阿江 竜介

Objectives: This study investigates the impact of xanthine oxidase inhibitors (XOI) on mortality in patients with cardiovascular diseases. XOI withdrawal has been reported to increased mortality risk due to rapid adenosine triphosphate (ATP) deficiency. This study aims to determine whether XOI treatment reduces mortality and whether XOI withdrawal increases mortality. Methods: This is a real-world database study using the Japanese Registry of All Cardiac and Vascular Diseases (J-ROAD). We analyzed 1,648,891 hospitalized patients aged 20-90 with acute coronary syndrome or heart failure. In the first study, mortality rates were compared between patients without urate-lowering agents (n = 1,292,486) and those with XOI agents (n = 315,388, excluding 41,017 on other urate-lowering agents). In the second study, mortality rates were compared between the XOI continuous medication group (n = 226,261) and the XOI withdrawal group (n = 89,127). Results: After multiple adjustments, XOI treatment group showed significantly lower mortality compared with that without any urate-lowering agent (odds ratio (OR), 0.576, 95% confidence interval (CI), 0.567-0.587, p < .001). In the sub-analysis, the group with allopurinol (OR, 0.578; 95% CI, 0.557-0.600), febuxostat (OR, 0.610; 95% CI, 0.599-0.622), and topiroxostat (HR, 0.545; 95% CI, 0.473-0.628) showed lower OR of mortality compared with that without any urate-lowering agent. XOI withdrawal group led to significantly higher death rates compared to XOI continuous group (19.8% vs. 0.03%; p < .001). Conclusion: XOI treatment for patients with cardiovascular diseases is associated with reduced mortality. Conversely, XOI withdrawal is linked to elevated mortality risk. This emphasizes the importance of both prescribing and discontinuing XOI carefully to optimize patient outcomes.

IMPORTANCE: Global studies have reported that the incidence of Kawasaki disease (KD) declined during the COVID-19 pandemic. These studies suggest that the global pandemic and its accompanying mitigation measures may provide an important opportunity to explore the hypothesis of a KD pathogenesis. OBJECTIVE: To compare changes in KD incidence in Japan before and after the start of the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using the data set from Japan's 26th nationwide KD survey that obtained information on patients who were diagnosed with KD in Japan from January 1, 2019, through December 31, 2020. MAIN OUTCOMES AND MEASURES: Kawasaki disease incidence rates were calculated by referring to the national population data in the vital statistics data for Japan. RESULTS: A total of 28 520 patients were identified (16 236 male individuals [56.9%]; median [IQR] age, 26 [14-44] months). A total of 17 347 patients were diagnosed with KD in 2019 and 11 173 were diagnosed in 2020, representing a 35.6% reduction in the number of patients diagnosed in 2020 compared with the previous year. Patient distributions for days of illness at the first hospital visit were almost identical in 2019 and 2020, suggesting that the decrease in KD incidence likely was not associated with pandemic-related delays in seeking treatment. The proportion of patients diagnosed with KD who were younger than 12 months was significantly larger in 2020 than in 2019 (21.6% vs 19.4%; P < .001). Compared with KD incidence among younger patients, the incidence among those 24 months and older declined rapidly after initiation of COVID-19 special mitigation measures, with a greater percentage reduction (58.3% reduction in July), but rebounded faster after the end of the special mitigation period. By contrast, the incidence among patients younger than 12 months declined moderately after the initiation of the special mitigation period, with a lower percentage reduction (40.3% reduction in October), and rebounded at a later phase. CONCLUSIONS AND RELEVANCE: In this cohort study, the number of patients diagnosed with KD decreased by approximately one-third across Japan in 2020, with no indication that parents avoided a hospital visit. Differences in KD incidence reduction patterns before and after the initiation of COVID-19 pandemic mitigation measures were found in patients with KD aged younger than 12 months compared with those 24 months or older, suggesting a potential KD pathogenesis involving transmission among children.

No studies have assessed differences between the Japanese and Z score criteria in the echocardiographic detection sensitivity of coronary artery (CA) abnormalities using large-scale data containing samples from multiple facilities engaged in daily clinical practices of Kawasaki disease (KD). We analyzed data from the 25th Japanese nationwide KD survey, which identified 30,415 patients from 1357 hospitals throughout Japan during 2017-2018. Hospitals were classified according to their use of Z score criteria. We assessed differences in hospital and patient background factors and compared the prevalence of CA abnormalities among groups using the Z score criteria. Multivariable logistic regression analyses were performed to evaluate differences in the detection sensitivity for CA abnormalities. The Z score criteria were more likely to be utilized in larger hospitals with more pediatricians and cardiologists. Even after controlling for potential confounders, detection sensitivities by the Z score criteria were significantly higher than by the Japanese criteria in patients with CA dilatations (adjusted odds ratio (95% confidence interval) 1.77 (1.56-2.01)) and aneurysms (1.62 (1.17-2.24)). No significant difference was found in patients with giant CA aneurysms. Compared with the Japanese criteria, the Z score criteria were significantly more sensitive for detecting patients with CA dilatations regardless of age, and for those with CA aneurysms only in patients aged ≤ 1 year. Our results indicate that differences in the detection sensitivity for CA abnormalities between the Z score and the Japanese criteria were dependent on the CA size and patient age.

INTRODUCTION/OBJECTIVES: Serum alanine aminotransferase (ALT) elevation is considered a risk factor for resistance to initial intravenous immunoglobulin (IVIG) treatment in patients with Kawasaki disease (KD). However, serum ALT levels change dramatically during acute KD illness. We tested the hypothesis that risk assessment for initial IVIG resistance based on serum ALT elevation may differ by examination day after KD onset. METHODS: We analyzed 18,492 population-based patients who developed KD throughout Japan. First, we epidemiologically evaluated the serum ALT variation at 1‒10 days after disease onset. Second, we conducted multivariable logistic regression to determine the association between serum ALT level and initial IVIG resistance according to timing of initial hospital visit by stratifying the patients into an early group (1‒5 days after onset) and a late group (6‒10 days after onset). RESULTS: Serum ALT rapidly increased after KD onset, peaked at day 4 of illness, and then declined regardless of IVIG responsiveness. The adjusted odds ratio (OR) increased with increasing serum ALT in the early group (adjusted OR [95% CI]: 1.44 [1.25-1.66], 1.94 [1.65-2.28], and 2.22 [1.99-2.48] for serum ALT 50-99, 100-199, and ≥ 200 IU/L, respectively; reference ALT level: 1-49 IU/L). No significant association was observed in the late group. CONCLUSIONS: The findings indicate that risk assessment for initial IVIG resistance based on serum ALT level may only be reliable for patients with KD who visit hospitals during early illness, specifically 1-5 days after disease onset. Key Points Serum alanine aminotransferase level differed markedly according to examination days after Kawasaki disease onset. Serum alanine aminotransferase level declined toward normal range after day 5 of illness regardless of intravenous immunoglobulin responsiveness. Elevated serum alanine aminotransferase level was no longer a significant risk factor for initial intravenous immunoglobulin resistance when measured on delayed hospital visits. Risk assessment for initial intravenous immunoglobulin resistance based on serum alanine aminotransferase level may only be reliable for patients who visit hospitals during early illness, specifically 1-5 days after disease onset.

