Development and validation of ischemic heart disease and stroke prognostic models using large-scale real-world data from Japan.

BACKGROUND: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data. METHODS: IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013-December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan. RESULTS: The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell's C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance. CONCLUSION: Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.

Cost-Effectiveness of Behavior Modification Intervention for Patients With Chronic Kidney Disease in the FROM-J Study.

OBJECTIVES: Chronic kidney disease (CKD) is a significant public health problem. An advanced, or innovative, CKD care system of clinical practice collaboration among general physicians (GPs), nephrologists, and other healthcare workers achieved behavior modification in patients with Stage 3 CKD in the Frontier of Renal Outcome Modifications in Japan (FROM-J) study. This behavior modification intervention consisted of educational sessions on nutrition and lifestyle, as well as encouragement of patients' regular visits. The intervention contributed to slowing CKD progression. This study aimed to evaluate the cost-effectiveness of the widespread diffusion of the behavior modification intervention proven effective by the FROM-J study. METHODS: A cost-effectiveness analysis was carried out to compare the behavior modification intervention with the current practice recommended by the latest CKD clinical guidelines for GPs. A Markov model with a societal perspective under Japan's health system was constructed. We assumed that the behavior modification intervention proven effective by the FROM-J study would be initiated by GPs for targeted patient cohorts-patients aged 40-74 years with Stage 3 CKD-as a part of the innovative CKD care system. RESULTS: The incremental cost-effectiveness ratio for the behavior modification intervention compared with current guideline-based practice was calculated as 145,593 Japanese yen (¥; $1,324 United States dollars [$]) per quality-adjusted life year (QALY). CONCLUSIONS: Using the suggested value of social willingness to pay for a one-QALY gain in Japan of ¥5 million (US$45,455) as the threshold to judge cost-effectiveness, the behavior modification intervention is cost-effective. Our results suggest that diffusing the behavior modification intervention proven effective by the FROM-J study could be justifiable as an efficient use of finite healthcare resources. GPs could be encouraged to initiate this intervention by revising the National Health Insurance fee schedule and strengthening clinical guidelines regarding behavior modification interventions.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Newspaper coverage before and after the HPV vaccination crisis began in Japan: a text mining analysis.

BACKGROUND: The human papillomavirus (HPV) vaccination coverage rate has fallen sharply in Japan since 2013, when newspapers began covering negative campaigns against the vaccination. We examined and compared contents from newspaper articles before and after the start of this HPV vaccination crisis. METHODS: We collected articles published between January 2005 and September 2017 in the four daily national Japanese newspapers with the highest domestic circulation. We then conducted text mining analysis to chronologically examine content distribution. RESULTS: From among the 1178 articles analyzed, 12 types of contents were identified. Contents related to cervical cancer prevention, such as on the risk of developing cervical cancer, causes of cervical cancer, and the effects of vaccination, were frequently conveyed until 2012. However, after March 2013, they were replaced with anti-vaccination contents, such as on adverse effects to vaccines, alleged victims, and related lawsuits. Meanwhile pro-vaccination contents, such as safety statements from the World Health Organization, scarcely received coverage. CONCLUSIONS: Newspaper contents changed profoundly before and after the start of the vaccination crisis. Those newspaper reports potentially had impact on readers' beliefs and actions. Journalists should strive for impartial coverage so readers can make more-informed decisions. Health professionals should be expected to work with journalists to help improve impartiality in newspaper coverage. The Ministry of Health, Labour and Welfare should discus benefits and risks of the HPV vaccination based on the scientific evidences, and consider to resume the proactive recommendation of HPV vaccination. Well-organized advocacy among medical societies, scientists and health professionals will also be needed to influence the government.

Japanese anti- versus pro-influenza vaccination websites: a text-mining analysis.

Anti-vaccination sentiment exists worldwide and Japan is no exception. Health professionals publish pro-influenza vaccination messages online to encourage proactive seeking of influenza vaccination. However, influenza vaccine coverage among the Japanese population is less than optimal. The contents of pro- and anti-influenza vaccination websites may contribute to readers' acceptance of one or the other position. We aimed to use a text-mining method to examine frequently appearing content on websites for and against influenza vaccination. We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan). Targeted websites were classified as 'pro', 'anti' or 'neutral' depending on their claims, with author(s) classified as 'health professionals', 'mass media' or 'laypersons'. Text-mining analysis was conducted, and statistical analysis was performed using a chi-squared test. Of the 334 websites analyzed, 13 content topics were identified. The three most frequently appearing content topics on pro-vaccination websites were vaccination effect for preventing serious cases of influenza, side effects of vaccination, and efficacy rate of vaccination. The three most frequent topics on anti-vaccination websites were ineffectiveness of influenza vaccination, toxicity of vaccination, and side effects of vaccination. The main disseminators of each topic, by author classification, were also revealed. We discuss possible tactics of online influenza vaccination promotion to counter anti-vaccination websites.

