Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Breastfeeding in Infancy in Relation to Subsequent Physical Size: A 20-year Follow-up of the Ibaraki Children's Cohort Study (IBACHIL).

BACKGROUND: Breastfeeding is said to prevent overweight and obesity in childhood but the evidence about its long-term impact on body size into adolescence and adulthood is scarce. We sought to examine the association between feeding types and subsequent physical size at the ages of 3, 6, 12, and 22 years. METHODS: The Ibaraki Children's Cohort (IBACHIL) Study, which began in 1992, involved a cohort of 4,592 Japanese children from 87 communities of a single prefecture whose parents answered health questionnaires about their child's health and life habits at the age of 3 years. Follow-up questionnaires were distributed to the same cohort when they were 6, 12, and 22 years old. Self-reported height and weight, body mass index (BMI), and overweight status at ages of 3 (n = 4,290), 6 (n = 1,999; proportion of participants analyzed = 47%), 12 (n = 2,227; 52%), and 22 (n = 1,459; 34%) years were compared according to feeding type (breastfeeding, formula feeding, and mixed feeding) during infancy. RESULTS: At the age of 3 years, multivariable adjusted-mean weight and prevalence of overweight were less for breastfed children than those formula-fed in both boys (weight: 14.6 kg vs 14.7 kg, P = 0.07, overweight: 6.3% vs 9.3%, P = 0.03) and in girls (14.0 kg vs 14.2 kg, P = 0.01 and 10.4% vs 13.6%, P = 0.06). However, there were no statistically significant differences in weight, BMI, and overweight at the ages of 6, 12, and 22 years according to feeding type. CONCLUSION: Breastfeeding may prevent overweight in childhood, but its impact is not significant in adolescence and adulthood.

Current status and future prospects of the Japanese orthopaedic association national registry (JOANR), Japan's first national registry of orthopaedic surgery.

The Japanese Orthopaedic Association National Registry (JOANR) is Japan's first national registry of orthopaedic surgery, which has been developed after having been selected for the Project for Developing a Database of Clinical Outcome approved by the Health Policy Bureau of the Ministry of Health, Labour and Welfare. Its architecture has two levels of registration, one being the basic items of surgical procedure, disease, information on surgeons, surgery-related information, and outcome, and the other being detailed items in the affiliated registries of partner medical associations. It has a number of features, including the facts that, because it handles medical data, which constitute special care-required personal information, data processing is conducted entirely in a cloud environment with the imposition of high-level data security measures; registration of the implant data required to assess implant performance has been automated via a bar code reader app; and the system structure enables flexible collaboration with the registries of partner associations. JOANR registration is a requirement for accreditation as a core institution or partner institution under the board certification system, and the total number of cases registered during the first year of operation (2020) was 899,421 registered by 2,247 institutions, providing real-world evidence concerning orthopaedic surgery.

Right bundle branch block and risk of cardiovascular mortality: the Ibaraki Prefectural Health Study.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards' models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06-1.38). The increased risk of cardiovascular mortality was particularly evident in women aged < 65 years (HR 2.00; 95% CI 1.34-2.98) and men aged ≥ 65 years (HR 1.28; 95% CI 1.06-1.55). CRBBB is associated with an increased risk of cardiovascular mortality in women aged < 65 years and men aged ≥ 65 years. Clinicians should be aware of the presence of CRBBB in young women and elderly men, even if they exhibit no symptoms.

Incidence of Metabolic Syndrome in Young Japanese Adults in a 6-Year Cohort Study: The Uguisudani Preventive Health Large-Scale Cohort Study (UPHLS).

