Yosikazu Nakamura

The performance of the Japanese version of the K6 and K10 in the World Mental Health Survey Japan

Two new screening scales for psychological distress, the K6 and K10, have been developed using the item response theory and shown to outperform existing screeners in English. We developed their Japanese versions using the standard backtranslaton method and included them in the World Mental Health Survey Japan (WMH‐J), which is a psychiatric epidemiologic study conducted in seven communities across Japan with 2436 participants. The WMH‐J used the WMH Survey Initiative version of the Composite International Diagnostic Interview (CIDI) to assess the 30‐day Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM‐IV). Performance of the two screening scales in detecting DSM‐IV mood and anxiety disorders, as assessed by the areas under receiver operating characteristic curves (AUCs), was excellent, with values as high as 0.94 (95% confidence interval = 0.88 to 0.99) for K6 and 0.94 (0.88 to 0.995) for K10. Stratum‐specific likelihood ratios (SSLRs), which express screening test characteristics and can be used to produce individual‐level predicted probabilities of being a case from screening scale scores and pretest probabilities in other samples, were strikingly similar between the Japanese and the original versions. The Japanese versions of the K6 and K10 thus demonstrated screening performances essentially equivalent to those of the original English versions. Copyright

Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey.

Background Although the number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan, the most recent epidemiologic features of KD are not known. Methods The 21st nationwide survey of KD was conducted in 2011 and included patients treated for the disease in 2009 and 2010. Hospitals specializing in pediatrics, and hospitals with a total of 100 or more beds and a pediatric department, were asked to report all patients with KD during the 2 survey years. Results A total of 1445 departments and hospitals reported 23 730 KD patients (10 975 in 2009 and 12 755 in 2010): 13 515 boys and 10 215 girls. The annual incidence rates were 206.2 and 239.6 per 100 000 children aged 0 to 4 years in 2009 and 2010, respectively; the 2010 rate was the highest ever reported in Japan. Monthly number of patients peaked during winter to spring months; lower peaks were noted during summer months. However, the seasonal patterns in 2009 and 2010 differed from those of previous years. The age-specific incidence rate had a monomodal distribution, with a peak during the latter half of the year of birth. The prevalences of cardiac lesions during acute KD and cardiac sequelae were higher among infants and older age groups. Despite a decrease in prevalence, the proportion of patients with giant coronary aneurysms—the most severe sequela of KD—did not substantially decrease. Conclusions The incidence rate and number of patients with KD continue to increase in Japan.

Cross-National Analysis of the Associations between Traumatic Events and Suicidal Behavior: Findings from the WHO World Mental Health Surveys

Background Community and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues. Methodology/Principal Findings Data on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries. Conclusions/Significance This study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.

Days out of role due to common physical and mental conditions: results from the WHO World Mental Health surveys

Days out of role because of health problems are a major source of lost human capital. We examined the relative importance of commonly occurring physical and mental disorders in accounting for days out of role in 24 countries that participated in the World Health Organization (WHO) World Mental Health (WMH) surveys. Face-to-face interviews were carried out with 62 971 respondents (72.0% pooled response rate). Presence of ten chronic physical disorders and nine mental disorders was assessed for each respondent along with information about the number of days in the past month each respondent reported being totally unable to work or carry out their other normal daily activities because of problems with either physical or mental health. Multiple regression analysis was used to estimate associations of specific conditions and comorbidities with days out of role, controlling by basic socio-demographics (age, gender, employment status and country). Overall, 12.8% of respondents had some day totally out of role, with a median of 51.1 a year. The strongest individual-level effects (days out of role per year) were associated with neurological disorders (17.4), bipolar disorder (17.3) and post-traumatic stress disorder (15.2). The strongest population-level effect was associated with pain conditions, which accounted for 21.5% of all days out of role (population attributable risk proportion). The 19 conditions accounted for 62.2% of all days out of role. Common health conditions, including mental disorders, make up a large proportion of the number of days out of role across a wide range of countries and should be addressed to substantially increase overall productivity.

Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment

The book on iatrogenic Creutzfeldt-Jakob disease (CJD) in humans is almost closed. This form of CJD transmission via medical misadventures was first detected in 1974. Today, only occasional CJD cases with exceptionally long incubation periods still appear. The main sources of the largest outbreaks were tissues from human cadavers with unsuspected CJD that were used for dura mater grafts and growth hormone extracts. A few additional cases resulted from neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infections from blood transfusions. Although the final solution to the problem of iatrogenic CJD is still not available (a laboratory test to identify potential donors who harbor the infectious agent), certain other measures have worked well: applying special sterilization of penetrating surgical instruments, reducing the infectious potential of donor blood and tissue, and excluding donors known to have higher than normal risk for CJD.

Lifestyle Modification and Prevention of Type 2 Diabetes in Overweight Japanese With Impaired Fasting Glucose Levels: A Randomized Controlled Trial

