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Biomedical subjects

Hisashi Yamanaka

Publications and source records attributed to Hisashi Yamanaka.

At least 19 recordsLinked to original sources

One third of Japanese patients with rheumatoid arthritis use complementary and alternative medicine.

We investigated the prevalence and predictors of complementary and alternative medicine (CAM) use by patients with rheumatoid arthritis (RA) in Japan. A cross-sectional descriptive study was performed using the database from a large observational cohort of RA patients in the Institute of Rheumatology, Tokyo Women's Medical University. Logistic regression analysis was carried out to reveal predictive factors for CAM use. Among 3815 RA patients, 1321 (34.6%; 174 males, 1147 females) used at least one type of CAM. Health foods, including dietary supplements, were the most commonly used. CAM was more frequently used by female patients (odds ratio: 0.578; 95% confidence interval [CI] = 0.451-0.740). A multiple logistic regression analysis revealed that sex (odds ratio: 0.489; 95% CI = 0.333-0.718) and degree of satisfaction with disease-modifying antirheumatic drugs (DMARDs) (odds ratio: 0.899; 95% CI = 0.852-0.948) were significant independent predictive factors for CAM use. The serum C-reactive protein level and erythrocyte sedimentation rate showed no significant associations with CAM use. Approximately 35% of RA patients used CAM in Japan. Female patients and patients dissatisfied with DMARDs used CAM more frequently, regardless of their disease activity.

Arthritis, Rheumatoid↗

Efficacy profile of bucillamine in rheumatoid arthritis patients in a large observational cohort study, IORRA.

Bucillamine (Buc) is a disease-modifying antirheumatic drug (DMARD) developed in Japan, which has been used as one of the first-line DMARDs for the treatment of rheumatoid arthritis (RA) in Japan. However, direct comparison of this drug with standard DMARDs including sulfasalazine (SASP) and methotrexate (MTX) has been scarcely reported. We therefore tried to evaluate the clinical efficacy of Buc by analyzing the database from the long-term observational cohort study IORRA (previously known as J-ARAMIS). The cross-sectional analysis revealed that responses to Buc treatment were better in males, patients with shorter duration of illness, and those who were rheumatoid factor-negative. In the longitudinal analysis, although there was no marked difference among the baseline variables of patients with Buc, SASP, and MTX, the percentage of patients exhibiting moderate or good response to treatment, as rated using the European League Against Rheumatism improvement criteria, was higher in the Buc group (41.0%) than in the MTX (32.6%) and SASP groups (25.6%). These data support Buc as a candidate for being a first-line drug for the treatment of patients with RA.

Anti-Inflammatory Agents, Non-Steroidal↗

Risk factors associated with incident clinical vertebral and nonvertebral fractures in Japanese women with rheumatoid arthritis: a prospective 54-month observational study.

OBJECTIVE: To evaluate the association between potential risk factors and incident clinical fractures in Japanese patients with rheumatoid arthritis (RA). METHODS: A total of 1733 female patients with RA over age 50 years were enrolled in a prospective observational cohort study. Participants were followed for 54 months from October 2000 to March 2005, and classified into 4 groups according to incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture); and those with any new nonvertebral fracture. Cox proportional hazard models were used to analyze independent contributions of various risk factors to fracture incidence. RESULTS: During the followup period, 33, 34, and 98 patients developed a vertebral, a main nonvertebral, and any nonvertebral fracture, respectively. The Japanese Health Assessment Questionnaire (J-HAQ) score was associated with relative risks (RR) of 2.42 (95% confidence interval 1.42-4.14), 1.76 (95% CI 1.07-2.89), and 1.73 (95% CI 1.29-2.32) for vertebral, main nonvertebral, and all nonvertebral fractures. The risks of vertebral and any nonvertebral fractures were increased for age over 70 years compared with age in the 50s (RR 3.25, 95% CI 1.19-8.86; and RR 2.22, 95% CI 1.20-4.10, respectively). Clinical variables and medications were associated with a new fracture. CONCLUSION: HAQ, age, history of any prior fracture, and orthopedic surgery for RA appear to be associated with fractures in Japanese women with RA.

