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Background Suicide amidst the coronavirus disease (COVID-19) pandemic is an important issue. In Japan, the number of suicides in April 2020 decreased by nearly 20% from that in 2019. To assess the impact of an infectious disease pandemic, excess mortality is often discussed. Our main purpose was evaluating excess mortality from suicide in Japan during the early pandemic period. Methods We used data on suicides collected by the National Police Agency of Japan until June 2020. We estimated excess mortality during the early pandemic period (March-June 2020) using a time-series model of the number of suicides before the pandemic. A quasi-Poisson model was employed for the estimation. We evaluated excess mortalities by the categories of age and sex, and by prefecture. Results No significant excess mortality was observed throughout the early pandemic; instead, a downward trend in the number of suicides for both sexes was noted. For males, negative values of excess mortalities below the lower bound of the 95% prediction interval were observed in April and May. All numbers of females during the period were included in the interval, and the excess mortalities in June were positive and higher than those in April and May. In Tokyo, the number of suicides was below the lower bound throughout the period. Conclusion Our results suggest that various changes, such as communication, and social conditions amid the early COVID-19 pandemic induced a decrease in suicides in Japan. However, continuous monitoring is needed to evaluate the long-term effects of the pandemic on suicides.

Aim To assess the teratogenic risk of domperidone by comparing the incidence of major malformation with domperidone to a control. Methods Pregnancy outcome data were obtained for women at two Japanese facilities that provide counseling on drug use during pregnancy between April 1988 and December 2017. The incidence of major malformation was calculated among infants born to women taking domperidone (n = 519), nonteratogenic drugs (control, n = 1673), or metoclopramide (reference, n = 241) during the first trimester of pregnancy. Using the control group as reference, the crude odds ratio (OR) of the incidence of major malformation in the domperidone and metoclopramide groups was calculated using univariable logistic regression analysis. Adjusted OR was also calculated using multivariable logistic regression analysis adjusted for various other factors. Results The incidence of major malformation was 2.9% (14/485, 95% confidence interval [CI]: 1.6–4.8) in the domperidone group, 1.7% (27/1554, 95%CI: 1.1–2.5) in the control group, and 3.6% (8/224, 95%CI: 1.6–6.9) in the metoclopramide group. The adjusted multivariable logistic regression analysis showed no significant difference in incidence between the control and domperidone groups (adjusted OR: 1.86 [95%CI: 0.73–4.70], p = 0.191) or between the control and metoclopramide groups (adjusted OR: 2.20 [95%CI: 0.69–6.98], p = 0.183). Conclusions This observational cohort study showed that domperidone exposure during the first trimester was not associated with increased risk of major malformation in infants. These results may help alleviate the anxiety of patients who took domperidone during pregnancy.

Background The prediction of COVID-19 disease behavior in the early phase of infection is challenging but urgently needed. MuLBSTA score is a scoring system that predicts the mortality of viral pneumonia induced by a variety of viruses, including coronavirus, but the scoring system has not been verified in novel coronavirus pneumonia. The aim of this study was to validate this scoring system for estimating the risk of disease worsening in patients with COVID-19. Methods This study included the patients who were treated between April 1 st and March 13 th , 2020. The patients were classified into mild, moderate, and severe groups according to the extent of respiratory failure. MuLBSTA score was applied to estimate the risk of disease worsening in each severity group and we validated the utility of the scoring system. Results A total of 72 patients were analyzed. Among the 46 patients with mild disease, 17 showed disease progression to moderate or severe disease after admission. The model showed a sensitivity of 100% and a specificity of only 34.5% with a cut-off value of 5 points. Among the 55 patients with mild or moderate disease, 6 deteriorated to severe disease, and the model showed a sensitivity of 83.3% and a specificity of 71.4% with a cut-off value of 11 points. Conclusions This study showed that MuLBSTA score is a potentially useful tool for predicting COVID-19 disease behavior. This scoring system may be used as one of the criteria to identify high-risk patients worsening to life-threatening status.

No study has investigated the clinical and radiographic risk factors for the deterioration of quality of life (QOL) beyond 6 months after osteoporotic vertebral fractures (OVF). The purpose of this study was to identify the predictors associated with poor QOL improvement after OVF. This post hoc analysis included 166 women aged 65–85 years with acute 1-level OVFs. For the patient-reported outcome measures, scores on the European Quality of Life-5 Dimensions (EQ-5D) scale, and visual analogue scale (VAS) for low back pain were used. Lateral radiography at 0, 12, and 48 weeks and magnetic resonance imaging (MRI) at enrollment and at 48 weeks were performed. The associations between baseline variables with change scores for EQ-5D were investigated using a multiple linear regression model. Univariate analysis showed that time since fracture, EQ-5D score, and VAS for low back pain at 0 week showed significant association with increased EQ-5D score from 0 to 48 weeks. According to the multiple regression analysis, the following equation was obtained: increased EQ-5D score from 0 to 48 weeks = 1.305 – 0.978 × EQ-5D at 0 week – 0.021 × VAS for low back pain at 0 week – 0.006 × age + (fluid-intensity T2-weighted MR image patterns: − 0.037, except for fluid-intensity T2-weighted MR image patterns: + 0.037). In conclusion, older patients with severe low back pain and fluid-intensity T2-weighted MR image patterns were more likely to have lower QOL improvements after OVFs and may therefore need extra support to improve QOL

Objective To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus-preserving surgery (UPS) in terms of survival prognosis. Methods A regional multi-institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables. Results Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6 years (range 12-87 years), and 56 (30.3%) women underwent UPS. After PS-based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence-free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non-UPS groups. Conclusion UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.