BACKGROUND Previous studies demonstrated that intensive lifestyle modification can prevent type 2 diabetes mellitus among those with impaired glucose tolerance, but similar beneficial results have not been proved among those with impaired fasting glucose levels. We investigated the efficacy of lifestyle modification on type 2 diabetes incidence among those with impaired fasting glucose levels. METHODS The present study was an unmasked, multicenter, randomized, controlled trial. A total of 641 overweight Japanese (aged 30-60 years) with impaired fasting glucose levels were recruited nationwide in Japan and randomly assigned to a frequent intervention group (n = 311) or a control group (n = 330). For 36 months after randomization, the frequent intervention group received individual instructions and follow-up support for lifestyle modification from the medical staff 9 times. The control group received similar individual instructions 4 times at 12-month intervals during the same period. The primary outcome was type 2 diabetes incidence in annual 75-g oral glucose tolerance tests, diagnosed according to World Health Organization criteria. RESULTS There were no significant differences between the allocation groups in baseline characteristics and dropout rates. Estimated cumulative incidences of type 2 diabetes were 12.2% in the frequent intervention group and 16.6% in the control group. Overall, the adjusted hazard ratio in the frequent intervention group was 0.56 (95% confidence interval, 0.36-0.87). In the post hoc subgroup analyses, the hazard ratio reduced to 0.41 (95% confidence interval, 0.24-0.69) among participants with impaired glucose tolerance at baseline, and to 0.24 (0.12-0.48) among those with baseline hemoglobin A(1c) levels of 5.6% or more (the Japan Diabetes Society method). Such risk reduction was not observed among those with isolated impaired fasting glucose findings or baseline hemoglobin A(1c) levels of less than 5.6%. CONCLUSIONS Lifestyle modifications can prevent type 2 diabetes among overweight Japanese with impaired fasting glucose levels. In addition, identifying individuals with more deteriorated glycemic status by using 75-g oral glucose tolerance test findings or, especially, measurement of hemoglobin A(1c) levels, could enhance the efficacy of lifestyle modifications. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: UMIN000001959.

Diagnostic Criteria, Clinical Features, and Incidence of Thyroid Storm Based on Nationwide Surveys

BACKGROUND Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively. METHODS We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2. RESULTS We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL. CONCLUSIONS TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.

Epidemiologic Features of Kawasaki Disease in Japan: Results from the Nationwide Survey in 2005-2006

Background The most recent epidemiologic features of Kawasaki disease are unknown. Methods The 19th nationwide survey of the disease was conducted in 2007, targeting patients who were affected by this disease in 2005 and 2006. All pediatric departments in hospitals with 100 or more beds and pediatric hospitals were asked to report all Kawasaki disease patients during the 2 survey years. Results From 1543 departments and hospitals, a total of 20475 patients (10041 in 2005 and 10434 in 2006) were reported. There were 11892 male patients and 8583 female patients. The average annual incidence rate was 184.6 per 100000 children aged 0-4 years. The number of patients and the incidence rate have increased significantly during the past 12 years. The age-specific incidence rate was distributed monomodally with a peak at 6-8 months of age. The prevalence of cardiac lesions in the acute phase of the disease and of cardiac sequelae were higher among infants and old patients. Conclusion The number of patients with Kawasaki disease and its incidence rate in Japan are continuously increasing.

PHYSICAL-STRENGTH TESTS AND MORTALITY AMONG VISITORS TO HEALTH-PROMOTION CENTERS IN JAPAN

A follow-up study was conducted to clarify the relationship between physical-strength level and risk of death from all causes and from cancer and cardiovascular disease. The 7286 persons who were examined at seven health-promotion centers throughout Japan between 1982 and 1987 were followed up. By January 1992, 6259 persons (85.9%) had been contacted by questionnaire. They included 3117 men (49.8% of all subjects studied) (average age 53.6 years at baseline, SD = 9.0 years, range 40-84 years), and 3142 women (50.2%) (average age 54.5 years at baseline, SD = 8.5 years, range 40-85 years). The follow-up period for each person averaged 6.1 years, for a total of 38,253 person-years. During this period, 155 deaths were reported. At baseline, five physical-strength tests (grip strength, side step, vertical jump, standing trunk flexion, and sit-ups) were performed. Five clinical laboratory tests (thickness of skinfold, blood sugar, total serum cholesterol, percent vital lung capacity, and blood pressure) were also conducted. The examinees were questioned about smoking status (current smoker, nonsmoker, and ex-smoker). Men with thicker skinfold [relative risk (RR) = 2.11] and higher levels of blood sugar (RR = 1.89) had an excess risk of death from all causes. Men with higher serum cholesterol (RR = 5.08), thicker skinfold (RR = 4.54), and elevated blood pressure (RR = 2.33) had an excess risk of death from cardiovascular disease. In women, no relationship was seen between clinical laboratory tests and an excess risk of death. Men exhibiting lower values for side step (RR = 2.43), vertical jump (RR = 2.37), sit-ups (RR = 1.93) and grip strength (RR = 1.92) also had an excess risk of death from all causes. Furthermore, men with lower heights for vertical jump (RR = 5.51) had an excess risk of death from cardiovascular disease. After adjustment for skinfold thickness, blood sugar, total serum cholesterol, blood pressure, percent vital lung capacity and smoking status, men with a lower level of side step, vertical jump, and grip strength had an excess risk of death from all causes. No such relationship was seen between physical-strength level and an excess risk of death in women. It is concluded that a low level of physical strength might be significantly correlated with subsequent health outcomes in men.

Quantifying prion disease penetrance using large population control cohorts

Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for a therapeutic strategy in prion disease. Share trumps rare No longer just buzz words, “patient empowerment” and “data sharing” are enabling breakthrough research on rare genetic diseases. Although more than 100,000 genetic variants are believed to drive disease in humans, little is known about penetrance—the probability that a mutation will actually cause disease in the carrier. This conundrum persists because small sample sizes breed imperfect alliance estimates between mutations and disease risk. Now, a patient-turned-scientist joined with a large bioinformatics team to analyze vast amounts of shared data—from the Exome Aggregation Consortium and the 23andMe database—to provide insights into genetic-variant penetrance and possible treatment approaches for a rare, fatal genetic prion disease. More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance—the probability that a carrier of the purported disease-causing genotype will indeed develop the disease—is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1 to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression.