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Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background and Aim: Strategies to reduce relapse using immunomodulators (IMs) after discontinuing anti-tumor necrosis factor-alpha (TNF-α) antibody treatment are controversial in patients with ulcerative colitis (UC). In this study, we assessed the association between IMs after discontinuing anti-TNF-α antibody treatment and relapse in patients with UC., Methods: This retrospective, multicenter cohort study included 257 patients with UC in clinical remission. These patients discontinued anti-TNF-α antibody treatment between June 2010 and March 2019 and were followed up until March 2020. We evaluated the differences in relapse rates between patients with IMs (IM group) and those without IMs (non-IM group) after discontinuing the treatment. Relapse was defined as further undergoing an induction treatment or colectomy. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for relapse. Exploratory analyses were performed to identify other factors that could predict relapse., Results: During the median follow-up period of 22 months (interquartile range: 10-41), 114 relapses occurred: 42/100 (42.0%) in the IM group and 72/157 (45.9%) in the non-IM group. In the multivariable analysis, IMs were not associated with relapse (HR, 0.95 [95% CI, 0.64-1.41]). In the exploratory analyses, discontinuation due to side effects (HR, 1.83 [95% CI, 1.18-2.82]) and younger age (HR, 0.99 [95% CI, 0.98-1.00]) predicted relapse., Conclusion: Immunomodulators were not associated with relapse after discontinuing anti-TNF-α antibody treatment in patients with UC. Careful patient follow-up is needed when discontinuing due to side effects or when the patient is of a younger age at the time of discontinuation., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A new chromatographic separation technique was developed for the measurement of the strontium (Sr) isotope abundance ratio using inductively coupled plasma mass spectrometry (ICP-MS). This technique, LC-ICP-MS, utilizes the addition of 18-crown-the eluent and an ODS column. The technique completely eliminates the spectral interference of 87 Rb (an isobar of 87 Sr) with 87 Sr during the ICP-MS measurement. 18-Crown-6 selectively forms a clathrate compound with some metals. When the Sr isotope abundances are measured using LC-ICP-MS with an ODS column, the addition of a specific amount of 18-crown-6 to the HNO 3 /0.1% methanol eluent elongates the retention time of Rb. Therefore, Rb can be completely separated from Sr using LC because Rb is captured into the 18-crown-6 molecule and forms a clathrate compound. The technique enables the measurement of Sr isotope abundance ratios easily, even in the presence of a large amount of Rb. The proposed technique was applied to the measurement of Sr isotope abundance ratios in rice samples. To validate the LC-ICP-MS technique, a fraction containing Sr was collected, and the 87 Sr/ 86 Sr isotope ratio was precisely measured using ICP-MS.

Purpose: An emergency caesarean section (CS) has more complications than a planned CS. The arrest of labour is a major indication for an emergency CS. This study aimed to develop a prediction model for the arrest of labour to be used in regular check-ups at 36 or 37 gestational weeks for primiparas., Methods: This was a retrospective cohort study conducted at a single institution in Japan using data from January 2007 to December 2013. Primiparas attending regular check-ups during 36 or 37 gestational weeks, with live single foetuses in a cephalic presentation were included. The outcome was the incidence of labour arrest. Candidate predictors included 25 maternal and foetal findings. We developed a prediction model using logistic regression analysis with stepwise selection. A score was assigned to each predictor of the final model based on their respective β coefficients., Results: A total of 739 women were included in the analysis. Arrest of labour was diagnosed in 47 women (6.4%), and all of them delivered by emergency CS. The predictors in the final model were a Bishop score ≤ 1, maternal height ≤ 154 cm, foetal biparietal diameter ≥ 91 mm, pre-pregnancy weight ≥ 54 kg, maternal haemoglobin concentration ≥ 11.0 g/dl, and amniotic fluid index ≥ 13. The area under the receiver operating characteristic curve was 0.783., Conclusion: We have developed the first model to predict arrested labour before its onset. Although this model requires validation using external samples, it will help clinicians and pregnant women to control gestational conditions and make decisions regarding planned CS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neuronal ceroid lipofuscinoses (NCLs) are autosomal-recessive fatal neurodegenerative diseases that occur in children and young adults, with symptoms including ataxia, seizures and visual impairment. We report the discovery of cynomolgus macaques carrying the CLN2/TPP1 variant and our analysis of whether the macaques could be a new non-human primate model for NCL type 2 (CLN2) disease. Three cynomolgus macaques presented progressive neuronal clinical symptoms such as limb tremors and gait disturbance after about 2 years of age. Morphological analyses using brain MRI at the endpoint of approximately 3 years of age revealed marked cerebellar and cerebral atrophy of the gray matter, with sulcus dilation, gyrus thinning, and ventricular enlargement. Histopathological analyses of three affected macaques revealed severe neuronal loss and degeneration in the cerebellar and cerebral cortices, accompanied by glial activation and/or changes in axonal morphology. Neurons observed throughout the central nervous system contained autofluorescent cytoplasmic pigments, which were identified as ceroid-lipofuscin based on staining properties, and the cerebral cortex examined by transmission electron microscopy had curvilinear profiles, the typical ultrastructural pattern of CLN2. These findings are commonly observed in all forms of NCL. DNA sequencing analysis identified a homozygous single-base deletion (c.42delC) of the CLN2/TPP1 gene, resulting in a frameshifted premature stop codon. Immunohistochemical analysis showed that tissue from the affected macaques lacked a detectable signal against TPP1, the product of the CLN2/TPP1 gene. Analysis for transmission of the CLN2/TPP1 mutated gene revealed that 47 (49.5%) and 48 (50.5%) of the 95 individuals genotyped in the CLN2-affected macaque family were heterozygous carriers and homozygous wild-type individuals, respectively. Thus, we identified cynomolgus macaques as a non-human primate model of CLN2 disease. The CLN2 macaques reported here could become a useful resource for research and the development of drugs and methods for treating CLN2 disease, which involves severe symptoms in humans., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The efficacy of sleep extension therapy using a remote support system (SET-R) was investigated in university students with increased social jetlag (SJL)., Methods: For this two-arm parallel randomized controlled trial, we recruited Japanese university students with SJL ≥ 60 min. The SET-R provided an individualized sleep schedule for gradual sleep extension using email and sleep hygiene education, stimulus control therapy, and progressive muscle relaxation as web content. The control group was sent an email that encouraged them to record their sleep. The duration of the intervention program was two weeks. The primary outcome was the mean change in SJL two weeks later, assessed using the Munich ChronoType Questionnaire (MCTQ). The other outcomes included Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Patient Health Questionnaire-9 (PHQ-9), and sleep quiz. A follow-up survey was conducted 6 months after the intervention., Results: Of 54 students, 26 were assigned to an intervention group and 28 to a control group. The difference in the mean change in SJL between the two groups ( n  = 26, n  = 27) at two weeks was statistically significant (27.7 min, P  = 0.048). The scores for the ESS, PHQ-9, and sleep quiz were improved in the intervention group relative to the control group. At the 6-month follow-up point, the difference in the mean change in SJL between the two groups ( n  = 22, n  = 27) was not statistically significant, but scores for the PHQ-9, and sleep quiz remained significant., Conclusions: This study demonstrated the efficacy of the SET-R among university students with increased SJL., Trial Registration: The study was registered with the UMIN Clinical Trials Registry (UMIN000042634, 2021/02/01)., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023, corrected publication 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

An online internal standard correction technique for high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was designed using an autosampler system equipped with HPLC to improve the analytical precision. The autosampler was programed to operate in the following sequence: it first takes up a portion of sample solution, rinses the nozzle, sucks air as a spacer, takes an internal standard solution and finally injects all of them into a sampling loop through an injection valve. The repeatability of the sampling (amount 20 μL) was improved from 2.5 to 1.2% using the online internal standard technique. This technique was applied to As speciation in food samples, since food safety monitoring requires high precision and high sample throughput. Rhenium was very suitable as an internal standard element due to its retention time, peak shape and water solubility. This technique effectively improved the analytical precision of the As speciation and got rid of the operation of adding an internal standard solution into samples.

