Abstract: Background The Edinburgh Postnatal Depression Scale (EPDS) is commonly used to screen for postpartum depression, but is difficult to consistently administer to all mothers during busy well-child visits owing to its time-consuming. Here, we evaluated the performance of a concise, two-question screening tool in the detection of mothers with postpartum depressive symptoms who had a high EPDS score. Methods The study involved 103 mothers attending a single hospital for 1-month well-child visits. The primary outcome measure was the detection of mothers with postpartum depressive symptoms, using the EPDS score as the reference standard. Visiting mothers were asked to complete both the EPDS questionnaire and a two-question questionnaire covering depressive mood and anhedonia while in the hospital waiting room. The sensitivity, specificity, predictive value, and likelihood ratio of the two-question instrument was evaluated using the EPDS as standard. Results Taking EPDS as standard, sensitivity of the two-question instrument was 88% (95% confidence interval, 64%-99%), specificity was 76% (6584%), positive predictive value was 42% (26%-59%), and negative predictive value was 97% (90%-100%). The stratified likelihood ratios of each of the two-question instrument test scores - 0, 1, and 2 were 0.2 (0.0-0.6), 3.4 (1.8-6.2) and 4.2 (1.5-12.3) respectively. Conclusions Our study showed that, with the cutoff point set at 1 the two-question instrument had high sensitivity in detecting postpartum depressive symptoms at 1-month well-child visits. In primary care setting, negative result with the two-question instrument may be a good indicator for no need for further evaluation for postpartum depression.

Abstract: OBJECTIVES: It is still unclear whether patients with diabetes feel excessive daytime sleepiness or dose/sleep during driving in patients more frequently. METHODS: A population-based cross-sectional survey was conducted in a rural town. Multivariable-adjusted logistic regression models were used to explore the association between prevalent diabetes cases and excessive daytime sleepiness or dose/sleep during driving. RESULTS: Of 4540 participants, a total of 470 diabetes cases were identified. Compared with those in the never doze/sleep category, multivariate-adjusted odds ratios of diabetes was 0.41 (95%CI, 0.12-1.35) in slight category of dozing or sleeping when stopped for a few minutes in traffic while driving and 2.97 (95%CI, 1.19-7.41) in the moderate to high categories of dozing or sleeping when stopped for a few minutes in traffic while driving. This association remained significant after adjusting for the presence of poor sleep quality defined by the global Pittsburgh Sleep Quality Index score equal or greater than 5. CONCLUSION: Compared to individuals without diabetes, patients with diabetes experienced excessive daytime sleepiness or dozing/sleeping when stopped for a few minutes in traffic while driving more often independent of poor sleep quality. From the public health perspective, all patients with diabetes should be asked about a history of excessive daytime sleepiness or dozing/sleeping while driving, which is a known risk factor for future traffic accidents.

Abstract: BACKGROUND: To our knowledge, no objective criterion has been identified for the diagnosis of lumbar spinal stenosis (LSS) and no study has evaluated the predictive value of self-reported patient information for the identification of LSS. OBJECTIVE: To develop and validate a prediction rule for the identification of LSS based on self-reported patient information alone. METHODS: Prospective derivation study using a coefficient-based multivariable logistic regression scoring method with internal validation with primary care clinics and orthopaedic departments of medical centres, as well as university and other hospitals. Participants were consecutive patients with primary symptoms of pain or numbness in the lower extremities. Physician-diagnosed LSS was the MAIN OUTCOME MEASURE: RESULTS: Of 468 patients included in the analysis, 47.3% were diagnosed with LSS and divided into derivation and validation sets. The following items were retained at the conclusion of the derivation process: age (<60, 60-70 and >70), duration of symptoms over 6 months, symptom improvement when bending forward, symptom improvement when bending backward, symptom exacerbation while standing up, intermittent claudication and urinary incontinence. To derive a risk score for each patient, integer-based scores were assigned and summed. In the validation data sets, prevalence of LSS in patients from the first to fourth risk score quartile were 13.3%, 47.6%, 55.2% and 65.5%, respectively. Further, the likelihood ratio in the low-risk category was 0.154. CONCLUSIONS: We developed a prediction rule for the identification of LSS based on self-reported patient information alone. Further, the likelihood ratio in the low-risk category was sufficiently low. This rule may be used for screening of LSS.

