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Objectives We aimed to investigate the epidemiological characteristics of osteonecrosis of the femoral head (ONFH) using the designated intractable diseases (DID) database in Japan. Methods Data on patients who had received public subsidies for medical costs due to ONFH from 2012 to 2013 were extracted from the DID database. The incidence and prevalence of ONFH, distribution of gender, age, and the prevalence of associated risk factors were assessed. These epidemiological characteristics were compared with those of another nationwide ONFH survey conducted during a similar period. Results Data on 3264 newly diagnosed patients (incident cases) and 20,042 patients registered until 2013 (prevalent cases) were evaluated. The corrected annual incidence and prevalence of ONFH per 100,000 were 3.0 and 18.2–19.2, respectively. The ratio of males to females was 1.4 in 2012 and 1.2 in 2013, respectively. Peak distribution was observed at ages 40s and 60s in males and females, respectively. The prevalence of the risk factors were steroid-associated: 39%, alcohol-associated: 30%, both: 4%, and none: 27%. Conclusions The DID database data showed a similar distribution of gender and age to that in other nationwide surveys but lower incidence and prevalence of ONFH. Sampling bias may affect the epidemiological characteristics of ONFH.

Background: Cronkhite-Canada syndrome (CCS), chronic enteropathy associated with SLCO2A1 gene (CEAS), and intestinal Behçet’s disease (BD) are classified as intractable intestinal disorders in Japan. However, the national prevalence of these diseases remains unknown. We performed a nationwide survey to estimate the patient numbers and prevalence rates of these diseases throughout Japan in 2017. Methods: We conducted a mail-based survey targeting hospitals across Japan to estimate the annual numbers of patients with CCS, CEAS, and intestinal BD in 2017. Using a stratified random sampling method, we selected 2,979 hospital departments and asked them to report the number of patients who met specific diagnostic criteria. The total number of patients for each disease was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. The corresponding prevalence rates per 1,000,000 population were calculated based on the mid-year population of Japan in 2017. Results: The overall survey response rate was 68.1% (2,029 departments). The estimated numbers of patients with CCS, CEAS, and intestinal BD were 473 (95% confidence interval [CI], 357–589), 388 (95% CI, 289–486), and 3,139 (95% CI, 2,749–3,529), respectively; the prevalence rates per 1,000,000 population were 3.7 (male: 4.0; female: 3.5), 3.1 (male: 3.0; female: 3.1), and 24.8 (male: 24.5; female: 25.0), respectively. The male-to-female ratios were 1.10, 0.94, and 0.93 for patients with CCS, CEAS, and intestinal BD, respectively. Conclusions: Estimates of the national prevalence of CCS, CEAS, and intestinal BD in Japan were generated and found to be higher than those previously reported.

In the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored.We evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP.The analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84-2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85-2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35-2.50).This study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results.

Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays.This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays.Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P 0.01 for all). GMT was significantly lower in the older age group after vaccination (P 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively.Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.

For the 2017-18 influenza season, A/Saitama/103/2014 (CEXP-002) (Saitama strain) was antigenically more similar to prior circulating strains than A/Hong Kong/4801/2014 (X-263) (Hong Kong strain) in a ferret model and was selected as the A(H3N2) vaccine virus strain in Japan. However, the Saitama strain grew poorly, and the Japanese government switched to the Hong Kong strain, raising public concerns of poor effectiveness. To enhance understanding of the correlation between antigenicity in experimental models and immunogenicity, as a surrogate measure of vaccine effectiveness, in the human population, we compared the immunogenicity of specially-prepared single dose monovalent influenza A(H3N2) vaccines containing the Saitama or the Hong Kong strain.A randomized controlled trial of 100 healthy adults aged 20-64 years (n = 50/group) was conducted. Virus neutralization assay was performed on sera from days 0 (pre-vaccination) and 21 (post-vaccination). Geometric mean titer (GMT), mean fold rise (MFR), seroconversion proportion (SCP), and seroprotection proportion (SPP) were calculated for vaccine strains and a representative circulating A(H3N2) virus strain (A/Osaka/188/2017).For the Hong Kong strain, post-vaccination GMT was significantly higher in the Hong Kong vaccine recipients (1:546 vs 1:260, p 0.01), but MFR, SCP, and SPP were similar for both vaccine groups. For the Saitama strain, post-vaccination GMT (1:116 vs 1:61, p = 0.01) and SPP (86% vs 68%, p = 0.03) were significantly higher in the Hong Kong vaccine recipients, but MFR and SCP were similar for both vaccine groups. Against A/Osaka/188/2017, post-vaccination GMT and MFR were similar in both vaccine groups, but SCP (32% vs 4%, p 0.01) and SPP (28% vs. 6%, p 0.01) were significantly higher in the Hong Kong vaccine recipients.The Hong Kong vaccine induced better or equivalent immunogenicity in comparison to the Saitama vaccine. Our trial showed that antigenic similarity in experimental models does not necessarily correlate with immunogenicity in the human population.UMIN000029293.