Background After the Fukushima Daiichi Nuclear Power Plant accident, a preliminary ultrasound-based screening for thyroid cancer was conducted to establish a baseline for subsequent evaluations. In this survey, we assessed the relationship between the proportion of non-examinees and characteristics of the target populations. Methods After summarizing a regional difference of non-examinees among the population of 359,200 (primary evaluation) and 2,246 (confirmatory testing) individuals who were living in Fukushima Prefecture on March 11, 2011, we estimated odds ratios (ORs) for each characteristic, including age, sex, area of residence, and moving after the accident, based on the proportion of non-examinees for the primary examination and the confirmatory testing, using a multivariate logistic regression model. Results The dataset included 64,117 non-examinees (primary evaluation) and 194 (confirmatory testing). The logistic regression result indicated that girls were not likely to be non-examinees compared to boys, with adjusted OR of 0.80 (95% confidence interval [CI], 0.78-0.81) for the primary evaluation. Odds were lowest for children 6-10 years old (OR 0.26; 95% CI, 0.25-0.27), and higher for those 11-15 years old (OR 1.28; 95% CI, 1.25-1.32) and over 16 years old (OR 5.30; 95% CI, 5.16-5.43) when compared to children 0-5 years old. Individuals residing in the western part of the prefecture showed higher ORs. There was a higher proportion of non-examinees among those who moved after the accident compared to those who did not in the primary evaluation (OR 1.72; 95% CI, 1.64-1.79). Conclusions In addition to demographic characteristics, a change of residence could be a potential factor that influenced the proportion of non-examinees. Our results will help proper interpretation of reports and prospective management of the survey.

Background Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. Methods Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. Results The ALL-COP SCORE rule included albumin (2/FIO2 ratio (2 (> 45 mmHg, 2 points), HCO3− ( 2/3, 2 points; 1/2–2/3, 1 point). Patients with 4–5, 6–7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. Conclusions ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. Trial registration This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia caused by impairment of arginine vasopressin (AVP) secretion. In this study, we evaluated plasma AVP concentrations during a hypertonic saline infusion test using a new AVP radioimmunoassay (RIA) which is now available in Japan. Thirteen control subjects, mostly with hypothalamo-pituitary disease but without CDI, and 13 patients with CDI were enrolled in the study. Whether or not subjects had CDI was determined based on the totality of clinical data, which included urine volumes and osmolality. Regression analysis of plasma AVP and serum Na concentrations revealed that the gradient was significantly lower in the CDI group than in the control group. The area under the receiver-operating-characteristic (ROC) curve was 0.99, and the

OBJECTIVES To determine whether a progressive early mobilization protocol improves patient outcomes, including in-hospital mortality and total hospital costs. DESIGN Retrospective preintervention and postintervention quality comparison study. SETTINGS Single tertiary community hospital with a 12-bed closed-mixed ICU. PATIENTS All consecutive patients 18 years old or older were eligible. Patients who met exclusion criteria or were discharged from the ICU within 48 hours were excluded. Patients from January 2014 to May 2015 were defined as the preintervention group (group A) and from June 2015 to December 2016 was the postintervention group (group B). INTERVENTION Maebashi early mobilization protocol. MEASUREMENTS AND MAIN RESULTS Group A included 204 patients and group B included 187 patients. Baseline characteristics evaluated include age, severity, mechanical ventilation, and extracorporeal membrane oxygenation, and in group B additional comorbidities and use of steroids. Hospital mortality was reduced in group B (adjusted hazard ratio, 0.25; 95% CI, 0.13-0.49; p < 0.01). This early mobilization protocol is significantly associated with decreased mortality, even after adjusting for baseline characteristics such as sedation. Total hospital costs decreased from $29,220 to $22,706. The decrease occurred soon after initiating the intervention and this effect was sustained. The estimated effect was $-5,167 per patient, a 27% reduction. Reductions in ICU and hospital lengths of stay, time on mechanical ventilation, and improvement in physical function at hospital discharge were also seen. The change in Sequential Organ Failure Assessment score and Sequential Organ Failure Assessment score at ICU discharge were significantly reduced after the intervention, despite a similar Sequential Organ Failure Assessment score at admission and at maximum. CONCLUSIONS In-hospital mortality and total hospital costs are reduced after the introduction of a progressive early mobilization program, which is significantly associated with decreased mortality. Cost savings were realized early after the intervention and sustained. Further prospective studies to investigate causality are warranted.

Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

Introduction There are no established risk classification for post-cardiac arrest syndrome (PCAS) patients at the Emergency Department (ED) undergoing targeted temperature management (TTM). The aim of this study was to externally validate a simplified version of our prognostic score, the “post-Cardiac Arrest Syndrome for Therapeutic hypothermia score” (revised CAST [rCAST]) and estimate the predictive accuracy of the risk classification based on it. Methods For the external validation, we used data from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multicenter, prospective registry of OHCA patients across Japan. Eligible patients were PCAS patients treated with TTM at 33–36 °C between June 2014 and December 2015. We validated the accuracy of rCAST for predicting the neurological outcomes at 30 and 90 days. Results Among the 12,024 OHCA patients, the data of 460 PCAS patients treated by TTM were eligible for the validation. The areas under the curve of rCAST for predicting the neurological outcomes at 30 and 90 days were 0.892 and 0.895, respectively. The estimated sensitivity and specificity of the risk categories for the outcomes were as follows: 0.95 (95% CI: 0.92–0.98) and 0.47 (0.40–0.55) for the low (rCAST: ≤5.5), 0.62 (0.56–0.68) and 0.48 (0.40–0.55) for the moderate (rCAST: 6.0–14.0), and 0.57 (0.51–0.63) and 0.95 (0.91–0.98) for the high severity category (rCAST: ≥14.5). Conclusions The rCAST was useful for predicting the neurological outcomes with high accuracy in PCAS patients, and the three grades was developed for a risk classification based on the rCAST.

In 2014, our hospital introduced inhaled nitric oxide (iNO) therapy combined with high-flow nasal cannula (HFNC) oxygen therapy after extubation following the Fontan procedure in patients with unstable hemodynamics. We report the benefits of HFNC-iNO therapy in these patients. This was a single-center, retrospective review of 38 patients who underwent the Fontan procedure between January 2010 and June 2016, and required iNO therapy before extubation. The patients were divided into two groups: patients in Epoch 1 (n = 24) were treated between January 2010 and December 2013, receiving only iNO therapy; patients in Epoch 2 (n = 14) were treated between January 2014 and June 2016, receiving iNO therapy and additional HFNC-iNO therapy after extubation. There were no significant differences between Epoch 1 and 2 regarding preoperative cardiac function, age at surgery, body weight, initial diagnosis (hypoplastic left heart syndrome, 4 vs. 2; total anomalous pulmonary venous return, 5 vs. 4; heterotaxy, 7 vs. 8), intraoperative fluid balance, or central venous pressure upon admission to the intensive care unit. Epoch 2 had a significantly shorter duration of postoperative intubation [7.2 (3.7-49) vs. 3.5 (3.0-4.6) hours, p = 0.033], pleural drainage [23 (13-34) vs. 9.5 (8.3-18) days, p = 0.007], and postoperative hospitalization [36 (29-49) vs. 27 (22-36) days, p = 0.017]. Two patients in Epoch 1 (8.3%), but none in Epoch 2, required re-intubation. Our results suggest that HFNC-iNO therapy reduces the duration of postoperative intubation, pleural drainage, and hospitalization.