Studies on the very early electroencephalography (EEG) features prior to the emergence of generalized periodic discharges (GPDs, generally known as periodic sharp-wave complexes) in Creutzfeldt-Jakob disease (CJD) are rare. Fourteen patients with sporadic CJD (sCJD) (eight with MM1/classic and six with MM2c) were included in this study. The predominant findings of the first EEG were categorized as 1) lateralized periodic discharges (LPDs), 2) central sagittal sporadic epileptiform discharges (CSSEDs) showing midline predominant generalized spike-and-wave complexes and/or sharp waves in the central sagittal regions, or 3) focal epileptiform discharges. Clinical records, magnetic resonance imaging (MRI), and changes in EEG were compared between three groups (LPD in MM1/classic, CSSED in MM1/classic, and focal epileptiform discharge in MM2c). Three (37.5%) and five (62.5%) patients with MM1/classic sCJD were classified into the LPD and CSSED groups, respectively. Patients in the LPD group were accompanied by cortical hyperintensities at the corresponding areas on MRI, while those in the CSSED group showed hyperintensities on MRI at unassociated cortical areas. Follow-up EEG of three (100%) patients in the LPD group and four (80%) in the CSSED group showed transitions to GPDs. All patients with MM1/classic sCJD showed myoclonus on initial EEG, and the symptomatic side was opposite to the hemisphere showing LPDs or higher-amplitude central sagittal epileptiform activity. The periodicity after these EEGs likely contributes to the diagnostic confidence of physicians when patients are in the very early stages of MM1/classic sCJD.

The study tested the hypothesis that human mobility may be a potential factor affecting reductions in droplet-transmissible pediatric infectious diseases (PIDs) during the coronavirus disease-2019 (COVID-19) pandemic mitigation period in 2020. An ecological study was conducted using two publicly available datasets: surveillance on infectious diseases collected by the Japanese government and COVID-19 community mobility reports presented by Google. The COVID-19 community mobility reports demonstrated percentage reductions in the movement of people over time in groceries and pharmacies, parks, and transit stations. We compared the weekly trends in the number of patients with droplet-transmissible PIDs identified in 2020 with those identified in the previous years (2015-2019) and assessed the correlations between the numbers of patients and percentage decreases in human mobility during 2020. Despite experiencing their peak seasons, dramatic reductions were found in the numbers of patients with pharyngoconjunctival fever (PCF) and group A streptococcal (GAS) pharyngitis after the tenth week of 2020. Beyond the 20th week, no seasonal peaks were observed in the number of patients with all PIDs identified in 2020. Significant correlations were found between the percentage decreases in human mobility in transit stations and the number of patients with hand-foot-and-mouth disease (Pearson correlation coefficient [95% confidence interval]: 0.65 [0.44-0.79]), PCF (0.47 [0.21-0.67]), respiratory syncytial virus infection (0.45 [0.19-0.66]), and GAS pharyngitis (0.34 [0.06-0.58]). The highest correlations were found in places underlying potential human-to-human contacts among adults. These findings suggest that reductions in human mobility for adults might contribute to decreases in the number of children with droplet-transmissible PIDs by the potential prevention of adult-to-child transmission.

BACKGROUND: Total knee arthroplasty (TKA) is a widely performed procedure to alleviate pain and restore function of patients with end-stage knee osteoarthritis. OBJECTIVE: The study aim was to determine if tibia-first (TF) total knee arthroplasty (TKA) using a novel computer-assisted surgery (CAS) system can yield better anterior and posterior (AP) knee stability. METHODS: Patients with knee osteoarthritis with obvious varus knee who met the indication for and underwent TKA from May 2019 to November 2020 were included. Forty-one measured resection (MR)-TKAs and 32 TF-TKAs were compared. The varus-valgus ligament balance and joint tension at a joint center-gap setting equal to the tibial-baseplate thickness were measured, and appropriate polyethylene inserts with 0∘, 30∘, 45∘, 60∘, 90∘, and 120∘ of knee flexion were placed. A Kneelax 3 arthrometer was used to measure knee AP laxity in the postoperative anesthetized patients with 30∘ and 90∘ of knee flexion. RESULTS: The horizontal gap balance was significantly closer in the TF-TKA group than the MR-TKA group for 0∘, 30∘, 45∘, and 60∘ of knee flexion. In contrast, no significant differences were observed for 90∘ and 120∘ of knee flexion. No significant differences in joint-gap tensions among all knee-flexion angles were observed. Translation was significantly smaller in the TF-TKA group than the MR-TKA group for AP laxity with 30∘ of knee flexion (8.8 ± 2.9 mm vs. 10.7 ± 3.1 mm, P= 0.0079). In contrast, no significant AP laxity was observed with 90∘ of knee flexion (7.2 ± 2.8 mm vs. 7.2 ± 3.5 mm). CONCLUSION: TF-TKA using a novel CAS system provided better AP knee stability with close to horizontal gap balances.

BACKGROUND: Few studies have assessed depression in healthcare workers (HCWs) in Japan owing to the coronavirus disease 2019 (COVID-19) pandemic, and no studies have proposed effective interventions to help support their mental health. AIMS: To test the hypothesis that enhancing access to mental healthcare professionals helps to improve HCWs' mental health. METHODS: This cross-sectional study assessed depressive symptoms in HCWs at three hospitals in Osaka prefecture between May and July, 2020. The survey obtained information on HCWs' mental state and related situations/perceptions. Multivariable logistic regression analysis was performed to identify factors associated with depressive symptoms. RESULTS: Of the 3291 eligible HCWs, 1269 (39%) completed the survey. Of all HCWs, 87 (7%) were physicians, and 700 (55%) were nurses. A total of 181 (14%) HCWs had moderate-to-severe symptoms of depression. Being a frontline worker was not significantly associated with depressive symptoms (odds ratio: 0.86 [95% confidence intervals: 0.54-1.37], P = 0.50). The unwillingness to consult with anyone was significantly associated with more severe depressive symptoms (1.70 [1.10-2.63], P < 0.01). HCWs who had no opportunity to confide in family/friends (1.66 [1.10-2.52], P < 0.01) or colleagues/supervisors (3.19 [2.22-4.58], P < 0.001) were significantly more likely to have depressive symptoms. CONCLUSIONS: Being a frontline HCW in a Japanese hospital treating patients with COVID-19 was not significantly associated with having depressive symptoms. The study highlights that encouraging daily communication with close persons (family, friends, colleagues and supervisors), rather than improving access to mental health professionals, might help to prevent depression in HCWs during the COVID-19 pandemic.

BACKGROUND: No studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset. METHODS: We conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Sträussler-Scheinker disease (GSS)). RESULTS: Of 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro/Leu. CONCLUSIONS: Methionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.

川崎病全国調査は1970年から2年に1回の間隔で実施されてきた。今回、2021年に実施された第26回調査の結果について、過去の調査結果と比較しつつ以下の項目に分けて報告した。1)患者数・罹患率の年次推移。2)月別患者数の推移(2017〜2020年の比較)。3)患者の地域分布。4)診断の確実度。5)心障害。6)初回免疫グロブリン治療。7)初回免疫グロブリン不応例への追加治療。8)主要6症状とBCG接種部位の発赤。9)新型コロナウイルスPCR検査を受けた患者の割合と検査結果。

Introduction: Arterial injury following total knee arthroplasty (TKA) can be life-threatening. There are some anatomical variations in the popliteal artery (PA) and its branches. In most cases, the PA branches into the anterior tibial artery (ATA) and posterior tibial artery (PTA), which are usually distal to the height of tibial resection in TKA. However, some cases show that the PA branches into the ATA and PTA proximal to the height of tibial resection in TKA. This study aimed to assess the distance from the posterior cortex of the proximal tibia to the anterior wall of the PA or ATA at the height of the tibial cut line, during TKA in the distal and proximal branch groups. Methods: 129 patients (6 patients in the proximal branch group and 123 patients in the distal branch group) were enrolled for this study. For prediction of the distance from the posterior cortex of the proximal tibia to the anterior wall of the PA or ATA, preoperative sagittal and coronal magnetic resonance images and postoperative radiographs were evaluated. Results: The distance between the posterior cortex of the proximal tibia and the anterior wall of the PA or ATA at the height of the tibial cut line was 1.8 ± 1.1 mm in the proximal branch group and 6.1 ± 2.6 mm in the distal branch group, which was significantly closer in the proximal group (P < .05). Discussion: The rate of proximal branching was 4.7%. This study clarified that the proximal branching of the ATA from PA significantly decreased the distance between the posterior cortex of the proximal tibia and the anterior wall of the artery. Conclusions: The proximal branch group has a high risk for arterial injury as the artery may be close to the saw, and appropriate retraction should be performed.