Background It is important to understand the mode of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for disease control. We aimed to clarify how soon SARS-CoV-2 transmission can occur after infection by asymptomatically infected individuals. Methods We analyzed the publicly available epidemiological information for a cluster of 108 cases of coronavirus disease 2019 (COVID-19) cases in Osaka, Japan. Results Among cases, 51 cases attended a live music club only once and were considered to have a single visit. Ten remained asymptomatic at the time of COVID-19 diagnosis by reverse-transcription polymerase chain reaction, which was on average 20 days after exposure. Three routes of secondary transmission were identified, with 2–4 days from infection to transmission. All index cases for secondary transmission were asymptomatic at the time of contact with other people. Based on the date of symptom onset in the remaining 41 cases, the period from exposure to illness ranged from 2 to 17 days. Conclusions Seemingly healthy people could spread SARS-CoV-2 during intense activities in enclosed environments without sufficient ventilation. Asymptomatically infected persons can transmit the virus as soon as 2 days after infection. Continuous efforts to avoid crowding and to maintain personal hygiene are needed for effective control of COVID-19., Investigation of a cluster of 108 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections linked to music clubs revealed that asymptomatically infected persons can transmit SARS-CoV-2 as soon as 2 days after infection. Asymptomatic transmission appeared to be efficient in crowded indoor settings.

Background Hepatocellular carcinoma develops in some patients with hepatitis C virus (HCV), even after achieving sustained virological response (SVR). This prospective cohort study of SVR patients examined factors associated with liver disease progression. Methods Participants were patients who had visited a hospital for clinical follow-up of chronic HCV infection in 2005 and had reached SVR as a result of subsequent antiviral treatment. Baseline information including lifestyle and dietary habits before SVR were collected in 2005 using self-administered questionnaires, and clinical information before SVR was collected from medical records in 2005. Study outcome was liver disease progression such as liver cirrhosis, hepatocellular carcinoma, and/or liver disease-related death after SVR. Logistic regression models were employed to calculate odds ratios (ORs) and 95% confidence intervals for each variable. Results Of 180 SVR patients, 27 patients (15%) showed liver disease progression after SVR: 26 (14%) were diagnosed with liver cirrhosis, two (1%) with hepatocellular carcinoma, and/or one (0.6%) with liver-disease related death. Besides older age at SVR (OR=6.65, P=0.01) and aspartate aminotransferase-to-platelet ratio index score ≥ 1.0 before SVR (OR=5.22, P

