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.

Providing Practical Knowledge and Skills to Handle Real-World Data? Lessons Learned from Med RWD Program.

Both lectures and hands-on education are essential for the development of human resources that can use real-world data (RWD). The University of Tokyo has launched a new hybrid-style RWD educational program entitled "Medical Real World Data Utilization Human Resource Development Project" from FY2019 onwards. We present an overview of the overall picture of the project, including the development process of the educational program and the challenges associated with it.

Development and evaluation of a patient-reported outcome measure specific for Gaucher disease with or without neurological symptoms in Japan.

BACKGROUND: Patients with Gaucher disease (GD), a rare lysosomal storage disorder, have reduced health-related quality of life (HRQOL). A patient-reported outcome measure (PROM) for HRQOL developed for type 1 GD (GD1) is not appropriate for patients with neuronopathic GD (nGD) types 2 (GD2) and 3 (GD3). In this study, we developed a new PROM for use in all GD types. We previously reported the qualitative analysis of interviews with Japanese patients with nGD, which was used to create nGD-specific PROM items. Here we evaluated the full PROM combining the type 1 questionnaire with the new nGD-specific items. METHODS: Patients with confirmed GD were recruited (Association of Gaucher Disease Patients in Japan or leading doctors) for pre-testing (May 2021) or the main survey (October-December 2021). The PROM had three parts: Parts 1 and 2 were translated into Japanese from the pre-existing GD1 PROM, whereas Part 3 was newly developed. Patients (or their caregivers, where necessary) completed the PROM questionnaire on paper and returned it by mail. Mean scores were determined overall and by GD type. Inter-item correlations, content consistency (Cronbach's alpha), and test-retest reliability (Cohen's kappa; main survey only, taken 2 weeks apart) were calculated. RESULTS: Sixteen patients (three with GD1; six with GD2; seven with GD3) and 33 patients (nine with GD1; 13 with GD2; 11 with GD3) participated in the pre-test and main survey, respectively. All GD2 patients and one-third (6/18) of GD3 patients required caregivers to complete the questionnaire. Mean scores indicated that the burden was highest in GD2 and lowest in GD1. In the main survey, internal consistency was high (Cronbach's alpha = 0.898 overall, 0.916 for Part 3), and test-retest reliability was high for Part 3 (kappa > 0.60 for 13/16 items) but low for Part 1 (kappa < 0.60 for 12/15 items). CONCLUSIONS: We have developed a flexible and reliable PROM that can be tailored for use in all types of GD and propose using Parts 1 and 2 for GD1, Parts 2 and 3 for GD2, and Parts 1, 2, and 3 for GD3.

Hypophosphatemia among severely malnourished children with sepsis in Bangladesh.

BACKGROUND: The interaction between hypophosphatemia (HP) and severe malnutrition has received little attention. This study investigated the prevalence, severity, and risk factors of HP among severely malnourished children with sepsis in Bangladesh. METHODS: Children aged 6-59 months admitted with sepsis to Dhaka Hospital from April 2010 to December 2011 were enrolled in the study and divided into two groups: severe acute malnutrition (SAM) and non-SAM groups. Plasma phosphate and the related biochemical parameters were measured upon admission and on the second and fourth days for both groups and the 10th day or discharge day for the SAM group. RESULTS: The prevalence of HP (plasma phosphate <3.7 mg/dL) was 72.9% and 62.5% (P = 0.26) for 48 SAM and for 56 non-SAM patients, respectively; that of moderate-severe HP (phosphate <2 mg/dL) was 25.0% and 19.6%, respectively (P = 0.51). The plasma phosphate level of 21 SAM patients was significantly lower on the second and fourth days than upon admission (P = 0.03, P = 0.01, respectively); it then recovered on the 10th day or discharge day. On multiple logistic regression analysis, plasma potassium <2.5 mmol/L upon admission was found to be a risk factor for moderate or severe HP (adjusted odds ratio, 7.21; 95% confidence interval: 1.88-27.7). CONCLUSION: HP is common among children with sepsis. Potassium <2.5 mmol/L upon admission is considered a risk factor for moderate or severe HP in children with sepsis.

Burden of caregivers of patients with neuronopathic and non-neuronopathic Gaucher disease in Japan: A survey-based study.