Background: Hospital-related coronavirus disease 2019 (COVID-19) infection is of utmost concern among patients and health care workers. Expanding the use of telemedicine may be required in daily outpatient practice; however, the acceptance of telemedicine use is still low, especially among older patients. In an orthopedic practice, no studies have investigated potential factors that can contribute to changes in the acceptance of using telemedicine. Focusing on older outpatients with knee osteoarthritis (KOA), we hypothesized that a drastic surge in the number of patients with COVID-19 could trigger changes in attitudes regarding the acceptance of telemedicine use. Methods: A baseline survey was conducted after the first wave of the COVID-19 pandemic in Japan to obtain information on the willingness to use telemedicine among patients aged ≥70 years who regularly consulted an orthopedic surgeon for KOA. A follow-up survey was subsequently conducted during the third wave of the pandemic period to assess changes in the acceptance of telemedicine use in response to the rapidly increasing number of patients with COVID-19. We compared the difference in acceptance of telemedicine use and knee pain status between the baseline and follow-up surveys. Results: In the baseline survey, 11 of 43 patients (25.6%) responded that they would be willing to use telemedicine. In the follow-up survey, patients' acceptance of telemedicine did not change, with the exact same number and percentage of patients who were willing to use telemedicine as in the baseline survey, despite that ∼20% of patients reported improvement in their knee pain status. Discussion: Our findings indicate that older outpatients with KOA did not change their willingness to accept use of telemedicine, even with a drastically increased risk of hospital-related transmission of a potentially fatal infectious disease when visiting a hospital. The acceptance of telemedicine use among older patients might not be less sensitive to external environmental factors but instead might be more sensitive to patients' personal factors, such as anxiety for information technology and resistance to changes in their lifestyle.

A high prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) may call for monitoring in geriatric long-term care facilities (g-LTCFs). We surveyed the distribution of ESBL-causative gene types and antimicrobial susceptibility in ESBL-PE strains from residents in g-LTCFs, and investigated the association between ESBL-causative gene types and antimicrobial susceptibility. First, we analyzed the types of ESBL-causative genes obtained from 141 ESBL-PE strains collected from the feces of residents in four Japanese g-LTCFs. Next, we determined the minimum inhibitory concentration values for alternative antimicrobial agents against ESBL-PE, including β-lactams and non-β-lactams. Escherichia coli accounted for 96% of the total ESBL-PE strains. Most strains (94%) contained blaCTX-M group genes. The genes most commonly underlying resistance were of the blaCTX-M-9 and blaCTX-M-1 groups. Little difference was found in the distribution of ESBL-causative genes among the facilities; however, antimicrobial susceptibility differed widely among the facilities. No specific difference was found between antimicrobial susceptibility and the number of ESBL-causative genes. Our data showed that ESBL-PEs were susceptible to some antimicrobial agents, but the susceptibility largely differed among facilities. These findings suggest that each g-LTCF may require specific treatment strategies based on their own antibiogram. Investigations into drug resistance should be performed in g-LTCFs as well as acute medical facilities.

BACKGROUND: Kawasaki disease (KD) can result in severe coronary artery abnormalities (CAAs). Corticosteroids added to initial standard intravenous immunoglobulin (IVIG) treatment may decrease the risk for these complications. Different corticosteroid regimens (single-day high dose pulse vs multiple lower doses) may contribute to the discrepant results of prior studies. METHODS: Using data from the 22nd, 23rd , and 24th Japanese nationwide KD surveys (2011-2016), we identified KD patients who did not have CAAs at first presentation and who were treated with either pulse or multiple-dose corticosteroids as part of their initial treatment. Occurrence of subsequent CAAs and treatment failure were compared between the treatment regimens and adjusted odds ratios were calculated controlling for sex, age group, illness day at first treatment, survey, and recurrent KD. RESULTS: There were 782 KD patients who received pulse corticosteroid treatment and 4,817 who received multiple dose treatment. Patients receiving multiple dose treatment were less likely to develop CAAs (5.5% vs 8.3%, OR 0.64; 95% CI: 0.48-0.85) or treatment failure (21.4% vs 41.6%; OR: 0.38; 95% CI: 0.33-0.45). Adjusted analyses showed similar protective effects of multiple-dose treatment against CAAs (OR: 0.67, 95% CI: 0.51-0.90) and treatment failure (OR: 0.39, 95% CI: 0.33-0.46). CONCLUSIONS: Multiple-dose corticosteroid combination treatment resulted in substantially improved outcomes in KD patients compared to pulse treatment. For patients who may be at elevated risk of treatment failure or CAA, use of multiple-dose corticosteroids in conjunction with IVIG is likely to provide considerable clinical benefit.

Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage. 260 residents from four Japanese LTCFs underwent ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1,75 patients with ≥ 2 months residence at study onset; Cohort 2, 185 patients with < 2 months residence at study onset or new admission during the study period. Three analyses were performed: (1) ESBL-E carriage statuses in Cohort 1 and Cohort 2; (2) changes in ESBL-E carriage statuses 3-12 months after the first testing and ≥ 12 months after the second testing; and (3) lengths of positive ESBL-E carriage statuses. Compared with the residents in Cohort 1, a significantly larger proportion of residents in Cohort 2 were positive for ESBL-E carriage (28.0% in Cohort 1 vs 40.0% in Cohort 2). In the subsequent testing results, 18.3% of residents who were negative in the first testing showed positive conversion to ESBL-E carriage in the second testing, while no patients who were negative in the second testing showed positive conversion in the third testing. The maximum length of ESBL-E carriage was 17 months. The findings indicated that some residents acquired ESBL-E through potential cross-transmission inside the LTCFs after short-term residence. However, no residents showed positive conversion after long-term residence, which indicates that residents with ESBL-E carriage may not accumulate inside LTCFs. Practical infection control and prevention measures could improve the ESBL-E prevalence in geriatric LTCFs.

Previous studies have found the prevention paradox in the association between stroke events and a single specific risk factor, indicating that a population-based strategy may be more effective than a high-risk-based strategy for prevention. We tested the hypothesis that the prevention paradox does not apply when focusing on multiple potential risk factors simultaneously. The study cohort included 9051 individuals from Japan aged 40-89 years. The time-dependent Cox proportional-hazards models were used to identify the primary risk factor associated with stroke onset. We classified participants based on risk factors in two distinct ways: 1) classifying the high-risk group participants according to a single specific risk factor that had a large association with stroke in both sexes and all ages and 2) classifying the high-risk group participants according to 1-3 risk factor(s) including hypertension, hyperglycemia, and/or dyslipidemia. Then, we compared the proportions of the total number of participants who developed stroke in both groups to assess the prevention paradox. We found that hypertension was a primary risk factor for stroke incidence, regardless of sex and age. The percentage of patients with a single specific risk of and developed stroke was 46%-63%, while the percentage of patients with 1-3 risk factor(s) was 71-83%. This finding leads to the conclusion that the prevention paradox does not hold when multiple stroke risk factors were associated, suggesting that a high-risk-based strategy that focuses on patients with multiple risk factors may be more effective in preventing strokes.