Improving health literacy in a Japanese community population-A pilot study to develop an educational programme.

OBJECTIVE: Although a growing number of interventional studies on health literacy have been conducted recently, the majority were designed in clinical settings, focusing mainly on functional health literacy. This study evaluated a programme designed to improve health literacy in a community population, with a scope of going beyond functional health literacy. METHODS: In collaboration with an Approved Specified Nonprofit organization (NPO), we evaluated a five-session programme designed to provide basic knowledge on health-care policy and systems, current issues in health care in Japan, patient roles and relationships with health-care providers and interpersonal skills. In total, 67 of 81 programme participants agreed to participate in the study, and 54 returned the completed questionnaires at baseline and at follow-up. Health literacy and trust in the medical profession were measured at baseline and at follow-up. Participants' learning through the programme was qualitatively analysed by thematic analysis. RESULTS: Quantitative examinations of the changes in health literacy and degree of trust in medical professionals between the baseline and follow-up suggested that health literacy significantly improved after implementing the programme. The thematic analysis of participants' learning throughout the programme suggested that they not only acquired knowledge and skills but also experienced a shift in their beliefs and behaviours. DISCUSSION: Providing individuals who are motivated to learn about health-care systems and collaborate with health-care providers with the necessary knowledge and skills may improve their health literacy, which could enable them to maintain and promote their health and that of their family and other people around them.

Increased adiponectin is associated with cerebral white matter lesions in the elderly with cognitive impairment.

Adiponectin is an adipocyte-derived peptide that increases with age and is thought to protect against atherosclerotic vascular changes and organ damage. However, paradoxically, higher adiponectin levels are associated with increased risk for cardiovascular events and mortality. We investigated whether this adiponectin paradox occurs in elderly people with cognitive impairment. Fifty-two elderly participants with mild cognitive impairment or dementia (20 male and 32 female, aged 60-93 years, mean 80.0) were recruited. We evaluated serum adiponectin levels and cerebral white matter lesions (WML), which are involved in cognitive decline and dementia, by computed tomography. Body mass index (BMI), Mini-Mental State Examination score, history of hypertension (HT), chronic kidney disease, and diabetes mellitus were also assessed. Stepwise multiple regression analysis was used to reveal the relationships between serum adiponectin and age, sex, BMI, HT, diabetes mellitus, chronic kidney disease, Mini-Mental State Examination, and WML scores. High serum adiponectin levels correlated with more severe WML (P = 0.013). Low BMI (P < 0.001), female sex (P = 0.025), and high WML scores (P = 0.039) were significant determinants of high serum adiponectin. HT (P = 0.032) and high adiponectin levels (P = 0.021) were independent risk factors for WML. Overall, we observed an association between serum adiponectin levels and WML severity in elderly people with cognitive decline. Our findings reveal that the adiponectin paradox occurs in this population, and this study may help guide future treatments for elderly people with mild cognitive impairment or dementia.

[Content analysis of newspaper reports on passive smoking regulations in Japan].

