論文

© 2018, The Author(s). Background: Hyperuricemia has a close relationship with cardiovascular diseases including heart failure. However, it is controversial whether xanthine oxidase inhibition has benefits for patients with chronic heart failure. We designed the Effect of Xanthine Oxidase Inhibitor in Chronic Heart Failure Patients Complicated with Hyperuricemia study (Excited-UA study) to compare the beneficial effects between a novel xanthine oxidoreductase inhibitor, topiroxostat, and a conventional agent, allopurinol, in patients with chronic heart failure and hyperuricemia. We focus on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiography-based cardiac function, vascular endothelial function, renal function, inflammation, and oxidative stress. Methods: The excited-UA is a prospective, randomized, open-label, blinded-endpoint clinical trial designed to prove our hypothesis that topiroxostat is more effective than allopurinol in patients with chronic heart failure and hyperuricemia. A total of 140 patients with chronic heart failure and hyperuricemia (plasma brain natriuretic peptide level ≥ 40 pg/mL and serum uric acid level ≥ 7.0 mg/dL) are randomly assigned (ratio 1:1) into either the topiroxostat group (40–160 mg/day) or allopurinol group (100–300 mg/day), to achieve the target uric acid level of 6.0 mg/dL. According to the protocol, all patients are followed up annually for 24 weeks. The primary endpoint is percent change in serum NT-proBNP level at 24 weeks from baseline. Conclusions: The Excited-UA study would provide novel evidence for the clinical relevancy of xanthine oxidoreductase inhibitor treatment in patients with chronic heart failure and hyperuricemia.

OBJECTIVES: The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach.METHODS: Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P ≤ 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study). The associations between OS and SNPs were investigated using log-rank test and Cox proportional hazards model.RESULTS: From the GEST study, the SNP rs4149086 in the 3' UTR of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene showed significant interaction with treatment (P = 0.02). In the gemcitabine group, the SNP was associated with short OS (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.30-10.8; P = 0.008) even after multiple-comparisons adjustment. In contrast, the SNP was not associated with OS in S-1 (HR, 0.77; 95% CI, 0.33-1.81; P = 0.55) or gemcitabine plus S-1 groups (HR, 1.18; 95% CI, 0.46-3.00; P = 0.72).CONCLUSIONS: Patients with advanced pancreatic cancer with the rs4149086 AG or GG genotype may obtain good clinical results when treated with S-1-containing regimens.

© 2018 by the Japan Society for Occupational Health. Objectives: The purposes of this study were to clarify 1) the prevalence of foot and ankle pain and 2) the factors associated with foot and ankle pain among nurses. Methods: Nurses working at a university hospital in Japan were recruited to participate in this crosssectional, questionnaire-based study. The occurrence of foot and ankle pain in the previous month was assessed by using the Standardized Nordic Questionnaire and the Manchester Foot Pain and Disability Index. Subjects also answered questions on footwear-related factors, including using the visual analog scale for shoe comfort. In addition, information on personal factors and psychosocial factors was collected using the Job Content Questionnaire. The relationships between the presence of foot and ankle pain and the associated factors were examined using multiple logistic regression analysis. Results: Responses of 636 nurses (response rate, 67%) were included for analysis. The prevalence of foot and ankle pain was 23% and 51% when using the Standardized Nordic Questionnaire and the Manchester Foot Pain and Disability Index, respectively. The prevalence of pain that prevented the nurses from performing activities of daily living and work was 4% and 17%, respectively. A low level of shoe comfort, personal factors (age and body mass index), and psychosocial factors (low job control and high job strain) was independently associated with the presence of foot and ankle pain. Conclusions: Foot and ankle pain occurred frequently in nurses. Shoe comfort, personal factors, and psychosocial factors were associated with foot and ankle pain.