Background: Although life satisfaction (LS) has been shown to predict mortality, research studying the relationship between LS and functional decline is scarce. This study examined the association between LS and functional decline across four time points in young-old Japanese adults., Methods: We analysed 1,899 community-dwelling 65-year-olds in this age-specific cohort study conducted between 2000 and 2005. The Life Satisfaction Index K was used to evaluate LS and was classified into quartiles. Functional decline was determined using the Japanese Long-Term Care Insurance (LTCI) system: 1) mild disability; 2) severe disability; 3) all-cause mortality; 4) mild or severe disability; 5) severe disability or death; 6) mild or severe disability, or death. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. The analyses were conducted in the 8 th , 10 th , 12 th , and 14 th years to assess the effect of LS on functional decline across time points., Results: The impact of LS gradually weakened over time. In the 8 th year (aged 72-73), a higher LS was associated with a lower risk of mild or severe disability among the women participants (adjusted HR [95% CI] = 0.30 [0.11-0.81]). However, the effect disappeared gradually (adjusted HR [95% CI] = 0.55 [0.27-1.14]) in the 10 th year (aged 74-75), 0.72 (0.41-1.26) in the 12 th year (aged 76-77), and 0.68 (0.41-1.14) in the 14 th year (aged 78-79). This trend continued in severe disability or death (adjusted HR [95% CI] = 0.24 [0.06-0.70], 0.31 [0.11-0.76], 0.57 [0.28-1.14], and 0.60 [0.32-1.12]) and mild or severe disability, or death (adjusted HR [95% CI] = 0.30 [0.14-0.68], 0.46 [0.24-0.87], 0.67 [0.41-1.10], and 0.65 [0.42-1.02]) in the 8 th , 10 th , 12 th , and 14 th years, respectively. No statistically significant association was found among men at any time points or in any classification of outcomes., Conclusions: Higher LS scores in 65-year-old women were associated with a lower risk for functional decline in any combination of mild disability, severe disability, or death. Additionally, the effect of LS was observed to weaken over time., Trial Registration: This is not an intervention survey and does not require registration.

Objective: This study aimed to investigate the association between daily sleep duration and incident dementia among physically and socially independent older people with/without diseases (hypertension, diabetes mellitus, cardiovascular diseases) in a Japanese age-specific cohort., Methods: We carried out a prospective cohort study including 1954 (1006 men and 948 women) Japanese individuals aged 64/65 years. Information on daily sleep duration, medical status, demographics, and lifestyle characteristics was collected by a baseline questionnaire survey and health checkup (2000-2005). Dates of incident dementia were confirmed using the nationally standardized dementia scale proposed by the Ministry of Health, Labor, and Welfare. A competing risk model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia. We treated censored cases due to death as competing events., Results: During a median of 15.6 years of follow-up, 260 participants reported incident dementia. Compared with participants without diseases and who slept 6-7.9 h/day, those with a shorter daily sleep duration of <6 h/day, presence of disease and shorter, moderate, or longer daily sleep duration ≥8 h/day had an increased risk of incident dementia (HR 1.73; 95% CI 1.04-2.88, HR 1.98; 95% CI 1.14-3.44, HR 1.44; 95% CI 1.03-2.00, and HR 2.09; 95% CI 1.41-3.09, respectively) with a significant interaction between the presence of diseases and sleep duration (p < 0.001)., Conclusions: The present findings suggest that habitual sleep duration predicts future risk of dementia., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There is a need for evidence-based medicine (EBM) education for laypersons. However, there are few materials or opportunities to learn EBM for Japanese laypersons., Objective: The aim of this study was to develop and test the usability of e-learning material on EBM for health-conscious laypersons in Japan., Methods: This study was conducted in two steps. First, content elements for the material were identified using purposive evaluation and a prototype of the e-learning material was developed. Following this, usability testing of the material was conducted. A questionnaire survey and qualitative semi-structured focus group interviews were conducted with health-conscious laypersons. Subsequently, the material was refined and finalized., Key Results: A total of 217 descriptions related to EBM were extracted from 12 materials and were integrated into 56 major elements. Each element was rated from the viewpoint of usefulness for laypersons and reviewed by four expert panelists, and finally 18 elements were confirmed, most of which were critical appraisal skills related to critical health literacy. For the usability testing after constructing the material, 25 laypersons participated, and 19 (76%) felt very / rather much interest in the contents of the material in the questionnaire. The results of five focus group interviews showed that the effectiveness of the e-learning material was influenced by the story and characters, and whether the contents of the material were consistent with interviewees' daily interests., Conclusions: The e-learning material on EBM was found to be of interest to health-conscious laypersons and appeared to be useful in participants' daily lives. This study successfully developed novel e-learning material on the essential components of EBM for laypersons in Japan. [ HLRP: Health Literacy Research and Practice . 2022;6(4):e290-e299. ] Plain Language Summary: This study developed and tested the usability of e-learning material to encourage health-conscious laypersons in Japan to learn the fundamentals of evidence-based medicine. Most of the contents of the material are related to critical health literacy. The usability testing showed that the material was of interest to non-health professionals and useful for dealing with health information in their daily lives.

Background: Crohn's disease (CD) is a disease with an impaired immune response characterized by chronic, relapsing-remitting, and progressive inflammation mainly affecting the gastrointestinal tract. Certolizumab pegol (CZP) is a biological agent that regulates the impaired immune response by controlling tumour necrosis factor-α (TNFα). However, the efficacy and safety of long-term administration of CZP for people with CD with inflammation under control are not well understood., Objectives: To assess the efficacy and safety of CZP for maintenance of remission in people with CD., Search Methods: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, and conference abstracts from inception to 23 March 2022. We contacted pharmaceutical companies involved with the production of CZP for further relevant information., Selection Criteria: We included randomized controlled trials (RCTs) comparing CZP with placebo in adults with CD., Data Collection and Analysis: Two review authors independently selected studies and extracted data. The main outcomes were failure to maintain clinical remission at week 26, failure to maintain clinical response at week 26, and serious adverse events. We planned to perform meta-analyses including all available studies if similar enough for pooling to be appropriate and calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. We analyzed the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) to indicate the magnitude of treatment effects. The same two review authors independently evaluated the risk of bias by using the Cochrane RoB 2 tool and evaluated the certainty of evidence using the GRADE framework., Main Results: We identified one study meeting our prespecified eligibility criteria. The included study enrolled 428 adults with CD who responded to induction therapy with CZP 400 mg at weeks 0, 2, and 4. The study evaluated long-term efficacy and safety of CZP administered subcutaneously every four weeks compared with placebo. The proportion of participants who failed to maintain clinical remission at week 26 was 52.3% (113/216) in the CZP group compared to 71.7% (152/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical remission at week 26 (RR 0.73, 95% CI 0.63 to 0.85). The NNTB was 5 (95% CI 4 to 9). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who failed to maintain clinical response at week 26 was 37.5% (81/216) in the CZP group compared to 64.2% (136/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical response at week 26 (RR 0.58, 95% CI 0.48 to 0.71). The NNTB was 4 (95% CI 3 to 5). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who developed serious adverse events was 5.6% (12/216) in the CZP group compared to 6.6% (14/212) in the placebo group. Treatment of CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment (RR 0.84, 95% CI 0.40 to 1.78). The NNTB was 95 (95% CI NNTH 19 to NNTB 25). We evaluated the risk of bias for this outcome as low. We evaluated the certainty of evidence as low due to the low number of events occurred and the CIs were not sufficiently narrow., Authors' Conclusions: CZP probably results in a large reduction in failure to maintain clinical remission and response at week 26 in people with CD. The evidence suggests that CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment. However, the current studies are limited to 26 weeks of follow-up and only included adults. Therefore, these conclusions cannot be used to guide longer term treatment or for treatment in children at present., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The increasing incidence of older-onset ulcerative colitis (UC), which has a higher risk of surgery, is a global health issue. However, data regarding intravenous steroid treatment, one of the important treatment options to avoid surgery, for older-onset UC is lacking., Aims: To evaluate the association between onset age and effectiveness of intravenous steroids in UC., Methods: This retrospective multicentre (27 facilities) cohort study included moderate-to-severe hospitalised UC patients who underwent their first intravenous steroids between April 2014 and July 2019. The primary outcome was clinical remission at day 30, using two-item patient-reported outcome scoring. The key secondary outcomes were risks of surgery and adverse events (death, infection and venous thrombosis) within 90 days. A modified Poisson regression model was used for analysis., Results: Overall, 467 UC patients (384 younger-onset and 83 older-onset) were enrolled. Clinical remission at day 30 was observed in 252 (65.6%) among younger-onset patients and 43 (51.8%) among older-onset patients (adjusted risk difference, -21.7% [95% CI, -36.1% to -7.2%]; adjusted risk ratio [ARR], 0.74 [95% CI, 0.59 to 0.93]). The risks of surgery and adverse events were higher in older-onset UC (20.5% vs. 3.1%; ARR, 8.92 [95% CI, 4.13 to 19.27], 25.3% vs. 9.1%; ARR, 2.19 [95% CI, 1.22 to 3.92], respectively). Four deaths occurred, all involving older-onset UC. The risks of infection and venous thrombosis were also higher in older-onset UC (18.1% vs. 8.6%, 7.2% vs. 0.5%, respectively)., Conclusions: Older-onset was associated with a lower effectiveness of intravenous steroids with higher risks of surgery and adverse events in UC., (© 2022 John Wiley & Sons Ltd.)