Abstract: OBJECTIVE: We investigated the impact of active smoking and exposure to passive smoke on the risk of developing diabetes. RESEARCH DESIGN AND METHODS: Data were analyzed from a cohort of participants in the High-Risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP) conducted in Japan from 1999 to 2004. Active and passive smoking status in the workplace was evaluated at baseline. RESULTS: Of 6,498 participants (20.9% women), a total of 229 diabetes cases were reported over a median 3.4 years of follow-up. In the workplace, compared with zero-exposure subjects, the multivariable-adjusted hazard ratios of developing diabetes were 1.81 (95% CI 1.06-3.08, P = 0.028) for present passive subjects and 1.99 (1.29-3.04, P = 0.002) for present active smokers. CONCLUSIONS: In this cohort, exposure to passive smoke in the workplace was associated with an increased risk of diabetes after adjustment for a large number of possible confounders.

Abstract: OBJECTIVE: We reassessed 1-month survival of patients with witnessed out-of-hospital cardiac arrest (OHCA) of cardiac origin with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) in Osaka, Japan, and identified factors associated with 1-month survival using updated data from 1998 to 2004 collected based on the Utstein Style. METHODS: Using the Utstein Osaka Project database, we analyzed 1028 cases which met the following criteria: (1) patient age 18 years or older; (2) presumed cardiac origin based on the definition of the Utstein Style; (3) witnessed by citizens; (4) VF or pulseless VT at the time of arrival of the ambulance. The main outcome measure was survival at 1 month after collapse. Variables to develop a predictive model for 1-month survival were selected by stepwise logistic regression. RESULTS: Survival at 1 month was 19.6%. Factors retained in the final logistic regression were age, sex, type of witness, and time interval from (a) ambulance call receipt to cardiopulmonary resuscitation (CPR) by the ambulance crew; (b) ambulance call to defibrillation; (c) CPR by the ambulance crew to hospital arrival. Area under the receiver-operating characteristic curve for the model developed with the six variables was 0.738 and Hosmer-Lemshow goodness-of-fit p-value was 0.94. CONCLUSION: We successfully developed a model to estimate the probability of 1-month survival using variables easy to collect in the early phase of resuscitation, and this model would help physicians and family members predict the likelihood of 1-month survival of OHCA patients on admission.

Abstract: Background Epidemiological data on aspirin use and the risk of diabetes are limited. The Physician's Health Study has accumulated 22 years of follow-up data, including 5 years of randomized data, from 22,071 apparently healthy men. Methods and results At baseline and in yearly follow-up questionnaires, participants self-reported a history of diabetes, aspirin use and various lifestyle factors. To evaluate the association between aspirin use and risk of subsequent diabetes, we used a Cox-proportional hazards model with time-varying regression coefficients. During the 22 follow-up years, 1719 cases of diabetes were reported. The multivariable-adjusted hazard ratio (HR) of developing diabetes was 0.86 (95% confidence interval [CI], 0.77-0.97) for those who selfselected any aspirin. During the 5 years of randomized treatment, 318 cases of diabetes were observed, with an HR of 0.91 (95%CI, 0.73-1.14) for those randomized to aspirin. Conclusions Our data suggest a small but not significant decrease in the risk of diabetes during 5 years of randomized comparison of 325 mg of aspirin every other day. This trend was continued during 22 years of follow-up, indicating that self-selection of any use of aspirin is associated with a significant, approximately 14% decrease in the risk of diabetes. Decreased risk of type 2 diabetes may be added to the list of the clinical benefits of aspirin.

Abstract: No clinical diagnostic support tool can help identify patients with LSS. Simple diagnostic tool may improve the accuracy of the diagnosis of LSS. The aim of this study was to develop a simple clinical diagnostic tool that may help physicians to diagnose LSS in patients with lower leg symptoms. Patients with pain or numbness of the lower legs were prospectively enrolled. The diagnosis of LSS by experienced orthopedic specialists was the outcome measure. Multivariable logistic regression analysis identified factors that predicted LSS; a simple clinical prediction rule was developed by assigning a risk score to each item based on the estimated beta-coefficients. From December 2002 to December 2004, 104 orthopedic physicians from 22 clinics and 50 hospitals evaluated 468 patients. Two items of physical examination, three items of patients' symptom, and five items of physical examination were included in the final scoring system as a result of multiple logistic regression analysis. The sum of the risk scores for each patient ranged from -2 to 16. The Hosmer-Lemeshow statistic was 11.30 (P = 0.1851); the area under the ROC curve was 0.918. The clinical diagnostic support tool had a sensitivity of 92.8% and a specificity of 72.0%. The prevalence of LSS was 6.3% in the bottom quartile of the risk score (-2 to 5) and 99.0% in the top quartile (12 to 16). We developed a simple clinical diagnostic support tool to identify patients with LSS. Further studies are needed to validate this tool in primary care settings.