© 2017 Japanese Society of Allergology Background In September 2015, Japan experienced an unusual increase in acute asthma hospitalizations of children that coincided with an enterovirus D68 (EV-D68) epidemic. The objective of this study is to investigate whether EV-D68 had a causal relationship with the spike in asthma hospitalizations. Methods A nation-wide retrospective survey of asthma hospitalizations of children was performed for the period from January 2010 through October 2015. The Japanese Society of Pediatric Allergy and Clinical Immunology asked its affiliated hospitals to report monthly numbers of hospitalizations, ICU admissions and mechanical ventilations due to acute asthma exacerbation. The data were retrieved from medical databases using predefined search criteria: diagnosis of asthma or asthmatic bronchitis, admission, and age <20 years. Monthly numbers of EV-D68 detection were also obtained from the Infectious Disease Surveillance Center of Japan. A Granger causality test was used to analyze the association of EV-D68 detections for asthma exacerbation. Results A total of 157 hospitals reported 87,189 asthma hospitalizations, including 477 ICU admissions and 1193 mechanical ventilations, during the survey period of 5 years and 10 months. The numbers of these events increased drastically in September 2015. The Granger causality test verified the association between EV-D68 and asthma hospitalizations/mechanical ventilations. The most-affected age group was 3–6 years old. Conclusions The spike in pediatric asthma hospitalizations in Japan in September 2015 was found to be associated with the EV-D68 epidemic. Respiratory pathogens can cause “epidemics” of asthma exacerbation. Coordinated surveillance of infectious diseases and asthma may be beneficial for prevention and better control of both illnesses.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Introduction Insomnia has severe consequences for health. Primary care physicians in Japan commonly provide hypnotics, which is far from optimal. The recommended treatment for insomnia is cognitive-behavioural therapy (CBT). Access to trained therapists, however, is limited. Rather than face-to-face CBT, several researchers have studied internet-delivered computerised CBT (ICBT). This paper describes the study protocol for a randomised controlled trial (RCT) to evaluate effectiveness and feasibility of our newly developed five-step ICBT as an adjunct to usual care (UC) compared with UC alone for patients with insomnia who remain symptomatic following hypnotics. Methods and analysis This proposed exploratory RCT comprises two parallel groups (ICBT+UC and UC alone) consisting of 15 participants each (n=30) diagnosed with insomnia who remain symptomatic after pharmacotherapy. We aim to evaluate the effectiveness of six intervention weeks. The primary outcome of insomnia severity will be the Pittsburgh Sleep Quality Index (PSQI) at week 6. Secondary outcomes include sleep onset latency, total sleep time, sleep efficiency extracted from PSQI, current feeling of refreshment and perceived soundness of sleep measured using visual analogue scale, number of awakenings, anxiety by Hospital Anxiety and Depression Scale, depression by Center for Epidemiologic Studies Depression Scale and quality of life by Euro Qol-5D. All measures will be assessed at weeks 0 (baseline), 6 (postintervention) and 12 (follow-up), and intention-to-treat analysis will be applied. The statistical analysis plan has been developed considering design of field materials. Ethics and dissemination This study will be conducted at the academic outpatient clinic of Chiba University Hospital, Japan. Ethics approval was granted by the Institutional Review Board of Chiba University Hospital. All participants will be required to provide written informed consent. The trial will be implemented and reported in accordance with Consolidated Standards of Reporting Trials recommendations. Trial registration number UMIN000021509; Pre-results.

