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Differential effects of synthetic estrogen on serum homocysteine levels before and after menopause

by Michael C. Reed, Ayako Suzuki, Allison Cruikshank, Mizuki Suzuki, H. Frederik Nijhout

Homocysteine (Hcy), a sulfur-containing amino acid, is produced in prodigious quantities by the methionine cycle in the liver. Hcy is the major biomarker for cardio-vascular disorders and is associated with many other diseases. In previous work, we have explained why menstruating women have lower serum homocysteine than men due to higher concentrations of estradiol. In this study, we first present epidemiological evidence from NHANES data that synthetic estradiol supplementation lowers serum Hcy in post-menopausal women, but raises Hcy in pre-menopausal women. Secondly, we give an explanation of this puzzling phenomenon using previously developed mathematical models of one-carbon and glutathione metabolism. The simulation analysis demonstrated that the non-monotonic response of glutathione to rising estradiol levels may account for the differing Hcy responses to estradiol supplementation in postmenopausal versus premenopausal women, through activation of cystathionine β-synthase, a key enzyme regulating tissue homocysteine levels. Our findings further highlight the importance of considering menopausal status and synthetic hormone use when evaluating the health effects of homocysteine.

Serum albumin and gamma gap levels, and combined effect for risk of mortality in a Japanese population from the J-MICC study

by Kenichi Shibuya, Rie Ibusuki, Daisaku Nishimoto, Shiroh Tanoue, Chihaya Koriyama, Shuhei Niiyama, Yasuyuki Kakihana, Toshiro Takezaki, Megumi Hara, Yuichiro Nishida, Sadao Suzuki, Takeshi Nishiyama, Mako Nagayoshi, Takashi Tamura, Yudai Tamada, Rieko Okada, Teruhide Koyama, Satomi Tomida, Kiyonori Kuriki, Jun Otonari, Hiroaki Ikezaki, Asahi Hishida, Masashi Ishizu, Sakurako Katsuura-Kamano, Kenji Wakai, Keitaro Matsuo, for the J-MICC Study group

Although the clinical importance of serum albumin and gamma gap levels is well established, it is unclear how these levels are associated with health risks in the general population. This cohort study aimed to clarify the association between serum albumin and gamma gap levels, and their combined effect, and mortality risk in a Japanese population. The participants totaled 35,746 (17,160 men and 18,586 women) aged 35–69 years from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The mean follow-up period was 11.8 years, with 1,529 deaths and 1,907 censoring. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals after adjusting for related factors. Increased HRs of low albumin and high gamma gap levels were respectively observed for deaths from all-causes, cancer, cardiovascular diseases, respiratory system diseases without pneumonia, and other-causes; and the HR was the highest on respiratory system diseases without pneumonia (HR = 7.31, 4.15–12.9). Low albumin and low gamma gap levels were strongly associated for pneumonia death (HR = 12.4, 3.98–38.5). The interaction between albumin and gamma gap levels was significant for deaths from all-causes, pneumonia and other-causes. The dose relationship for each association was dose-dependent in albumin and threshold-type in gamma gap, except for other-causes. This study suggests that albumin and gamma gap levels are independent indicators of an increased risk of mortality in a Japanese population. Combined effect was apparent for mortality from all-causes, pneumonia, and other-causes.

Associations between heart failure-related quality of life and clinical parameters in patients with hypertrophic cardiomyopathy: a cross-sectional analysis of data from a multicentre Japanese registry

Por: Saotome · M. · Akita · K. · Kageyama · S. · Suzuki · S. · Ohno · K. · Kamakura · M. · Nawada · R. · Takanaka · C. · Wakabayashi · Y. · Kanda · T. · Tawarahara · K. · Muto · M. · Matsunaga · M. · Suwa · S. · Takeuchi · Y. · Sakamoto · H. · Saito · H. · Hayashi · K. · Wakahara · N. · Unno · K.
Objective

To investigate the relationship between a quality of life (QOL) score and clinical parameters in patients with hypertrophic cardiomyopathy (HCM).