Background Dietary fatty acids can affect chronic intestinal inflammation and have been reported to be associated with the development of ulcerative colitis (UC), mainly in Europe and the United States. The association of dietary intake of fatty acids and the risk for UC was investigated in Japan, where dietary habits lead to lower meat and higher fish consumption than in Western countries. Methods A multicenter case-control study of 83 newly diagnosed patients with UC and 128 age- and sex-matched control patients in the hospital was conducted from 2008 to 2014. Dietary fatty acid intake in the preceding 1 month and 1 year were examined using a self-administered diet history questionnaire that was developed for Japanese people. Results About 92% of patients had experienced the first symptoms of UC within the preceding 11 months. Regarding dietary habits in the preceding year, the risk for UC was significantly decreased in patients who consumed n-6/n-3 polyunsaturated fatty acids at a ratio of ≥5.2 (odds ratio [OR] = 0.26; 95% confidence interval [CI], 0.10-0.68). Conversely, an increased risk for UC was observed in the highest tertiles of consumption of docosahexaenoic acid (OR = 7.22; 95% CI, 2.09-24.95), eicosapentaenoic acid (OR = 6.91; 95% CI, 1.88-25.44), and docosapentaenoic acid (OR = 4.83; 95% CI, 1.56-14.95). Conclusions The ratio of n-6/n-3 polyunsaturated fatty acid intake was associated with a decreased risk for UC development. However, high intakes of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid may increase the risk for UC development.

Background and Aim The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, in relation to the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virologic response (SVR). Methods This cross‐sectional study was conducted between 2014 and 2017 using self‐administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR without HCC following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the development of post‐SVR HCC for each factor. Results Of 202 participants, 18 patients were diagnosed with post‐SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95% CI, 1.08–83.90) and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95% CI, 1.37–12.46) were significantly associated with HCC. In addition, among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with never smokers, with marginal significance (OR, 5.61; 95% CI, 0.97–32.63). Conclusions In chronic hepatitis C patients with severe fibrosis, continuing smoking after achieving SVR could be a risk factor for post‐SVR HCC. The relationship between gastric or duodenal ulcer history and post‐SVR HCC should be investigated further., A cross‐sectional study was conducted to investigate lifestyle risk factors associated with hepatocellular carcinoma (HCC) that developed in patients treated for chronic hepatitis C. Continued smoking might be a risk factor for HCC after sustained virilogical response (SVR), especially in patients with chronic hepatitis C with severe fibrosis. In addition, a history of gastric or duodenal ulcers could be a risk factor for developing post‐SVR HCC.

Background: Pregnant women are in the highest priority group for receiving influenza vaccination. However, they may be reluctant to receive the vaccination due to concerns about the influence of vaccination on the fetuses. Methods: This prospective cohort study of 10 330 pregnant women examined the safety of influenza vaccination in terms of adverse birth outcomes. Influenza vaccination during pregnancy was determined from questionnaires before and after the 2013/2014 influenza season. All subjects were followed until the end of their pregnancy. Adverse birth outcomes, including miscarriage, stillbirth, preterm birth, low birth weight, and malformation, were assessed by obstetrician reports. Results: Adverse birth outcomes were reported for 641 (10%) of the 6387 unvaccinated pregnant women and 356 (9%) of the 3943 vaccinated pregnant women. Even after adjusting for potential confounders, vaccination during pregnancy showed no association with the risk of adverse birth outcomes (odds ratio 0.90, 95% confidence interval 0.76–1.07). Vaccination during the first or second trimester displayed no association with adverse birth outcomes, whereas vaccination during the third trimester was associated with a decreased risk of adverse birth outcomes (odds ratio 0.70, 95% confidence interval 0.51–0.98). Conclusions: Influenza vaccination during pregnancy did not increase the risk of adverse birth outcomes, regardless of the trimester in which vaccination was performed, when compared to unvaccinated pregnant women. Keywords: Adverse birth outcomes, Influenza vaccine, Pregnant women, Prospective cohort study, Vaccine safety

Background The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, associated with the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virological response (SVR). Methods This cross-sectional study was conducted between 2014 and 2017 using self-administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for post-SVR HCC. Results Of 202 participants, 18 had been diagnosed with post-SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95%CI, 1.08 to 83.90), and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95%CI, 1.37 to 12.46) were significantly associated with HCC. Among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with non-smokers, with marginal significance (OR, 5.61; 95%CI, 0.97 to 32.63). Conclusions In chronic hepatitis C patients with severe fibrosis, continued smoking could be a risk factor for post-SVR HCC. The relationship between gastric or duodenal ulcer history and post-SVR HCC should be investigated further. Key messages Smoking cessation may be preferred for chronic hepatitis C patients with severe fibrosis to prevent post-SVR HCC.