©AANS 2018. OBJECTIVE Previous Japanese Leksell Gamma Knife Society studies (JLGK0901) demonstrated the noninferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for patients with 5–10 brain metastases (BMs) compared with those with 2–4 BMs in terms of overall survival and most secondary endpoints. The authors studied the aforementioned treatment outcomes in a subset of patients with BMs from non–small cell lung cancer (NSCLC). METHODS Patients with initially diagnosed BMs treated with SRS alone were enrolled in this prospective observational study. Major inclusion criteria were the existence of up to 10 tumors with a maximum diameter of less than 3 cm each, a cumulative tumor volume of less than 15 cm3, and no leptomeningeal dissemination in patients with a Karnofsky Performance Scale score of 70% or better. RESULTS Among 1194 eligible patients, 784 with NSCLC were categorized into 3 groups: group A (1 tumor, n = 299), group B (2–4 tumors, n = 342), and group C (5–10 tumors, n = 143). The median survival times were 13.9 months in group A, 12.3 months in group B, and 12.8 months in group C. The survival curves of groups B and C were very similar (hazard ratio [HR] 1.037; 95% CI 0.842–1.277; p < 0.0001, noninferiority test). The crude and cumulative incidence rates of neurological death, deterioration of neurological function, newly appearing lesions, and leptomeningeal dissemination did not differ significantly between groups B and C. SRS-induced complications occurred in 145 (12.1%) patients during the median post-SRS period of 9.3 months (IQR 4.1–17.4 months), including 46, 54, 29, 11, and 5 patients with a Common Terminology Criteria for Adverse Events v3.0 grade 1, 2, 3, 4, or 5 complication, respectively. The cumulative incidence rates of adverse effects in groups A, B, and C 60 months after SRS were 13.5%, 10.0%, and 12.6%, respectively (group B vs C: HR 1.344; 95% CI 0.768–2.352; p = 0.299). The 60-month post-SRS rates of neurocognitive function preservation were 85.7% or higher, and no significant differences among the 3 groups were found. CONCLUSIONS In this subset analysis of patients with NSCLC, the noninferiority of SRS alone for the treatment of 5–10 versus 2–4 BMs was confirmed again in terms of overall survival and secondary endpoints. In particular, the incidence of neither post-SRS complications nor neurocognitive function preservation differed significantly between groups B and C. These findings further strengthen the already-reported noninferiority hypothesis of SRS alone for the treatment of patients with 5–10 BMs.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Dental procedures under sedation can cause hypoxic events and even death. However, the mechanism of such hypoxic events is not well understood. WHAT THIS ARTICLE TELLS US THAT IS NEW: Apnea and hypopnea occur frequently during dental procedures under sedation. The majority of the events are not detectable with pulse oximetry. Insertion of a nasal tube with small diameter does not reduce the incidence of apnea/hypopnea. BACKGROUND: Intravenous sedation is effective in patients undergoing dental procedures, but fatal hypoxemic events have been documented. It was hypothesized that abnormal breathing events occur frequently and are underdetected by pulse oximetry during sedation for dental procedures (primary hypothesis) and that insertion of a small-diameter nasopharyngeal tube reduces the frequency of the abnormal breathing events (secondary hypothesis). METHODS: In this nonblinded randomized control study, frequency of abnormal breathing episodes per hour (abnormal breathing index) of the patients under sedation for dental procedures was determined and used as a primary outcome to test the hypotheses. Abnormal breathing indexes were measured by a portable sleep monitor. Of the 46 participants, 43 were randomly allocated to the control group (n = 23, no nasopharyngeal tube) and the nasopharyngeal tube group (n = 20). RESULTS: In the control group, nondesaturated abnormal breathing index was higher than the desaturated abnormal breathing index (35.2 [20.6, 48.0] vs. 7.2 [4.1, 18.5] h, difference: 25.1 [95% CI, 13.8 to 36.4], P < 0.001). The obstructive abnormal breathing index was greater than central abnormal breathing index (P < 0.001), and half of abnormal breathing indexes were followed by irregular breathing. Despite the obstructive nature of abnormal breathing, the nasopharyngeal tube did not significantly reduce the abnormal breathing index (48.0 [33.8, 64.4] h vs. 50.5 [36.4, 63.9] h, difference: -2.0 [95% CI, -15.2 to 11.2], P = 0.846), not supporting the secondary hypothesis. CONCLUSIONS: Patients under sedation for dental procedure frequently encounter obstructive apnea/hypopnea events. The majority of the obstructive apnea/hypopnea events were not detectable by pulse oximetry. The effectiveness of a small-diameter nasopharyngeal tube to mitigate the events is limited.