INTRODUCTION: To clarify the incidences of metabolic syndrome (MS) and risks in young Japanese adults by gender. METHODS: A total of 58,901 adults who had undergone annual health check-ups in 2010 without a diagnosis of MS or missing data were divided into three age groups (20s through 40s) by gender. Participants were followed up for 6 years for new-onset MS according to Japanese criteria. The incidences of MS and risks were analyzed using the Cox proportional hazards model to adjust for confounding factors. RESULTS: The incidences of MS per 1,000 person-years were 2.2, 5.5, and 10.2 for women aged in their 20s, 30s, and 40s, respectively, and 26.3, 40.5, and 57.4 in the respective men groups. Compared with the group aged in their 40s, the hazard ratios of new MS were 0.19 (95% confidence interval [CI], 0.13-0.29) for women in their 20s and 0.50 (95% CI, 0.41-0.61) for women in their 30s, and 0.46 (95% CI, 0.42-0.50) and 0.70 (95% CI, 0.66-0.73) for men in their 20s and 30s, respectively, after adjustment for lifestyle factors. For women, MS was associated with smoking in their 20s and 30s, and eating speed in their 30s, and for men, was associated with physical activity, eating speed, alcohol intake in their 20s and 30s, and smoking in their 30s. CONCLUSION: Our findings suggest that the incidences of MS in the 20s and 30s are lower, but account for about 20-50% of women with MS and 50-70% of men with MS in their 40s. However, the data are not negligible and early lifestyle intervention for MS is necessary in young adults.

Japan Trial in High-Risk Individuals to Enhance Their Referral to Physicians (J-HARP)-A Nurse-Led, Community-Based Prevention Program of Lifestyle-Related Disease.

BACKGROUND: It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. METHODS: We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. RESULTS: The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. CONCLUSIONS: We expect to provide scientific evidence on the effectiveness of health counselling.

Does Cigarette Smoking Increase Traffic Accident Death During 20 Years Follow-up in Japan? The Ibaraki Prefectural Health Study.

BACKGROUND: Annually, more than 1.2 million deaths due to road traffic accidents occur worldwide. Although previous studies have examined the association between cigarette smoking and injury death, the mortality outcome often included non-traffic accident-related deaths. This study aimed to examine the association between cigarette smoking and traffic accident death. METHODS: We conducted a prospective cohort study using data from the Ibaraki Prefectural Health Study conducted from 1993 through 2013. The cohort included 97,078 adults (33,138 men and 63,940 women) living in Ibaraki Prefecture who were aged 40-79 years at an annual health checkup in 1993. We divided participants into four smoking status groups: non-smokers, ex-smokers, and current smokers who smoked <20 and ≥20 cigarettes per day. Hazard ratios (HRs) of traffic accident death were calculated using a Cox proportional hazards model. RESULTS: During 20 years of follow-up, the average person-years of follow-up were 16.8 and 18.2 in men and women, respectively. Among men, after adjusting for age and alcohol intake, HRs for traffic accident death among current smokers of <20 cigarettes/day and ≥20 cigarettes/day compared to non-smokers were 1.32 (95% confidence interval [CI], 0.79-2.20) and 1.54 (95% CI, 0.99-2.39), respectively. In contrast, among women, we found no association between smoking status and traffic accident deaths. CONCLUSION: In this prospective cohort study, we found a positive association, though marginally significant, between smoking and traffic accident death among men in Japan. Among women, because of the smaller number of deaths among smokers, adequate estimation could not be obtained.

Diagnostic value of a nested polymerase chain reaction for diagnosing cutaneous sporotrichosis from paraffin-embedded skin tissue.

BACKGROUND: The gold standard for diagnosis of cutaneous sporotrichosis involves the isolation of the fungus, Sporothrix, by a culture test. Generally, the sampling for the culture test is performed at the same time as skin biopsy under local anaesthesia. However, the culture test may occasionally return a false negative result. OBJECTIVE: The aim of our study was to investigate the diagnostic value of a molecular method for diagnosing cutaneous sporotrichosis from formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: Over a 30-year period, we collected 52 cases of cutaneous sporotrichosis from biopsied specimens that had been positively diagnosed by a culture test. A nested PCR specific for Sporothrix detection was applied using FFPE tissue as template. The results were compared with control samples from 79 patients diagnosed with other cutaneous diseases according to histopathological, clinical findings and a cutler test. RESULTS: Of the 52 patients who were tested positive on the culture test, all cutaneous diseases were detected by PCR. Of the 59 patients in the control group, 58 tested negative by PCR. Under our conditions, the calculated sensitivity of this method was 100%, the specificity was 98.7% and the kappa coefficient was 0.984 (95% CI: 0.953-1.000). CONCLUSIONS: The specific PCR assay used appears to be a useful tool for the prompt and accurate diagnosis of sporotrichosis. Using this method, it would be possible to diagnose cutaneous sporotrichosis for patients who were suspected of cutaneous sporotrichosis but tested negative on culturing, and for pathologically suspected cutaneous sporotrichosis patients for whom the culture test was not undertaken.

