Studies of the efficacy and safety of methotrexate at dosages over 8 mg/week using the IORRA cohort database

The maximum dosage of methotrexate (MTX) for treatment of rheumatoid arthritis (RA) formally approved in Japan is 8 mg/week. We intended to examine the efficacy and safety of MTX at dosages over 8 mg/week in Japanese rheumatoid arthritis patients using the large Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort database. Among 9,122 patients registered in the IORRA database from the October 2000 survey to the October 2007 survey, 5,201 patients who had been treated with MTX were selected. We attempted to overcome the drawbacks innate to nonrandomized studies by using longitudinal analyses and multifactorial logistic regression analyses. Cross-sectional analysis of data obtained from the October 2007 survey indicated that dosages of MTX higher than 8 mg/week were used in 27.5% of patients treated with MTX. Longitudinal analyses based on data from three consecutive phases showed that final Disease Activity Score-28 (DAS28) values were significantly lower [n = 260, mean difference 0.563, 95% confidence interval (CI) 0.438–0.688, P < 2.2 × 10−22, two-sided paired t test] than initial values when MTX was increased from 8 mg/week or lower to over 8 mg/week. In addition, longitudinal analyses based on data from two consecutive phases indicated decreases in DAS28 values of 0.26 ± 1.04 (n = 690, P = 6.78 × 10−11, two-sided paired t test) when MTX dosages were increased from 8 mg/week or lower to over 8 mg/week, compared with decreases of 0.07 ± 0.89 (n = 2,125, P = 0.000307) when the dosage was maintained at 8 mg/week. The decreases in DAS28 values were significantly larger in the former than the latter (P = 2.27 × 10−6, two-sided unpaired t test). Concerning safety of MTX at dosages over 8 mg/week, we performed logistic regression analysis in which the objective variable was the existence or nonexistence of self-reported side-effects and the explanatory variable was the MTX dosage in the former phase, with adjustments made for age, sex, body mass index (BMI), steroid administration, folic acid administration, concomitant pulmonary diseases, and renal dysfunction. The results indicated that MTX dosages over 8 mg/week did not have any association with either severe or severe + moderate side-effects. These data regarding both efficacy and safety of MTX at dosages over 8 mg/week in Japanese RA patients would provide the basis for use of the drug at dosages currently not formally approved by the Japanese government

A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans

Impact of a New Medical Record System for Emergency Departments Designed to Accelerate Clinical Documentation: A Crossover Study.

Recording information in emergency departments (EDs) constitutes a major obstacle to efficient treatment. A new electronic medical records (EMR) system focusing on clinical documentation was developed to accelerate patient flow. The aim of this study was to examine the impact of a new EMR system on ED length of stay and physician satisfaction.We integrated a new EMR system at a hospital already using a standard system. A crossover design was adopted whereby residents were randomized into 2 groups. Group A used the existing EMR system first, followed by the newly developed system, for 2 weeks each. Group B followed the opposite sequence. The time required to provide overall medical care, length of stay in ED, and degree of physician satisfaction were compared between the 2 EMR systems.The study involved 6 residents and 526 patients (277 assessed using the standard system and 249 assessed with the new system). Mean time for clinical documentation decreased from 133.7 ± 5.1 minutes to 107.5 ± 5.4 minutes with the new EMR system (P < 0.001). The time for overall medical care was significantly reduced in all patient groups except triage level 5 (nonurgent). The new EMR system significantly reduced the length of stay in ED for triage level 2 (emergency) patients (145.4 ± 13.6 minutes vs 184.3 ± 13.6 minutes for standard system; P = 0.047). As for the degree of physician satisfaction, there was a high degree of satisfaction in terms of the physical findings support system and the ability to capture images and enter negative findings.The new EMR system shortened the time for overall medical care and was associated with a high degree of resident satisfaction

Effect of the sample work function on alkali metal dosing induced electronic structure change

Alkali metal dosing (AMD) has been widely used as a way to control doping without chemical substitution. This technique, in combination with angle resolved photoemission spectroscopy (ARPES), often provides an opportunity to observe unexpected phenomena. However, the amount of transferred charge and the corresponding change in the electronic structure vary significantly depending on the material. Here, we report study on the correlation between the sample work function and alkali metal induced electronic structure change for three iron-based superconductors: FeSe, Ba(Fe$_{0.94}$Co$_{0.06}$)$_{2}$As$_{2}$ and NaFeAs which share a similar Fermi surface topology. Electronic structure change upon monolayer of alkali metal dosing and the sample work function were measured by ARPES. Our results show that the degree of electronic structure change is proportional to the difference between the work function of the sample and Mulliken's absolute electronegativity of the dosed alkali metal. This finding provides a possible way to estimate the AMD induced electronic structure change.Comment: 4 page

Biometric assessment of deep-sea vent megabenthic communities using multi-resolution 3D image reconstructions

This paper describes a method to survey the distribution of megabenthos over multi-hectare regions of the seafloor. Quantitative biomass estimates are made by combining high-resolution 3D image reconstructions, used to model spatial relationships between representative taxa, with lower-resolution reconstructions taken over a wider area in which the distribution of larger predatory animals can be observed. The method is applied to a region of the Iheya North field that was the target of scientific drilling during the IODP Expedition 331 in 2010. An area of 2.5 ha was surveyed 3 years and 4 months after the site was drilled. More than 100,000 organisms from 6 taxa were identified. The visible effects of drilling on the distribution of megabenthos were confined to a 20 m radius of the artificially created hydrothermal discharges, with the associated densities of biomass lower than observed in nearby naturally discharging areas

Impact of laparoscopic surgery on short‐term and long‐term outcomes in elderly obese patients with colon cancer

[Background] Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. [Methods] Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse-free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (<70 y). [Results] Data of 1549 patients (elderly, n = 598; nonelderly, n = 951) satisfied the selection criteria for analysis. Length of stay was shorter and surgical wound infection was less common in elderly obese patients who underwent laparoscopic surgery than in those underwent open surgery. There were no significant between-group differences in overall complications, anastomotic leakage, ileus/small bowel obstruction, or RFS. There were also no significant differences in RFS after laparoscopic surgery according to patient age. [Conclusion] Laparoscopic surgery is safe in elderly obese patients with colon cancer and does not worsen their prognosis. There was no significant difference in the effectiveness of laparoscopic surgery between obese patients who were elderly and those who were nonelderly