© 2018 The Authors Objective: To compare the efficacy and safety of blastocyst transfer derived from small follicles (SF; ≤10 mm) and large follicles (LF; ≥11 mm). Design: Retrospective cohort study. Setting: Private clinic. Patient(s): Patients (n = 1,072) 30–40 years old who underwent blastocyst transfer (BT; n = 1,247) between January 2012 and December 2014. Intervention(s): Oocytes retrieved during a modified natural cycle from both LF and SF were fertilized by a conventional method or intracytoplasmic sperm injection. The blastocysts were frozen, thawed, and transferred one by one in the following spontaneous ovulatory cycles or hormone replacement cycles. Main Outcome Measure(s): BT resulted in live births and major congenital anomalies. Result(s): SF-derived BTs (n = 597) yielded 55 chemical abortions (9.2%), 73 clinical abortions (12.2%), and 261 live births (43.8%), whereas LF-derived BTs (n = 650) yielded 71 chemical abortions (10.9%), 73 clinical abortions (11.2%), and 311 live births (47.9%). These incidences were not statistically different between SF- and LF-derived BTs. The incidence of abnormal karyotypes was also not statistically different between SF- and LF-derived spontaneous abortions (71% [39/55] vs. 72% [40/55], respectively). The incidence of major congenital anomalies in neonates did not differ between SF- and LF-derived pregnancies (1.5% and 1.3%, respectively; relative risk = 1.10, 95% confidence interval [0.55–3.21]). Conclusion(s): SF-derived BT is as efficacious and safe as LF-derived BT.

©AANS 2018. OBJECTIVE With the aging of the population, increasing numbers of elderly patients with brain metastasis (BM) are undergoing stereotactic radiosurgery (SRS). Among recently reported prognostic grading indexes, only the basic score for brain metastases (BSBM) is applicable to patients 65 years or older. However, the major weakness of this system is that no BM-related factors are graded. This prompted the authors to develop a new grading system, the elderly-specific (ES)–BSBM. METHODS For this IRB-approved, retrospective cohort study, the authors used their prospectively accumulated database comprising 3267 consecutive patients undergoing Gamma Knife SRS for BMs during the 1998–2016 period at the Mito GammaHouse. Among these 3267 patients, 1789 patients ≥ 65 years of age were studied (Yamamoto series [Y-series]). Another series of 1785 patients ≥ 65 years of age in whom Serizawa and colleagues performed Gamma Knife SRS during the same period (Serizawa series [S-series]) was used for validity testing of the ES-BSBM. RESULTS Two factors were identified as strongly impacting longer survival after SRS by means of multivariable analysis using the Cox proportional hazard model with a stepwise selection procedure. These factors are the number of tumors (solitary vs multiple: HR 1.450, 95% CI 1.299–1.621; p < 0.0001) and cumulative tumor volume (≤ 15 cm3 vs > 15 cm3: HR 1.311, 95% CI 1.078–1.593; p = 0.0067). The new index is the addition of scores 0 and 1 for these 2 factors to the BSBM. The ES-BSBM system is based on categorization into 3 classes by adding these 2 scores to those of the original BSBM. Each ES-BSBM category has 2 possible scores. For the category ES-BSBM 4–5, the score is either 4 or 5; for ES-BSBM 2–3, the score is either 2 or 3; and for ES-BSBM 0–1, the score is either 0 or 1. In the Y-series, the median survival times (MSTs, months) after SRS were 17.5 (95% CI 15.4–19.3) in ES-BSBM 4–5, 6.9 (95% CI 6.4–7.4) in ES-BSBM 2–3, and 2.8 (95% CI 2.5–3.6) in ES-BSBM 0–1 (p < 0.0001). Also, in the S-series, MSTs were, respectively, 20.4 (95% CI 17.2–23.4), 7.9 (95% CI 7.4–8.5), and 3.2 (95% CI 2.8–3.6) (p < 0.0001). The ES-BSBM system was shown to be applicable to patients with all primary tumor types as well as to those 80 years or older. CONCLUSIONS The authors found that the addition of the number of tumors and cumulative tumor volume as scoring factors to the BSBM system significantly improved the prognostic value of this index. The present study is strengthened by testing the ES-BSBM in a different patient group.