Background There is limited quantitative research on the effect of physician attire on patient–physician relationships. This study aimed to measure the influence of Japanese family physicians’ attire on the “human” aspects of medical care in terms of patient-perceived relational empathy. Methods This was a multicenter, prospective, controlled trial conducted in primary clinics in Japan. We explored the effects of family physician attire (white coat vs. casual attire) on patient-perceived empathy. Family physicians were allocated to alternate weeks of wearing a white coat or casual attire during consultations. Patients’ perceptions of physician empathy were evaluated using the self-rated Japanese Consultation and Relational Empathy (CARE) Measure. We used a linear mixed model to analyze the CARE Measure scores, adjusting for cluster effects of patients nested within doctor, age, and sex of patients, and doctors’ sex and years of clinical experience. We used the same method with Bonferroni adjustment to analyze patient sex differences in perceived empathy. Results A total of 632 patients of seven family physicians were allocated to white coat-wearing consultations (n = 328), and casual attire-wearing consultations (n = 304). There was no difference in CARE Measure scores between white coat and casual primary care consultations overall (p = 0.162). Subgroup analysis of patient sex showed that CARE Measure scores of male patients were significantly higher in the Casual group than in the White coat group (adjusted p-value = 0.044). There was no difference in female patient scores between White coat and Casual groups (adjusted p-value = 1.000). Conclusions This study demonstrated that physician attire (white coat or casual attire) in a primary care setting did not affect patient-perceived relational empathy overall. However, male patients of physicians wearing casual attire reported higher physician empathy. Although empathy cannot be reduced to simple variables such as attire, white coats may have a negative effect on patients, depending on the context. Family physicians should choose their attire carefully. Trial registration Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000037687 (Registered August 14, 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042749). The study was prospectively registered.

Background Anterior decompression with fusion (ADF) has often been performed for degenerative cervical myelopathy (DCM) in patients with poor cervical spine alignment and/or anterior cord compression. We aimed to identify clinical and radiological predictors associated with neurological recovery after ADF. Methods This post-hoc analysis from a prospective multicenter study included patients who were scheduled for ADF for DCM. The patients who received other surgeries (laminoplasty, posterior decompression and fusion) were excluded. The associations between baseline clinical and radiographic variables (age, sex, body mass index, etiology, cervical lordosis, range of motion, C7 slope, C2-7 sagittal vertical axis [SVA], thoracic kyphosis [TK], lumbar lordosis, sacral slope, SVA, pelvic tilt, T1 pelvic angle [TPA], the Japanese Orthopedic Association score for the assessment of cervical myelopathy [C-JOA], European Quality of Life Five Dimensions Scale [EQ-5D], Neck Disability Index [NDI], Physical Component Summary of the SF-36 [PCS], and Mental Component Summary of the SF-36) and the recovery rates as the outcome variables were investigated in the univariate regression analysis. Then, the independent predictors for increased recovery rates were evaluated using a stepwise multiple regression analysis. Results In total, 37 patients completed the 1 year follow-up. The recovery rate was significantly correlated with SVA (p = 0.001) and TPA (p = 0.03). Univariate regression analyses showed that age (Regression coefficient = − 0.92, p = 0.049), SVA (Regression coefficient = − 0.57, p = 0.004) and PCS (Regression coefficient = 0.80, p = 0.03) score were significantly associated with recovery rate. Then, a stepwise multiple regression analysis identified the independent predictors of recovery rate after ADF as TK (p = 0.01), PCS (p = 0.03), and SVA (p = 0.03). According to this prediction model, the following equation was obtained: recovery rate = − 8.26 + 1.17 × (TK) − 0.45 × (SVA) + 0.85 × (PCS) (p = 0.002, R2 = 0.44). Conclusion Patients with lower TK, lower PCS score, and higher SVA were more likely to have poor neurological recovery after ADF. Therefore, patients with DCM and these predictors who undergo ADF should be warned about poor recovery and be required to provide adequate informed consent.

Identifying risk factors from pregnancy is essential for preventing child maltreatment. However, few studies have explored prenatal risk factors assessed at pregnancy registration. This study aimed to identify prenatal risk factors for child maltreatment during the first three years of life using population-level survey data from pregnancy notification forms. This prospective cohort study targeted all mothers and their infants enrolled for a 3- to 4-month-old health check between October 2013 and February 2014 in five municipalities in Aichi Prefecture, Japan, and followed them until the child turned 3 years old. Administrative records of registration with Regional Councils for Children Requiring Care (RCCRC), which is suggestive of child maltreatment cases, were linked with survey data from pregnancy notification forms registered at municipalities (n = 893). Exact logistic regression was used for analysis. A total of 11 children (1.2%) were registered with RCCRC by 3 years of age. Unmarried marital status, history of artificial abortion, and smoking during pregnancy were significantly associated with child maltreatment. Prenatal risk scores calculated as the sum of these prenatal risk factors, ranging from 0 to 7, showed high predictive power (area under receiver operating characteristic curve 0.805, 95% confidence interval (CI), 0.660–0.950) at a cut-off score of 2 (sensitivity = 72.7%, specificity = 83.2%). These findings suggest that variables from pregnancy notification forms may be predictors of the risk for child maltreatment by the age of three.

