survey show that overall medication adherence is high in Japanese patients on maintenance hemodialysis. While many patients perceive an absence of mental burden, they still prefer to avoid oral medication when possible.

A Survey of Drug Burden in Patients Undergoing Maintenance Hemodialysis in Japan.

Objective This report presents a part of a survey pertaining to drug burden in maintenance hemodialysis patients in Japan. Methods A patient-reported questionnaire-based survey was conducted from September to November 2016 in six regions in Japan. Patients A total of 700 patients (50-79 years old) on maintenance hemodialysis for >3 years and members of the Japan Association of Kidney Disease Patients (JAKDP) were provided with the questionnaire. They were randomly selected using stratified sampling according to patient distribution observed from the Japanese Society for Dialysis Therapy Renal Data Registry (JSDT JRDR). Results A total of 524 (74.9%) patient questionnaires were evaluated [mean (standard deviation; SD) age, 66.6 (7.2) years; males, 63.4%; dialysis vintage, 16.9 (9.1) years]. Patients' age, gender, and regional distribution were similar to the JSDT JRDR. They were taking an average (SD) of 16.4 (8.34) and 16.3 (8.55) oral medications/day on dialysis and nondialysis days, respectively. A majority of the patients were taking ≥10 oral medications/day on dialysis (75.1%) and nondialysis (74.4%) days, with phosphate binders being the most taken (7.0 tablets/day). A similar proportion (74.4%, 72.9%, respectively) was taking ≥6 different types of oral medications/day. Most patients were taking oral medications 3 (31%, 33%), 4 (24%, 22%), and ≥5 times (31%, 30%) a day, respectively. The drug burden was similar on dialysis and nondialysis days and did not vary with dialysis vintage. Conclusion The number, type, and frequency of oral medications in maintenance hemodialysis patients are high in Japan. The proportion of phosphate binders was highest among the prescription medications.

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression.

BACKGROUND: Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). METHODS: 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. RESULTS: Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. CONCLUSION: Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events.

FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells.

BACKGROUND: FGF23 plays an important role in calcium-phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium-phosphorus metabolism. METHODS: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. RESULTS: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. CONCLUSION: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells.

Severe refractory infection due to renocolic fistula in a patient with a giant kidney and ADPKD undergoing long-term hemodialysis.

Renocolic fistula is rare. Renal cyst infection is a serious complication in patients with autosomal dominant polycystic kidney disease (ADPKD). We present a case of refractory renal cyst infection due to renocolic fistula in a patient with ADPKD. A 65-year-old man with ADPKD on hemodialysis visited our hospital with complaints of fever and left abdominal pain. We diagnosed renal cyst infection with abdominal computed tomography scans. After hospitalization, gas shadow was observed in the left renal cyst. Percutaneous puncture of the cyst was performed. Because contrast medium into the left renal cyst through nephrostomy was flowing into the descending colon, renocolic fistula was diagnosed. The patient underwent nephrectomy combined with partial descending colonic resection and splenectomy, but he died. Renocolic fistula is probably hidden in some refractory renal cyst infection cases. This case report aims to create awareness of renocolic fistula, so that early diagnosis and intervention can salvage such patients.

Preventive Strategies for Vascular Calcification in Patients with Chronic Kidney Disease.

BACKGROUND: Vascular calcification is significant because of the close association between the degree of vascular calcification and cardiovascular mortality in chronic kidney disease (CKD) patients. SUMMARY: There are 2 types of vascular calcification in CKD patients. One is endothelial vascular calcification, a common type of vascular calcification. Another is medial vascular calcification, a specific type that is common in CKD patients. The former is mainly associated with atherosclerosis due to hyperlipidemia, especially hypercholesterolemia. The latter CKD-specific type is called Moenckeberg's arteriosclerosis. A known risk factor for this type of vascular calcification is hyperphosphatemia. In this review article, we mainly discuss a preventive strategy for Moenckeberg type vascular calcification in CKD, primarily involving the treatment of hyperphosphatemia. Several possible modalities are considered. However, at present, dietary restriction of phosphate is not recommended so as to avoid malnutrition in CKD patients. The first consideration is the enhancement of phosphate removal by renal replacement therapy in dialysis patients. Various phosphate binder therapies can be beneficial and effective. Surgical and pharmacological parathyroidectomies are also useful for treating secondary hyperparathyroidism. Good quality bone provides a good pool of calcium and phosphate. Thus, bone protection is another option for preventing vascular calcification. Several therapeutic agents have been developed to manage osteoporosis. These trial agents may be reasonably effective in impeding the progression of vascular calcification in CKD patients. Key Messages: We should make full use of several modalities so as to completely prevent vascular calcification.

Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor.

AIM: Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD-mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD-mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. METHODS: Aortic segments from 7-week-old male Sprague-Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. RESULTS: Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p＜0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. CONCLUSION: These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor.

[Treatment for CKD-MBD(Chronic Kidney Disease-Mineral and Bone Disorder)].

CKD is a common disease that is estimated to develop one in eight persons in Japan. The CKD itself is highly risk factor on the cardiac/vascular mortality. In addition,a new concept has been proposed "CKD-MBD". CKD-MBD is composed of a combination of abnormal mineral metabolism, abnormal bone, and extra skeletal calcification with cardiovascular high mortality. Treatment for CKD-MBD is a wide-ranging. We aim to decline cardiovascular event, fracture, and mortality rate of patients with CKD. The main therapeutic target for CKD-MBD becomes the phosphate control. Today, we can use of the VRDA, Calcimimetics and muti-phosphate binders as a lot of pharmacological intervention.

[An autochthonous outbreak of dengue type 1 in Tokyo, Japan 2014].

OBJECTIVES: An outbreak of autochthonous dengue fever was reported in August 2014, with cases suspected mainly from Yoyogi Park in Tokyo. This is the first epidemic of dengue fever in Japan since 1945. METHODS: From August to October 2014, the following measures were taken to control the outbreak: 1) risk communication and information sharing; 2) active case finding; 3) vector surveillance in affected sites; and 4) laboratory testing. We also reviewed the surveillance data as reported to the National Epidemiological Surveillance of Infectious Diseases during the 44 epidemiological weeks. results: An official dengue fever call center was set up temporarily for the general public and 3,005 calls were received. The Tokyo Metropolitan Government issued 39 press releases regarding patients and nine related to dengue virus (DENV) detection and vector control activities for the media. Confirmed autochthonous dengue fever cases were reported between the 35th and 44th epidemiological weeks. Out of 160 cases of outbreak, 108 (67.5%) confirmed cases were reported in Tokyo. The estimated illness onset dates were between August 9 and October 7, and estimated dates of infections were between August 3 and October 3, 2014. The data suggest that the infective mosquitoes had already been present in Yoyogi Park at the end of July 2014. During the weekly vector surveillance at Yoyogi Park, a total of 1,152 adult mosquitoes, of which 856 (73.3%) were Aedes mosquitoes, were collected over 11 weeks by a light trap with dry ice. DENV was detected from adult Aedes mosquito samples collected on the 2nd, 9th, and 16th of September, 2014. Serum samples from 240 suspected cases were examined at the Tokyo Metropolitan Institute of Public Health, and 78 were positive for the DENV NS1 antigen, DENV-specific IgM antibody, or DENV nucleic acid with reverse transcriptase polymerase chain reaction (RT-PCR) (NS1: 66 cases; IgM: 50 cases; PCR: 57 cases). Genetic analysis of DENV-positive serum and mosquito samples found all to be categorized as DENV-serotype 1 (gene type I). Phylogenetic analysis of the envelope protein genome sequence from patients and mosquitoes in Tokyo revealed more than 99% similarity with each other and with the strain from the first outbreak-associated patient in Saitama. CONCLUSION: Measures important for control of infectious disease epidemic were learned during this recent indigenous dengue outbreak in Tokyo. It also highlighted the importance of preparedness for epidemics of indigenous or imported infectious diseases, especially in light of the fact that Tokyo is in preparation for the Olympic and Paralympic Games in 2020.

[Factors associated with willingness to undergo vaccination against haemophilus influenzae type B (Hib)].

OBJECTIVES: The purpose of this study was to examine factors that affect the willingness to undergo Hib vaccination and to pay (WTP) for it. METHODS: The subjects of the survey were 1,185 parents with infants attending nursery schools in Machida city, Tokyo. A total of 46.3% returned the completed questionnaire, which covered information about Hib willingness to undergo vaccination, their WTP for it, and components of the health belief model (HBM). RESULT: Approximately half (50.3%) of the respondents were willing to have vaccination. The mean WTP was 2581 JPY, and approximately 80% of those who stated their WTP were willing to pay 3000 JPY or less. Perceived susceptibility, severity, and benefits were positively correlated with the willingness to have vaccination and the WTP, while perceived economic barriers were negatively correlated. Also, WTP was positively correlated with income. CONCLUSION: In order to promote the Hib vaccination program, it is necessary to provide information based on the HBM, especially information that affects the perception of benefits of vaccination, and to take measures to reduce the level of out-of-pocket payment, considering households who have lower incomes.