© 2019 The American Association for Thoracic Surgery Objective: Several risk factors for late aortic events in patients with uncomplicated type B aortic dissection (UTBAD) have been reported; however, they remain controversial. We developed and validated a new risk prediction score system for late aortic events in patients with UTBAD. Methods: We reviewed 187 consecutive patients diagnosed with UTBAD from 2004 to 2017 at 2 centers (derivation cohort) and 219 consecutive patients diagnosed with UTBAD from 2012 to 2016 in 4 other centers (validation cohort). We explored predictors of late aortic events using Fine-Gray generalization of the proportional hazards model, then developed a risk prediction score model and determined the test reliability using time-dependent receiver operating characteristic analyses. Finally, we validated the model using external multicenter data. Results: The risk prediction score system was developed using the following independent predictors: initial aortic diameter of ≥40 mm (2 points), false lumen diameter larger than true lumen diameter (2 points), ulcer-like projection (1 point), and age ≥70 years (1 point). Receiver operating characteristic analysis showed that a cut-off total additive score of 2 points. In the validation cohort, the low-risk group (score, 0-1 point) demonstrated lower 1- and 3-year incidence rates of late aortic events than the high-risk group (score, 2-6 points) (0.9% vs 32.5% and 0.9% vs 47.1%, respectively; P < .0001). Conclusions: We developed a simple risk prediction score system for late aortic events in patients with UTBAD. High-risk patients can be identified using our model, and they should be closely monitored and considered for interventions at the appropriate timing.

© 2019 S. Karger AG, Basel The JLGK0901 study showed the non-inferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for 5-10 as compared to 2-4 brain metastases (BM) in terms of overall survival and most secondary endpoints [Lancet Oncol 2014;15:387-395]. A trend for patients with 5-10 tumors to undergo SRS alone has since become apparent. The next step is to reappraise whether results of SRS treatment alone for tumor numbers ≥10 differ from those for 2-9 tumors. During the past 2 decades, several retrospective studies have demonstrated the SRS alone treatment strategy to have certain benefits for carefully selected patients with ≥10 BM, i.e., a sufficiently long survival period with lower incidences of neurological death, neurological deterioration, local recurrence, and SRS-related complications. Herein, we introduce our Mito experiences with SRS for ≥10 BM, employing a case-matched study on 934 patients, 467 each in groups with 2-9 BM and ≥10 BM. Post-SRS treatment results, i.e., median survival time, neurological death-free survival time and cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications, were not inferior for patients with ≥10 BM as compared to those with 2-9 BM. We conclude that patients with ≥10 tumors are not unfavorable candidates for SRS alone.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Purpose: Stereotactic radiosurgery (SRS) has been increasingly used for elderly patients with brain metastases (BMs). However, no studies based on a large sample size have been reported. To compare SRS treatment results between elderly and non-elderly patients, we performed a subset study of elderly patients using our prospectively-accumulated multi-institution study database (JLGK0901 Study, Lancet Oncol 15:387–395, 2014). Methods: During the 2009–2011 period, 1194 eligible patients undergoing gamma knife SRS alone for newly diagnosed BMs were enrolled in this study from 23 gamma knife facilities in Japan. Observation was discontinued at the end of 2013. The 1194 patients were divided into the two age groups, 693 elderly (≥ 65 years) and 501 non-elderly (< 65 years) patients. Our study protocol neither set an upper age limit nor required dose de-escalation. Results: Median post-SRS survival time was significantly shorter in the elderly than in the non-elderly patient group (10.3 vs 14.3 months, HR 1.380, 95% CI 1.218–1.563, p < 0.0001). However, regarding all secondary endpoints including neurological death, neurological deterioration, SRS-related complications, leukoencephalopathy, local recurrence, newly-developed tumors, meningeal dissemination, salvage SRS, whole brain radiotherapy and surgery and decreased mini-mental state examination scores, the elderly patient group was not inferior to the non-elderly patient group. In the 693 elderly patients, there was no post-SRS median survival time difference between those with 5–10 versus 2–4 tumors (10.8 vs 8.9 months, HR 0.936, 95% CI 0.744–1.167, p = 0.5601). Conclusions: We conclude that elderly BM patients are not unfavorable candidates for SRS alone treatment.