Objectives　Ever since Tokyo was awarded the privilege to host the 2020 Olympic Games, the Japanese Ministry of Health, Labour, and Welfare has worked toward implementing a ban on passive smoking. This study examined the present situation of passive smoking in Japan, and the coverage of passive smoking regulations in newspaper reports, based on a content analysis. This was followed by a comparison with the contents of the "White Paper on Tobacco," published by the Japanese Ministry of Health, Labour, and Welfare in August, 2016.Methods　In total, 182 articles published from September 7, 2013 to March 31, 2017 were collected from three major newspapers based in Tokyo (Asahi, Yomiuri, and Mainichi). The article search criteria included the presence of the following keywords in the title or main text: "passive smoking OR entire surface smoking cessation OR indoor smoking OR indoor smoking cessation OR smoking cessation in the site OR smoking cessation in the building." Online posts and articles that did not focus mainly on the regulation of passive smoking were excluded. The 37 coding categories that were developed were classified either as positive or negative (with respect to coverage of passive smoking regulations). The assessment of passive smoking in the White Paper on Tobacco informed the coding categories, to allow the evaluation of the extent to which the contents of the White Paper were reflected in newspaper reports.Results　Among the 182 articles examined, 107 addressed only the positive aspects of the regulations, while 7 addressed only the negative aspects. Further, 50 articles addressed both positive and negative aspects, while 18 addressed neither. Among those addressing both positive and negative aspects, 14 (28%) included counterarguments to the negative comments, which consistently reflected the contents of the White Paper on Tobacco.Conclusions　Majority of the articles reported only on the positive aspects of the regulations. Persuasive articles that presented both the positive and negative aspects of the issue, which included counterarguments to the negative opinions, were scarce. However, such articles were found to some degree in the editorials of newspapers. The influence of such editorials may increase if newspapers include the pros or cons of this issue, and present counterarguments. Additionally, some topics were not reported sufficiently. Thus, problems were observed in the newspaper reports regarding passive smoking regulations.

Evaluation of the Validity of a Novel CKD Assessment Checklist Used in the Frontier of Renal Outcome Modifications in Japan Study.

OBJECTIVE: This study aimed to assess the validity of a novel chronic kidney disease (CKD) evaluation checklist method used in the Frontier of Renal Outcome Modifications in Japan study. METHODS: Nineteen patients with CKD were recruited, and each patient was assessed by 2 dietitians using the checklist and provided with lifestyle modification instructions based on their assessment. We evaluated the concordance between dietitians, and we assessed the accuracy of the protein and salt intake estimates made by dietitians who only had access to patients' food diaries and verbal reports through comparison with assessments made by an independent dietitian who additionally had access to patients' meal photographs and urine collections. RESULTS: The most frequently given instructions concerned blood pressure control (46%), followed by body mass index control (28%), and potassium control (9%). The instructions provided to patients corresponded between dietitians at rates of 94% for patients' 1st evaluation and 74% for their 2nd evaluation. The evaluated items showed good agreement between dietitians except for their estimates of salt and protein intakes. The dietitians categorized salt and protein intakes into 3 groups each (<6, 6-12, and >12 g and <0.8, 0.8-1.2, and >1.2 g/kg, respectively). The concordance rates between dietitians were 77.1% and 80.8%, and Cohen's κ coefficients were 0.633 and 0.613 for salt and protein intakes, respectively. The concordance rates between the dietitians' estimates and the independent dietitian's objective assessment were 78.5% and 45.1%, and Cohen's κ coefficients were 0.616 and 0.311 for salt and protein intakes, respectively. The estimates and objective assessments were strongly correlated for salt intake, but weakly correlated for protein intake. CONCLUSION: We concluded that the checklist method was appropriate for the evaluation of CKD patients except for protein intake estimation. We hope it will be useful for the instruction of CKD patients widely in the future.

The Speckle Tracking Imaging for the Assessment of Cardiac Resynchronization Therapy (START) study.

BACKGROUND: We sought to identify the feasibility of speckle tracking echocardiography (STE) to predict cardiac resynchronization therapy (CRT) responders in a prospective multicenter study. METHODS AND RESULTS: Patients who were newly implanted with a CRT device were enrolled. Time (T) from QRS to maximum peak radial and circumferential strain (CS) in 6 segments on the left ventricular (LV) short-axis plane, and to the maximum peak of longitudinal strain in 18 segments on 3 apical LV planes was measured (Tmax). In segments with multiple peaks on the time-strain curves, time to the first peak (Tfirst) was also assessed. Difference in T between the earliest and latest segment and standard deviation (SD) of T in each strain component were assessed. CRT responders were defined as having LV end-systolic volume reduction >15% at 6 months after CRT. Clinical outcomes were assessed with a composite endpoint of death from cardiac causes or unplanned hospitalization for heart failure. Among 180 patients, 109 patients were identified as responders. Tfirst-SD of CS >116 ms was selected as the best independent predictor of CRT responders (P<0.001, hazard ratio=9.83, 95% confidence interval 3.78-25.6). In addition, Tfirst-SD of CS was associated with the clinical endpoints. CONCLUSIONS: This prospective multicenter study revealed the high feasibility of dyssynchrony assessment by STE, which may improve the ability to predict CRT responders.