BACKGROUND: There is a need for a novel therapeutic strategy for an earlier prediction of long bone union failure as compared to previous methodologies. This study aimed to determine whether a combination of two diagnostic tools would result in a more accurate diagnosis of delayed union. METHODS: The inclusion criteria were as follows: patients with tibial shaft fracture who underwent treatment with intramedullary nailing (IMN) as definitive internal fixation (IF). The study included a total of 114 patients with 116 tibial shaft fractures treated with IMN as definitive IF. Radiographic apparent bone gap (RABG) and nonunion risk determination score (NURDS) can be used to predict nonunion. However, this study aimed to determine whether combination of RABG and NURDS could help deduce a more accurate prediction of delayed union. RESULTS: The union rate was found to be 85% (99 fractures), the delayed union rate was found to be 15% (17 fractures), and the rate of nonunion requiring additional surgical intervention was estimated to be 4% (5 out of the 17 delayed union cases). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RABG were found to be 82.3%, 76.0%, 36.8%, and 96.2%, respectively, when an RABG cutoff value of 5.0 mm was applied to our patient cohort. The sensitivity, specificity, PPV, and NPV of NURDS were found to be 47.1%, 82.0%, 30.8%, and 90.1%, respectively, when a NURDS cutoff value of 8.0% was applied to our patient cohort. When RABG and NURDS were above their respective cutoff values, the sensitivity and PPV were estimated to be 90.0% and 56.3%, respectively. When RABG and NURDS were below their respective cutoff values, the specificity and NPV were estimated to be 90.1% and 98.5%, respectively. CONCLUSIONS: The combination of RABG and NURDS evaluation immediately after surgery helps surgeons identify patients who are at a high risk of delayed union, facilitating careful monitoring of these patients and consideration of additional treatments.

INTRODUCTION: The AO/OTA classification for diagnosing femoral trochanteric fractures (31A fractures) was revised in 2018. No studies have investigated whether the addition of CT to radiographic diagnosis improves the inter-rater reliability of classifying 31A fractures with the current AO/OTA criteria. The study aimed to test the hypothesis that the addition of three-dimensional CT (3D-CT) to radiographic diagnosis would improve diagnostic reliability. METHODS: A retrospective review was conducted to assess the diagnostic reliability of classification of 31A fractures with current AO/OTA criteria. Radiographs and 3D-CT images from 89 cases were assessed. Major fracture types (A1, A2, and A3) and subgroups were diagnosed by nine orthopedic surgeons who were classified into three groups (high-, intermediate-, and low-experience) according to their clinical experience. Anterior-posterior and lateral radiographs were provided to diagnose fracture type (first assessment). After a 6-week interval, radiographs and 3D-CT images of all cases were evaluated by each rater (second assessment). Fleiss's Kappa was used to determine inter-rater reliability. RESULTS: In the first assessment, the Kappa value indicated fair inter-rater reliability in all groups (high-experience group: κ = 0.296, 95% confidence interval [CI] 0.239-0.352; intermediate-experience group: κ = 0.367, 95% CI 0.305-0.428; low-experience group: κ = 0.304, 95% CI 0.246-0.362). With the addition of 3D-CT (second assessment), reliability improved from fair to moderate in the high- and intermediate-experience groups (κ = 0.483, 95% CI 0.428-0.539 and κ = 0.409, 95% CI 0.352-0.466, respectively). By contrast, reliability remained fair in the low-experience group (κ = 0.322, 95% CI 0.322-0.431). The inter-rater reliability of diagnosing subgroup fracture types improved for A2.3 and A3.1 in all three groups and for A3.2 and A3.3 in the intermediate- and low-experience groups. CONCLUSION: The current AO/OTA classification revised in 2018 provided fair reliability in diagnosing femoral trochanteric fractures in all three surgeon groups. The addition of 3D-CT to radiographic image evaluation improved reliability in high- and middle-expertise groups. The addition of 3D-CT to radiographic evaluation often improved the diagnostic reliability for unstable fractures, although there was some variation among fracture subgroups.

Introduction Although new techniques and devices have been introduced, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high. To reduce the risk of POPF, we developed an innovative ligation band and conducted this pilot study to assess the possibility of reducing the incidence of POPF and pancreatic necrosis after distal pancreatectomy. Methods Distal pancreatectomy was performed in three pigs. In two animals, ligation of the pancreas was performed while maintaining arterial blood flow to the stump, and in one animal, the arterial blood flow was occluded. After ligation, the pancreas was sharply divided. Animals were sacrificed seven days later, and the remnant pancreas was assessed histologically. POPF was defined as amylase in ascites > 3x the preoperative serum amylase level. The following equation was used to quantify the extent of necrotic tissue: necrotic tissue residual rate = necrotic tissue area/ cross-sectional area. Results All animals survived, and no POPF developed. For two animals in which arterial blood flow to the stump was maintained, necrotic tissue residual rates at the ligation line were 24% and 31%. At the pancreatic stump, necrotic tissue residual rates were 37% and 50%. In the animal in which arterial blood flow to the stump was occluded, the necrotic tissue residual rate at the ligation line was 83% and that at the pancreatic stump was 78%, both higher than that in animals in which arterial blood flow was maintained. In all animals, there was no injury to pancreatic tissue at the ligation line. Conclusion The pancreas ligation band can potentially prevent POPF after distal pancreatectomy by atraumatic ligation, and the band ligates the pancreatic stump while maintaining arterial blood flow and limiting pancreatic necrosis.

INTRODUCTION/OBJECTIVES: Hyponatremia is a potential risk factor for the development of coronary artery lesions (CALs) identified after acute Kawasaki disease (KD). However, the serum sodium distribution corresponding to the reference intervals differs between infants (< 1 year of age) and older children. We hypothesized the association of serum sodium level with CAL complications differs between infants and older patients with KD. METHODS: We analyzed 21,610 population-based patients who developed KD throughout Japan during 2013-2014. We performed multivariable logistic regression analyses to evaluate the association between serum sodium and CAL complications. Additionally, we stratified the serum sodium distribution associated with CAL complications by infants and older patients. RESULTS: CALs were identified in 158 (3.6%) infants and 302 (1.8%) older patients. Infants were more likely to develop CALs when within the normal sodium range compared with older patients (75% vs. 29%), whereas most older patients developed CALs with a sodium level lower than the reference interval. Serum sodium ≤ 130 mEq/L indicated significantly higher risk for development of CALs in both groups (adjusted odds ratio [95% confidence intervals] = 3.21 [1.65-6.25] in infants and 1.74 [1.18-2.57] in older patients). CONCLUSIONS: Serum sodium distribution associated with CAL complications differed greatly between infants and older patients. Older patients developed CALs with sodium levels lower than the reference interval; however, among infants, hyponatremia was not necessarily a risk factor for developing coronary artery lesion. When considering risk assessments for CALs using serum sodium levels, infants with KD should be distinguished from older patients. Key Points • Hyponatremia is a potential risk factor for the development of coronary artery lesions (CALs) among patients with Kawasaki disease. • However, the serum sodium distribution corresponding to the reference intervals differs between infants (< 1 year of age) and older children. • Most infants developed CALs within the normal sodium range, whereas older patients developed at a range lower than the reference interval. • These findings highlight that when considering risk assessments for CALs using serum sodium levels, infants should be distinguished from older patients.

OBJECTIVE: To assess the epidemiologic association between Kawasaki disease and common pediatric infectious diseases (PIDs) identified during the coronavirus disease 2019 (COVID-19) pandemic period to confirm whether the infection-triggered theory is a plausible hypothesis for the pathogenesis of Kawasaki disease. STUDY DESIGN: A retrospective epidemiologic study was conducted using datasets obtained from Web-based surveillance of Kawasaki disease and PIDs in Japan. We compared weekly numbers of patients who developed Kawasaki disease and specific PIDs between 2020 and 2017-2019 and evaluated the association between the percent reduction in the number of patients with these diseases. RESULTS: A total of 868 patients developed Kawasaki disease in 2020. During the social distancing period in 2020, the number of patients with Kawasaki disease was approximately 35% lower than in 2017-2019. Time from the onset of Kawasaki disease until the first hospital visit did not differ significantly among the examined years. The proportion of older children with Kawasaki disease decreased more than that of infants with Kawasaki disease (age <1 year), resulting in a significant difference in the proportion of infant patients between 2020 and 2017-2019 (24% vs 19%; P < .01). The number of patients with incomplete Kawasaki disease was unchanged from that of previous years. The weekly percent reduction in patient numbers differed between Kawasaki disease and PIDs during 2020, with no strong correlation between the 2 diseases. CONCLUSIONS: Our data indicate that parents of patients with Kawasaki disease did not avoid hospital visits during the COVID-19 pandemic period. The findings indicate the possibility that triggering Kawasaki disease might be associated with presently unidentified respiratory pathogen(s) that potentially might be acquired from both within and outside the household.