Background: Gaucher disease (GD), a rare lysosomal storage disorder, is associated with considerable patient and caregiver burden. We examined the applicability of existing caregiver questionnaires and assessed the level of burden in caregivers of patients with GD. Methods: This cross-sectional, non-interventional study was conducted in Japan. Caregivers of patients with confirmed GD (any type) were recruited (patient association group and referral) for pre-testing (May 2021) or the main survey (October-December 2021). Caregivers completed the Caregiver Impact Questionnaire (CIQ; 30 items) and Zarit Caregiver Burden Interview (ZBI; 22 items) on paper. Total CIQ and ZBI scores and subscores were determined overall and by GD type. Inter-item correlations and test-retest reliability (2 rounds, 2 weeks apart) were calculated. The relationship between caregiving duration and caregiver burden was also analyzed. Results: Nine caregivers (type 2 [GD2]: n = 6; type 3 [GD3]: n = 3) and 25 caregivers (type 1 [GD1]: n = 2; GD2: n = 17; GD3: n = 6) completed the pre-test and main survey, respectively. In the main survey, mean total CIQ score, all CIQ subscores (except emotional function), and total ZBI score were highest in caregivers of patients with GD2 compared with caregivers of patients with GD1/GD3. High test-retest reliability (Kappa >0.6) was observed for 15 CIQ items and 16 ZBI items. CIQ and ZBI scores appeared to be positively correlated with each other and negatively correlated with caregiving duration. Conclusions: The CIQ and ZBI are applicable, reliable measures to assess burden in caregivers of patients with GD in Japan. Caregiver burden was highest in caregivers of patients with GD2 and decreased with caregiving duration.

Sex- and Age-Based Disparities in Public Access Defibrillation, Bystander Cardiopulmonary Resuscitation, and Neurological Outcome in Cardiac Arrest.

Importance: Younger females with out-of-hospital cardiac arrest (OHCA) in public locations have less likelihood to receive public access defibrillation and bystander cardiopulmonary resuscitation (CPR). However, the association between age- and sex-based disparities and neurological outcomes remains underexamined. Objective: To investigate the association between sex and age and the rate of receiving bystander CPR, automated external defibrillator defibrillation, and neurological outcomes in patients with OHCA. Design, Setting, and Participants: This cohort study used the All-Japan Utstein Registry, a prospective, population-based, nationwide database in Japan containing data on 1 930 273 patients with OHCA between January 1, 2005, and December 31, 2020. The cohort comprised patients with OHCA of cardiac origin that was witnessed by citizens and treated by emergency medical service personnel. The data were analyzed from September 3, 2022, to May 5, 2023. Exposure: Sex and age. Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 30 days after an OHCA. Favorable neurological outcome was defined as a Cerebral Performance Category score of 1 (indicating good cerebral performance) or 2 (indicating moderate cerebral disability). The secondary outcomes were the rates of receiving public access defibrillation and bystander CPR. Results: The 354 409 included patients who experienced bystander-witnessed OHCA of cardiac origin had a median (IQR) age of 78 (67-86) years and 136 520 were females (38.5%). The rate of receiving public access defibrillation was higher in males than females (3.2% vs 1.5%; P < .001). Stratified by age, age- and sex-based disparities in prehospital lifesaving interventions by bystanders and in neurological outcomes were observed. Although younger females had a lower rate of receiving public access defibrillation and bystander CPR than males, younger females had a higher favorable neurological outcome compared with males of the same age (odds ratio [OR], 1.19; 95% CI, 1.08-1.31). In younger females with OHCA that was witnessed by nonfamily bystanders, receiving public access defibrillation (OR, 3.51; 95% CI, 2.34-5.27) or bystander CPR (OR, 1.62; 95% CI, 1.20-2.22) was associated with a favorable neurological outcome. Conclusions and Relevance: Results of this study suggest a pattern of significant sex- and age-based differences in bystander CPR, public access defibrillation, and neurological outcomes in Japan. Improvement in neurological outcomes in patients with OHCA, especially younger females, was associated with increased use of public access defibrillation and bystander CPR.

Machine Learning Models Predicting Cardiovascular and Renal Outcomes and Mortality in Patients with Hyperkalemia.