Background There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. Objectives This study aimed to investigate the factors associated with the clinical improvement of COVID-19. Methods Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. Results Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002–1.114), no hypertension (HR, 2.077; 95% CI, 1.006–4.287), and low D-dimer levels (

Background The coronavirus disease 2019 (COVID-19) has severely impacted the lives of children and adolescents. School closure, one of the critical changes during the first COVID-19 wave, caused decreases in social contacts and increases in family time for children and adolescents. This can have both positive and negative influences on suicide, which is one of the robust mental health outcomes. However, the impact of the COVID-19 crisis on children and adolescents in terms of suicide is unknown. Objective This study investigates the acute effect of the first wave of the COVID-19 pandemic on suicide among children and adolescents during school closure in Japan. Data Total number of suicides per month among children and adolescents under 20 years old between January 2018 and May 2020. Methods Poisson regression was used to examine whether suicide increased or decreased during school closure, which spanned from March to May 2020, compared with the same period in 2018 and 2019. Robustness check was conducted using all data from January 2018 to May 2020. Negative binomial regression, a model with overdispersion, was also performed. Results We found no significant change in suicide rates during the school closure (incidence rate ratio (IRR) = 1.15, 95% confidence interval (CI): 0.81 to 1.64). We found the main effect of month, that is, suicides significantly increased suicides in May (IRR: 1.34, 95% CI: 1.01 to 1.78) compared to March, but the interaction terms of month and school closure were not significant (p > 0.1). Conclusions As preliminary findings, this study suggests that the first wave of the COVID-19 pandemic has not significantly affected suicide rates among children and adolescents during the school closure in Japan.

Background Fibrotic hypersensitivity pneumonitis (HP) is a chronic interstitial lung disease caused by allergic responses to repeated exposures to a causative antigen. Therapeutic evidence of the use of corticosteroids to treat fibrotic HP remains lacking, although corticosteroids are recognized as a major treatment option. The purpose of this study was to evaluate the efficacy of corticosteroid treatment in patients with fibrotic HP in a propensity score-matched cohort. Methods A retrospective review of the medical records from 2005 to 2019 in a single center was conducted, and 144 patients with fibrotic HP were identified. Semiquantitative scores for lung abnormalities on HRCT were evaluated. Patients who received (PDN group) and did not receive (non-PDN group) corticosteroid treatment were matched using a propensity score method. Survival rates, serial changes in pulmonary function and annual changes in HRCT scores were compared in the matched cohort. Results In the matched analysis, 30 individuals in the PDN group were matched with 30 individuals in the non-PDN group, the majority of whom had ILD without extensive fibrosis. The survival rate was significantly better in the PDN group (P = 0.032 for the stratified Cox proportional hazards model; HR, 0.250). The absolute changes in FVC at 6, 12, and 24 months from baseline were significantly better in the PDN group. Fewer patients in the PDN group experienced annual deterioration, as reflected in the HRCT score, due to ground-glass attenuation, consolidation, reticulation, traction bronchiectasis and honeycombing. Conclusion We demonstrated that corticosteroids improved survival and slowed fibrotic progression in a matched cohort, the majority of whom had ILD without extensive fibrosis. Fibrotic HP with less severe fibrosis may benefit from corticosteroid treatment. We propose that the early initiation of corticosteroids should be considered for fibrotic HP when worsening fibrosis is observed.

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures. This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed. Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65–85 years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6 months. At 48 weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0 weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment. Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures. III

Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high-risk for recurrence and poor postoperative outcome. Methods Exosomal miR-4525, miR-451a and miR-21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. Results Exosomal miR-4525, miR-451a and miR-21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR-4525, miR-451a and miR-21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR-4525, miR-451a and miR-21 levels in PVB were independent prognostic factors for overall survival and disease-free survival. There was a negative correlation between the expressions of miR-4525 and MEN1 mRNA, miR-451a and CAB39 mRNA, and t miR-21 and PDCD4 mRNA. Conclusions miR-4525, miR-451a and miR-21 in PVB are potential biomarkers identifying patients at high-risk for recurrence and poor survival in resected PDAC patients.

Background Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). Methods We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. Results The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8). Conclusions The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

Introduction The aim of this study was to evaluate the differential effects of mild therapeutic hypothermia (MTH) in post-cardiac arrest syndrome (PCAS) patients depending on the presence/absence of hypoxic encephalopathy (HE) in the early brain CT images obtained before the initiation of MTH. Methods We conducted a retrospective review of the data of a total of 129 patients with PCAS who were treated by MTH (34 °C) or normothermia treatment (NT) (35 °C or 36 °C), and had undergone brain CT examination prior to the initiation of these treatments. We divided the subjects into 4 groups, namely, the HE(−)/MTH, HE(−)/NT, HE(+)/MTH, and HE(+)/NT groups, for evaluating the interaction effect between the two variables. Then, we compared the neurological outcomes between the HE(−)/MTH and HE(−)/NT groups by multivariate logistic analysis. Good outcome was defined as a Cerebral Performance Category score of ≤2 at 30 days. Results The percentages of subjects with a good outcome in the HE(−)/MTH and HE(−)/NT group were 68.9% (42/61) and 36.1% (13/36), respectively (p = .003), while those in the HE(+)/MTH and HE(+)/NT groups were lower, at 7.4% (2/27) and 20.0% (1/5), respectively (p = .410), suggesting a statistically significant interaction effect between the two variables (pinteraction = 0.002). In the HE(−) group, MTH was associated with a higher odds ratio of a good outcome as compared to NT (OR 6.80, 95% CI 1.19–38.96, p = .031). Conclusions The effect of MTH in patients with PCAS differed depending on the presence/absence of evidence of HE on the early CT images.

Background Reducing near‐fatal asthma exacerbations is a critical problem in asthma management. Objectives To determine patterns of factors preceding asthma exacerbations in a real‐world setting. Methods In a nationwide prospective study of 190 patients who had experienced near‐fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2‐week period before admission. Results Three distinct clusters of symptoms were defined employing the self‐reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle‐aged patients with low Body mass index and tendency to depression who had stopped anti‐asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle‐aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long‐acting beta‐agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild‐moderate symptoms. There were no differences in overuse of short‐acting beta‐agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. Conclusion To reduce severe or life‐threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti‐type 2 response‐targeted therapies should be considered for cluster C.

