Studies of Health Insurance Claims Data in Japan: A Scoping Review.

Background: Health insurance claims data are used in various research fields; however, an overview on how they are used in healthcare research is scarce in Japan. Therefore, we conducted a scoping review to systematically map the relevant studies using Japanese claims data. Methods: MEDLINE, EMBASE, and Ichushi-Web were searched up to April 2021 for studies using Japanese healthcare claims data. We abstracted the data on study characteristics and summarized target diseases and research themes by the types of claims database. Moreover, we described the results of studies that aimed to compare health insurance claims data with other data sources narratively. Results: A total of 1,493 studies were included. Overall, the most common disease classifications were "Diseases of the circulatory system" (18.8%, n = 281), "Endocrine, nutritional, and metabolic diseases" (11.5%, n = 171; mostly diabetes), and "Neoplasms" (10.9%, n = 162), and the most common research themes were "medical treatment status" (30.0%, n = 448), "intervention effect" (29.9%, n = 447), and "clinical epidemiology, course of diseases" (27.9%, n = 417). Frequent diseases and themes varied by type of claims databases. A total of 19 studies aimed to assess the validity of the claims-based definition, and 21 aimed to compare the results of claims data with other data sources. Most studies that assessed the validity of claims data compared to medical records were hospital-based, with a small number of institutions. Conclusions: Claims data are used in various research areas and will increasingly provide important evidence for healthcare policy in Japan. It is important to use previous claims database studies and share information on methodology among researchers, including validation studies, while informing policymakers about the applicability of claims data for healthcare planning and management.

Sleep Disturbance of Evacuees in Minamisanriku Town after Great East Japan Earthquake: Risk Factors and Treatment.

In 2011, Minamisanriku Town lost all of its medical facilities during the Great East Japan Earthquake. Using 10,459 anonymized disaster medical records of affected people in Minamisanriku Town, we assessed the prevalence and risk factors of sleep disturbance, which is known to exacerbate non-communicable diseases (NCDs) and anxiety disorder. Because sleep disturbance is a part of mental health issues, we divided the patients into two groups: patients (n = 492) with mental health issues other than sleep disturbance and the remaining (n = 9,967) with other comorbidities. Out of 492 patients with mental health issues, 295 patients (60.0%, 114 male, 158 female and 23 unknown) had sleep disturbance who might have required specific treatments. Out of the remaining 9,967 patients, 1,203 patients (12.1%, 361 male and 769 female and 73 unknown) had sleep disturbance. Univariate and multivariate analyses of the 9,967 patients revealed that the odds ratio (OR) of sleep disturbance was higher for female (OR 1.95), elderly persons over 60 (OR 16.15) and residing in evacuation centers (OR 1.36). Patients with two or more NCD had higher risk (OR 1.42). Importantly, sleep disturbance affects younger patients without NCD residing in evacuation center. Emergency medical teams most frequently prescribed benzodiazepines both for sleep induction and anxiolysis. In addition to high risk groups (female, older, with other mental health issues, residing in evacuation center), it is important to survey sleep disturbance in younger and healthier populations especially in evacuation centers and to provide psychosocial and medical support for them.

Medical Needs in Minamisanriku Town after the Great East Japan Earthquake.

The medical records of service in disaster provided at a place other than a medical facility are defined as disaster medical records (DMRs). In this epidemiological study, to clarify medical need characteristics and trends after disaster, we analyzed the all anonymized DMRs of Minamisanriku Town that lost medical facilities in 2011 Great East Japan Earthquake and its consequent tsunami. After screening of duplicated or irrelevant documents, there were 10,464 DMRs with 18,532 diagnoses from March 11 through May 13. From 34 diagnostic groups according to International Classification of Diseases (ICD)-10, we integrated diagnostic groups into five modules that might require treatment concepts of different types: non-communicable disease (NCD), infectious disease, mental health issue, trauma, and maternal and child health (MCH). Age and sex distributions of the patients were similar to those of population before the disaster. The largest diagnostic module was NCD (68%), followed by infectious disease (21%), mental health issues (6%), trauma (4%), and MCH (0.2%). The age-specific rate of NCD exhibited a similar or suppressed level from that of nationwide survey, with higher rate of pollinosis among young population. Infectious disease increased in most age groups but there was no apparent outbreak because of early interventions. Sleep deprivation was twice as frequent in middle-aged women, compared with men. Trauma and MCH were less frequent, but each exhibited a unique time trend. Trauma onset was continuously recorded, while MCH visits were concentrated on a specific day. The medical need after disaster dynamically changes, and appropriate anticipatory countermeasures are necessary.