High Hematocrit Levels Are Associated with Risk of Cardiovascular Mortality among Middle-Aged Japanese Women: The Ibaraki Prefectural Health Study (IPHS).

In Japan, heart disease and cerebrovascular disease were the second and fourth leading cause of death, respectively in 2014. Hematocrit, the ratio of the red blood cells to the total volume of blood is known to play a role in cardiovascular diseases. However, the relationship between elevated hematocrit and the risk of cardiovascular disease based on sex has not been examined in Asian countries. We analyzed data from the Ibaraki Prefectural Health Study, a community-based large cohort study, which included 87,533 individuals, aged 40 to 79 years living in 38 municipalities of the Ibaraki Prefecture, who had completed an annual health checkup in 1993, and were followed until 2013. The hematocrit levels of the subjects were categorized into 5 quintiles (Q1-Q5), and hazard ratios for cause-specific mortality were calculated using the Cox proportional hazards regression models. Age and other cardiovascular risk factors were the covariates in the study. During the follow-up for a mean of 17.9 years, 1,207 deaths (615 men and 592 women) due to acute myocardial infarction (AMI) were reported in this population. The p values for the trend in the Q3-Q5 groups were 0.661 for men and 0.020 for women. Additionally, these values were significant in younger (40 to 59 years) women but not in older (60 to 79 years) women. This study is the first one to demonstrate an association between high hematocrit level and risk of AMI mortality in younger Japanese women, but not in men and older women.

Development of Risk Prediction Equations for Incident Chronic Kidney Disease.

Importance: Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions. Objective: To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR). Design, Setting, and Participants: Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540). Exposures: Demographic and clinical factors. Main Outcomes and Measures: Incident eGFR of less than 60 mL/min/1.73 m2. Results: Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. Conclusions and Relevance: Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Validity of a Risk Prediction Equation for CKD After 10 Years of Follow-up in a Japanese Population: The Ibaraki Prefectural Health Study.

BACKGROUND: Chronic kidney disease (CKD) is an important health problem for which risk equations have been developed for Western populations. This study aimed to develop and validate a risk prediction equation for CKD in a Japanese population. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The study included 135,007 participants who completed an annual health checkup in 1993 to 1996 in the Ibaraki Prefecture in Japan. Participants were initially free of CKD (defined as stage 3, 4, or 5 CKD or proteinuria [2+ or 3+] by dipstick). Follow-up information was available from health checkups 10 years after the initial evaluation. We used data from 40,963 women and 17,892 men in the northern region of the prefecture for the development of risk prediction equations and 53,042 women and 23,110 men in the southern region for external validation. PREDICTORS: Age, estimated glomerular filtration rate (eGFR), body mass index, proteinuria, hematuria, hypertension, diabetes mellitus, smoking, and drinking. OUTCOME: Occurrence of CKD (defined as eGFR<60mL/min/1.73m2 and/or proteinuria [2+ or 3+] by dipstick). ANALYTICAL APPROACH: Logistic regression analysis to estimate risk for CKD stratified by sex. RESULTS: During follow-up, 7,500 cases of CKD developed in the northern region and 8,964, in the southern region. Older age, proteinuria (1+), higher systolic blood pressure, medication for hypertension, and current smoking were associated with increased risk for CKD in both sexes, whereas higher eGFR and daily alcohol intake were associated with lower risk. C statistics of risk estimation equations for CKD at 10 years were >0.8 for both the development and external validation populations, and discrimination of the risk estimation was fairly good in women and men. LIMITATIONS: Fluctuations in variables were not evaluated because the study used annual health checkups. This study excluded a large number of people for whom a 10-year health checkup was not available. CONCLUSIONS: Estimations of risk for CKD after 10 years of follow-up in a general Japanese population can be achieved with a high level of validity.