Background Norovirus infection and Clostridioides difficile infection (CDI) are major causes of acute infectious diarrhea at medical facilities. “Geriatric intermediate care facilities” are a type of medical facility that tend to the daily life needs of elderly Japanese people. However, there is no research about norovirus- or CDI-related diarrhea at Japanese geriatric intermediate care facilities. Methods This prospective cohort study included 1445 residents at 10 geriatric intermediate care facilities in Osaka between November 2018 and October 2019. The study subjects were followed regarding the occurrence of acute infectious diarrhea and the results of rapid diagnostic tests for norovirus and CDI. We calculated incidence rates and hazard ratios (HR) with 95% confidential intervals (CI) to identify the risk factors of infectious diarrhea. Results Thirty-seven residents developed diarrhea during the observation period, although none of them was positive for norovirus or CDI. The total incidence rate was 1.21/10,000 person-days (95%CI: 0.82-1.60). Compared with residents aged 87-91 years, those aged ≤ 80 years had a significantly higher risk of diarrhea (HR = 3.85, 95%CI: 1.27-11.66). Moreover, residents with thyroid diseases had a significantly higher risk of diarrhea than those without thyroid disease (HR = 5.33, 95%CI: 2.32-12.25). Conclusions The incidence of acute infectious diarrhea is relatively low. However, residents who are < 80 years old and those with thyroid diseases are more likely to develop diarrhea. Key messages We describe the situation of acute infectious diarrhea at Japanese geriatric intermediate care facilities

Background The prevalence of Crohn’s disease is increasing in Japan, but risk factors for this disease have yet to be characterized. A recent study using mice, indicated that Klebsiella strains in the oral cavity may be associated with inflammatory bowel disease. We investigated the association between oral hygiene and Crohn’s disease onset. Methods We conducted a multicenter case-control study and compared oral hygiene in 69 patients with newly diagnosed Crohn’s disease to that in 113 control patients (patients with other diseases matched for institution, age, and sex). The exposure variables were number of teeth, use of dentures, implant treatment, and frequency of brushing. A conditional logistic model was used to calculate odds ratios and 95% confidence intervals of these factors for Crohn’s disease onset. Results The decreased odds ratios of brushing teeth were observed with increasing daily frequency (trend for p = 0.039), with 0.52 (0.20–1.33) for twice daily brushings and 0.26 (0.07–0.97) for three or more daily brushings, (reference category: brushing no or once a day). No other oral hygiene factors were associated with the onset of Crohn's disease. Conclusions Our findings suggest that frequent brushing may have a protective association with the development of Crohn's disease. Key messages This result may provide a clue to the possible involvement of oral bacteria in the development of inflammatory bowel disease.

Background Evidence is limited for influenza vaccine effectiveness (VE) against laboratory-confirmed influenza among young children. Using test-negative design (a modified case-control study) which minimizes confounding by health care-seeking behavior and misclassification of diseases, we aimed to monitor influenza VE among young children in Japan where all approved influenza vaccines are egg-propagated, inactivated formulations (IIV). Methods For seasons spanning 2013-14 to 2017-18 in Osaka and Fukuoka Prefectures, Japan, we employed prospective, active, and systematic recruitment of children aged Results We analyzed 4,614 subjects including 1,917 cases. VEs of IIV with 2 doses approximated 50%, ranging from 41% (95% confidence interval [CI]: 14 % to 60%) in 2016-17 season to 63% (95% CI: 45% to 76%) in 2017-18 season. Significant VEs were also shown for predominant circulating strains every season, irrespective of their antigenic match to vaccine strains (56% and 65% for A[H1N1]pdm, 37% and 50% for A[H3N2], and 60% for B[Yamagata]). Conclusions IIV provided modest and significant protection against laboratory-confirmed influenza in young Japanese children. Key messages Test-negative design is useful for monitoring influenza VE.