Low carbohydrate diet-based intervention for obstructive sleep apnea and primary hypothyroidism in an obese Japanese man.

BACKGROUND: Obesity is a major risk factor for obstructive sleep apnea (OSA), and weight loss is necessary in the overall management of obese patients with OSA. However, primary care physicians can provide only limited weight loss with lifestyle interventions, usually reducing a patient's body weight by only 2.5 kg or less after 6-18 months. CASE PRESENTATION: A 45-year-old Japanese man was referred to our clinic owing to obesity, daytime sleepiness, and snoring during sleep. His weight was 130.7 kg and his body mass index (BMI) was 41.0 kg/m(2). He underwent polysomnography, which revealed OSA with an apnea-hypopnea index of 71.2 events/h (normal, <5 events/h). His laboratory results were as follows: thyroid stimulating hormone, >500 µIU/mL; free triiodothyronine, 1.4 pg/mL; free thyroxine, <0.15 ng/dL; thyroid peroxidase antibody, 10 IU/mL; thyroglobulin antibody, >4000 IU/mL; total cholesterol (TC), 335 mg/dL; high-density lipoprotein cholesterol, 45 mg/dL; triglycerides (TGs), 211 mg/dL; low-density lipoprotein cholesterol, 248 mg/dL; fasting blood sugar, 86 mg/dL; and glycated hemoglobin (HbA1c), 6.1 %. These results showed that he also had primary hypothyroidism (Hashimoto's disease). Continuous positive airway pressure (CPAP), levothyroxine replacement, and a low-carbohydrate diet (LCD) were initiated. CPAP use and a euthyroid condition induced by 175 µg/day levothyroxine allowed the patient to proactively reduce his body weight. After 18 months, the patient achieved a weight reduction of 32.4 kg (25 % of his initial weight) and a BMI reduction of 10.2 kg/m(2), as well as improved laboratory results, including an HbA1c level of 5.3 %, TC level of 194 mg/dL, and TG level of 89 mg/dL. CONCLUSION: An LCD may be an effective intervention for weight loss in obese Japanese patients with OSA. Further studies are needed to investigate the weight loss effect of an LCD compared with a conventional calorie-restricted diet. Hopefully, this case report will help to improve the management of obese Asian patients with OSA who typically consume a higher amount of carbohydrates.

Serum levels of pigment epithelium-derived factor (PEDF) are positively associated with visceral adiposity in Japanese patients with type 2 diabetes.

BACKGROUND: Pigment epithelium-derived factor (PEDF) inhibits endothelial cell injury. Further, serum levels of PEDF are elevated in the metabolic syndrome. These observations suggest that PEDF may be elevated as a counter-system against vascular cell damage in the metabolic syndrome. However, little is known about the regulation of PEDF in patients with diabetes. In order to clarify the determinants of serum PEDF, here, we examined the relationship between the 1-year changes in PEDF levels and those in anthropometric and metabolic variables in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes underwent a complete history and physical examination, determination of blood chemistries, and serum levels of PEDF at baseline and 1 year after. PEDF gene expression in cultured subcutaneous or omental adipocytes were analysed by quantitative real-time reverse transcription-polymerase chain reactions. RESULTS: Multiple regression analyses revealed that waist circumference, triglycerides, creatinine, and TNF-alpha were independently associated with PEDF. Further, the percent changes in serum levels of PEDF during 1-year observational periods were positively correlated with those of BMI. In addition, PEDF mRNA levels in cultured adipocytes were increased in parallel to the BMI values of subjects from whom adipocytes were derived, especially in omental adipocytes. CONCLUSION: These results demonstrated that serum levels of PEDF were positively associated with metabolic components and TNF-alpha in Japanese patients with type 2 diabetes. Our present study suggests that PEDF may be generated from adipose tissues and play some role in visceral obesity in type 2 diabetic patients.

Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are positively associated with circulating AGEs and soluble form of VCAM-1 in patients with type 2 diabetes.

We have recently found that soluble form of receptor for advanced glycation end products (sRAGE) levels are positively associated with inflammatory biomarkers and the presence of coronary artery disease (CAD) in type 2 diabetic patients. Since advanced glycation end products (AGEs) up-regulate RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, it is conceivable that sRAGE is positively associated with circulating AGEs levels in diabetes. In this study, we examined whether sRAGE were correlated to circulating levels of AGEs and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes. Eighty-two Japanese type 2 diabetic patients underwent a complete history and physical examination, determination of blood chemistries, sRAGE, AGEs, sVCAM-1 and sICAM-1. Multiple regression analysis revealed that serum levels of AGEs and sVCAM-1 were independently correlated with sRAGE. This study demonstrated that serum levels of sRAGE were positively associated with circulating AGEs and sVCAM-1 levels in type 2 diabetic patients. Our present observations suggest sRAGE level may be elevated in response to circulating AGEs, thus being a novel marker of vascular injury in patients with type 2 diabetes.