Abstract: BACKGROUND: The effect of sleep on the risk of developing diabetes has not been explored in an Asian population. The objective of this study is to investigate the effect of self-reported sleep duration and sleep quality on the risk of developing diabetes in a prospective cohort in Japan. METHODS: Data were analyzed from the cohort of participants in a High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP), conducted in Japan from the year 1999 until 2004. A Cox proportional hazard model was used to evaluate the association between sleep duration or sleep quality and the risk of diabetes. RESULTS: Of 6509 participants (26.1% of women, 19-69 years of age), a total of 230 type 2 diabetes cases were reported over a median 4.2 years of follow-up. For participants who often experienced difficulty in initiating sleep, the multivariate-adjusted hazard ratios for diabetes were 1.42 (95%CI, 1.05-1.91) in participants with a medium frequency of difficulty initiating sleep, and 1.61 (95%CI, 1.00-2.58) for those with a high frequency, with a statistically significant linear trend. Significant association was not observed in the association between difficulty of maintaining sleep or duration of sleep, and risk of diabetes. CONCLUSION: Medium and high frequencies of difficulty initiating sleep, but not difficulty in maintaining sleep or in sleep duration, are associated with higher risks of diabetes in relatively healthy Asian workers, even after adjusting for a large number of possible further factors.

Abstract: The objective of this study is to ascertain if higher normal fasting glucose levels are also an independent risk of developing diabetes in an Asian population, and we thus analysed data from a cohort of healthy Japanese workers. We used data from the non-randomised trial on health promotion intervention, High-risk and Population Strategy for Occupational Health Promotion (HIPOP-OHP) Study. Diabetes cases and those who had fasting blood glucose levels equal to or greater than 100 mg/dl at baseline were excluded, and the Cox proportional-hazards model was used for the analysis. During the four-year follow-up of 2212 participants, we found 37 diabetes cases. In the multivariable model, people with blood glucose levels in the 4th quartile had a higher risk of diabetes than those in the bottom quartile; the multivariable-adjusted odds ratio was 2.52. The risk of diabetes abruptly rose in persons with blood glucose levels higher than 94 mg/dl (fourth quartile). A significant linear trend was not observed in the 1st to 3rd quartiles (p=0.726). In conclusion, higher fasting glucose level was associated with the risk of diabetes, and we found a threshold in the association between fasting blood glucose levels and risk of diabetes in an Asian population.

Abstract: AIMS/HYPOTHESIS: There are few data on the target level of glycaemic control among patients with diabetes on haemodialysis. We investigated the impact of glycaemic control on mortality risk among diabetic patients on haemodialysis. SUBJECTS AND METHODS: Data were analysed from the Dialysis Outcomes Practice Pattern Study (DOPPS) for randomly selected patients on haemodialysis in Japan. The diagnosis of diabetes at baseline and information on clinical events during follow-up were abstracted from the medical records. A Cox proportional hazards model was used to evaluate the association between presence or absence of diabetes, glycaemic control (HbA(1c) quintiles) and mortality risk. RESULTS: Data from 1,569 patients with and 3,342 patients without diabetes on haemodialysis were analysed. Among patients on haemodialysis, those with diabetes had a higher mortality risk than those without (multivariable hazard ratio 1.37, 95% CI 1.08-1.74). Compared with those in the bottom quintile of HbA(1c) level, the multivariable-adjusted hazard ratio for mortality was not increased in the bottom second to fourth quintiles of HbA(1c) (HbA(1c) 5.0-5.5% to 6.2-7.2%), but was significantly increased to 2.36 (95% CI 1.02-5.47) in the fifth quintile (HbA(1c) > or = 7.3%). The effect of poor glycaemic control did not statistically correlate with baseline mortality risk (p = 0.27). CONCLUSIONS/INTERPRETATION: Among dialysis patients, poorer glycaemic control in those with diabetes was associated with higher mortality risk. This suggests a strong effect of poor glycaemic control above an HbA(1c) level of about 7.3% on mortality risk, and that this effect does not appear to be influenced by baseline comorbidity status.

Abstract: End-stage renal disease (ESRD) affects 230,000 Japanese, with about 36,000 cases diagnosed each year. Recent increases in ESRD incidence are attributed mainly to increases in diabetes and a rapidly aging population. Renal transplantation is rare in Japan. In private dialysis clinics, the majority of treatment costs are paid as fixed fees per session and the rest are fee for service. Payments for hospital-based dialysis are either fee-for-service or diagnosis-related. Dialysis is widely available, but reimbursement rates have recently been reduced. Clinical outcomes of dialysis are better in Japan than in other countries, but this may change given recent ESRD cost containment policies.

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Abstract: BACKGROUND: Screening for coronary artery disease (CAD) in asymptomatic diabetic patients with atherogenic risk factors is recommended by the American College of Cardiology/American Diabetes Association. It is not clear whether these guidelines apply to the Japanese population with a different epidemiology of CAD. This study evaluates the applicability of the U.S. guidelines to Japan, taking account of cost-effectiveness. DESIGN: A cost-effectiveness analysis using a Markov model was performed to measure the clinical benefit and cost of CAD screening in asymptomatic patients with diabetes and additional atherogenic risk factors. We evaluated cohorts of patients stratified by age, gender, and atherogenic risks. The incremental cost-effectiveness of not screening, exercise electrocardiography, exercise echocardiography, and exercise single-photon emission-tomography (SPECT) was calculated. The data used were obtained from the literature. Outcomes are expressed as US dollars per quality-adjusted life year (QALY). RESULTS: Compared with not screening, the incremental cost-effectiveness ratio (ICER) of exercise electrocardiography was $31,400/QALY for 60-year-old asymptomatic diabetic men, and 46,600 for 65-year-old women with hypertension and smoking. The ICER of exercise echocardiography was $31,500/QALY and of SPECT was $326,000/QALY, compared with the next dominant strategy. Sensitivity analyses found that these results varied according to age, gender, the combination of additional atherogenic risk factors, and the frequency of screening. CONCLUSION: From a societal perspective the U.S. guidelines on screening for CAD in high risk diabetic patients are applicable to the Japanese population. However, the population subjected to screening should be carefully selected to obtain greatest benefit from screening.

Abstract: BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) reported high incidence of depression in haemodialysis patients. Hypercalcaemia and high parathyroid hormone (PTH) levels are aetiological factors of psychological disorders. We examined the association between mineral metabolism abnormalities and mental health in Japanese-DOPPS patients. METHODS: We used baseline data of Japan-DOPPS, Phase 1 (2755 patients, 1999-2001) and Phase 2 (2286 patients, 2002-03). The outcome variable was mental health using the mental health domain of SF-36. We examined the association between serum corrected calcium, phosphorus, calcium x phosphorus product and intact PTH concentrations, and mental health using analysis of covariance and also the associations between corrected calcium levels and current use of vitamin D and calcium-containing phosphate binder. RESULTS: There was a significant association between mental health and corrected calcium levels. A significantly lower mental health score was noted in patients with corrected calcium > or = 11 mg/dl than in <8.4 (P = 0.04), > or =8.4 to <10.2 (P = 0.009) and > or =10.2 to <11 mg/dl (P = 0.003). The association was significant even after adjustment for age, sex and other confounders. However, there was no relationship between intact PTH and mental health. High-corrected calcium levels were significantly associated with the use of intravenous active vitamin D and calcium-containing phosphate binder. CONCLUSIONS: Hypercalcaemia, but not high intact PTH, is associated with poor mental health in dialysis patients. While a cause-effect relationship between hypercalcaemia and deterioration of mental health needs further confirmation by longitudinal and prospective studies, our observational findings suggest the importance of control of serum calcium concentration in dialysis patients.