In Japan, a monovalent mumps vaccine is provided on a voluntary basis. Due to public concerns over post-vaccination aseptic meningitis, the vaccination coverage is not high enough. The present study investigated the incidence of adverse events, including aseptic meningitis, after Torii strain-derived mumps vaccination.This retrospective, observational study used data collected by a vaccine manufacturer regarding adverse events following mumps vaccinations at medical institutions between 1992 and 2018. In addition, the number of Torii strain-derived mumps vaccines shipped each year was obtained. The incidence (per 100,000 doses) and 95% confidence intervals (CIs) were calculated for all adverse events and each adverse event, categorized as aseptic meningitis, encephalitis, mumps, mumps complications, and others.During the study period, 8,262,121 mumps vaccine doses were shipped, and 688 subjects reported adverse events. The incidence for all adverse events (per 100,000 doses) was 8.33, and the incidence was 4.19 for aseptic meningitis, 0.33 for encephalitis, 0.80 for mumps, 0.25 for mumps complications, and 3.78 for others. The incidence of aseptic meningitis (per 100,000 doses) was 7.90 (95% CI: 5.61-10.18) between 1998 and 2000 but declined by half, to 3.91 (2.46-5.36), between 2001 and 2003. The most recent incidence (per 100,000 doses) of aseptic meningitis, for the period 2016 to 2018, was 2.78 (1.94-3.62).The incidence of post-vaccination aseptic meningitis has declined significantly since 2001, and the incidence has remained stable at fewer than 3 cases per 100,000 doses since 2010. Multiple factors might have contributed to the decline in aseptic meningitis incidence, including (i) lowered misclassification of aseptic meningitis resulting from echovirus infection; (ii) changes in the vaccine manufacturing process in 2000; and (iii) publication in 2008 of the recommendation for vaccination of children at 1 year of age.

Background: Severe pediatric cases of hand, foot, and mouth disease (HFMD), herpangina (HA), and associated complications caused by enterovirus 71 (EV71) infection have brought substantial public health impact in Asia. This study aimed to elucidate the epidemiology of these pediatric cases in Japan. Methods: A nationwide survey was conducted using stratified random sampling of hospital pediatric departments. We estimated the number of inpatients with HFMD, HA, and associated complications between April 1 and September 30, 2010, during which EV71 was circulating predominantly. Factors associated with severe cases with ≥7 days of admission, sequelae, or outcome of death were analyzed using multivariate logistic regression. Results: During the 6-month epidemic period, the number of pediatric inpatients aged

Background and purpose A nationwide survey was conducted to understand the epidemiology of cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-related ICH) and cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri) in Japan. Methods To estimate the total number and clinical features of patients with CAA-related ICH and CAA-ri between January 2012 and December 2014 and to analyze their clinical features, questionnaires were sent to randomly selected hospitals in Japan. Results In the first survey, 2348 of 4657 departments responded to the questionnaire (response rate 50.4%). The total numbers of reported patients with CAA-related ICH and CAA-ri were 1338 and 61, respectively, and their total numbers in Japan were estimated to be 5900 [95% confidence interval (CI) 4800-7100] and 170 (95% CI 110-220), respectively. The crude prevalence rates were 4.64 and 0.13 per 100 000 population, respectively. The clinical information of 474 patients with CAA-related ICH obtained in the second survey was as follows: (i) the average age of onset was 78.4 years; (ii) the prevalence increased with age; (iii) the disease was common in women; and (iv) hematoma most frequently occurred in the frontal lobe. Sixteen patients with CAA-ri for whom data were collected in the second survey had the following characteristics: (i) median age of onset was 75 years; (ii) cognitive impairment and headache were the most frequent initial manifestations; and (iii) focal neurological signs, such as motor paresis and visual disturbance, were frequently observed during the clinical course. Conclusions The numbers of patients with CAA-related ICH and CAA-ri in Japan were estimated.