Impact of Speed-Eating Habit on Subsequent Body Mass Index and Blood Pressure Among Schoolchildren　- The Ibaraki Children's Cohort Study (IBACHIL).

BACKGROUND: Habitual speed eating is a risk factor of obesity but evidence of this in children is limited. We examined the association between speed-eating habit and subsequent body mass index (BMI) and blood pressure (BP) among Japanese children.Methods and Results:The community-based study comprised 1,490 Japanese boys and girls who were born in 1989, involved in the Ibaraki Children's Cohort Study at age 3 years, and had returned questionnaires at both ages 6 and 12 years. In a subsample, we measured BP (n=263). Speed-eating habit was categorized into 4 groups: Never, Quit, Newly, and Continuous. Sex-specific mean values of questionnaire-based BMI and measured BPs at age 12 were examined according to speed-eating habit. Children with continuous speed eating had a higher BMI at age 12 than those who had never had a speed-eating habit (20.0 vs. 17.9 kg/m2for boys (P<0.001); 20.0 vs. 18.4 kg/m2(P<0.001) for girls). Systolic BP at age 12 was higher in boys with continuous speed eating than in those without (117 vs. 110 mmHg, P=0.01), but such a difference was not observed in girls (112 vs. 111 mmHg, P=0.95). CONCLUSIONS: Habitualspeed eating was positively associated with subsequent BMI among boys and girls as well as with systolic BP among boys.

A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Personal status of general health checkups and medical expenditure: A large-scale community-based retrospective cohort study.

BACKGROUND: We sought to clarify the association between the personal utilization of general health checkups (GHCs) and medical expenditures (MEs) in a middle-aged Japanese population. METHODS: A retrospective cohort study was conducted. Subjects were 33,417 residents (15,819 males and 17,598 females) aged 48 years or older in 2010 who were invited to undergo GHCs every year. Official records on GHCs from 2002 to 2007 and MEs from 2008 to 2010 were provided by Soka City, Saitama Prefecture, Japan. The utilization of GHCs was divided into zero times (non-utilizers), 1-3 times (low-frequency utilizers), and 4-6 times (high-frequency utilizers). Tweedie distributions in the generalized linear model were used to analyze the association between MEs and the subgroups of GHC utilization after adjustment for age and sex. RESULTS: Of the 33,417 subjects, 20,578 (61.6%) were non-utilizers, 5,777 (17.3%) were low-frequency utilizers, and 7,062 (21.1%) were high-frequency utilizers, based on the attendance to GHCs from 2002 to 2007. Compared with the non-utilizers, the high-frequency utilizers showed significantly higher outpatient MEs (JPY394,700 vs. JPY373,100). The low- and high-frequency utilizers showed significantly lower inpatient MEs (JPY224,000 and JPY181,500 vs. JPY309,300) and total MEs (JPY610,600 and JPY580,700 vs. JPY689,600) than the non-utilizers based on the pooled data from 2008 to 2010. CONCLUSIONS: This study suggests that the outpatient MEs rise when annual GHCs are increasingly attended (not including the GHC cost), but inpatient and total MEs are lower. To reduce MEs, increasing the rates of attendance at GHCs by the general public may be important.

Impact and attribute of each obesity-related cardiovascular risk factor in combination with abdominal obesity on total health expenditures in adult Japanese National Health insurance beneficiaries: The Ibaraki Prefectural health study.