Hyperkalemia is associated with increased risks of mortality and adverse clinical outcomes. The treatment of hyperkalemia often leads to the discontinuation or restriction of beneficial but potassium-increasing therapy such as renin-angiotensin-aldosterone inhibitors (RAASi) and high-potassium diet including fruits and vegetables. To date, limited evidence is available for personalized risk evaluation in this heterogeneous and multifactorial pathophysiological condition. We developed risk prediction models using extreme gradient boosting (XGB), multiple logistic regression (LR), and deep neural network. Models were derived from a retrospective cohort of hyperkalemic patients with either heart failure or chronic kidney disease stage ≥3a from a Japanese nationwide database (1 April 2008−30 September 2018). Studied outcomes included all-cause death, renal replacement therapy introduction (RRT), hospitalization for heart failure (HHF), and cardiovascular events within three years after hyperkalemic episodes. The best performing model was further validated using an external cohort. A total of 24,949 adult hyperkalemic patients were selected for model derivation and internal validation. A total of 1452 deaths (16.6%), 887 RRT (10.1%), 1,345 HHF (15.4%), and 621 cardiovascular events (7.1%) were observed. XGB outperformed other models. The area under receiver operator characteristic curves (AUROCs) of XGB vs. LR (95% CIs) for death, RRT, HHF, and cardiovascular events were 0.823 (0.805−0.841) vs. 0.809 (0.791−0.828), 0.957 (0.947−0.967) vs. 0.947 (0.936−0.959), 0.863 (0.846−0.880) vs. 0.838 (0.820−0.856), and 0.809 (0.784−0.834) vs. 0.798 (0.772−0.823), respectively. In the external dataset including 86,279 patients, AUROCs (95% CIs) for XGB were: death, 0.747 (0.742−0.753); RRT, 0.888 (0.882−0.894); HHF, 0.673 (0.666−0.679); and cardiovascular events, 0.585 (0.578−0.591). Kaplan−Meier curves of the high-risk predicted group showed a statistically significant difference from that of the low-risk predicted groups for all outcomes (p < 0.005; log-rank test). These findings suggest possible use of machine learning models for real-world risk assessment as a guide for observation and/or treatment decision making that may potentially lead to improved outcomes in hyperkalemic patients while retaining the benefit of life-saving therapies.

Health-related quality of life in patients with alopecia areata: Results of a Japanese survey with norm-based comparisons.

Alopecia areata (AA) is a non-scarring hair loss disorder affecting approximately 2% of the global population. AA is reported to have a significant negative impact on the emotional and psychological well-being of the patients. This study aimed to evaluate the health-related quality of life (HRQoL) of Japanese patients with AA in comparison to the Japanese population norms (national standard values for Japanese) using Short Form Health Survey 36 Item Version 2.0 (SF-36v2). The study also aimed to access the negative effect of AA on patients' daily lives and the proportion of patients having anxiety and/or depression. This cross-sectional, non-interventional web-based survey study included 400 participants aged 17-84 years currently suffering from medically diagnosed AA. The assessment tools integrated in the online questionnaire included SF-36v2, the Dermatology Life Quality Index (DLQI), and the Hospital Anxiety and Depression Scale (HADS). All outcome measures from the tools were evaluated across the study population. SF-36v2 subscale scores for patients with AA revealed lower scores specifically for mental health (45.7 ± 10.1 points), social functioning (45.8 ± 10.9 points), vitality (46.2 ± 9.8 points), and role emotional (46.9 ± 11.6 points) as compared to the Japanese population norms of 50 ± 10 points each. The DLQI questionnaire-based analysis indicated that 32.1% of respondents showed a moderate to extremely large effect on their lives; and HADS-A (anxiety) and HADS-D (depression) scores categorized 46.0% and 41.8% respondents as doubtful-to-definite cases, respectively. Multivariate linear regression revealed that hair loss range, age, comorbidities, and depression significantly worsened DLQI scores. In conclusion, the results of this survey demonstrated that a significant decrease in the HRQoL scores was observed in Japanese patients with AA in comparison with the national norms. Hence, emphasis on mental health is crucial for AA management.

Association between calcium in cord blood and newborn size in Bangladesh.

Ca status in the uterus during pregnancy has been suggested to affect fetal growth and size at birth. In Bangladesh, low Ca levels in pregnant women and low birth weight in infants are common. The present study explored the association between Ca levels in cord blood and newborn size at birth (birth weight and birth length) in Bangladesh. Samples and data included 223 women with live-born singleton deliveries in rural Bangladesh. Newborn weight and length were measured at birth. From cord blood obtained at delivery, Ca, 25-hydroxy vitamin D, bone-specific alkaline phosphatase and intact parathyroid hormone levels were determined. An association between size at birth and Ca levels in cord blood was found (birth weight, P = 0.022; birth length, P = 0.001). Associations between Ca and newborn size were further analysed using multivariate regression analyses. After adjusting for several covariates of characteristics in mothers and newborns (gestational weeks at birth, sex of newborn, socio-economic status, maternal height, BMI, age and season at birth), birth length still exhibited a significant relationship with Ca levels in cord blood (birth length, P = 0.030). The present study indicates that Ca status in cord blood might be associated with the birth length of newborns. Ca levels during gestation may affect fetal growth.