Design

A multicentre cross-sectional study.

Setting

We analysed data from the Searching for Atrial Fibrillation and Early Recruitment of Heart Failure in HCM registry, collected between 2018 and 2023.

Participants

Patients with HCM (n=499) aged ≥18 years from 12 institutions (Shizuoka Prefecture, Japan) were consecutively enrolled.

Outcome measures

Clinical parameters, along with data from a short form of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), were collected. The association between each clinical parameter and the KCCQ-12 score was analysed. Clinical parameters with a significant univariable association (p

Results

In the univariable analysis, KCCQ-12 scores exhibited significant associations with 21 clinical parameters, including sex, left ventricular morphology and the Pittsburgh Sleep Quality Index (PSQI). The multiple regression model with 12 parameters that had a significant univariable association exhibited an adjusted R2 of 0.48. In this model, the PSQI (standardised coefficient –0.39; p

Conclusions

In patients with HCM, we investigated the association between the KCCQ-12 score and various clinical parameters. PSQI, as well as known heart failure-related clinical parameters, was significantly associated with the KCCQ-12 score. Visualising the associations of various clinical parameters with the KCCQ-12 score will help physicians to consider factors linked to the decline in QOL in patients with HCM.

Development and Validation of a Negative Emotions Scale for Public Health Nurses Engaged in Child Abuse Prevention Activities

ABSTRACT

Aims

To assess the reliability and validity of a negative emotion scale for public health nurses conducting child abuse prevention activities.

Design

A four-phase mixed method design.

Methods

Participants were public health nurses with experience in child abuse prevention across Japan. The initial scale was developed and refined based on previous studies, expert panel reviews, interviews with public health nurses, and a questionnaire-based pilot study. In 2024, 549 public health nurses completed a questionnaire on scale items. Item analysis, exploratory factor analysis, confirmatory factor analysis, comparisons with a preexisting scale, the number of times negative attitudes and the types of behaviours exhibited by parents were used to narrow the scale and assess its psychometric properties.

Results

Item analysis and exploratory factor analysis reduced the scale to 15 items on two factors: ‘negative emotions toward aggressive and emotional attitudes’ and ‘negative emotions toward rejecting and uncooperative attitudes.’ Confirmatory factor analysis indicated a good model fit. The Cronbach's alpha was high, and the negative emotions scale score positively correlated with the pre-existing scale, negative attitudes and parental behaviours.

Conclusions

The Cronbach's alpha coefficient and other factors confirmed the scale's reliability, and correlations with other scales confirmed its validity.

Implications for the Profession

Evaluating negative emotions provides critical insights into the quality of support and its influence on psychological well-being.

Impact

By assessing negative emotions that public health nurses find difficult using this scale, the support system for them can be examined.

Reporting Methods

STROBE checklist for cross-sectional studies was followed.

Patient or Public Contribution

Public health nurses were involved in the generation of items for the scale. Their perspective was sought in determining the items for the scale.

Trial and Protocol Registration

Registered in the UMIIN Clinical Trial Registry (UMIN-CTR ID UMIN000054650).

Intensive care with endovascular catheter rewarming for accidental severe hypothermia (ICE-CRASH II): a protocol for a randomised controlled study

Por: Takauji · S. · Hayakawa · M. · Yokobori · S. · Kano · H. · Shimizu · K. · Horikoshi · Y. · Shimazaki · J. · Tachino · J. · Inoue · A. · Moriyama · T. · Sawano · H. · Fukushima · H. · Sugiyama · K. · Sunada · D. · Toyohara · T. · Sawamoto · K. · Isokawa · S. · Morikawa · M. · Suzuki · G. · Om
Introduction

Accidental hypothermia (AH) can occur in mild-to-severe cases; however, its management is crucial in severe cases as it can cause ventricular fibrillation and lead to death. Among various rewarming therapies for AH, endovascular catheter rewarming has been the focus of recent studies as a minimally invasive alternative to invasive internal rewarming, such as extracorporeal membrane oxygenation (ECMO). However, no study has demonstrated the efficacy and safety of endovascular catheter rewarming therapy. This study aimed to validate the efficacy and safety of endovascular catheter rewarming for patients with AH.