Abstract: BACKGROUND: The extent of clinical exposure needed to ensure quality care has not been well determined during internal medicine training. We aimed to determine the association between clinical exposure (number of cases seen), self- reports of clinical competence, and type of institution (predictor variables) and quality of care (outcome variable) as measured by clinical vignettes. METHODS: Cross-sectional study using univariate and multivariate linear analyses in 11 teaching hospitals in Japan. Participants were physicians-in-training in internal medicine departments. Main outcome measure was standardized t-scores (quality of care) derived from responses to five clinical vignettes. RESULTS: Of the 375 eligible participants, 263 (70.1%) completed the vignettes. Most were in their first (57.8%) and second year (28.5%) of training; on average, the participants were 1.8 years (range = 1-8) after graduation. Two thirds of the participants (68.8%) worked in university-affiliated teaching hospitals. The median number of cases seen was 210 (range = 10-11400). Greater exposure to cases (p = 0.0005), higher self-reports of clinical competence (p = 0.0095), and type of institution (p < 0.0001) were significantly associated with higher quality of care, using a multivariate linear model and adjusting for the remaining factors. Quality of care rapidly increased for the first 100 to 200 cases seen and tapered thereafter. CONCLUSION: The amount of clinical exposure and levels of self-reports of clinical competence, not years after graduation, were positively associated with quality of care, adjusting for the remaining factors. The learning curve tapered after about 200 cases.

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Abstract: PURPOSE: To perform meta-analysis of literature about the role of helical computed tomography (CT) and ventilation-perfusion (V-P) scanning in detection of acute pulmonary embolism (PE) by using summary receiver operating characteristic (ROC) curve analysis. MATERIALS AND METHODS: V-P scanning articles published from January 1985 to March 2003 and helical CT articles published from January 1990 to March 2003 in MEDLINE and EMBASE databases were included if (a) tests were performed for evaluation of acute PE, (b) conventional angiography was the reference standard, and (c) absolute numbers of true-positive, false-negative, true-negative, and false-positive results were available. Sensitivity analysis was conducted by excluding articles published before 1995. RESULTS: A total of 12 articles discussing helical CT and/or V-P scanning were included. With a random-effects model, pooled sensitivity for helical CT was 86.0% (95% confidence interval [CI]: 80.2%, 92.1%), and specificity was 93.7% (95% CI: 91.1%, 96.3%). V-P scanning yielded low sensitivity of 39.0% (95% CI: 37.3%, 40.8%) but high specificity of 97.1% (95% CI: 96.0%, 98.3%) with high probability threshold. V-P scanning yielded high sensitivity of 98.3% (95% CI: 97.2%, 99.5%) and low specificity of 4.8% (95% CI: 4.7%, 4.9%) with normal threshold. Regression coefficients for helical CT angiography were 0.588 (95% CI: -1.55, 2.74) and 4.14 (95% CI: -0.002, 8.28) versus V-P scanning with high and normal thresholds, respectively. Regression coefficients for helical CT angiography were 0.588 (95% CI: -1.55, 2.74) and 4.14 (95% CI: -0.002, 8.28) versus V-P scanning with high and normal thresholds, respectively. CONCLUSION: Helical CT has greater discriminatory power than V-P scanning with normal and/or near-normal threshold to exclude PE, while helical CT and V-P scanning with high probability threshold had similar discriminatory power in the diagnosis of PE.

Abstract: BACKGROUND: This study evaluates the statistical and discriminatory powers of three statistical test methods (Begg's, Egger's, and Macaskill's) to detect publication bias in meta-analyses. METHODS: The data sources were 130 reviews from the Cochrane Database of Systematic Reviews 2002 issue, which considered a binary endpoint and contained 10 or more individual studies. Funnel plots with observers'agreements were selected as a reference standard. We evaluated a trade-off between sensitivity and specificity by varying cut-off p-values, power of statistical tests given fixed false positive rates, and area under the receiver operating characteristic curve. RESULTS: In 36 reviews, 733 original studies evaluated 2,874,006 subjects. The number of trials included in each ranged from 10 to 70 (median 14.5). Given that the false positive rate was 0.1, the sensitivity of Egger's method was 0.93, and was larger than that of Begg's method (0.86) and Macaskill's method (0.43). The sensitivities of three statistical tests increased as the cut-off p-values increased without a substantial decrement of specificities. The area under the ROC curve of Egger's method was 0.955 (95% confidence interval, 0.889-1.000) and was not different from that of Begg's method (area=0.913, p=0.2302), but it was larger than that of Macaskill's method (area=0.719, p=0.0116). CONCLUSION: Egger's linear regression method and Begg's method had stronger statistical and discriminatory powers than Macaskill's method for detecting publication bias given the same type I error level. The power of these methods could be improved by increasing the cut-off p-value without a substantial increment of false positive rate.