Measurement of health-related quality of life in patients with chronic kidney disease in Japan with EuroQol (EQ-5D).

BACKGROUND: Chronic kidney disease (CKD) is a health-related quality-of-life (HRQOL) deteriorating disease which is not only a public health but also a socioeconomic problem. Interest in developing cost-effective interventions to control CKD has increased. The aim of this study was to measure HRQOL in terms of quality-adjustment weights for cost-effectiveness analysis using EQ-5D in patients with CKD. The relationships between the measured HRQOL and clinical indices/complications were also analyzed. METHODS: EQ-5D, a generic preference-based instrument, was administered to 569 CKD outpatients at Tsukuba University Hospital between November and December 2008. The response rate was 94.4% (537/569). Data on sex, age, creatinine, hemoglobin, serum albumin and eGFR were obtained from the patients' records. Data on the presence of complications such as hypertension, diabetes, and history of cardiovascular disease (CVD) were also retrieved. RESULTS: Measured quality-adjustment weights by the CKD stage were 0.940 (95% CI 0.915-0.965), 0.918 (0.896-0.940), 0.883 (0.857-0.909), 0.839 (0.794-0.884), and 0.798 (0.757-0.839) for stages 1-5, respectively. The decrease in weight was significant by ANOVA (P < 0.0001), and the weight for all stages was 0.885 (0.871-0.898). There was a positive relationship between hemoglobin/serum albumin and the weight. The presence of hypertension lowered the weight from 0.910 (0.885-0.936) to 0.874 (0.858-0.891), diabetes from 0.901 (0.886-0.917) to 0.840 (0.811-0.869), and CVD from 0.892 (0.878-0.906) to 0.783 (0.718-0.848). CONCLUSIONS: HRQOL decreases with progression of CKD stage and/or presence of anemia, undernutrition, hypertension, diabetes, or history of CVD.

[Effects of weight-loss tools and a group-based weight-loss support program: rationale and study design of a randomized controlled trial].

UNLABELLED: Purpose We have focused on providing weight-loss tools and implementing group-based weight-loss support programs and here document the first steps in implementation of a randomized controlled trial for determining the effectiveness of program components for weight change. METHODS: The present study covered 6-month weight-loss and 2-year follow-up periods. Participants were randomly assigned to the following 3 intervention groups: control (CON), weak intervention (WI), and strong intervention (SI). The CON group attended a single motivational lecture on weight loss. Participants in the WI group attended this lecture and were also provided with textbooks, notebooks, and a pedometer as weight-loss tools. Participants in the SI group attended the lecture, were given the aforementioned tools, and underwent a 6-month group-based support program for weight loss (8 sessions). The recruitment target was 180 participants--60 in each group. Individuals who were 40-64 years old, had a body mass index (BMI) of 25-40 kg/m2, and satisfied at least one of the following criteria were eligible: (i) waist circumference > or = 85 cm in males and 90 cm in females; (ii) systolic blood pressure > or = 130 mmHg; (iii) diastolic blood pressure > or = 85 mmHg; (iv) triglyceride level > or = 150 mg/dL; (v) high-density lipoprotein (HDL) cholesterol level < 40 mg/dL; and (vi) fasting plasma glucose level > or = 110 mg/dL. The primary outcome measure was body weight, and the secondary outcome measures were parameters associated with the metabolic syndrome, such as waist circumference, systolic blood pressure, diastolic blood pressure, serum levels of triglycerides and HDL cholesterol, and fasting plasma glucose. The protocol was registered with the UMIN Clinical Trials Registry (UMIN000001259). RESULTS: Participants were recruited through advertisements placed in local newspapers until March 2009 and were screened for eligibility through baseline measurements. In total, 188 adults (145 females, 43 males) were eligible and randomly assigned to the CON (n = 63), WI (n = 62), or SI (n = 63) groups. The weight-loss period was from April to October 2009 (for all 3 groups), and the follow-up duration extends from October 2009 to October 2011 (for the WI and SI groups). CONCLUSION: The present study should reveal the short-term (6 months) effectiveness of weight-loss tools and a group-based weight-loss support program as well as the long-term (30 months) effectiveness of the group-based weight-loss support program.