Background: Pulmonary hypertension (PH) is an important cause of morbidity and mortality, which leads to a substantial loss of exercise capacity. PH ultimately leads to right ventricular overload and subsequent heart failure and early death. Although early detection and treatment of PH are recommended, due to the limited responsiveness to therapy at late disease stages, many patients are diagnosed at a later stage of the disease because symptoms and signs of PH are nonspecific at earlier stages. While direct pressure measurement with right-heart catheterisation is the clinical reference standard for PH, it is not routinely used due to its invasiveness and complications. Trans-thoracic Doppler echocardiography is less invasive, less expensive, and widely available compared to right-heart catheterisation; it is therefore recommended that echocardiography be used as an initial diagnosis method in guidelines. However, several studies have questioned the accuracy of noninvasively measured pulmonary artery pressure. There is substantial uncertainty about the diagnostic accuracy of echocardiography for the diagnosis of PH., Objectives: To determine the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH., Search Methods: We searched MEDLINE, Embase, Web of Science Core Collection, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform from database inception to August 2021, reference lists of articles, and contacted study authors. We applied no restrictions on language or type of publication., Selection Criteria: We included studies that evaluated the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH, where right-heart catheterisation was the reference standard. We excluded diagnostic case-control studies (two-gate design), studies where right-heart catheterisation was not the reference standard, and those in which the reference standard threshold differed from 25 mmHg. We also excluded studies that did not provide sufficient diagnostic test accuracy data (true-positive [TP], false-positive [FP], true-negative [TN], and false-negative [FN] values, based on the reference standard). We included studies that provided data from which we could extract TP, FP, TN, and FN values, based on the reference standard. Two authors independently screened and assessed the eligibility based on the titles and abstracts of records identified by the search. After the title and abstract screening, the full-text reports of all potentially eligible studies were obtained, and two authors independently assessed the eligibility of the full-text reports., Data Collection and Analysis: Two review authors independently assessed the risk of bias and extracted data from each of the included studies. We contacted the authors of the included studies to obtain missing data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity regarding types of PH, methods to estimate the right atrial pressure, and threshold of index test to diagnose PH. All analyses were performed using the Review Manager 5, SAS and STATA statistical software., Main Results: We included 17 studies (comprising 3656 adult patients) assessing the diagnostic accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH. The included studies were heterogeneous in terms of patient distribution of age, sex, WHO classification, setting, country, positivity threshold, and year of publication. The prevalence of PH reported in the included studies varied widely (from 6% to 88%). The threshold of index test for PH diagnosis varied widely (from 30 mmHg to 47 mmHg) and was not always prespecified. No study was assigned low risk of bias or low concern in each QUADAS-2 domain assessed. Poor reporting, especially in the index test and reference standard domains, hampered conclusive judgement about the risk of bias. There was little consistency in the thresholds used in the included studies; therefore, common thresholds contained very sparse data, which prevented us from calculating summary points of accuracy estimates. With a fixed specificity of 86% (the median specificity), the estimated sensitivity derived from the median value of specificity using HSROC model was 87% (95% confidence interval [CI]: 78% to 96%). Using a prevalence of PH of 68%, which was the median among the included studies conducted mainly in tertiary hospitals, diagnosing a cohort of 1000 adult patients under suspicion of PH would result in 88 patients being undiagnosed with PH (false negatives) and 275 patients would avoid unnecessary referral for a right-heart catheterisation (true negatives). In addition, 592 of 1000 patients would receive an appropriate and timely referral for a right-heart catheterisation (true positives), while 45 patients would be wrongly considered to have PH (false positives). Conversely, when we assumed low prevalence of PH (10%), as in the case of preoperative examinations for liver transplantation, the number of false negatives and false positives would be 13 and 126, respectively., Authors' Conclusions: Our evidence assessment of echocardiography for the diagnosis of PH in adult patients revealed several limitations. We were unable to determine the average sensitivity and specificity at any particular index test threshold and to explain the observed variability in results. The high heterogeneity of the collected data and the poor methodological quality would constrain the implementation of this result into clinical practice. Further studies relative to the accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH in adults, that apply a rigorous methodology for conducting diagnostic test accuracy studies, are needed., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Although bystanders' performance is important to improve outcomes of patients after cardiac arrests, few studies have investigated the barriers of bystanders, including those who could not perform cardiopulmonary resuscitation or any other rescue actions in emergency situations. This study aimed to assess the relationship between the psychological barriers of laypersons who encountered emergency situations and their rescue actions., Methods and results: A questionnaire survey was conducted and this included laypersons who had encountered emergency situations during the last 5 years. Six questions were about the psychological barriers and 8 questions were about the laypersons' rescue actions. The primary outcome was any rescue actions performed by laypersons in an actual emergency situation. Overall, 7,827 (92.8%) of 8,430 laypersons responded; of them, 1,361 (16.1%) had encountered emergency situations during the last 5 years, and 1,220 (14.5%) were eligible for inclusion in the analyses. Of the 6 psychological barriers, "fear of approaching a collapsed person" (adjusted odds ratio [AOR] 0.50; 95% confidence interval [95% CI] 0.32-0.79) and "difficulties in judging whether to perform any rescue action" (AOR 0.63; 95% CI 0.40-0.99) were significantly associated with performing any rescue actions., Conclusions: The fear of approaching a collapsed person and difficulties in judging whether to take any actions were identified as the psychological barriers in performing any rescue actions by laypersons who encountered emergency situations.