Background Surgical results of patients with resected distal cholangiocarcinoma (DCC) were evaluated to elucidate prognostic impact of the type of preoperative biliary drainage (PBD). Methods Eighty-eight patients with resected DCC were stratified into two groups according to the type of PBD: the percutaneous transhepatic biliary drainage (PTBD) group (n = 25) and the endoscopic biliary drainage (EBD) group (n = 63). Results Overall 5-year survival rate of the patients in the PTBD group was poorer than in the EBD group (24% vs. 52%, P = 0.020). On univariate analysis, PTBD, pancreatic invasion, perineural invasion, and lymph node involvement were significant prognostic factors for poor overall survival. On multivariate analysis, PTBD was the only significantly independent prognostic factor for poor overall survival. The incidence of liver metastasis was significantly higher in the PTBD group than in the EBD group (32.0% vs. 13.3%, P = 0.034). Conclusions PTBD should be avoided as much as possible in patients with DCC since the patients who underwent PTBD had poorer overall survival and higher incidence of liver metastasis than those who underwent EBD.

Summary Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a coordinated beating motion that drives directional cerebrospinal fluid (CSF) flow and guides neuroblast migration. At the apical cortex of these multi-ciliated cells, asymmetric localization of planar cell polarity (PCP) proteins is required for the planar polarization of microtubule dynamics, which coordinates cilia orientation. Daple is a disheveled-associating protein that controls the non-canonical Wnt signaling pathway and cell motility. Here, we show that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies required for the directional cerebrospinal fluid flow. These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells.

ObjectivesThe association between near-misses/minor injuries and moderate/severe injuries has yet to be investigated longitudinally. This study aimed to examine the longitudinal association between near-misses/minor injuries and moderate/severe injuries by the presence/absence of depressive symptoms using 1-year follow-up data obtained from a nationally representative sample of workers in Japan.MethodsOf the 18 231 eligible participants at time 1 (T1), 12 127 who responded to the 1-year follow-up survey at time 2 (T2) (response rate: 66.5%; 4370 females and 7757 males; mean age (SD), 45.3 (10.5) years) were included in the analysis. Multivariate logistic regression analyses were performed with the presence/absence of moderate/severe injuries at T2 as the dependent variable.ResultsIn total, 36.4% of participants reported depressive symptoms at T1. During the follow-up period, 1.6% of participants reported moderate/severe injuries in industrial settings. After adjusting for relevant variables, participants who reported near-misses (OR=1.7 (95% CI, 1.3 to 2.4)) and minor injuries (OR=2.5 (95% CI, 1.3 to 4.7)) at T1 were more likely to have moderate/severe injuries at T2 compared to those who reported no near-misses/minor injuries. However, this association was stronger in participants who did not have depressive symptoms at T1 than in those who had depressive symptoms.ConclusionsWhile the predictive value of near-misses/minor injuries for the occurrence of moderate/severe injuries by the presence/absence of depressive symptoms should be cautiously interpreted, our findings suggest that the development and utilisation of near-miss/minor injury reporting systems may help reduce the likelihood of moderate/severe injuries among workers, especially those without depressive symptoms.

Background The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. Methods We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Results Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. Conclusions The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.

Purpose: A posterior staphyloma has been reported to be present in some eyes with retinitis pigmentosa (RP), and the purpose of this study was to determine the macular curvature of non-highly myopic RP eyes. Methods: This was a retrospective, observational study. The medical charts of the right eyes of 143 patients with RP and 60 controls whose axial length ranged from 21.5 mm to 26.0 mm were reviewed. The mean curvature of Bruch's membrane within 6 mm of the central macula obtained from the horizontal optical coherence tomographic images were evaluated as the mean macular curvature index (MMCI). The relationships between the MMCI and other clinical factors were assessed. Results: The mean MMCI of RP patients (-13.73 ± 9.63 × 10-5 μm-1) was significantly lower than that of the controls (-6.63 ± 5.63 × 10-5 μm-1). This indicated a deeper concave shape of the macula in RP eyes (P < 0.001). The MMCI was significantly correlated with the age (r = 0.20; P = 0.016) and the axial length (r = -0.24; P = 0.004). Further analysis suggested a nonlinear effect of the ellipsoid zone width on the macular curvature in the RP eyes. Conclusions: There is a high incidence of steeper macular curvatures even in non-highly myopic RP eyes, and the steepness was also affected by the degree of photoreceptor degeneration. (Less)

Supplemental Digital Content is available in the text, Since Fukushima nuclear accident in 2011, thyroid ultrasound examinations have been conducted. The first full-scale examination detected 71 thyroid-cancer cases. This study examined whether radiation exposure was associated with thyroid-cancer incidence. Subjects were participants in the baseline screening and newborns during the 2011 fiscal year. Under nested matched case-control study design, 10 controls per each case were selected by matching the age, sex, baseline screening results, and interval between examinations. With 3 dose levels of external radiation: 1.3 + mSv (upper), 0.8 to 1.3 (middle), and 0.0 to 0.8 (reference), we applied 2 logistic models adjusting for 3 participation-proportions (primary, secondary, and fine-needle aspiratory cytology), overweight, and the B-result of baseline screening (Model 1), and past medical history, family history of thyroid cancer, and frequencies of eating seafood and seaweed in addition to the parameters in Model 1 (Model 2). We examined each model in 3 ways: (a) excluding subjects with a missing radiation exposure dose; and substituting (b1) median or (b2) mean dose of the municipality with missing dose. Odds ratios (ORs) of middle-dose exposure were (a) 1.35 (0.46–3.94), (b1) 1.55 (0.61–3.96), and (b2) 1.23 (0.50–3.03) for Model 1, and (a) 1.18 (0.39–3.57), (b1) 1.31 (0.49–3.49), and (b2) 1.02 (0.40–2.59) for Model 2. For upper-dose exposure, similar results were obtained. Past medical history was significantly associated (odds ratio = 2.04–2.08) with both (b1) and (b2) in Model 2. No significant associations were obtained between the external radiation exposure and thyroid-cancer incidence.