©AANS 2018. OBJECTIVE The results of 3-stage Gamma Knife treatment (3-st-GK-Tx) for relatively large brain metastases have previously been reported for a series of patients in Chiba, Japan (referred to in this study as the C-series). In the current study, the authors reappraised, using a competing risk analysis, the efficacy and safety of 3-st-GK-Tx by comparing their experience with that of the C-series. METHODS This was a retrospective cohort study. Among 1767 patients undergoing GK radiosurgery for brain metastases at Mito Gamma House during the 2005–2015 period, 78 (34 female, 44 male; mean age 65 years, range 35–86 years) whose largest tumor was > 10 cm3, treated with 3-st-GK-Tx, were studied (referred to in this study as the M-series). The target volumes were covered with a 50% isodose gradient and irradiated with a peripheral dose of 10 Gy at each procedure. The interval between procedures was 2 weeks. Because competing risk analysis had not been employed in the published C-series, the authors reanalyzed the previously published data using this method. RESULTS The overall median survival time after 3-st-GK-Tx was 8.3 months (95% CI 5.6–12.0 months) in the M-series and 8.6 months (95% CI 5.5–10.6 months) in the C-series (p = 0.41). Actuarial survival rates at the 6th and 12th post–3-st-GK-Tx months were, respectively, 55.1% and 35.2% in the M-series and 62.5% and 26.4% in the C-series (HR 1.175, 95% CI 0.790–1.728, p = 0.42). Cumulative incidences at the 12th post–3-st-GK-Tx, determined by competing risk analyses, of neurological deterioration (14.2% in C-series vs 12.8% in M-series), neurological death (7.2% vs 7.7%), local recurrence (4.8% vs 6.2%), repeat SRS (25.9% vs 18.0%), and SRS-related complications (2.3% vs 5.1%) did not differ significantly between the 2 series. CONCLUSIONS There were no significant differences in post–3-st-GK-Tx results between the 2 series in terms of overall survival times, neurological death, maintained neurological status, local control, repeat SRS, and SRS-related complications. The previously published results (C-series) are considered to be validated by the M-series results.

© 2019 Asian Pacific Journal of Cancer Prevention. Background: The associations between ABO blood type and risk of diseases including cancer have been reported from epidemiological studies. Self-reporting is one of the most widely used methods of collecting the ABO blood type information. Verifying the accuracy of self-reporting is important to consider measurement errors. We aimed to conduct validation of self-reported ABO blood types in the Japan Nurses' Health Study (JNHS), which is a large prospective cohort study. Methods: The concordance rate between self-reported and serologically or genetically inferred ABO blood groups was investigated for a subsample of 41 subjects from the Gunma Nurses' Health Study, which was a pilot cohort study that preceded the JNHS. The presence of antibodies to A or B antigens in serum (serological test) and allele types of the ABO gene (genotyping test) were determined by using frozen blood samples that were preserved for approximately 7 years. ABO blood types were determined from these tests and compared with self-reported data. Results: All of the nurses reported that their ABO blood groups were concordant with those determined by a serological and/or genotyping test. Self-reported ABO blood types of 35 of 38 (92.1%) participants were consistent with the results from serological typing, while the answers of three participants were not. In these three participants, ABO genotypes that were inferred from genotyping of three single nucleotide polymorphisms in ABO loci perfectly matched with their self-reported ABO types, and all of these were O-type. Conclusions: Japanese health professionals report their blood type with a high degree of accuracy. Special attention should be paid to the O-type group in serological analysis of blood samples that have been preserved for several years in longitudinal studies.