BACKGROUND: Some patients with Kawasaki disease (KD) have siblings who developed the same disease. Using a large-scale epidemiologic dataset, the present study aimed to determine the clinical characteristics of this population. METHODS: We analyzed 89,725 patients diagnosed with KD during 2011-2018 who were registered in the nationwide Japanese KD survey database. Multivariable logistic regression analyses were performed to determine factors associated with sibling history of KD. RESULTS: Of the 89,725 patients, 1777 (2%) had sibling history of KD. Annual prevalence ranged from 1.5% to 2.3% during the study period and showed a tendency toward an increasing trend. Patients with recurrent KD and parental history of KD were significantly associated with sibling history of KD (adjusted odds ratio [95% confidence interval] = 2.15 [1.82-2.54] and 2.64 [2.02-3.47], respectively). Although patients with a sibling history of KD were significantly associated with initial intravenous immunoglobulin treatment resistance (1.14 [1.02-1.28]), no significant association was found between sibling history and coronary artery abnormality development. Among patients with a sibling history of KD, male patients were less likely to have recurrent KD than female patients (0.68 [0.49-0.96]). CONCLUSIONS: The significant association between sibling history and parental history may indicate genetic susceptibility to KD onset. Among those with a sibling history, recurrent KD was more likely to occur in female patients. Further studies focusing on this population may contribute toward identification of the cause of KD onset.

Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population-based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9-10, 4.30 [3.58-5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1-4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness. Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.

A giant coronary artery (CA) aneurysm is a potentially fatal cardiac complication resulting from Kawasaki disease (KD). We aimed to identify epidemiologic characteristics and potential risk factors associated with giant CA aneurysms identified after acute KD. We analyzed 90,252 patients diagnosed with KD from 2011 to 2018, using data obtained in nationwide KD surveys conducted in Japan. Multivariable logistic regression analyses were performed to evaluate potential risk factors associated with subsequent giant CA aneurysm complications (defined as lumen size ≥ 8 mm), adjusting for all potential factors. Giant CA aneurysms were identified in 144 patients (0.16%) after acute KD. The annual prevalence ranged from 0.07 to 0.20% during the study period. In the multivariate analyses, male sex (adjusted odds ratio 2.09 [95% confidence interval 1.41-3.11], recurrent KD (1.90 [1.09-3.33]), IVIG administration at 1-4 days of illness (1.49 [1.04-2.15]) and ≥ 8 days after KD onset (2.52 [1.38-4.60]; reference, 5-7 days), detection of CA dilatations and aneurysms at initial echocardiography (4.17 [1.85-5.41] and 46.5 [28.8-74.8], respectively), and resistance to IVIG treatment (6.09 [4.23-8.75]) were significantly associated with giant CA aneurysm complications identified after acute KD. The annual prevalence of giant CA aneurysms identified after acute KD did not increase during the study period. Patients with larger CA abnormalities detected at initial echocardiography were independently associated with progression to giant CA aneurysm complications after acute KD regardless of the number of days from onset at treatment initiation.

Influenza outbreaks at geriatric long-term care facilities (g-LTCFs) can be deadly and their prevention is important. However, the factors influencing disease transmission in g-LTCFs remain controversial. In this descriptive study, we tried to identify the potential risk factors influencing influenza outbreaks that occurred in different influenza seasons within a single g-LTCF with 100 residents in Gunma Prefecture. We reviewed the detailed facility records for all influenza cases in both residents and staff between January 2012 and June 2020. Facility preventive measures were also reviewed. We found that community meals may have been a potential source of transmission leading to the outbreaks. When influenza infection is noted, implementation of strict preventive measures and restriction of meal provision to resident rooms may help to prevent disease transmission and the development of an outbreak. Such measures may also be useful to prevent the transmission of other serious droplet-borne diseases within g-LTCFs.

OBJECTS: The number of workers dispatched to developing countries has increased recently. The sanitary conditions in these countries are different from those in developed countries and from what the workers are used to. Therefore, health control, especially infection control, is an important consideration for working there. In this study, we investigate workers' needs as well as the occupational physicians' skills concerning working in developing countries. We propose a more effective education system for health control. METHODS: Regarding workers who have lived in developing countries, we surveyed the company profiles, duration of stay, vaccination status, infectious education, medical assistance, and satisfaction with infection control strategies of their employer companies. Regarding occupational physicians, we surveyed their profiles, their experiences in consultation, and advice from/to the workers dispatched to developing countries as well as their suggestive advice for staying there. RESULTS: Factors that contributed to workers' satisfaction with their employment companies were prior education and health consulting services in addition to company size. Many occupational physicians believed that this kind of information should be supplied but they did not have the confidence to provide it. CONCLUSIONS: Workers who are dispatched overseas should receive prior education and access to health consulting services. It is necessary for information providers such as occupational physicians to be knowledgeable in travel medicine.

INTRODUCTION: Hand hygiene is crucial for infection control in long-term care facilities for elderly (LTCFEs), because it can be easily implemented in the low-resource settings of LTCFEs. This study investigated the actual status of hand hygiene adherence in LTCFEs, identified the factors inhibiting its appropriate implementation, and evaluated the effectiveness of a hand hygiene promotion program. METHODS: In this before-and-after study, participants were staff members (n = 142) at two LTCFEs in Gunma Prefecture, Japan. We modified the World Health Organization's "five moments for hand hygiene" and assessed participants' hand hygiene adherence rates in four situations: (1) Before touching around a resident's mucous membrane area; (2) Before medical practice or clean/aseptic procedures; (3) After body fluid exposure/risk or after touching around a resident's mucous membrane area; and (4) After touching a resident's contaminated environments. The study was divided into four phases. In Phase 1, participants self-assessed their hand hygiene adherence using a questionnaire. In Phase 2, we objectively assessed participants' pre-intervention adherence rates. In Phase 3, an intervention comprising various hand hygiene promotion measures, such as education and hands-on training on hand hygiene practices and timings, was implemented. In Phase 4, participants' post-intervention adherence rates were objectively measured. RESULTS: Although most participants reported high hand hygiene adherence rate in the self-assessment (93.1%), the pre-intervention evaluation revealed otherwise (16.8%). Participants' post-intervention adherence rates increased for all four situations (77.3%). CONCLUSION: The intervention program helped increase participants' hand hygiene adherence rates, indicating its effectiveness. Similar interventions in other LTCFEs may also improve adherence rates.