BACKGROUND: The aim of this study was to examine the attribution of each cardiovascular risk factor in combination with abdominal obesity (AO) on Japanese health expenditures. METHODS: The health insurance claims of 43,469 National Health Insurance beneficiaries aged 40-75 years in Ibaraki, Japan, from the second cohort of the Ibaraki Prefectural Health Study were followed-up from 2009 through 2013. Multivariable health expenditure ratios (HERs) of diabetes mellitus (DM), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and hypertension with and without AO were calculated with reference to no risk factors using a Tweedie regression model. RESULTS: Without AO, HERs were 1.58 for DM, 1.06 for high LDL-C, 1.27 for low HDL-C, and 1.31 for hypertension (all P < 0.05). With AO, HERs were 1.15 for AO, 1.42 for DM, 1.03 for high LDL-C, 1.11 for low HDL-C, and 1.26 for hypertension (all P < 0.05, except high LDL-C). Without AO, population attributable fractions (PAFs) were 2.8% for DM, 0.8% for high LDL-C, 0.7% for low HDL-C, and 6.5% for hypertension. With AO, PAFs were 1.0% for AO, 2.3% for DM, 0.4% for low HDL-C, and 5.0% for hypertension. CONCLUSIONS: Of the obesity-related cardiovascular risk factors, hypertension, independent of AO, appears to impose the greatest burden on Japanese health expenditures.

Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study in Japan using a nationwide registry.

Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been evaluated in clinical trials and has not been approved in any developed country. We aimed to test the efficacy and safety of octreotide for diazoxide-unresponsive CHI through a combination of a single-arm, open-label clinical trial (SCORCH study) and an observational study to collect data on the clinical course of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5 patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose infusion, and treated by continuous subcutaneous octreotide infusion at a dose of 5-25 µg/kg/day. Continuous blood glucose monitoring was performed between -24 and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was achieved and therapy was continued. The glucose infusion was gradually decreased and stopped after 5, 11, and 174 days, respectively. In one case, remission of CHI was reached after 606 days and octreotide was discontinued. The SCORCH registry included 19 diazoxide-unresponsive patients treated by subcutaneous octreotide, by continuous infusion or multiple daily injections. Of the 17 patients treated with hypertonic glucose infusion, the infusion rate was reduced after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%). During the combined observation period of 695.4 patient-months in both studies, no severe adverse events related to octreotide were observed. In conclusion, subcutaneous octreotide injection was effective and well tolerated in the majority of patients with diazoxide-unresponsive CHI.

Distribution of serum 25-hydroxyvitamin D levels of reproductive age Japanese women.

Objectives　The distribution of serum 25-hydroxyvitamin D [25(OH)D] levels among reproductive age Japanese perinatal (prepartum, intrapartum, postpartum) and non-perinatal women remains unknown. In addition to this, vitamin D deficiency cut-off values, which consider the effects of these levels during the perinatal period and infant development, have not been determined. Thus, we systematically reviewed the distribution of serum 25(OH)D levels among reproductive age Japanese women, in order to provide basic data to determine vitamin D deficiency cut-off values.Methods　A systematic literature review was conducted on research published between 1963 and 2015, using PubMed web and Japan Medical Abstracts Society web. The key words "Japan," "Vitamin D," "women," and "pregnant women," were used. After filtering for age, sex, race, indication of numerical number, and duplications, 18 papers were extracted and categorized into reproductive age non-perinatal women (13 papers/22 groups), and reproductive age perinatal women (6 papers/8 groups). The mean serum 25(OH)D levels were grouped by age, test period, and measuring methods.Results　Mean serum 25(OH)D levels among reproductive age non-perinatal women were lower than 20 ng/ml in 10 out of 22 groups (45.4%), and lower than 30 ng/ml in 21 groups (95.5%). The mean serum 25(OH)D level among reproductive age perinatal women was lower than those among reproductive age non-perinatal women. Among reproductive age perinatal women, except for one group that included women in the first trimester of pregnancy (5-10 weeks), the mean serum 25(OH)D levels of the other groups were lower than 20 ng/ml.Conclusion　Serum 25(OH)D levels among reproductive age Japanese women, especially perinatal women, appear to be low. Studies of serum 25(OH)D levels among reproductive age Japanese women are limited; hence, further investigation is required.