Background: Mucosal healing is a treatment target for patients with ulcerative colitis. However, the relevance of proactive treatment for residual inflammation limited to the distal colon is unclear., Materials and Methods: Patients with ulcerative colitis who had extensive colitis in clinical remission and underwent colonoscopy were retrospectively enrolled and followed up for 2 years. Patients with complete endoscopic remission (CER; Mayo endoscopic subscore [MES] of 0) and those with short-segment distal inflammation (SS; active inflammation only in the sigmoid colon and/or rectum with a proximal MES of 0) were compared for the incidence of minor (only symptomatic) and major (need for induction treatments or hospitalization) relapses., Results: A total of 91 patients with CER and 54 patients with SS were identified and 63 relapses (47 minor and 16 major) were analyzed. Univariate analysis showed that minor relapses were significantly more frequent in the SS group than in the CER group (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.25-3.97), but major relapses were not more frequent in the SS group than in the CER group (HR, 1.78; 95% CI, 0.65-4.83). Multivariable analysis showed that SS was the only risk factor significantly associated with minor relapse (HR, 2.38; 95% CI, 1.31-4.36). When the SS group was stratified by MES of 1 vs 2/3, minor relapses were significantly more frequent in the subgroup with MES of 2/3 than in the CER group, whereas the incidence of major relapse remained similar., Conclusions: Residual short-segment distal inflammation is not a risk factor for major relapses as long as endoscopic remission is achieved in the proximal colon. Therefore, reactive but not proactive treatment may be appropriate for such lesions., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory bowel disease (IBD). NUDT15-associated subcellular thiopurine metabolism has not been investigated in primary lymphocytes. We hypothesized that NUDT15 mutation increases DNA-incorporated deoxythioguanosine (dTG) and induces apoptosis in lymphocytes., Methods: DNA-incorporated dTG in peripheral blood mononuclear cells (PBMCs) and 6-thioguanine nucleotides (6-TGN) in red blood cells were measured in patients with IBD undergoing thiopurine treatment. The association of a single nucleotide polymorphism for NUDT15 (rs116855232) with dTG PBMC was examined. The pro-apoptotic effect of DNA-incorporated dTG was examined ex vivo in association with NUDT15 genotypes by co-culturing patient-derived peripheral CD4 + T lymphocytes with 6-thioguanine (6-TG)., Results: dTG PBMC was significantly higher in NUDT15 variants than in non-variants. dTG PBMC , but not 6-TGN RBC , negatively correlated with peripheral lymphocyte counts (r =  - 0.31 and  - 0.12, p = 0.012 and 0.173, respectively). DNA-incorporated dTG significantly accumulated to a greater extent in lymphocytes from NUDT15 variants when co-cultured with 6-TG ex vivo than in those from non-variants and was associated with decreased proliferation and increased apoptosis., Conclusion: Increased DNA-incorporated dTG may be responsible for thiopurine-induced leukocytopenia through cell apoptosis in IBD patients with NUDT15 mutation., (© 2021. Japanese Society of Gastroenterology.)

Background: Concurrent chemoradiotherapy (CCRT) with tri-weekly high-dose cisplatin (HDC) is considered the standard regimen. However, due to significant toxicity, various weekly low-dose schedules have been increasingly used. We investigated the tolerability and survival of patients with head and neck squamous cell carcinoma (HNSCC) who underwent CCRT with low-dose weekly cisplatin (LDC) for Japanese population., Methods: A retrospective review was conducted among patients with HNSCC who were treated with CCRT/LDC in our institute. Ninety-five patients who met the criteria were enrolled in this study. We evaluated the cycle and cumulative cisplatin dose, completion rate of radiotherapy, adverse events, and survival outcome., Results: The mean cycles and cumulative cisplatin dose were 4.7 cycles and 187 mg/m 2 . All patients completed planned dose of radiation without prolonged breaks. Leucopoenia was the most frequent dose-limiting factor and 44% patients developed grade 3 or 4 toxicity. The 2-year overall survival and recurrence-free survival were 93% and 74%, respectively. The significant differences of survival outcomes between the patients with total cisplatin dose (⩾200 mg and <200 mg) or among age distribution (35-55, 56-75, and ⩾76) were not observed., Conclusions: Concurrent chemoradiotherapy/LDC can be safely administered with acceptable toxicity and survival outcome even if the patients with higher age, lower eGFR, and so on., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background and Aim: Thiopurines are often used in combination with mesalazine for the treatment of ulcerative colitis (UC). Mesalazine formulations are delivered to the digestive tract by various delivery systems and absorbed as 5-aminosalicylic acid (5-ASA). 5-ASA is known to inhibit thiopurine S-methyltransferase (TPMT) activity and to affect thiopurine metabolism. There have been no studies comparing TPMT inhibition by multimatrix mesalazine (MMX) with other formulations. We investigated the difference in TPMT inhibition by different mesalazine formulations and prospectively confirmed the clinical relevance., Methods: Plasma concentrations of 5-ASA, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), and TPMT activities were measured in UC patients receiving various mesalazine formulations (time-dependent or pH-dependent mesalazine or MMX) as monotherapy. Patients already on both time-dependent or pH-dependent mesalazine and thiopurines switched their mesalazine to MMX, examining 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) 0 and 8 weeks after switching. Clinical relapse after switching was also monitored for 24 weeks., Results: Plasma 5-ASA and N-Ac-5-ASA levels were significantly higher in patients receiving time-dependent mesalazine (n = 12) compared with pH-dependent mesalazine (n = 12) and MMX (n = 15), accompanied by greater TPMT inhibition. Prospective switching from time-dependent mesalazine to MMX decreased 6-TGN levels, increased those of 6-MMP, and increased 6-MMP/6-TGN ratios. Furthermore, this resulted in significantly more relapses than switching from pH-dependent mesalazine to MMX., Conclusions: Time-dependent mesalazine has higher plasma 5-ASA and N-Ac-5-ASA levels and greater TPMT inhibition than MMX. Therefore, switching from time-dependent mesalazine to MMX may lead to an increase of 6-MMP/6-TGN, which may reduce the clinical effectiveness of thiopurines, warranting close monitoring after switch., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We performed this study to provide the latest evidence of the diagnostic accuracy of all Aspergillus antibodies for chronic pulmonary aspergillosis (CPA). In this meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and other databases, until 19 March 2020, for studies that examined the diagnostic accuracy of each Aspergillus-specific antibody for CPA and assessed the risk of bias using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. We integrated the results using a hierarchical summary receiver operating characteristic (HSROC) model and calculated the point estimates of specificity with sensitivity fixed at 0.90 using the HSROC curve. We identified 32 published and one unpublished studies, including 75 studies on five antibody test types: 18 of precipitin test (2810 participants), 46 of IgG (8197), three of IgA (283), six of IgM (733) and two of combined IgG and IgM (IgG + IgM) (920). The results of specificity with sensitivity fixed at 0.90 were as follows: precipitin test, 0.93 (95% credible intervals: 0.86, 1.00); IgG, 0.90 (0.86, 0.95); IgA, 0.74 (0.00, 1.00); IgM, 0.50 (0.37, 0.53); IgG + IgM, 0.47 (0.00, 1.00). However, the precipitin test showed imprecision and instability in the sensitivity analysis. Most studies had a high risk of bias due to the case-control design. Although there is lack of applicability for malignancy or immunosuppressive patients, our study suggests a preference for IgG over other antibody tests in CPA screening. Particularly, IgG should be used as an adjunct when ruling out CPA., (© 2021 Wiley-VCH GmbH.)

Background & Aims: The accuracy of ultrasound for evaluation of individual colorectal segments in patients with inflammatory bowel diseases (IBD) has not been evaluated in a systematic review. We evaluated the diagnostic accuracy of ultrasound in different colorectal segments of patients with IBD., Methods: We searched publication databases from inception through March 2019 for studies that assessed the accuracy of ultrasound in detection of inflammation in right, transverse, and left colon and in rectum in patients with IBD, using findings from colonoscopy as the reference standard. Subgroup analyses were performed including IBD type, patient age, body mass index, and study design. The risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool., Results: Nineteen studies (1101 patients) were included in the qualitative synthesis. After we assessed the risk of bias, 7 studies (comprising 84 patients with Crohn's disease and 420 patients with ulcerative colitis) were included in the meta-analysis. Bowel wall thickness ≥ 3 mm identified colorectal segments with inflammation with 86.4% pooled sensitivity (95% CI, 76.1%-92.7%) and 88.3% pooled specificity (95% CI, 58.1%-97.6%). In rectum only, bowel wall thickness ≥ 3 mm identified inflammation with 74.5% sensitivity (95% CI, 53.0%-88.3%) and 69.5% specificity (95% CI, 33.6%-91.1%). Diagnostic accuracy was comparable among subgroups. Increased bowel wall flow and loss of stratification had higher true-positive odds ratios., Conclusions: Based on meta-analysis of patient-level data, ultrasound has higher diagnostic accuracy for detecting inflammation in colon than rectum in patients with IBD. Studies are needed to increase the accuracy of ultrasound detection of inflammation in rectum., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Predicting adverse health events and implementing preventative measures are a necessary challenge. It is important for healthcare planners and policymakers to allocate the limited resource to high-risk persons. Prediction is also important for older individuals, their family members, and clinicians to prepare mentally and financially. The aim of this study is to develop a prediction model for within 11-year dependent status requiring long-term nursing care or death in older adults for each sex., Methods: We carried out age-specified cohort study of community dwellers in Nisshin City, Japan. The older adults aged 64 years who underwent medical check-up between 1996 and 2000 were included in the study. The primary outcome was the incidence of the psychophysically dependent status or death or by the end of the year of age 75 years. Univariable logistic regression analyses were performed to assess the associations between candidate predictors and the outcome. Using the variables with p-values less than 0.1, multivariable logistic regression analyses were then performed with backward stepwise elimination to determine the final predictors for the model., Results: Of the 1525 female participants at baseline, 105 had an incidence of the study outcome. The final prediction model consisted of 15 variables, and the c-statistics for predicting the outcome was 0.763 (95% confidence interval [CI] 0.714-0.813). Of the 1548 male participants at baseline, 211 had incidence of the study outcome. The final prediction model consisted of 16 variables, and the c-statistics for predicting the outcome was 0.735 (95% CI 0.699-0.771)., Conclusions: We developed a prediction model for older adults to forecast 11-year incidence of dependent status requiring nursing care or death in each sex. The predictability was fair, but we could not evaluate the external validity of this model. It could be of some help for healthcare planners, policy makers, clinicians, older individuals, and their family members to weigh the priority of support.