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes.

BACKGROUND: Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. RESULTS: Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. CONCLUSION: The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.

Serum levels of sRAGE, the soluble form of receptor for advanced glycation end products, are associated with inflammatory markers in patients with type 2 diabetes.

Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in accelerated atherosclerosis in diabetes. We have recently found that the soluble form of RAGE (sRAGE) levels are significantly higher in type 2 diabetic patients than in nondiabetic subjects and positively associated with the presence of coronary artery disease in diabetes. In this study, we examined whether serum levels of sRAGE correlated with inflammatory biomarkers in patients with type 2 diabetes. Eighty-six Japanese type 2 diabetic patients (36 men and 50 women, mean age 68.4+/-9.6 years) underwent a complete history and physical examination, determination of blood chemistries, sRAGE, monocyte chemotactic protein-1 (MCP-1), adiponectin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Univariate regression analysis showed that serum levels of sRAGE positively correlated with alanine aminotransferase (ALT) (r=0.437, P=0.0001), MCP-1 (r=0.359, P=0.001), TNF-alpha (r=0.291, P=0.006), and hyperlipidemia medication (r=0.218, P=0.044). After multiple regression analyses, ALT (P<0.0001), MCP-1 (P=0.007), and TNF-alpha (P=0.023) remained significant. The present study demonstrates for the first time that serum levels of sRAGE are positively associated with MCP-1 and TNF-alpha levels in type 2 diabetic patients. These observations suggest the possibility that sRAGE level may become a novel biomarker of vascular inflammation in type 2 diabetic patients.

Elevation of soluble form of receptor for advanced glycation end products (sRAGE) in diabetic subjects with coronary artery disease.

BACKGROUND: Advanced glycation end products (AGEs)-receptor (RAGE) axis is implicated in diabetic vascular complication. Since a soluble form of RAGE (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC damage. In this study, we examined whether sRAGE levels were elevated in type 2 diabetic patients compared with non-diabetic healthy subjects. METHODS: Serum sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46 women; mean age 66 +/- 11 years) and 75 age- and sex-matched non-diabetic healthy control subjects. We explored the association between sRAGE levels and coronary artery disease (CAD) in diabetic patients. RESULTS: Serum sRAGE levels were significantly higher in diabetic patients than in non-diabetic subjects (965.3 +/- 544.2 vs 415 +/- 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol, hemoglobin A(1c), and creatinine were significantly associated with sRAGE. After performing multivariate analyses, the presence of diabetes (p < 0.0001) was a sole independent determinant of sRAGE. Furthermore, there was a significant difference in sRAGE levels between diabetic patients with CAD and those without CAD (1680.6 +/- 891.1 vs 855.2 +/- 372.1 pg/mL, p < 0.001). Multiple stepwise regression analysis revealed that sRAGE and creatinine levels were independent determinants of CAD. CONCLUSIONS: The present study demonstrated that serum sRAGE levels were significantly higher in type 2 diabetic patients than in non-diabetic subjects and positively associated with the presence of CAD.

Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension.

There is a growing body of evidence that the advanced glycation end product (AGE)-their receptor (RAGE) system plays a central role in the pathogenesis of diabetic vascular complication. The renin-angiotensin system (RAS) contributes to the development and progression of diabetic angiopathy as well. However, the cross-talk between the AGE-RAGE system and the RAS is not fully understood. In this study, we examined the role of angiotensin II (Ang II) type 1 receptor system for RAGE expression in cultured endothelial cells (ECs) and in patients with essential hypertension. Ang II up-regulated RAGE mRNA levels of microvascular ECs and subsequently increased the soluble form of RAGE (sRAGE) expression in the medium of ECs, both of which were completely blocked by telmisartan, a commercially available Ang II type 1 receptor antagonist. Furthermore, telmisartan was found to decrease serum levels of sRAGE in patients with essential hypertension. These results demonstrate that sRAGE is released from the cell surface of Ang-II-exposed ECs. Our present study indicates that a cross-talk exists between the AGE-RAGE system and the RAS and suggests that serum levels of sRAGE may reflect endothelial RAGE expression.