Abstract: BACKGROUND: Chronic heart failure (CHF) is a common medical problem and B-type natriuretic peptide (BNP)-guided heart failure management for outpatients with symptomatic CHF was found to reduce the readmission rate and mortality, but the costs of treatment may provoke concern in the current cost-conscious clinical setting. METHODS: We conducted a cost-effectiveness analysis using a Markov model of regular BNP measurement in the outpatient setting. The target population was symptomatic CHF patients aged 35-85 years recently discharged from the hospital. Intervention was BNP measurement once every 3 months (BNP group) or no BNP measurement (clinical group). Clinical and utility data were retrieved from published studies. Costs were based on published data in the US. Cost-effectiveness was measured by $ per quality-adjusted life year (QALY). RESULTS: The baseline analysis during the 9-month period after hospitalization showed the QALY to be longer for the BNP group (0.57 for the BNP group and 0.55 for the clinical group) and the costs were also lower for the BNP group ($9577 and 10,131). The dominance of the BNP group continued during the 1-year follow-up. The incremental costs would be $3491-7787 per QALY. In sensitivity analyses, two parameters with strong effects on the cost-effectiveness were the probability of the first readmission for CHF in the clinical group and the costs for inpatient CHF care. When these two parameters were simultaneously put on the simulation model, the incremental costs of the BNP group may exceed $50,000. CONCLUSIONS: Introduction of BNP measurement in heart failure management may be cost-effective.

Abstract: BACKGROUND: Graft dysfunction mimicking autoimmune hepatitis (AIH) develops only rarely after liver transplantation for nonautoimmune liver disease. The long-term prognosis and risk factors of de novo AIH after living-donor liver transplantation (LDLT) are unknown. METHODS: We review our LDLT series to investigate the incidence and outcome of this form of graft dysfunction, focusing on follow-up histology. RESULTS: Of 633 patients who underwent LDLT at Kyoto University from 1990 to 2002, 13 (2.1%) developed graft dysfunction with interface hepatitis resembling AIH (2 males, 11 females). The median age at LDLT of these 13 patients was 10 years (8 months to 26 years). All received tacrolimus-based immunosuppression. The dysfunction presented at a median interval of 3.1 (0.7-9.5) years after LDLT. Nine had definite AIH, and four had probable AIH at the onset of hepatitis. Patients were followed after a median of 3.5 (0.1-8) years from the onset of de novo AIH. Of 11 patients who underwent follow-up histologic evaluation, 3 underwent retransplantation, and 8 continued to have similar findings on subsequent biopsies, with fluctuations in the amount of necroinflammatory activity and an increase in fibrosis despite treatment. In a multivariate analysis, acute rejection episodes and recipient age between 11 and 15 years at LDLT independently had predictive value for the development of de novo AIH. Human leukocyte antigen-A, B, and DR mismatches and sex mismatch did not influence the occurrence of de novo AIH. CONCLUSION: This series highlights the more severe histologic outcome of de novo AIH with longer follow-up despite immunosuppressive treatment. De novo AIH may arise from alloimmunologic injury, marked by clinically obvious episodes of acute rejection.

Abstract: We describe 3 unrelated Japanese patients with familial Mediterranean fever (FMF) due to a compound heterozygous E148Q/M694I mutation in the MEFV gene. The first patient is a 38-year-old man who also has chronic myelogenous leukemia (CML). Because genomic DNA analysis of the patient's nail revealed the E148Q/M694I mutation, we concluded that the individual mutations were obtained congenitally. Interferon alpha therapy was effective against not only the CML but also the FMF. The second patient is a 42-year-old man with consanguineous parents and a 14-year history of recurrent lower abdominal and back pain associated with fever. He successfully responded to colchicine treatment. The third patient is a 23-year-old woman who has a family history of FMF and since the age of 11 years has had recurrent chest and abdominal pain with fever. The onset of FMF was at an early age in this case, in contrast with the late onset of the disease in the first 2 cases. This patient's mother also has a heterozygous M694I mutation and experienced the same symptoms until 30 years of age. Our data suggest that it should be recognized that there are more FMF patients in Japan than previously expected and that the frequency of the E148Q/M694I mutation may be significant in Japanese FMF patients.