Background and Aim: The usefulness of second-generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission., Methods: Forty-one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C-reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared., Results: The correlations of CSUC with white blood cell, platelet, albumin, C-reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were r s  = 0.13, 0.27, -0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1 year than in 29 patients who remained in clinical remission (2.83 ± 1.95 vs 0.72 ± 1.00, P < 0.01). Receiver operator characteristic curve analysis showed that CSUC ≥ 1 was a predictor of relapse (area under the curve of 0.82, sensitivity of 83.3%, specificity of 58.6%) and maybe superior to fecal biomarkers. In the univariate analysis, patients with CSUC of 0 had a lower relapse rate than those with CSUC of ≧ 1 (P = 0.03, log-rank test). After analyzing patients who underwent CCE2 within 6 months after the successful induction treatment, results showed that those with CSUC of ≤ 1 remained in clinical remission for a year., Conclusion: CSUC predicts relapse within 1 year in UC patients in clinical remission, especially when used 6 months after induction treatment., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Evaluating the effects of dietary intake on mortality in older populations has become increasingly important in modern aging societies. The objective of the present study was to investigate the associations between food group intakes and all-cause mortality among a young older population. We conducted a prospective study on 1,324 men and 1,338 women aged 64-65 years at baseline who were living in a suburban city from 1996 to 2005. The participants were followed for all-cause mortality from 1996 through 2015 to assess the effects of 17 food group intakes (g) per 1,000 kcal after multivariable adjustments in proportional hazard models. During follow-up (mean: 13.2 years), 339 deaths were registered. In women, total mortality was significantly and inversely associated with the consumption of milk and dairy products and vegetables. The hazard ratios across intake quartiles after multivariable adjustment were 1, 0.70 (95% confidence interval: 0.42-1.17), 0.66 (0.40-1.10), and 0.40 (0.22-0.75) ( P for trend = 0.003) for milk and dairy products, and 1, 0.77 (0.46-1.28), 0.83 (0.50-1.38), and 0.42 (0.23-0.78) ( P for trend = 0.008) for vegetables. In men, a positive association was found between total mortality and sugar and sweetener consumption ( P for trend = 0.038). Higher consumption of milk and dairy products and vegetables was suggested to reduce all-cause mortality in young older women., Competing Interests: The authors declare no competing financial interests.

Gadolinium chelates are widely used as contrast agents for magnetic resonance imaging (MRI). In recent decades, the amount of Gd in river water has been increasing owing to the input of Gd-based contrast agents. To identify and quantify the Gd-based contrast agents in river water, the novel technique of hydrophilic interaction liquid chromatography (HILIC) hyphenated with inductively coupled plasma-mass spectrometry (ICP-MS) was developed. To avoid deposition of carbon on the ICP-MS interface, a mobile phase consisting of an ammonium acetate buffer diluted with pure water was applied to separate Gd-based contrast agents. Despite the absence of an organic solvent in the mobile phase, six Gd-based contrast agents, Gd-DTPA, Gd-EOB-DTPA, Gd-DOTA, Gd-DTPA-BMA, Gd-BT-DO3A, and Gd-HP-DO3A, were successfully separated. This technique was applied for river water samples. As a result, Gd-DOTA, Gd-BT-DO3A, and Gd-HP-DO3A were observed from the sample near the outfall of a wastewater treatment plant (WWTP), indicating that at least some of the Gd-based contrast agents are passed through treatment in a WWTP. In addition to Gd-based contrast agents, unidentified Gd compounds were found to be present in river water. These results infer that transformation and/or dissociation of Gd chelates may be caused during the treatment procedure in a WWTP., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Based on structural data on the nasal cavity and brain of the cynomolgus monkey, species differences in the olfactory bulb and cribriform plate were discussed from the viewpoint of direct delivery from the nose to the brain. Structural 3D data on the cynomolgus monkey skull were obtained using X-ray computed tomography. The dimensions of the nasal cavity of the cynomolgus monkey were 5 mm width × 20 mm height × 60 mm depth. The nasal cavity was very narrow and the olfactory region was far from the nostrils, similar to rats and humans. The weight and size of the monkey brain were 70 g and 55 mm width × 40 mm height × 70 mm depth. The olfactory bulb of monkeys is plate-like, while that of humans and rats is bulbar, suggesting that the olfactory area connected with the brain of monkeys is narrow. Although the structure of the monkey nasal cavity is similar to that of humans, the size and shape of the olfactory bulb are different, which is likely to result in low estimation of direct delivery from the nose to the brain in monkeys.

Background: Little is known about the association between serum potassium level on hospital arrival and neurological outcome after out-of-hospital cardiac arrest (OHCA). We investigated whether the serum potassium level on hospital arrival had prognostic indications for patients with OHCA., Methods: This prospective, multicenter observational study conducted in Osaka, Japan (CRITICAL study) enrolled consecutive patients with OHCA transported to 14 participating institutions from 2012 to 2016. We included adult patients aged ⩾18 years with OHCA of cardiac origin who achieved return of spontaneous circulation and whose serum potassium level on hospital arrival was available. Based on the serum potassium level, patients were divided into four quartiles: Q1 (K ⩽3.8 mEq/L), Q2 (3.8< K⩽4.5 mEq/L), Q3 (4.5< K⩽5.6 mEq/L) and Q4 (K >5.6 mEq/L). The primary outcome was one-month survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2., Results: A total of 9822 patients were registered, and 1516 of these were eligible for analyses. The highest proportion of favorable neurological outcome was 44.8% (189/422) in Q1 group, followed by 30.3% (103/340), 11.7% (44/375) and 4.5% (17/379) in the Q2, Q3 and Q4 groups, respectively ( p <0.001). In the multivariable analysis, the proportion of favorable neurological outcome decreased as the serum potassium level increased ( p <0.001)., Conclusions: High serum potassium level was significantly and dose-dependently associated with poor neurological outcome. Serum potassium on hospital arrival would be one of the effective prognostic indications for OHCA achieving return of spontaneous circulation.

Background: Little is known about the association between prehospital cardiopulmonary resuscitation duration for adults with out-of-hospital cardiac arrest and outcome by the location of arrests. This study aimed to investigate the association between prehospital cardiopulmonary resuscitation duration and one-month survival with favourable neurological outcome., Methods: We analysed 276,391 adults aged 18 years and older with out-of-hospital cardiac arrest of medical origin before emergency medical service arrival. Prehospital cardiopulmonary resuscitation duration was defined as the time from emergency medical service-initiated cardiopulmonary resuscitation to prehospital return of spontaneous circulation or to hospital arrival. The primary outcome was one-month survival with favourable neurological outcome (cerebral performance category 1 or 2). The association between prehospital cardiopulmonary resuscitation duration and favourable neurological outcome was assessed using univariable and multivariable logistic regression analyses., Results: The proportion of favourable neurological outcomes was 2.3% in total, 7.6% in public locations, 1.5% in residential locations and 0.7% in nursing homes ( P  < 0.001). In univariable and multivariable logistic regression analyses, longer prehospital cardiopulmonary resuscitation duration was associated with poor neurological outcome, regardless of arrest location ( P for trend < 0.001). Patients with shockable rhythm in both public and residential locations had better neurological outcome than those in nursing homes at any time point, and residential and public locations had a similar neurological outcome tendency among patients with shockable rhythm., Conclusions: Longer prehospital cardiopulmonary resuscitation duration was independently associated with a lower proportion of patients with favourable neurological outcomes. Moreover, the association between prehospital cardiopulmonary resuscitation duration and neurological outcome differed according to the location of arrest and the first documented rhythm.