Aged↗

Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values.

OBJECTIVE: To estimate the disease activity score (DAS)28-C-reactive protein (CRP) threshold values that correspond to DAS28-erythrocyte sedimentation rate (ESR) values for remission, low disease activity and high disease activity in patients with rheumatoid arthritis. METHODS: DAS28 data were analysed using a large observational study (Institute of Rheumatology Rheumatoid Arthritis) database of 6729 patients with rheumatoid arthritis. Firstly, the relationship between the DAS28-ESR and the DAS28-CRP values was analysed. Secondly, the best DAS28-CRP trade-off values for each threshold were calculated using receiver operating characteristic (ROC) curves. RESULTS: The correlation coefficient of ESR versus CRP was 0.686, whereas that of DAS28-ESR versus DAS28-CRP was 0.946, showing the strong linear relationship between DAS28-ESR and DAS28-CRP values. DAS28-CRP threshold values corresponding to remission, low disease activity and high disease activity were 2.3, 2.7 and 4.1, respectively. The sensitivity and specificity from the ROC curves were gradually reduced as DAS28 values became lower. CONCLUSIONS: This study showed that DAS28-CRP and DAS28-ESR were well correlated, but the threshold values should be reconsidered. As the results were derived from only Japanese patients, it is essential to compare DAS28-CRP threshold values in people of other ethnic groups.

Aged↗

Potential impact of observational cohort studies in Japan on rheumatoid arthritis research and practice.

For better management of rheumatoid arthritis (RA) patients, we need information both from well-designed clinical trials, such as randomized controlled trials, and from observational cohorts. Observational cohort study has not been developed in Japanese RA patients; however, two cohorts, IORRA (formerly J-ARAMIS) from 2000 and NinJa by iR-net from 2002, have been established. These two cohorts are an important source not only for better management of Japanese RA patients but also for solutions to a variety of issues concerning RA clinical practice in general. In this minireview, necessities of observational cohort studies are discussed.

Antirheumatic Agents↗

Disability and patient's appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan.

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify "depressed patients." A total of 1875 (41.1%) were identified as "depressed patients" who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient's VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable "probability of depressed patients." Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.

Arthritis, Rheumatoid↗

Acceptability and usefulness of mizoribine in the management of rheumatoid arthritis in methotrexate-refractory patients and elderly patients, based on analysis of data from a large-scale observational cohort study.

This report documents the results of a study performed to examine clinical use of mizoribine (MZR), using data from a large-scale prospective cohort study, IORRA (Institute of Rheumatology Rheumatoid Arthritis). The number of patients with RA entered in this study from October 2000 through October 2003 was 6238. Three hundred and six patients (4.9%) received MZR therapy. Mizoribine users who were taking methotrexate (MTX) (MTX-MZR group, n = 94) and over 70 years of age (elderly group, n = 45) were collected. Cumulative retention rates of MZR were calculated by Kaplan-Meier analysis. Median drug survival of MZR was 28 months for the poor responders to MTX and 43 months for the poor responders to MZR, with no significant difference between these groups. Cumulative retention rate of MZR in the elderly group did not show a significant difference compared to that in patients aged under 70 years. Ten patients (10.6%) in the MTX-MZR group and 10 patients (22.2%) in the elderly group experienced adverse effects of MZR. None of these adverse effects was serious. This study indicated that, although MZR has not been frequently prescribed for RA patients, it may be useful and relatively safe for patients who are poor responders to MTX as an additional regimen to MTX therapy as well as for elderly patients.

Age Factors↗

Hypersensitivity reaction against influenza vaccine in a patient with rheumatoid arthritis after the initiation of etanercept injections.