Objective The aim of this study was to investigate the clinical characteristics of young patients with stage I clear-cell carcinoma (CCC) and evaluate the prognostic factors and effects of fertility-sparing surgery (FSS) using propensity score (PS) adjustment. Methods We conducted a regional multi-institutional study between 1986 and 2017. Among 4,277 patients with ovarian tumor, clinical and pathological data of 103 fertile women with stage I unilateral CCC were collected. We evaluated survival and reproductive outcomes in these patients. Additionally, to analyze the effects of FSS, baseline imbalance between patients with and those without FSS was adjusted with an inverse probability of treatment weighting using PSs involving independent clinical variables. Results The mean patient age was 39.4 years, and the median follow-up period for surviving patients was 55.6 months. In multivariate analysis, stage IC2/IC3 (vs. IA/IC1) was the only independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS). FSS was not associated with poorer prognosis when compared to the prognosis with non-preserving surgery with regard to both RFS and OS. No statistical difference in survival outcomes between FSS and other approaches was confirmed after PS adjustment. Among patients who underwent FSS, four deliveries with healthy neonates were noted without any gestational complications. Conclusion FSS can be considered in stage I CCC, specifically in stage IA and IC1 patients who strongly desire to have children in the future. Further clinical research is needed to clarify the optimal application of FSS for CCC.

Long working hours and a lack of sleep have been suggested to negatively affect the safety of workers. Here, we examined the association between long working hours/sleep-related problems and near-misses/injuries in industrial settings using a nationally representative sample of workers in Japan. Based on the composition ratio of workers by industry, sex, and age in Japan, data from a web-based cross-sectional survey for 18,682 participant full-time workers (7,098 female and 11,584 male; mean age, 43.7 [standard deviation 11.1] years) were analyzed. Nearly 30% and 5% of participants reported any types of near-misses during the past six months and injuries during the past year, respectively. For all types of near-misses and some types of injuries, a significant difference in frequency distribution was observed by industry. After adjustment for demographic, job-, and life-related variables, participants who worked long hours (i.e., more than 51 hours per week) were more likely to report job-related near-misses/injuries than those who worked 35-40 hours per week. The presence of sleep-related problems was also significantly related to near-misses and injuries. However, while sleep-related problems were significantly associated with near-misses/injuries in all industries, the association between long working hours and near-misses/injuries differed by industry. Odds ratios for near-misses/injuries were strongly significant in the "transport/postal services" industry for those who worked more than 51 hours per week compared to those who worked 35-40 hours per week. Comprehensive protective measures for workers, including (1) reducing total hours of service/job-related fatigue, (2) maintaining sufficient sleep hours/good sleep, and (3) increasing awareness about the impact of overwork/long working hours and sleep-related problems on workers' safety among employers, workers, clients/customers, and the general public might be effective for preventing near-misses and injuries in industrial settings among workers, especially those who work long hours in the "transport/postal services" industry.

Recent studies have analyzed dietary patterns to assess overall dietary habits, but there have been no studies of dietary patterns among the contemporary Japanese population nationwide. The objective of this study was to identify dietary patterns based on consumption of food items among Japanese adults, and to examine whether these dietary patterns were associated with nutrient intake, demographic characteristics, and lifestyle factors.The study population included 25,754 Japanese adults aged 20 years and older registered in the nationwide National Health and Nutrition Survey database in 2012. Dietary patterns were analyzed by factor analysis of 29 food items from the dietary intake survey and household-based semiweighed dietary records.Five dietary patterns were identified: high-bread and low-rice, high-meat and low-fish, vegetable, wheat-based food, and noodle and alcohol patterns. The lowest quartile of factor scores for high-meat and low-fish, wheat-based food, and noodle and alcohol patterns had higher nutrient intakes, and the highest quartile of factor scores for the vegetable pattern had a higher nutrient intake overall (all p0.01). Dietary pattern scores were associated with demographic and lifestyle factors such as sex, age, region, smoking status, and alcohol intake.Five major dietary patterns among Japanese adults were identified by factor analysis. Dietary pattern scores were associated with differences in nutrient intakes and demographic and lifestyle factors. These patterns were further used for examining the association between Japanese diets and health outcomes.

Background Empathy is widely regarded as being key to effective consultation in general practice. The Consultation and Relational Empathy (CARE) Measure is a widely used and well-validated patient-rated measure in English. A Japanese version of the CARE Measure has undergone preliminary validation, but its ability to differentiate between individual doctors has not been established. The current study sought to investigate the reliability of the Japanese version of the CARE Measure in terms of discrimination between doctors. Methods We conducted secondary analysis of a dataset involving 252 patients assessed by nine attending General Practitioners. The intra-cluster correlation coefficient was evaluated as an index of the reliability of the Japanese version of the CARE Measure for discriminating between doctors. With a criterion of intra-cluster correlation coefficient = 0.8, we conducted a decision (D) study using generalizability theory to determine the required number of patients for reliable CARE Measure estimates. Results The ability of the CARE Measure to discriminate between doctors increased with the number of patients assessed per doctor. A sample size of 38 or more patients provided an average intra-cluster correlation coefficient of 0.8. Conclusions The Japanese CARE Measure appears to reliably discriminate between doctors with a feasible number of patient-ratings per doctor. Further studies involving larger numbers of doctors with a multicenter analysis are required to confirm the results of the current study, which was conducted at a single institution.

We present a case of critical Ebstein's anomaly with circular shunting, diagnosed in utero. The fetal cardiothoracic area ratio was elevated; tricuspid regurgitation and pulmonary regurgitation worsened with fetal hydrops. At 35 weeks 6 days of gestation, elective caesarean section delivery was performed. Planned bilateral pulmonary artery banding and pulmonary trunk ligation were performed as a palliative operation 4 hours after birth, with the infant in a stable condition. At age 5 days, we performed the Starnes operation. The postoperative course was uneventful and a bidirectional Glenn operation was performed at age 4 months.