Almost a quarter century has passed since the first nationwide survey on ulcerative colitis (UC) and Crohn’s disease (CD) was conducted in Japan. In this study, we used a nationwide survey to estimate the number of patients and prevalence of these diseases in Japan in 2014. We conducted a mail-based survey targeting hospitals to estimate the annual numbers of patients with UC and CD in 2014. Respondents were asked to report the numbers of patients who met specific diagnostic criteria for these two conditions. A stratified random sampling method was used, and a total of 3712 departments (internal medicine, surgery, pediatrics, and pediatric surgery) were selected for analysis. The overall and sex-specific annual numbers of UC and CD patients were estimated. The corresponding prevalence rates per 100,000 population were calculated by dividing the number of patients with each disease by the mid-year population of Japan in 2014. The overall survey response rate was 56.7% (2016 departments). The estimated numbers of patients with UC and CD were 219,685 (95% confidence interval: 183,968–255,403) and 70,700 (56,702–84,699), respectively. The annual prevalence rates of UC and CD per 100,000 population were 172.9 (men: 192.3; women: 154.5) and 55.6 (men: 79.5; women: 33.1), respectively. These numbers are almost tenfold increase in comparing the previous survey (22,300 in UC and 7,400 in CD). The male-to-female ratios were 1.24 for UC and 2.40 for CD, and the UC-to-CD ratio was 3.11. The prevalence of UC and CD in Japan has risen substantially over the past two decades, and their disease burden requires further examination.

Background Older adults are vulnerable to hospitalization or death from norovirus infection, but the actual disease burden remains unknown. Therefore, we conducted a nationwide survey to estimate the number of inpatients with norovirus gastroenteritis and associated deaths among Japanese older adults. Methods We performed a nationwide two-step query targeting 4184 hospital departments selected from 17,575 departments using stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of inpatients with infectious gastroenteritis and associated deaths between administrative years 2012 and 2014, and the implementation status of norovirus infection testing. In a second query, we investigated the annual number of inpatients with norovirus gastroenteritis and associated deaths in departments that had reported infectious gastroenteritis inpatients in the first query. Clinical information was collected for inpatients with norovirus gastroenteritis in administrative year 2014. Results Norovirus testing for patients hospitalized for acute gastroenteritis was routinely conducted in 16% of the responding departments. Although half the departments responded that some acute gastroenteritis inpatients received such testing but others did not. In this situation, numbers of inpatients with norovirus gastroenteritis in Japan were estimated as 31,800 (95% CI: 25,700-37,900) in administrative year 2012, 21,600 (95% CI: 17,700–25,500) in administrative year 2013, and 15,700 (95% CI: 12,900–18,500) in administrative year 2014. The estimated number of associated deaths was approximately 600 in each administrative year. Factors associated with death included higher age, living in long-term care facilities, underlying illnesses such as chronic respiratory diseases, and complications such as aspiration pneumonia. Conclusions The actual number of norovirus inpatient would be higher than the estimated here due to the low rate of routinely implemented norovirus testing. Considering Japan’s rapidly aging society and the disease burden of norovirus infection among Japanese older adults, it is important to protect this high-risk population from norovirus infection. Electronic supplementary material The online version of this article (10.1186/s12879-019-4007-2) contains supplementary material, which is available to authorized users.

Aim Idiopathic portal hypertension (IPH), extrahepatic portal obstruction (EHO), and Budd-Chiari syndrome (BCS) are characterized by aberrant portal hemodynamics of unknown etiology. The aim of this study was to explore trends in the descriptive epidemiology of these diseases through periodical nationwide surveys. Methods Nationwide epidemiologic surveys were undertaken in 1999, 2005, and 2015 using the same protocol. The survey targets were selected from all departments of gastrointestinal medicine, surgery, pediatrics, and pediatric surgery in Japan by stratified random sampling according to the number of beds. We asked each department to complete a mail-back questionnaire on the annual numbers of patients with IPH, EHO, and BCS during the preceding year. Results The estimated number of BCS patients increased from 280 (95% confidence interval, 200-360) in 1999 survey to 410 (300-530) in 2015 survey, whereas the number of IPH and EHO patients has remained largely unchanged during the 15 years (IPH was approximately 1000; EHO was approximately 770 in 2015 survey). The mean age at symptom onset was approximately 45 years for IPH, 30 years for EHO, and 40 years for BCS over the past 15 years. Those who described disease aggravation from the time of diagnosis accounted for approximately 10% of IPH, 15% of EHO, and 20% of BCS patients in each of the three surveys. Conclusions In Japan, the prevalence of BCS is increasing, while those of IPH and EHO appear to be stable. Clinical characteristics, including prognoses, have remained largely unchanged in the past 15 years.