© 2018 Oishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background A significant portion of patients with schizophrenia who respond to initial antipsychotic treatment acquire treatment resistance. One of the possible pathogeneses of treatment-resistant schizophrenia (TRS) is antipsychotic-induced dopamine supersensitivity psychosis (Ai-DSP). Patients with this disease progression might share some genetic vulnerabilities, and thus determining individuals with higher risks of developing Ai-DSP could contribute to preventing iatrogenic development of TRS. Therefore, we decided to examine whether combinations of functional single nucleotide polymorphisms (SNPs) known to affect dopaminergic functions are related to Ai-DSP development. Methods In this case-control study, 357 Japanese participants diagnosed with schizophrenia or schizoaffective disorder were recruited and divided into two groups, those with and without Ai-DSP. As functional SNPs, we examined rs10770141 of the tyrosine hydroxylase gene, rs4680 of the catechol-O-methyltransferase gene, and rs1799732 and rs1800497 of the DRD2 genes, which are known to possess strong directional ties to dopamine synthesis, dopamine degradation and post-synaptic DRD2 prevalence, respectively. Results Among the 357 Japanese patients with schizophrenia or schizoaffective disorder, 130 were classified as Ai-DSP(+) and the other 227 as Ai-DSP(-). Significantly higher proportions of Ai-DSP(+) patients were found to have the SNP combinations of rs10770141/rs4680 (57.9%, OR2.654, 95%CI1.036–6.787, P = 0.048) and rs10770141/rs4680/rs1800497 (64.3%, OR4.230, 95%CI1.306–13.619, P = 0.029). However, no single SNP was associated with Ai-DSP. Conclusions We preliminarily found that carrying particular combinations of functional SNPs, which are related to relatively higher dopamine synthesis and dopamine degradation and lower naïve DRD2, might indicate vulnerability to development of Ai-DSP. However, further studies are needed to validate the present results.

© 2018 Elsevier B.V. Background and purpose: Complications after stereotactic radiosurgery (SRS) for brain metastases (BMs) were analyzed in detail using our database including nearly 3000 BM patients. Materials and methods: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3271 consecutive patients who underwent gamma knife SRS for BMs during the 1998–2016 period. Excluding four patients lost to follow-up, 112 with three-staged treatment and 189 with post-operative irradiation, 2966 who underwent a single-session of SRS only as radical irradiation were studied. Results: The overall median survival time after SRS was 7.8 (95% CI; 7.4–8.1) months. Post-SRS complications occurred in 86 patients (2.9%) 1.9–211.4 (median; 24.0, IQR; 12.0–64.6) months after treatment. RTOG neurotoxicity grades were 2, 3 and 4 in 58, 25 and 3 patients, respectively. Cumulative incidences determined with a competing risk analysis were 1.4%, 2.2%, 2.4%, 2.6% and 2.9% at the 12th, 24th, 36th, 48th and 60th post-SRS month, respectively. Among various pre-SRS clinical factors and radiosurgical parameters, multivariable analyses demonstrated solitary tumor (Adjusted HR; 0.584, 95% CI; 0.381–0.894, p = 0.0133), controlled primary cancer (Adjusted HR; 2.595, 95% CI; 1.646–4.091, p < 0.0001), no extra-cerebral metastases (Adjusted HR; 1.608, 95% CI; 1.028–2.514, p = 0.0374), KPS ≥80% (Adjusted HR; 2.715, 95% CI; 1.245–5.924, p = 0.0121) and largest tumor volume ≥3.3 cc (Adjusted HR; 0.516, 95% CI; 0.318–0.836, p = 0.0072) to be independently significant predictors of a higher incidence of complications. Conclusion: The post-SRS complication incidence is acceptably low (2.9%). Meticulous long-term follow-up after SRS is crucial for all patients.