Background Over 100,000 patients are diagnosed every year as out-of-hospital cardiac arrest (OHCA) cases in Japan and their number has continued to rise for the last decade, presenting a challenge for preventive public health research as well as emergency medical care. The purpose of this study was to identify whether there are any temporal patterns in daily OHCA presentations in Japan. Methods Records of OHCA patients (n = 701,651) transported by ambulance over the course of six years (1st January 2005 to 10th March 2011) in Japan were obtained from the All-Japan Utstein registry data of cardiopulmonary arrest patients. Time periods within which the incidence of OHCA significantly increased were identified by a temporal cluster detection test using scan statistics. The risk ratios of OHCA for the detected periods were calculated and adjusted according to a Poisson regression model accounting for effects of other factors. Results The risk of OHCA significantly rises 1.3–1.6 times around New Year's Day in Japan. Conclusions Our analysis revealed the increased daily incidence of OHCA around every New Year's Day in Japan. Postprint

The aim of this study is to determine the progress of the visual field defects obtained by the Humphrey Field Analyzer 10-2 program (HFA 10-2) in patients with retinitis pigmentosa (RP). The medical records of 45 eyes of 45 RP patients who had at least 3 visual field tests were reviewed. Linear mixed models were used to follow the changes of the mean deviation and the average sensitivity of 4, 12, and 20 points in three concentric squares, designated as S4, S12, and S20. The median follow-up time was 3.86 years [range: 1.93 to 9.86, IQR (Interquartile range): 3.01 to 4.93]. The median number of the visual field tests was 3 (range: 3 to 15, IQR: 3 to 4). The mean change of the MD was −0.46 dB/year (−5.80%/year). When the patients were grouped by the average initial MD, the less advanced group had slower progressions than the more advanced group in S4, S12, and S20. These results should be useful in understanding the pathological changes of RP in the central visual field.

Objectives In patients with pulmonary atresia with an intact ventricular septum (PA/IVS), there are no reports about the impact of sinusoidal communication (SC) on left ventricular (LV) performance after a Fontan operation; therefore, the purpose of this study was to fill this gap in the literature. Methods We performed a single-centre, retrospective study of 46 patients with PA/IVS. Nineteen patients who underwent the Fontan procedure were enrolled and divided into 2 groups: those with SC (SC group) and those without SC (N group). The 2 groups were compared in terms of postoperative cardiac function. Results Thirteen patients were in the SC group (4 patients with right ventricle-dependent coronary circulation) and 6, in the N group. Although 2 of the patients with right ventricular (RV)-dependent coronary circulation showed focal asynergy of the LV wall, others showed no findings of myocardial infarction. The patients' preoperative age and age during the observation period after the Fontan operation did not differ. There was no difference in LV ejection fraction, cardiac index and RV and pulmonary artery pressure before and after the Fontan operation. Preoperative RV volume in the N group was greater than that in the SC group. Brain natriuretic peptide levels were higher in the SC group after the Fontan operation. On ventricular efficacy analysis, contractility was lower (1.8 ± 0.32 vs 2.5 ± 0.40 mmHg/ml/m2, P = 0.001) and ventricular efficacy was worse (1.0 ± 0.15 vs 0.86 ± 0.11, P = 0.046) in the SC group during the postoperative period. Conclusions Compared to patients with PA/IVS without SC, patients with PA/IVS with SC had a low cardiac contractility and decreased cardiac output efficiency after the Fontan procedure.

We report the case of a female neonate born at 40 weeks' gestation with no known risk factors. On postnatal day 27, she was transferred to the pediatric intensive care unit and intubated for cardiorespiratory failure; she was diagnosed with group B streptococcus infective endocarditis. Mitral valve vegetations did not improve with antibiotic therapy. Mitral valve surgery was performed on postnatal day 36. A mechanical mitral valve with short-segment polytetrafluoroethylene skirt was inserted into the supra-annular position; gentian violet was applied to the sewing ring and skirt. She was discharged from the hospital after 6 weeks with good cardiac function and normal sinus rhythm.

Drug-resistant pathogen (DRP) risk stratification is important for choosing a treatment strategy for community-onset pneumonia. Evidence for benefits of non-antipseudomonal β-lactam plus macrolide combination therapy (BLM) on mortality is limited in patients at low DRP risk. Risk factors for mortality remain to be clarified.Post hoc analysis using a prospective multicentre study cohort of community-onset pneumonia was performed to assess 30-day differences in mortality between non-antipseudomonal β-lactam monotherapy (BL) and BLM groups. Logistic regression analysis was performed to assess the therapeutic effect and risk factors for mortality in patients at low DRP risk.In total, 594 patients with community-onset pneumonia at low DRP risk (369 BL and 225 BLM) were analysed. The 30-day mortality in BL and BLM was 13.8% and 1.8%, respectively (P 0.001). Multivariate analysis showed that BLM reduced the 30-day mortality (adjusted odds ratio: 0.28, 95% CI: 0.09-0.87) compared with BL. Independent prognostic factors for 30-day mortality included arterial partial pressure of carbon dioxide (PaCOIn patients with community-onset pneumonia at low DRP risk, BLM treatment reduced 30-day mortality compared with BL. Independent risk factors for mortality are potential confounding factors when assessing antibiotic effects in randomized clinical trials.

Background Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. Methods and results After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. Conclusion The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application.

Spatial scan statistics are widely used tools for detection of disease clusters. Especially, the circular spatial scan statistic proposed by Kulldorff (1997) has been utilized in a wide variety of epidemiological studies and disease surveillance. However, as it cannot detect noncircular, irregularly shaped clusters, many authors have proposed different spatial scan statistics, including the elliptic version of Kulldorff's scan statistic. The flexible spatial scan statistic proposed by Tango and Takahashi (2005) has also been used for detecting irregularly shaped clusters. However, this method sets a feasible limitation of a maximum of 30 nearest neighbors for searching candidate clusters because of heavy computational load. In this paper, we show a flexible spatial scan statistic implemented with a restricted likelihood ratio proposed by Tango (2008) to (1) eliminate the limitation of 30 nearest neighbors and (2) to have surprisingly much less computational time than the original flexible spatial scan statistic. As a side effect, it is shown to be able to detect clusters with any shape reasonably well as the relative risk of the cluster becomes large via Monte Carlo simulation. We illustrate the proposed spatial scan statistic with data on mortality from cerebrovascular disease in the Tokyo Metropolitan area, Japan.