Background Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. Objective The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. Methods We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. Results An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). Conclusions The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

BACKGROUND AND AIM The prevalence of ulcerative colitis (UC) has been increasing in Japan. Trace elements, such as iron, zinc, magnesium, and copper, can cause digestive symptoms where there is a deficiency or excess. We focused on the dietary intake of trace elements and their associations with UC development. METHODS A multicenter, hospital-based case-control study was conducted in Japan. Cases were 127 newly diagnosed UC patients, and 171 age-matched and sex-matched hospital controls were recruited. We considered that UC patients had potentially changed their dietary habits due to disease symptoms. The dietary habits were investigated using a self-administered diet history questionnaire to analyze the dietary intakes and frequencies at two points, the previous 1 month and 1 year before. RESULTS In the assessment of dietary habits 1 year before, the highest intake of iron showed an increased odds ratio (OR) for UC on multivariate analysis (OR = 4.05, 95% confidence interval, 1.46-11.2, P

The causal effects of vaccines on Kawasaki disease (KD) remain elusive. We aimed to examine the association between vaccines administered during infancy and the development of KD in Japan. We conducted a multicenter prospective case-control study using questionnaires and compared the vaccination status of infants (age: 6 weeks to 9 months) who developed KD (KD group, n = 102) and those who did not develop KD (non-KD group, n = 139). Next, we performed a case-crossover study of 98 cases in the KD group and compared the status of vaccinations between the case and control periods. We also compared the incidence of KD in children for each 5-year period before and after the addition of new vaccines (2012–2013) using data from the Nationwide Survey of KD. In the case-control study, the vaccination status of the KD and control groups did not differ to a statistically significant extent. Multivariable analysis of the vaccination status and patient backgrounds showed no significant association between vaccination and KD development. In the case-crossover study, the status of vaccinations during the case and control periods did not differ to a statistically significant extent. In the analysis of data from the Nationwide Survey of KD, the incidence of KD in children of ages subject to frequent vaccination showed no significant increases in the latter five years, 2014–2018. Based on these prospective analyses, we confirmed that vaccination in early infancy did not affect the risk of KD.

Objectives Alcohol intake and smoking are modifiable lifestyle-related risk factors for osteonecrosis of the femoral head (ONFH). We investigated geographic differences in ONFH incidence in Japan and the correlation with alcohol intake and smoking to develop prevention strategies for ONFH in Japan. Methods This ecological study was conducted in Japan primarily using the following data sources: nationwide epidemiological survey and national survey. We estimated the annual ONFH incidence and the prevalence of alcohol drinking and smoking in each prefecture. Prefectural incidence and prevalence were calculated by sex and age-standardization. Results The mean annual ONFH incidence per 100,000 population was 3.08 in men and 1.63 in women, respectively. There was no significant correlation between ONFH incidence and the prevalence of any levels of alcohol intake, while smoking ≥20 cigarettes/day showed a significant and moderate correlation in men (r = 0.47, p = .01). This correlation remained significant after adjustment for the prevalence of any levels of alcohol intake (standardized partial regression coefficient = 0.47–0.49, p = .009–.01). Conclusion ONFH incidence is geographically variable in Japan, and this may be partly explained by the distribution of smoking prevalence. Smoking cessation may contribute to an effective decline in the overall ONFH incidence in Japan.