Solid-organ transplant recipients require long-term immunosuppressants to prevent graft rejection. However, immunosuppressant use increases the risk of malignancy. Radiotherapy can be a treatment option for patients who are medically inoperable or refuse surgery; however, whether the irradiation of transplanted organs is safe remains unclear. We present two patients with malignancies that developed in transplanted organs and were treated with dynamic tumor-tracking (DTT) stereotactic body radiation therapy (SBRT). The first patient underwent transplantation owing to liver cirrhosis caused by hepatitis C virus and subsequently developed hepatocellular carcinoma in the donated liver. There was no evidence of recurrence 12 months post-treatment, and liver function enzyme levels did not deviate from their pre-SBRT baselines. The second patient had a solitary tongue cancer metastasis in a transplanted lung; she also had a history of interstitial pneumonia caused by scleroderma. Six weeks after DTT-SBRT, she developed grade 3 radiation pneumonitis but recovered with oral steroids; she experienced no tumor recurrence after 14 months, although her respiratory function was worse than it was pre-SBRT owing to post-transplant rejection. DTT-SBRT is thus feasible for treating tumors that arise in transplanted lungs and livers., Competing Interests: Conflict of interestTakashi Mizowaki has an advisory contract with Hitachi, Ltd., Japan., (© The Japan Society of Clinical Oncology 2020.)

Introduction: The aim of this trial was to investigate whether a digital device that provides real-time visualized brushing instructions would contribute to the removal of dental plaque over usual brushing instructions., Methods: We conducted a single-center, parallel-group, stratified permuted block randomized control trial with 1:1 allocation ratio. Eligibility criteria included people aged ≥ 18 years, and exclude people who met the following criteria: severely crowded teeth; using interdental cleaning implement; having external injury in the oral cavity, or stomatitis; having less than 20 teeth; using orthodontic apparatus; visited to a dental clinic; having the possibility of consulting a dental clinic; having a dental license; not owning a smartphone or tablet device; smoker; taken antibiotics; pregnant; an allergy to the staining fluid; and employee of Sunstar Inc. All participants received tooth brushing instructions using video materials and were randomly assigned to one of two groups for four weeks: (1) an intervention group who used the digital device, providing real-time visualized instructions by connection with a mobile application; and (2) a control group that used a digital device which only collected their brushing logs. The primary outcome was the change in 6-point method plaque control record (PCR) score of all teeth between baseline and week 4. The t-test was used to compare the two groups in accordance with intention-to-treat principles., Results: Among 118 enrolled individuals, 112 participants were eligible for our analyses. The mean of PCR score at week 4 was 45.05% in the intervention group and 49.65% in the control group, and the change of PCR score from baseline was -20.46% in the intervention group and -15.77% in the control group (p = 0.088, 95% confidence interval -0.70-10.07)., Conclusions: A digital device providing real-time visualized brushing instructions may be effective for the removal of dental plaque., Competing Interests: The authors have read the journal’s policy, and the authors have the following competing interests to declare: NT, MN, and YO are employees of Sunstar Inc. (manufacturer of GUMPLAY, the study device in this project). GUMPLAY has been on the market since before the start of research. It was supplied and used to conduct the study, however, there was no other conflict of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development associated with this research to declare.

This study investigated the association between intake of common alcoholic and non-alcoholic beverages and breast cancer risk among Japanese women. This study included 33,396 Japanese women aged 40-79 years from 24 areas in Japan from the Collaborative Cohort study. During the follow-up period (≥20 years), 245 incidents or mortal breast cancers were documented. Multivariable logistic regression analysis was performed to assess the independent association between breast cancer risk and the intake of Japanese green tea, coffee, and alcohol. Japanese green tea was the most commonly consumed non-alcoholic beverage (81.6% of participants), followed by coffee (34.7%) and alcohol (23.6%). No significant associations were identified between the intake of green tea and coffee with breast cancer risk (odds ratio OR 1.15, 95% confidence interval [CI] 0.82-1.60, and OR 0.84, 95% CI 0.64-1.10, respectively). Alcohol intake was associated with significant breast cancer risk (OR 1.46, 95% CI 1.11-1.92), and even infrequent alcohol consumption (.

Background: Although schools are key places that conduct cardiopulmonary resuscitation (CPR) and public-access defibrillation (PAD) programs, out-of-hospital cardiac arrest (OHCA) in educational institutions is poorly understood. This study describes the characteristics and outcomes of such OHCAs., Methods and results: Data for OHCAs of any cause occurring in educational institutions between 2013 and 2015 were extracted from the All-Japan Utstein Registry. Patient characteristics and outcomes were documented. Subjects were divided into 6 age groups (0-1, 2-5, 6-11, 12-14, 15-17, and ≥18 years). Among the 783 eligible OHCA patients, most received bystander CPR regardless of age, ranging from 73.9% in those aged ≥18 years to 90.0% in those aged 2-5 years. However, the proportion receiving PAD differed by age group, ranging from 2.9% in those aged 0-1 years to 66.7% in those aged 12-14 years. The proportion of patients with 1-month survival with favorable neurological outcome differed significantly by age group, being extremely low among patients aged 0-1 years (zero for OHCA of cardiac origin), but high among patients aged 6-11, 12-14, and 15-17 years (69.2%, 77.5%, and 70.0%, respectively) for OHCA of cardiac origin., Conclusions: The outcomes of OHCA occurring in educational institutions, where PAD is available, differed significantly by age.

We investigated the impact of bystander-initiated cardiopulmonary resuscitation (CPR), dispatcher assistance (DA), and location of arrest on survival and outcomes after out-of-hospital cardiac arrest (OHCA).From a nationwide population-based registry of OHCA patients in Japan, we enrolled adult patients with bystander-witnessed OHCA of medical origin between 2013 and 2015. The primary outcome measure was a neurologically favorable outcome, defined by cerebral performance category 1 or 2. Multivariable logistic regression analysis was used to assess the effects of bystander CPR and DA by location of arrest. A total of 104,621 cases were included (15,984 bystander CPR without DA [15.3%], 40,087 bystander CPR with DA [38.3%], and 48,550 no bystander CPR [46.4%]). In public locations, both the bystander-CPR-with-DA group (22.9% [1,068/4,665]; adjusted odds ratio (AOR), 1.62; 95% confidence interval (CI), 1.43-1.85) and the bystander-CPR-without-DA group (25.8% [918/3,557]; AOR, 1.43; 95% CI, 1.24-1.65) had neurologically favorable outcomes compared with the no-bystander-CPR group (9.9% [610/6,133]). In residential locations, the AORs were 1.44 (95% CI, 1.22-1.70) in the bystander-CPR-without-DA group and 1.60 (95% CI, 1.45-1.77) in the bystander-CPR-with-DA group. However, in nursing homes, bystander CPR was not associated with improved outcomes of OHCA, regardless of the implementation of DA.Bystander CPR with or without DA had better outcomes after OHCA in residential and public locations but not in nursing homes.