A 58-year-old Japanese woman with rheumatoid arthritis (RA) suffered from high fever triggered by administration of an influenza vaccine after a 4-month-long effective treatment course with the TNF-alpha inhibitor etanercept. Influenza vaccine had been previously administrated safely to the patient before initiation of etanercept therapy. The fever occurred without other symptoms soon after vaccine administration, progressed to high fever 1 day later, and spontaneously resolved the second day. The clinical course appears to be compatible with drug fever closely associated with immediate hypersensitivity (in particular, late-phase type I allergic reaction), in which T helper (Th) 2 cells play a crucial role. Etanercept can strongly suppress Th1-mediated reactions; therefore, Th2 activity may be augmented by etanercept treatment in aspect of antagonism between Th1 and Th2 mechanisms. In RA patients who receive treatment with TNF-alpha inhibitor such as etanercept, activation of Th2-mediated immune responses such as immediate hypersensitivity may be a necessary side effect for those who receive vaccinations.

Antirheumatic Agents↗

Impact of shoulder, elbow, and knee joint involvement on assessment of rheumatoid arthritis using the American College of Rheumatology Core Data Set.

OBJECTIVE: To determine the most sensitive scoring method for assessment of rheumatoid arthritis (RA) disease activity using the American College of Rheumatology Core Data Set. METHODS: The subjects were 4,530 patients with RA (mean age 57.9 years, mean disease duration 12.7 years) who participated in a large observational cohort study of RA patients. The 68 joints assessed were classified into 15 joint areas, and each joint variable was categorized based on the presence or absence of swelling or pain in these areas. Multiple linear regression and analysis of variance were used to evaluate the significance of effects of these 15 joint areas on variables for assessment of RA disease activity such as patient's assessment of pain on a visual analog scale (VAS), patient's and physician's global assessment of disease activity on a VAS, HAQ (Health Assessment Questionnaire), and Japanese HAQ. RESULTS: Although the 3 most frequently affected joints were the wrist, metacarpophalangeal joints, and proximal interphalangeal joints, the 5 joints with the largest contributions to all of the variables assessed for disease activity were the shoulder, elbow, and knee joints, followed by the wrist and ankle joints. The combination of shoulder, elbow, and knee joints accounted for approximately 70% of the contribution to all the variables, while addition of the wrist and ankle joints increased this value to approximately 90%. CONCLUSION: Scoring for assessment of RA disease activity would be more sensitive if separate joints such as the shoulder, elbow, knee, wrist, and ankle joints were weighted differently.

Arthritis, Rheumatoid↗

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites.

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

Arthritis, Rheumatoid↗

Association between PADI4 and rheumatoid arthritis: a replication study.

OBJECTIVE: The peptidylarginine deiminase type 4 gene (PADI4) was recently reported to be associated with rheumatoid arthritis (RA) in a Japanese population. The presence of a single-nucleotide polymorphism (SNP) located in intron 3 of PADI4 provided the strongest evidence of this association. Moreover, functional haplotypes that affect stability of transcripts were identified. However, subsequent research failed to confirm the observed association in a UK population. The present study was undertaken to further investigate the association of PADI4 with RA, using a series of population-based samples from subjects with the same ethnic background as the subjects in the original study. METHODS: DNA samples were obtained from 1,230 Japanese RA patients and 948 ethnically matched controls. Genotyping was performed using 5' allele discrimination assays. All samples were genotyped for 3 SNPs on PADI4 (padi4_94, padi4_104, and padi4_102), which comprised the reported haplotypes. Chi-square testing was performed for a case-control study and the PENHAPLO program was used for haplotype estimation. RESULTS: All tested SNPs were found to show significant differences in frequency between cases and controls (P = 0.010-0.0008), which confirmed the association observed in the original study. Odds ratios calculated for allele frequencies were 1.23, 1.21, and 1.36 in padi4_94, padi4_104, and padi4_102 respectively. CONCLUSION: Replication of association in individual samples strongly suggests that PADI4 is a true susceptibility gene for RA.

Adult↗

Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan.

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58-0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori-/NSAID- group, 1.24% in the H. pylori-/NSAID+ group, 1.06% in the H. pylori+/NSAID- group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19-7.38) and 4.31 (95% CI: 0.57-32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA.

Journal Article↗

Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study.

Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 +/- 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 +/- 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.

Journal Article↗