OBJECTIVE: To investigate whether redness and crusting at the bacille Calmette-Guérin inoculation site (BCGitis), identified during acute illness owing to Kawasaki disease (KD), is an independent risk factor for development of cardiac complications. DESIGN: Retrospective cohort study using data from the nationwide KD survey in Japan. SETTING: Survey respondents included hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan. PATIENTS: We included 17 181 patients with KD across Japan during 2005-2006. MAIN OUTCOME MEASURES: BCGitis and cardiac complications resulting from KD. RESULTS: BCGitis was identified in 7549 (44%) patients with KD. Compared with patients without BCGitis, those with BCGitis were younger, more likely to be male, less likely to have recurrent status and visited a hospital and underwent initial intravenous immunoglobulin (IVIG) treatment earlier after KD onset. In the unadjusted model, patients with BCGitis were significantly less likely to have cardiac complications (crude OR 0.81, 95% CI 0.71 to 0.92). However, after including treatment factors (days of illness at initial IVIG and treatment responsiveness) in the adjusted model, the association was no longer significant (adjusted OR 0.89, 95% CI 0.77 to 1.03), indicating that BCGitis was not an independent factor associated with cardiac complication and might be confounded by treatment factors. CONCLUSIONS: BCGitis was identified in comparatively early illness stages of KD. Our findings indicated that BCGitis was not an independent factor associated with developing cardiac complications but was confounded by prompt initial IVIG administration, which might result in successful treatment and prevention of cardiac complications.

BACKGROUND: A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization has been reported among residents in geriatric long-term care facilities (LTCFs). Some studies indicate that MRSA might be imported from hospitals into LTCFs via resident transfer; however, other studies report that high MRSA prevalence might be caused by cross-transmission inside LTCFs. We aimed to assess which factors have a large impact on the high MRSA prevalence among residents of geriatric LTCFs. METHODS: We conducted a cohort study among 260 residents of four geriatric LTCFs in Japan. Dividing participants into two cohorts, we separately analyzed (1) the association between prevalence of MRSA carriage and length of LTCF residence (Cohort 1: n = 204), and (2) proportion of residents identified as MRSA negative who were initially tested at admission but subsequently identified as positive in secondary testing performed at ≥2 months after their initial test (Cohort 2: n = 79). RESULTS: Among 204 residents in Cohort 1, 20 (9.8%) were identified as positive for MRSA. Compared with residents identified as MRSA negative, a larger proportion of MRSA-positive residents had shorter periods of residence from the initial admission (median length of residence: 5.5 vs. 2.8 months), although this difference was not statistically significant (p = 0.084). Among 79 residents in Cohort 2, 60 (75.9%) were identified as MRSA negative at the initial testing. Of these 60 residents, only one (1.7%) had subsequent positive conversion in secondary MRSA testing. In contrast, among 19 residents identified as MRSA positive in the initial testing, 10 (52.6%) were negative in secondary testing. CONCLUSIONS: The prevalence of MRSA was lower among residents with longer periods of LTCF residence than among those with shorter periods. Furthermore, few residents were found to become MRSA carrier after their initial admission. These findings highlight that MRSA in LTCFs might be associated with resident transfer rather than spread via cross-transmission inside LTCFs.

OBJECTIVE: To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity. METHODS: We reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases. RESULTS: According to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death. Compared with other types of sCJD, patients with MM2C-sCJD showed slower progression of the disease and cortical distribution of hyperintensity lesions on diffusion-weighted images of brain MRI. Patients with MM2T-sCJD also showed relatively slow progression and negative results for most of currently established investigations for diagnosis of sCJD. To clinically diagnose MM2C-sCJD, we propose the new criteria; diagnostic sensitivity and specificity to distinguish 'probable' MM2C-sCJD from other subtypes of sCJD, genetic or acquired prion diseases and non-prion disease controls were 77.8% and 98.5%, respectively. As for MM2T-sCJD, clinical and laboratory features are not characterised enough to develop its diagnostic criteria. CONCLUSIONS: MM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.

OBJECTIVE: To report the epidemiologic characteristics, treatments, and cardiac complications of Kawasaki disease, using data from the nationwide survey in Japan. STUDY DESIGN: The nationwide Kawasaki disease survey in Japan has been conducted biennially since 1970. The most recent survey was completed in 2019, obtaining information for patients who developed Kawasaki disease during 2017-2018. Survey respondents were hospitals specializing in pediatrics and those with ≥100 beds and a pediatric department throughout Japan, where patients with Kawasaki disease were eventually hospitalized. RESULTS: The survey identified 32 528 patients with Kawasaki disease, which consisted of 15 164 (46.6%) in 2017 and 17 364 (53.4%) in 2018. The highest annual incidence rate was recorded in 2018 (359 per 100 000 children aged 0-4 years). After 1982, patients with ≤4 principal Kawasaki disease signs gradually increased, resulting in 6847 (21.1%) patients diagnosed during 2017-2018. Among the 30 784 patients receiving initial intravenous immunoglobulin administration, 6061 (19.7%) did not respond. Within 30 days of Kawasaki disease onset, 9.0% of patients were diagnosed with cardiac complications, and 2.6% of patients developed cardiac sequelae after the acute illness. CONCLUSIONS: The annual number of patients developing Kawasaki disease in Japan increased from 1970 through 2018, whereas the proportion of patients with Kawasaki disease with cardiac complications decreased in the most recent 2 decades. Early diagnosis of Kawasaki disease as well as advances in initial treatments could explain these findings.

BACKGROUND Randomized controlled trials previously provided different conclusions about the superiority of adding corticosteroids to initial intravenous immunoglobulin treatment for the prevention of coronary artery abnormalities in patients with Kawasaki disease (KD). To further assess this issue, we analyzed large-scale data from nationwide KD surveys in Japan, where combination treatment (corticosteroids added to initial standard intravenous immunoglobulin treatment) has become commonly used for patients at high risk for KD. METHODS AND RESULTS Standard intravenous immunoglobulin treatment and combination treatment were compared using data from time periods with and without combination treatment. Outcome measures were coronary artery abnormalities and initial intravenous immunoglobulin treatment failure. Hospitals where ≥20% of patients received combination treatment were identified, and treatment and control groups were selected via matching by age, sex, illness day at initial treatment, and KD recurrence. Matched group selection and subsequent analyses were conducted 1000 times to minimize sampling bias and potential confounders (bootstrapping). From 115 hospitals, 1593 patients with KD in the treatment group and 1593 controls were selected for each of the 1000 sample iterations. The median proportion of patients who developed coronary artery abnormalities among the treatment group and controls were 4.6% (95% CI, 3.8%-5.8%) and 8.8% (95% CI, 7.5%-10.0%), respectively: an estimated risk ratio of 0.53 (0.41-0.67). A median of 14.1% (95% CI, 12.4%-15.9%) of the patients in the treatment group and 21.7% (95% CI, 19.8%-23.4%) in the controls had treatment failure: an estimated risk ratio of 0.65 (0.56-0.75). CONCLUSIONS Combination treatment reduced coronary artery abnormality risk by an estimated 47% and treatment failure by 35%. Multiple-dose corticosteroids may provide benefit in selected patients at high risk for KD.

栃木県の調査データを二次利用し、在宅医療的ケア児の生活状況について分析した。医療的ケア児は県内に約300人、20歳未満人口1000人対0.91みられ、年齢分布では6歳未満が50%を占め、寝たきりや座位の児が50%、歩行や走ることが可能な児が31%であった。サービスについては人工呼吸器使用者で「送迎がない」「利用できるサービスの量が不足」「費用負担が大きい」などの項目が有意に高かった。また、介護者で睡眠5時間未満の者は児に経管栄養がある場合において有意に高かった。以上、これらの結果からも、在宅医療的ケア児の運動・知的機能には個人差があり、個々に応じたサービスの提供が必要であると考えられた。

BACKGROUND: Previous studies demonstrated that coronary artery lesions (CALs) resulting from Kawasaki disease (KD) can improve over time. However, limited information is available on sub-acute outcomes of CALs detected at admission during KD illness. METHODS: The nationwide Japanese KD survey contained substantial information on KD patients with CALs detected at admission and who received standard IVIG treatment within 10 days of disease onset. Coronary outcomes were evaluated by changes in CALs from admission to the first assessment at 30 days from disease onset in three categories: improved, unchanged, and progressed. Ordinal logistic regression analysis was performed to evaluate factors associated with the outcomes. RESULTS: Of 2024 patients with CALs detected at admission, improved, unchanged, and progressed outcomes were found in 1548 (76.5%), 390 (19.3%), and 86 (4.2%), respectively. Over 80% of patients with coronary artery (CA) dilatations had improved outcome. Independent factors associated with worse outcomes were larger-size CALs (adjusted ORs [95% CIs]: CA aneurysm = 5.13 [3.65-7.22] and giant CA aneurysms = 7.49 [3.56-15.72] compared with CA dilatation, respectively), age ≥ 60 months (1.45 [1.08-1.94] compared with 12-59 months), recurrent KD (1.57 [1.07-2.29]), parental history of KD (2.23 [1.02-4.85]), and delayed admission (8-10 days from disease onset: 1.76 [1.21-2.57] compared with 1-4 days). CONCLUSIONS: KD patients with larger CALs, ≥60 months old, and with recurrent status or parental history may require more rigorous treatment. In addition, delayed admission may result in worse coronary outcome, indicating that prompt diagnosis and treatment are required.