Ulcerative colitis and Crohn's disease, the most common types of inflammatory bowel disease, are idiopathic, intractable disease characterized by chronic inflammation in the intestine. In recent years, studies elucidating the clinical characteristics of these diseases and basic researches have suggested that the diseases are induced by the immunological abnormalities through the involvement of environmental factors with their predisposition. In Japan, significant progress of basic and epidemiological researches has been developed for these diseases and the clinical guidelines have been established. However, no fundamental treatment for these diseases has been established yet. The current number of patients in Japan continues to increase, with at least 180,000 patients suffering from ulcerative colitis and 40,000 suffering from Crohn's disease. Thus, further studies are required to understand these diseases and improve medical treatments., Competing Interests: Conflicts of Interest Toshifumi Hibi received lecture fees from Mitsubishi-Tanabe Pharma, Kyorin Pharmaceutical, Abbvie GK, Janssen, Mochida Pharmaceutical, JIMRO, Takeda Pharmaceutical, Gilead Sciences, Kissei Pharmaceutical, Zeria Pharmaceutical, Ferring Pharmaceutical and Nippon Kayaku, advisory/consultancy fees from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical, EA Pharma, Janssen, Eli Lilly, Pfizer and Zeria Pharmaceutical and research grant from Abbvie GK, JIMRO and Zeria Pharmaceutical., (Copyright © 2020 by The Japan Society of Coloproctology.)

Background: Randomized controlled trials or observational studies showed that the use of public-access automated external defibrillator (AED) was effective for patients with out-of-hospital cardiac arrest (OHCA). However, it is unclear whether public-access AED use is effective for all patients with OHCA irrespective of first documented rhythm. We aimed to evaluate the effect of public-access AED use for OHCA patients considering first documented rhythm (shockable or non-shockable) in public locations., Methods: From the Utstein-style registry in Osaka City, Japan, we obtained information on adult patients with OHCA of medical origin in public locations before emergency-medical-service personnel arrival between 2011 and 2015. Primary outcome was 1-month survival with favorable neurological outcome. Multivariable logistic regression analysis was performed to assess the association between the public-access AED pad application and favorable neurological outcome after OHCA by using one-to-one propensity score matching analysis., Results: Among 1743 eligible patients, a total of 336 (19.3%) patients received public-access AED pad application. The proportion of patients who survived 1-month with favorable neurological outcome was significantly higher in the pad application group than in the non-pad application group (29.8% vs. 9.7%; adjusted odds ratio [AOR], 2.85; 95% confidence interval [CI], 1.73-4.68, AOR after propensity score matching, 2.46; 95% CI, 1.29-4.68). In a subgroup analysis, the AORs of patients with shockable or non-shockable rhythms were 3.36 (95% CI, 1.78-6.35) and 2.38 (95% CI, 0.89-6.34), respectively., Conclusions: Public-access AED pad application was associated with better outcome among patients with OHCA of medical origin in public locations irrespective of first documented rhythm., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The use of public-access automated external defibrillators (AEDs) has become common in Japan. To provide a strategy for appropriate public-access AED deployment, we assessed public-access defibrillation (PAD) by laypersons and the outcomes following out-of-hospital cardiac arrest (OHCA) among adult patients by location of arrest., Methods: From a nationwide, prospective, population-based registry of patients after OHCA in Japan, we enrolled adult patients with bystander-witnessed OHCA of medical origin in public locations between 2013 and 2015. The primary outcome measure was one-month favorable neurological outcome defined by cerebral performance category 1 or 2. Factors associated with favorable neurological outcome after ventricular fibrillation (VF) were assessed by multivariable logistic regression analysis., Results: A total of 20,970 adult bystander-witnessed OHCAs of medical origin occurred in public locations. Of those, the proportions of PAD by location were: 13.1% (757/5761) in public areas, 15.9% (333/2089) at workplaces, 26.0% (544/2095) in recreation/sports areas, 36.1% (112/310) in educational institutions, and 5.8% (241/4151) on streets/highways. In a multivariable analysis of VF arrests, both bystander cardiopulmonary resuscitation [adjusted odds ratio (AOR), 1.78; 95% confidence interval (CI), 1.54-2.07] and PAD (AOR, 2.33; 95% CI, 2.05-2.66), and emergency medical service (EMS) response time (AOR, 0.89; 95% CI, 0.87-0.90) were associated with improved outcomes. Earlier PAD initiated by bystanders before EMS arrival was also associated with better outcomes after OHCA., Conclusions: In Japan, where public-access AEDs are well-disseminated, the PAD program worked effectively for adult OHCA of medical origin occurring in public locations. Notably, the proportions of PAD differed substantially according to specific public locations., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aim: This study aimed to investigate the association between daily sleep duration and incident disability among younger elderly individuals in Japan., Methods: We carried out a prospective cohort study, the New Integrated Suburban Seniority Investigation Project, including 1895 (962 men and 933 women) Japanese physically and socially independent individuals aged ≥65 years. Information on daily sleep duration, demographic, lifestyle characteristics and medical status were collected by questionnaire and health checkup every year from 1996 through 2005. Dates of incident disability were confirmed using the certification for the long-term care insurance in Japan. We treated censored cases due to death as competing events. A competing risk model was used to calculate the hazard ratio and 95% confidence interval for incident disability., Results: During a median of 12.7 years of follow up, 256 participants (114 men and 142 women) reported incident disability. Compared with a sleep duration of 7-7.9 h/day, sleeping <6 h/day showed an increased risk of incident disability (hazard ratio 1.64, 95% confidence interval 1.13-2.38 for total; hazard ratio 1.90, 95% confidence interval 1.19-3.03 for women)., Conclusions: The present findings suggest that shorter sleep duration was associated with a higher risk of incident disability among older Japanese people. Geriatr Gerontol Int 2019; 19: 945-949., (© 2019 Japan Geriatrics Society.)

Background: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response., Objectives: The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD., Search Methods: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP., Selection Criteria: We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients., Data Collection and Analysis: We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI)., Main Results: Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy., Authors' Conclusions: Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.

Background: Little is known about the associations between the duration of prehospital cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) and outcomes among paediatric patients with out-of-hospital cardiac arrests (OHCAs). We investigated these associations and the optimal prehospital EMS CPR duration by the location of arrests., Methods: We included paediatric patients aged 0-17 years with OHCAs before EMS arrival who were transported to medical institutions after resuscitation by bystanders or EMS personnel. We excluded paediatric OHCA patients for whom CPR was not performed, who had cardiac arrest after EMS arrival, whose EMS CPR duration were < 0 min or ≥120 min and who had cardiac arrest in healthcare facilities. Prehospital EMS CPR duration was defined as the time from CPR initiation by EMS personnel to the time of prehospital return of spontaneous circulation or to the time of hospital arrival. The primary outcome was 1-month survival with a favourable neurological outcome (cerebral performance category scale 1 or 2). Statistical analysis was performed with Mann-Whitney U tests for numerical variables and chi-squared test for categorical variables. Univariable and multivariable logistic regression analyses were applied to assess the association between prehospital EMS CPR duration and a favourable neurological outcome, and crude and adjusted odds ratios and their 95% confidence intervals were calculated., Results: The proportion of patients with a favourable neurological outcome was lower in residential locations than in public locations (2.3% [66/2865] vs 10.8% [113/1048]; P < .001). In both univariable and multivariable logistic regression analyses, the proportion of patients with a favourable neurological outcome decreased as prehospital EMS CPR duration increased, regardless of the location of arrests (P for trend <.001). However, some patients achieved a favourable neurological outcome after a prolonged prehospital EMS CPR duration (> 30 min) in both groups (1.4% [6/417] in residential locations and 0.6% [1/170] in public locations)., Conclusions: A longer prehospital EMS CPR duration is independently associated with a lower proportion of patients with a favourable neurological outcome. The association between prehospital EMS CPR duration and neurological outcome differed significantly by location of arrests.

Background: This study assessed whether the dissemination of public-access defibrillation (PAD) at the population level is associated with an increase in neurologically favorable outcomes among patients experiencing ventricular fibrillation (VF) in public vs. residential locations in Japan., Methods and results: We enrolled adult patients with bystander-witnessed VF between 2013 and 2015. The primary outcome measure was 1-month neurologically favorable outcome defined by cerebral performance category 1 or 2. The number of survivors with neurologically favorable outcome attributed to PAD after VF arrest was estimated by location of arrest. A total of 16,252 adult patients with bystander-witnessed VF arrest were analyzed. In public locations, 29.3% (2,334/7,973) of out-of-hospital cardiac arrest (OHCA) patients received PAD, whereas 1.1% (89/8,279) of OHCA patients received PAD in residential locations. OHCA patients with PAD had significantly better neurological outcomes compared with those without PAD in public locations (51.8% vs. 25.5%, P<0.001), whereas there were no significant differences in neurologically favorable outcome between patients with or without PAD in residential locations (22.5% vs. 18.6%, P=0.357). The total number of patients with neurologically favorable outcomes attributed to PAD was estimated at 615 in public locations, but only 3 in residential locations., Conclusions: In Japan, when compared with residential locations, PAD works more successfully in public locations for adults with bystander-witnessed VF arrest.