© 2018 Background: The purpose of this study was to clarify the 2-year clinical and radiological outcomes of nonoperative treatment using foot orthosis for hallux valgus patients. Methods: Patients who underwent nonoperative treatment using foot orthosis were surveyed prospectively. Foot orthoses were made by one certified orthotist using the standardized method. Pain and quality of life were evaluated using subjective and objective assessment measures at 3, 6, 12, 18, and 24 months. Furthermore, radiological outcomes, patient satisfaction, and adherence to treatment were surveyed. Results: A total of 53 patients (50 women and 3 men; median age, 63 years) were included for analysis. The pain visual analogue scale score significantly decreased over time, with the lowest score observed at 12 months. The treatment effect was maintained over 24 months (median score, 52, 21, and 27 points at baseline, 12 months, and 24 months, respectively; P < .001). The Japanese Society for Surgery of the Foot hallux scale, American Academy of Orthopaedic Surgeons Foot and Ankle Scale, and 36-Item Short-Form Health Survey bodily pain subscale also improved, although the treatment effects were maximal at 6 months and decreased thereafter. At 24 months, 43 (81%) patients continued to use the orthosis, with the median visual analogue scale score for patient satisfaction of 76 points. The hallux valgus angle and intermetatarsal angle did not change during the 24-month period. Conclusion: Nonoperative treatment using foot orthoses decreased pain in patients with hallux valgus. The effect of treatment was maintained up to 2 years with a relatively high degree of patient satisfaction. However, treating physicians should inform patients to set realistic expectations and be aware that a limited degree of pain reduction is expected.

© 2018 Journal of Medical Internet Research. All rights reserved. Background: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. Objectives: This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. Methods: A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants' points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. Results: A significant reduction in symptom of obsession-compulsion (Y-BOCS=-6.2; Cohen d=0.74; 95% CI -9.4 to -3.0, P=.002), panic (PDSS=-5.6; Cohen d=0.89; 95% CI -9.83 to -1.37; P=.02), social anxiety (LSAS=-33.6; Cohen d=1.10; 95% CI -59.62 to -7.49, P=.02) were observed. In addition, depression (PHQ-9=-1.72; Cohen d=0.27; 95% CI -3.26 to -0.19; P=.03) and general anxiety (GAD-7=-3.03; Cohen d=0.61; 95% CI -4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336; Cohen d=-0.202; 95% CI -0.0198 to 0.00869; P=.21), there were high therapeutic alliance (ie, WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14; 95% CI 1.24 to 7.04; P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face-to-face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30). Conclusions: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.

© © 2017 Lobna Alkebsi et al. Background: Although several studies have shown that blood type O is associated with increased risk of peptic ulcer, few studies have investigated these associations in Japan. We sought to investigate the association between the ABO blood group and risk of gastroduodenal ulcers (GDU) using combined analysis of both retrospective and prospective data from a large cohort study of Japanese women, the Japan Nurses’ Health Study (JNHS; n = 15,019). Methods: The impact of the ABO blood group on GDU risk was examined using Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI), with adjustment for potential confounders. Results: Compared with women with non-O blood types (A, B, and AB), women with blood type O had a significantly increased risk of GDU from birth (multivariable-adjusted HR 1.18; 95% CI, 1.04–1.34). Moreover, the highest cumulative incidence of GDU was observed in women born pre-1956 with blood type O. In a subgroup analysis stratified by birth year (pre-1956 or post-1955), the multivariable-adjusted HR of women with blood type O was 1.22 (95% CI, 1.00–1.49) and 1.15 (95% CI, 0.98–1.35) in the pre-1956 and post-1955 groups, respectively. Conclusion: In this large, combined, ambispective cohort study of Japanese women, older women with blood type O had a higher risk of developing GDU than those with other blood types.

© 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2018; 129:901-11 Background: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients. Methods: In anesthetized elderly (n = 20; 76.9 ± 5.0 yr of age) and nonelderly patients (n = 20; 53.7 ± 12.8 yr of age) under deep paralysis with rocuronium, change of train-of-four ratio per minute (primary outcome variable) was measured with an accelero-myograph neuromuscular monitor during spontaneous recovery from rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose sugammadex (50 µg · kg-1 · min-1). Recurarization was defined as the negative change of train-of-four ratio. Results: Spontaneous train-of-four ratio recovery rate was significantly slower in the elderly group (median [25th percentile, 75th percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96, 4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of recurarization was significantly higher in the elderly group than in the nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses indicate that slower spontaneous train-of-four ratio recovery rate and impaired renal function are two major contributing factors that decrease train-of-four ratio change rate in response to low-dose sugammadex. Conclusions: Elderly patients are at greater risk for recurarization and residual muscle paralysis when low-dose sugammadex is administered.