We previously reported a phenotype of Creutzfeldt-Jakob disease (CJD), CJD-MMiK, that could help identify iatrogenic CJD. To find cases mimicking CJD-MMiK, we investigated clinical features and pathology of 1,155 patients with diagnosed sporadic CJD or unclassified CJD with and without history of neurosurgery. Patients with history of neurosurgery more frequently had an absence of periodic sharp-wave complexes on electroencephalogram than patients without a history of neurosurgery. Among 27 patients with history of neurosurgery, 5 had no periodic sharp-wave complexes on electroencephalogram. We confirmed 1 case of CJD-MMiK and suspected another. Both had methionine homozygosity at codon 129 of the prion protein gene and hyperintensity lesions in the thalamus on magnetic resonance images of the brain, which might be a clinical marker of CJD-MMiK. A subgroup with a history of neurosurgery and clinical features mimicking dura mater graft-associated CJD might have been infected during neurosurgery and had symptoms develop after many years.

The potential contribution of serum osmolarity in the modulation of blood pressure has not been evaluated. This study was done to examine the relationship between hyperosmolarity and hypertension in a five-year longitudinal design. We enrolled 10,157 normotensive subjects without diabetes who developed hypertension subsequently as determined by annual medical examination in St. Luke's International Hospital, Tokyo, between 2004 and 2009. High salt intake was defined as >12 g/day by a self-answered questionnaire and hyperosmolarity was defined as >293 mOsm/L serum osmolarity, calculated using serum sodium, fasting blood glucose, and blood urea nitrogen. Statistical analyses included adjustments for age, gender, body mass index, smoking, drinking alcohol, dyslipidemia, hyperuricemia, and chronic kidney disease. In the patients with normal osmolarity, the group with high salt intake had a higher cumulative incidence of hypertension than the group with normal salt intake (8.4% versus 6.7%, p = 0.023). In contrast, in the patients with high osmolarity, the cumulative incidence of hypertension was similar in the group with high salt intake and in the group with normal salt intake (13.1% versus 12.9%, p = 0.84). The patients with hyperosmolarity had a higher incidence of hypertension over five years compared to that of the normal osmolarity group (p < 0.001). After multiple adjustments, elevated osmolarity was an independent risk for developing hypertension (OR (odds ratio), 1.025; 95% CI (confidence interval), 1.006-1.044), regardless of the amount of salt intake. When analyzed in relation to each element of calculated osmolarity, serum sodium and fasting blood glucose were independent risks for developing hypertension. Our results suggest that hyperosmolarity is a risk for developing hypertension regardless of salt intake.

BACKGROUND: Some patients with Kawasaki disease (KD) develop cardiac sequelae, which increase the risk of subsequent ischemic heart events. Knowing the cumulative incidence (CI) of KD with cardiac sequelae may contribute to developing health policies to prevent subsequent ischemic events in these patients. METHODS: Study participants consisted of 254 984 patients aged 0-9 years with KD who were registered in nationwide surveys in Japan from 1991-2016. We calculated the incidence probabilities by dividing the number of patients with KD aged 0-9 years by the population used in vital statistics of each calendar year. We calculated the cumulative proportion of those not affected by KD, by multiplying each probability in patients aged from age 0-9 years. The CI of KD was obtained by subtracting this value from 1. We also calculated the number of patients in each birth cohort (BC). The same was done to calculate the CI of KD-related cardiac sequelae. RESULTS: The CIBC steadily increased from 0.005067 in males and 0.003668 in females in 1991 to 0.011431 in males and 0.0088253 in females in 2007. The CIBC of KD with cardiac sequelae decreased from 0.000478 in males and 0.000213 in females in 1997 to 0.000339 in males and 0.000169 in females in 2007. CONCLUSION: The increasing CIBC of KD indicates an increased susceptibility to KD in accordance with birth year. The decreasing CIBC of cardiac sequelae suggests the efficacy of KD treatment.

BACKGROUND: Platelet count is considered as a biomarker for the development of coronary artery abnormalities (CAAs) among Kawasaki disease (KD) patients. However, previous studies have reported inconsistent results. We addressed the controversial association of platelet count with CAAs using a large-scale dataset. METHODS: A retrospective cohort study was conducted using KD survey data from Japan (2015-2016; n = 25,448). Classifying patients by intravenous immunoglobulin (IVIG) responsiveness, we described the trends in platelet count using the lowest and highest values along with the specific illness days. Multivariate logistic regression analysis was performed to evaluate the association between platelet count and CAAs, adjusting for relevant factors. RESULTS: Platelet counts rapidly decreased from admission, reached the lowest count at 6-7 days, and peaked after 10 days. Platelet counts in IVIG non-responders decreased with a lower minimum value than IVIG responders, but subsequently rebounded toward a higher maximum. Compared with patients with normal platelet counts (150-450 × 10/L), patients with abnormally high platelet counts (>450 × 10/L) were more likely to have CAAs at admission (adjusted odds ratio: IVIG responders, 1.50 [95% confidence interval 1.20-1.87] and non-responders, 1.46 [1.01-2.12]). By contrast, IVIG non-responding patients whose counts were below normal (<150 × 10/L) after hospitalization were at higher risk for developing CAAs (2.27 [1.44-3.58]). CONCLUSIONS: Platelet count varied widely by illness day and was confounded by IVIG responsiveness, which might have contributed to previous inconsistent findings. KD patients with abnormally high platelet counts at admission or abnormally low counts after hospitalization were at higher risk for CAAs.

Tap water contamination is a growing concern in healthcare facilities, and despite chlorination, tap water in these facilities contains several pathogenic microorganisms causing healthcare-associated waterborne infections or nosocomial outbreaks. Shower units are particularly prone to contamination as they are conducive for bacterial growth and can even produce bioaerosols containing pathogenic bacteria. Shower units coupled with point-of-use (POU) water filters are a simple and safe option; however, their efficacy has been under-reported. Therefore, we determined the efficacy of showerheads attached with a POU filter capsule in preventing infections in our hospital. We investigated the presence of pathogenic bacteria in water sampled from three shower units. After replacing the original shower units with new ones incorporated with a sterile-grade water filter capsule (0.2 µm; QPoint™), the water samples were analyzed for up to 2 months. The POU filters removed several pathogenic bacteria (Mycobacterium, Pseudomonas, Stenotrophomonas, Aeromonas, and Klebsiella spp.). Filter effectiveness depends on regional water quality and we believe that effective tap water treatment combined with the use of POU filters (introduced at a reasonable cost in healthcare facilities) can considerably minimize waterborne diseases in hospitals and improve patient care.