Background: It is recommended globally that shocks by automated external defibrillators (AEDs) should be delivered immediately when a shockable out-of-hospital cardiac arrest (OHCA) occurs. However, the actual time-interval from collapse to first shock by public-access AED and its impact on subsequent outcome has not been extensively investigated in real-world settings., Methods: OHCA data from 2013 to 2015 were obtained from the All-Japan Utstein Registry. Bystander-witnessed OHCA patients with shockable rhythm who were shocked by public-access AED in public locations were included. The primary endpoint was 1-month survival with favourable neurological outcome, and the association between time-interval from collapse to first shock by public-access AED and subsequent outcome was assessed., Results: During the study period, 28% (2282/8126) of bystander-witnessed OHCA cases with shockable rhythm were shocked by public-access AED in public locations. The proportion of OHCA patients who were shocked by public-access AED within 5 min from collapse was 58% (1323/2282). Among these patients, the proportion of 1-month survival with favourable neurological outcome was 62% (815/1317). The proportion significantly decreased with increased time from collapse to shock by public-access AED (48% for 6-10 min, 38% for 11-15 min, 30% for 16-20 min, and 7% for 21-25 min; p-for-trend <0.001), and no patient survived if shock delivery occurred more than 26 min after OHCA., Conclusion: In Japan, earlier shock by public-access AED led to better outcome after bystander-witnessed OHCA with shockable rhythm in public locations. However, the proportion of OHCA patients who received early shock was still low in public locations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Our objective was to assess the characteristics such as public-access defibrillation (PAD) by laypersons and the outcomes after pediatric out-of-hospital cardiac arrest by location in the PAD era., Methods: From a nationwide, prospective, population-based registry of out-of-hospital cardiac arrest patients in Japan, we enrolled consecutive pediatric patients aged ≤17 years before emergency medical service (EMS) arrival between 2013 and 2015. The primary outcome measure was 1-month survival, with favorable neurologic outcome defined as cerebral performance category 1 or 2. Factors associated with favorable neurologic outcome were assessed using multivariable logistic regression analysis., Results: Among 3991 eligible pediatric out-of-hospital cardiac arrests, the proportion of PAD was 0.2% (5/2888) at residence, 1.6% (2/125) in public areas, 0.9% (3/321) on streets/highways, 21.6% (11/51) at recreation/sports event areas, 46.1% (82/178) at education institutions, and 1.2% (5/428) in others. In the multivariable analysis, arrest witnessed by family members (adjusted odds ratio [AOR], 5.25; 95% confidence interval [CI], 3.22-8.58) and nonfamily members (AOR, 2.45; 95% CI, 1.26-4.77), first documented ventricular fibrillation (AOR, 12.29; 95% CI, 7.08-21.35), PAD (AOR, 2.63; 95% CI, 1.23-5.62), and earlier EMS response time (AOR for 1-min increment, 0.88; 95% CI, 0.81-0.94) were associated with improving outcome. As for locations, recreation/sports event areas (AOR, 3.43; 95% CI, 1.17-10.07) and education institutions (AOR, 3.03; 95% CI, 1.39-6.63) were also associated with favorable neurologic outcome., Conclusions: In Japan, where public-access automated external defibrillators are well disseminated, characteristics such as PAD and outcomes for pediatric out-of-hospital cardiac arrest before EMS arrival differed substantially by location., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To let the early elderly live well, understanding how lifestyle and psychosocial factors related to a decline in competence in daily living is important., Methods: We investigated the associations between lifestyle and psychosocial factors at age 64 years and a decline in the Tokyo Metropolitan Institute of Gerontology Index of Competence score of ≥ 2 points at age 70 years among the participants in comprehensive medical check-ups living in a city in Japan. Multivariable logistic regression analyses were performed separately for men and women., Results: Of the 1113 eligible men and 1203 eligible women, 110 men and 80 women showed a deteriorated competence in daily living during the 6 years. In men, risk was increased with ≥ 2 nighttime awakenings (multivariable odds ratio [mOR] 2.14, 95% confidence interval [CI] 1.19-3.86) and living alone (mOR 4.68, 95% CI 1.22-18.0), whereas risk was significantly decreased with a medium or fast gait (mOR 0.37 and 0.21, 95% CI 0.21-0.67 and 0.08-0.58) and high academic achievement (mOR 0.32 and 0.43, 95% CI 0.19-0.53 and 0.25-0.72). In women, risk was decreased with high life satisfaction (mOR 0.39, 95% CI 0.16-0.91) and participation in community activities (mOR 0.50, 95% CI 0.29-0.86) but increased with depressive mood (mOR 1.86, 95% CI 1.09-3.18)., Conclusion: Living alone for men and low life satisfaction for women at age 64 years were markedly associated with the risk of a subsequent declining competence in daily living.

Although majority of out-of-hospital cardiac arrests (OHCAs) occur in private residential locations, that is, at home, the details of emergency patients with OHCAs occurring at home have not been sufficiently investigated at the national level. We obtained data of OHCA cases from the All-Japan Utstein Registry, including detailed information of the location of cardiac arrest. Cases of OHCA occurring at home from 2013 to 2015 were included. Patient characteristics and outcomes after OHCA were described based on the location of cardiac arrest. During the 3-year study period, a total of 212,722 cases of OHCA were documented at home (186,219 in detached houses and 26,503 in multiple dwelling houses), and it accounted for 65.0% of all OHCA cases in Japan. The majority of OHCAs occurred in the living room/bedroom (67.7%), followed by the bathroom (12.9%), entrance/corridor (5.3%), and toilet (4.8%). The characteristics of OHCA at home, widely varied by location of cardiac arrest and residence type. The proportion of bystander-initiated cardiopulmonary resuscitations was less than half at all locations and ranged from 27.9% to 47.1%. The proportion of public-access defibrillation was also low regardless of the location of arrest and ranged from 0.0% to 0.2%. Consequently, the proportion of 1-month survival with favorable neurological outcome was low regardless of the location of arrest and ranged from 0.3% to 2.3%. In conclusion, OHCA occurrence at home accounted for approximately 2/3 of all OHCA cases in Japan, but their outcomes were extremely poor regardless of the location of cardiac arrest., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To assess whether sex-based disparities occur by location of arrest in out-of-hospital cardiac arrest (OHCA) victims receiving bystander cardiopulmonary resuscitation (BCPR)., Patients and Methods: This secondary analysis of the All-Japan Utstein Registry included patients 18 years and older with OHCA of medical origin in public or residential locations, witnessed by bystanders, from January 1, 2013, through December 31, 2015. We assessed the likelihood of receiving BCPR based on sex differences and by arrest location. Sex-based disparities in receiving BCPR stratified by age and location were assessed via multivariable logistic regression analyses., Results: During the study period, 373,359 OHCAs were registered, and 84,734 were eligible for analysis. Overall, 54.2% of women (3123 of 5766) and 57.0% of men (8672 of 15,213) received BCPR in public locations (P<.001), and 46.5% of women (11,263 of 24,216) and 44.0% of men (17,390 of 39,539) received BCPR in residential locations (P<.001). In the multivariable logistic regression analyses, there was no significant difference between the sexes in terms of who received BCPR in public locations (adjusted odds ratio [AOR], 0.99; 95% CI, 0.92-1.06), and women had a higher likelihood of receiving BCPR in residential locations (AOR, 1.08; 95% CI, 1.04-1.13). In public locations, women aged 18 to 64 years were less likely to receive BCPR (AOR, 0.86; 95% CI, 0.74-0.99), and when witnessed by a non-family member, women were less likely to receive BCPR regardless of age group., Conclusion: The reasons for this sex-based disparity should be better understood to facilitate public health interventions., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background/aims: The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis., Methods: Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day)., Results: The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group., Conclusions: Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.