Abstract: OBJECTIVE: Screening for coronary artery disease (CAD) in asymptomatic diabetic patients with two additional atherogenic risk factors has been recommended by the American College of Cardiology/American Diabetes Association, but its cost-effectiveness is yet to be determined. The present study aims to evaluate the cost-effectiveness of screening and determine acceptable strategies. DESIGN: Cost-effectiveness analysis using a Markov model was performed from a societal perspective to measure the clinical benefit and economic consequences of CAD screening in asymptomatic men with diabetes and two additional atherogenic risk factors. We evaluated cohorts of patients stratified by different age groups, and 10 possible combination pairs of atherogenic risks. Incremental cost-effectiveness of no screening, exercise electrocardiography, exercise echocardiography, or exercise single-photon emission-tomography (SPECT) was calculated. Input data were obtained from the published literature. Outcomes were expressed as U.S. dollars per quality-adjusted life-year (QALY). MEASUREMENTS AND MAIN RESULTS: Compared with no screening, incremental cost-effectiveness ratio of exercise electrocardiography was $41,600/QALY in 60-year-old asymptomatic diabetic men with hypertension and smoking, but was weakly dominated by exercise echocardiography. Exercise echocardiography was most cost-effective, with an incremental cost-effectiveness ratio of $40,800/QALY. Exercise SPECT was dominated by other strategies. Sensitivity analyses found that results varied depending on age, combination of additional atherogenic risk factors, and diagnostic test performance. CONCLUSIONS: Incremental cost-effectiveness ratio of CAD screening in asymptomatic patients with diabetes and two or more additional atherogenic risk factors is shown to be acceptable from a societal perspective. Exercise echocardiography was the most cost-effective strategy, followed by exercise electrocardiography.

Abstract: The objective of this study is to investigate the degree of Japan's contribution to the research in rheumatology in the past decade. Articles published in 1991–2000 in highly reputed journals in rheumatology and general medicine were assessed through the MEDLINE database. Then, the number of articles having an affiliation with a Japanese institution was counted and summed up as a whole and also separately for each journal with statistical time trend analysis. The proportions of randomized controlled studies (RCT), case-control/cohort studies, and case reports in articles from Japan were also determined. Of total articles in rheumatology, Japan's contribution to the research reported in journals of rheumatology was 5.7% and ranked fourth in the world; in journals of general medicine, it was 1.2% and ranked eighth. The recent increase in contribution was significant (P &equals; 0.01). Compared with other countries, the proportions of RCTs (1.1%) and case-control/cohort studies (6.4%) were smaller and that of case reports similar (5.9%) among the articles from Japan. In conclusion, we should determine and remove the factors that restrain high-quality clinical research to achieve a more significant contribution of Japan to research in rheumatology.

Abstract: Thrombotic thrombocytopenic purpura (TTP) is an unusual complication of systemic lupus erythematosus (SLE). Although the reported association between SLE and TTP is increasing, a few cases do improve without plasmatherapy. We report a case of TTP which was successfully treated without plasmatherapy, which might be underestimated as an etiology of thrombocytopenia in SLE. TTP should always be considered as a concomitant disease when Coombs'' negative hemolytic anemia or thrombocytopenia is seen in SLE patients.

Abstract: Japan's contribution to the research on cardiovascular disease in the past decade was analyzed by accessing journal articles published in 1991-2000 in the MEDLINE database. The number of articles having an affiliation with a Japanese institution was counted and summed up as a whole and also separately for each journal with statistical time trend analysis. The proportions of randomized controlled study (RCT), case - control/cohort study, and case reports in articles from Japan were also determined. Of the total articles, Japan's contribution to the research on cardiovascular disease was 8.9% and ranked 2nd in the world. The recent increase in the contribution was not significant (p=0.25). Compared with other countries, the proportions of RCT (2.3%) and case - control/cohort study (2.3%) were smaller and that of case reports was similar (5.7%). Although the overall contribution from Japan in the field of cardiovascular disease is satisfactory, high-quality clinical research is as meager as in other clinical fields.

Abstract: We report an unusual case of Gaucher's disease in which central nervous system symptoms developed in the fifth decade of life. A 53-year old woman was admitted to Tenri Hospotal with generalized convulsive seizure. At age 43 years she was diagnosed as having Gaucher's disease by bone marrow aspiration and enzyme analysis. There was mild splenomegaly and thrombocytopenia, Electroencephalogram revealed sharp waves and a photo-convulsive response. After valproic acid administration her myoclonus disappeared and electroencephalographic findings were improved.