Following the Fukushima Daiichi Nuclear Power Plant (FNPP) accident on 11 March 2011, there have been concerns regarding the health impacts of the ensuing radioactive environmental contamination, which was spatially heterogeneous. This study aimed to assess the geographical variability of thyroid cancer prevalence among children and adolescents in Fukushima Prefecture. We computed the sex- and age-standardised prevalence ratio using 115 diagnosed or suspected thyroid cancer cases among approximately 300,000 examinees at the first-round ultrasound examination during 2011–2015 from 59 municipalities in the prefecture, under the Fukushima Health Management Survey. We applied flexibly shaped spatial scan statistics and the maximised excess events test on the dataset to detect locally anomalous high-prevalence regions. We also conducted Poisson regression with selected regional indicators. Furthermore, approximately 200 examinees showed positive ultrasound examination results but did not undergo confirmatory testing; thus, we employed simulation-based sensitivity tests to evaluate the possible effect of such undiagnosed cases in the statistical analysis. In conclusion, this study found no significant spatial anomalies/clusters or geographic trends of thyroid cancer prevalence among the ultrasound examinees, indicating that the thyroid cancer cases detected are unlikely to be attributable to regional factors, including radiation exposure resulting from the FNPP accident.

The present study examined temporal trends and geographic clustering of amyotrophic lateral sclerosis (ALS) mortality in Japan, during 1995-2004, using vital statistics based on death certificates. ALS was usually diagnosed by neurologists according to clinical guidelines that complied with the El Escorial Criteria. The underlying cause of death for ALS was coded as G12.2A. Regression analysis was used to examine temporal trends. Spatial scan statistic was used to detect any area of elevated risk as a cluster. A total of 12,173 (6864 male and 5309 female) ALS deaths were reported. Annual crude mortality rate per 100,000 population was 1.07 (1.26 for males and 0.89 for females) in 2004. Although the overall temporal trend was stable, the trend increased in the 70+ years age group (p for trend

Unintentional injury is the leading cause of death in young children. A previous study reported the protective effect of maternal parenting on young childhood injury; however, few studies have shown an association between paternal involvement in childcare and young childhood injury. The purpose of this study is to investigate the impact of paternal involvement in childcare to reduce the likelihood of childhood injury.A population-based birth cohort study in Japan (2001-02), the 'Longitudinal Survey of Babies Born in 21st Century', was used (n = 42 144). The impact of paternal involvement in childcare of 6-month-old infants (feeding, diaper change, bathing, putting the child to sleep, playing, taking a walk) on the incidence of young childhood injury (fall, near-drowning, accidental ingestion or burn) until 18 months of age was analysed by multiple logistic regression.Infants who received a high degree of paternal involvement in childcare at 6 months were less likely to suffer from all unintentional injuries at 18 months than those who received a low degree of paternal involvement in childcare (adjusted odds ratio 0.91, 95% confidence interval 0.85-0.98). Taking the child for a walk by the father strongly prevented all unintentional injuries, and there were dose-effect relationships (P(trend)0.001).Paternal involvement in childcare at 6 months of age prevented childhood injury at 18 months of age. Paternal involvement in childcare might be a useful indicator for predicting childhood injury.

Background: There is suggested to be a geographical difference in Creutzfeldt-Jakob disease (CJD) mortality in Japan. We performed a study to detect localized clusters and hot-spot areas of deaths from CJD in Japan during the 10-year period from 1995 to 2004. Methods: The diagnosis of CJD was taken from the death certificate (coded as A81.0 in the ICD-10). A total number of 1,168 CJD deaths (500 males and 668 females) were used for analysis using empirical Bayes estimates of standardized mortality ratios and the flexible spatial scan statistic to detect clusters. To detect the most likely cluster, p values were obtained using Monte Carlo hypothesis testing (with p < 0.05 as statistical significance).Results: The most likely cluster of CJD mortality was located in the northwest region from the base of Mt. Fuji, stretching over the two neighboring prefectures of Yamanashi and Shizuoka (relative risk = 2.28, p = 0.021). Some other clusters were detected but were not significant. Conclusions: The present study supports the evidence of geographical clustering of deaths from CJD at a specific location in Japan.

Background Elucidating public concerns regarding vaccinations is important for successful immunization programs. The objective of the present study was to categorize public concerns regarding influenza vaccinations in Japan by analyzing a massive web-based question dataset. Methods The Yahoo! Chiebukuro (Japanese Yahoo! Answers) Dataset, which includes more than 16 million questions collected between April 2004 and April 2009, was used in this study. We sequentially filtered data to obtain questions on influenza vaccinations. Any questions that met our exclusion criteria concerning veterinary vaccines or computer virus vaccines were removed from the analysis. Filtered questions and their answers were manually analyzed for their content by a team of board-certified pediatricians. Results After filtering data, we obtained 1950 questions regarding influenza vaccinations. The three most frequently asked questions were regarding the vaccination schedule, safety, and effectiveness. When we analyzed monthly trends in question contents, we noted the emergence of similar questions in the same period every year. Therefore, we classified the time periods of each year into three parts: (1) from April to the commencement of seasonal influenza vaccinations (September), (2) from October until the epidemic period, and (3) the epidemic period. Two interesting results were obtained: concerns regarding effectiveness abruptly increased during the epidemic period, and pregnant or breastfeeding women increasingly asked questions regarding feasibility between October and the epidemic period. Conclusions The questions and concerns collected and analyzed in this study illustrate that the public have questions about the influenza vaccine and also that questions changed with periodical consistency. These results highlight the possible usefulness of providing the public with the latest and correct information to their questions in a timely manner, for example via an official health website.

During the 4 years following the nuclear power plant accident of 2011, 39 males and 77 females were diagnosed with or suspected of having cancer based on the first-round thyroid examination of the Fukushima Health Management Survey (FHMS) targeting residents aged

In prognostic studies, a summary statistic such as a hazard ratio is often reported between low-expression and high-expression groups of a biomarker with a study-specific cutoff value. Recently, several meta-analyses of prognostic studies have been reported, but these studies simply combined hazard ratios provided by the individual studies, overlooking the fact that the cutoff values are study-specific. We propose a method to summarize hazard ratios with study-specific cutoff values by estimating the hazard ratio for a 1-unit change of the biomarker in the underlying individual-level model. To this end, we introduce a model for a relationship between a reported log-hazard ratio for a 1-unit expected difference in the mean biomarker value between the low-expression and high-expression groups, which approximates the individual-level model, and propose to make an inference of the model by using the method for trend estimation based on grouped exposure data. Our combined estimator provides a valid interpretation if the biomarker distribution is correctly specified. We applied our proposed method to a dataset that examined the association between the biomarker Ki-67 and disease-free survival in breast cancer patients. We conducted simulation studies to examine the performance of our method. Copyright © 2016 John WileySons, Ltd.