Background: There is no report yet on the application of telemedicine in orthopedic practice in Japan. With a focus on patients with KOA, we investigated the willingness of patients to use telemedicine by assessing factors such as the patient's age, smartphone possession, hospital visiting time, and severity of KOA. Methods: Data of patients who regularly consulted orthopedic surgeons at our institutions from April 2020 to June 2020 were retrospectively analyzed using an electronic medical database. The patients were diagnosed with KOA according to clinical and radiological findings, according to the Kellgren-Lawrence (KL) classification. included were patients with KOA with KL classification above grade 2. All patients were asked: 1) whether they were willing to use telemedicine (Yes or No), 2) the reason why they answered Yes, 3) the reason why they answered No, 4) if they possessed a smartphone, 5) their numeric rating scale for pain at their last outpatient visit after the Sars-CoV-2 epidemic emerged, and 6) the time required for visiting hospital from their house. Patients were stratified into 2 groups depending on whether they answered Yes (Group Y) or No (group N). Comparisons between the groups concerning smartphone possession, NRS pain, hospital visiting times, and distribution of KL grade were made. Results: Only 36.7% of the patients with KOA said they were willing to use telemedicine. The average age of group Y was significantly younger than that of group N (67.9 ± 9.1 vs 73.1 ± 8.0, P = 0.0026) and the cutoff age was 70.0 years. In addition, the rate of smartphone possession was significantly higher in group Y than in group N (82.5% vs 34.5%, P < 0.001). Hospital visit times and the severity of KOA did not differ between the groups. Conclusion: Age is a barrier to the adoption of telemedicine.

OBJECTIVE: To determine whether preventive trials in genetic prion disease could be designed to follow presymptomatic mutation carriers to onset of disease. METHODS: We assembled age at onset or death data from 1,094 individuals with high penetrance mutations in the prion protein gene (PRNP) in order to generate survival and hazard curves and test for genetic modifiers of age at onset. We used formulae and simulations to estimate statistical power for clinical trials. RESULTS: Genetic prion disease age at onset varies over several decades for the most common mutations and neither sex, parent's age at onset, nor PRNP codon 129 genotype provided additional explanatory power to stratify trials. Randomized preventive trials would require hundreds or thousands of at-risk individuals in order to be statistically powered for an endpoint of clinical onset, posing prohibitive cost and delay and likely exceeding the number of individuals available for such trials. CONCLUSION: The characterization of biomarkers suitable to serve as surrogate endpoints will be essential for the prevention of genetic prion disease. Parameters such as longer trial duration, increased enrollment, and the use of historical controls in a postmarketing study could provide opportunities for subsequent determination of clinical benefit.

Objective: Few studies have reported the influence of clinical background factors on the outcome of Helicobacter pylori eradication therapy in primary care practice. We aimed to determine which clinical background factors influence the outcome of eradication therapy in a primary care setting. Methods: This was a retrospective study of patients who received H pylori eradication therapy at Higashiohmi City Gamo Medical Center, Shiga, Japan, from January 2012 to December 2015. We investigated clinical background factors associated with success, failure, and self-interruption of H pylori eradication therapy: patients' age, gender, first- or second-line treatment, reasons for receiving gastroenterological endoscopic examination, method of drug administration, and attending physicians' age and their specialties. Results: There were 369 patients (208 females, 161 male), with a mean age of 59 years (range 30-88 years). The middle-aged group (50-69 years) was associated with successful eradication therapy compared with the young group (30-49 years). The elderly group (>70 years) was associated with eradication therapy failure compared with the middle-aged group. The young group was associated with self-interruption of eradication therapy. There was a marginally significant association between male patients and self-interruption. Older attending physicians (>50 years) were also associated with failure compared with younger physicians. There was no difference in outcome of eradication therapy between generalists and gastroenterology specialists. Conclusion: We have identified clinical factors associated with success, failure, and self-interruption of H pylori eradication therapy in a primary care setting.

BACKGROUND: Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD-positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non-responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016. METHODS: In these datasets, the IVIG therapy non-responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non-responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non-responders and responders were compared. RESULTS: From a total of 113 691 KD-positive patients, 15.7% were IVIG non-responders, and 61% were male. The proportion of non-responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non-responders, with the proportion of responders tending to increase in autumn through winter, while the non-responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex. CONCLUSIONS: The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non-responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non-responders.

BACKGROUND: Approximately 50 years have passed since Kawasaki disease (KD) was first reported. The KD nationwide survey began in 1970. Although >360 000 cases have already been reported in Japan, the cause is still unknown. In Japan, the number of patients and incidence rate of KD has continued to increase. It is necessary to examine the trend of the occurrence in the surveillance of KD. METHODS: The nationwide survey of patient incidence in 2015 and 2016 was conducted in 2017, as the 24th nationwide survey of KD. A questionnaire was sent to pediatric departments in hospitals with >100 beds and specialized pediatric hospitals, and was responded to by the attending pediatricians. RESULTS: The total number of patients in 2 years was 31 595, and the sex ratio (male/female) was 1.34. The incidence rate (/100 000 children aged 0-4 years/year) was 330.2 (371.2 in boys, 287.3 in girls) in 2015, and 309.0 (343.2 in boys, 273.2 in girls) in 2016. The number of patients by month peaked in January. The age-specific incidence rate according to sex was highest in children between 9 and 11 months of age, after which the incidence rate gradually decreased with advancing age. CONCLUSIONS: We summarize the most recent nationwide survey of KD and consider the change in the epidemiologic picture.

BACKGROUND: Although intravenous immunoglobulin (IVIG) therapy is the standard therapy for Kawasaki disease (KD) to prevent coronary aneurysms including dilatations, it is unclear whether early IVIG therapy is more efficient in the acute stage of KD. METHODS: We conducted a cohort study using data from the 22nd nationwide survey of KD in Japan from January 2011 to December 2012. We excluded patients with recurrent KD and whose first admission day was later than seven days from the onset of symptoms. Finally, 20,933 patients with echocardiography assessment and IVIG therapy were divided into three groups according to the start of the IVIG therapy: 1) early: ≤4 days, 2) conventional: 5-7 days, and 3) late: 8-10 days. Then we investigated whether the early IVIG therapy prevented coronary dilatation or aneurysm after multiple adjustments for age, sex, total amount of IVIG, use of steroids, infliximab, other immunosuppressive agents, and plasma exchange. RESULTS: After multiple adjustments, conventional therapy had similar risks for coronary dilatation or aneurysm compared with early therapy (odds ratio [OR]:0.95; 95% confidence interval [CI], 0.78-1.16), whereas late therapy had a higher risk (OR:1.66; 95% CI, 1.03-2.68). Other risk factors for coronary dilatation or aneurysm were young male, older age, use of steroids, infliximab, other immunosuppressive agents, and a larger amount of total IVIG. CONCLUSIONS: Early IVIG therapy for KD did not reduce the risk for coronary dilatation or aneurysm compared with conventional therapy. It is recommended to start IVIG therapy within 7 days from the onset of symptoms.

BACKGROUND: Globally, few published studies have tracked the temporal trend of dioxin levels in the human body since 2000. This study describes the annual trend of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015. METHODS: An observational study was conducted from 1998 through 2015. Participants were 1,194 healthy mothers following their first delivery who were recruited annually in Japan. Breast milk samples obtained from participants were analyzed using gas chromatography and mass spectrometry for dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). RESULTS: Mean age was 29.5 years, and 53% of participants were 20-25 years old. A declining trend in total dioxin levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to 7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a plateau at minimal levels. In contrast, an increasing trend was found in the mean age of participants during the last 5 years. Although significantly higher dioxin levels were observed in samples from older participants, an upward trend in dioxin levels was not observed, indicating that dietary and environmental exposure to dioxins had greatly diminished in recent years. CONCLUSIONS: Dioxin levels in human breast milk may be approaching a minimum in recent years in Japan. The findings may contribute to global reference levels for environmental pollution of dioxins, which remains a problem for many developing countries.