Methods and analyses

The intensive care with endovascular catheter rewarming in accidental severe hypothermia (ICE-CRASH II) study is a multicentre, randomised study of patients with AH. This study will include patients with AH (age ≥65 years, core temperature

Ethics and dissemination

This study was approved by the Hokkaido University Certified Review Board (approval number: 024-00013). Written informed consent will be obtained from all the participants or their legally acceptable representatives. The results will be disseminated through publications and presentations.

Trial registration number

Japan Registry of Clinical Trials (jRCT1012240051).

Association of dropout history and HbA1c levels with subsequent dropout risk in patients with diabetes: a secondary analysis of the Japan Diabetes Outcome Intervention Trial-2 Large-Scale Trial 008 (J-DOIT2-LT008)

Por: Goto · A. · Hayashino · Y. · Takamoto · I. · Suzuki · H. · Yamazaki · K. · Izumi · K. · Noda · M.
Objectives

Adherence to treatment strategies is essential for preventing future complications during diabetes management. This study evaluated the association between dropout history, glycated haemoglobin (HbA1c) levels and subsequent risks of dropout (missed appointment)in patients with type 2 diabetes.

Design

This was a secondary analysis of a cluster-randomised trial (the Japan Diabetes Outcome Intervention Trial 2 Large-Scale Trial), focusing on the non-intervention group over the study period.

Setting

Data were obtained from a multisite trial conducted in Japan, encompassing patients with type 2 diabetes who received routine clinical care at participating clinics.

Participants

A total of 996 patients with type 2 diabetes from the non-intervention group were included in the analysis. Baseline characteristics (eg, age, sex, smoking status, occupational status and diabetes medication use) were recorded at study entry.

Outcome measures

The primary outcome measure was subsequent treatment dropout. The Cox proportional hazards model with the Huber/White method was used to estimate HRs and 95% CIs, with adjustment for age, sex, smoking status, occupational status and diabetes medication use at baseline.

Results

Participants with treatment dropout history had a higher dropout rate than those without dropout history (multivariable-adjusted HR=3.59; 95% CI=2.25 to 5.71). Overall, HbA1c levels were not significantly associated with dropout risk. However, among the 855 participants without dropout history, the dropout risk was higher in the group with HbA1c level ≥10.0% (HR=3.76; CI=1.29 to 10.9) than in the group with HbA1c level of 6.0–6.9%.

Conclusions

This prospective cohort study of Japanese patients with type 2 diabetes suggests that dropout history is strongly associated with a higher subsequent dropout risk. High HbA1c levels (≥10%) may be related to a higher dropout risk in patients without a dropout history. These findings may provide actionable indicators for tailored interventions, enhancing targeted healthcare strategies and improving continuity of care.

Trial registration number

UMIN000002186.

Antimicrobial use for influenza-like illnesses in Nha Trang, Vietnam: a cross-sectional study

Por: Tsuzuki · S. · Nguyen · H.-A. T. · Toizumi · M. · Vo · H. M. · Le · H. H. · Dang · D. A. · Beutels · P. · Yoshida · L. M.
Objectives

This study aimed to investigate the characteristics and management of influenza-like illnesses (ILIs) in the outpatient and inpatient settings in Vietnam.

Design

A cross-sectional, observational study.

Setting and participants

We conducted a questionnaire survey of 407 individuals with ILI symptoms who presented to public community health centres and the paediatric ward of a public hospital in the city of Nha Trang, Khanh Hoa Province, Vietnam, from December 2022 to March 2023.

Interventions

Not applicable.

Primary and secondary outcome measures

No primary and secondary outcomes were pre-specified because this study was an explanatory study. The basic characteristics of the participants are presented using descriptive statistics. We conducted multivariable logistic regression analysis to examine the factors associated with the prescription of antibiotics to outpatients with ILIs.

Results

A total of 198 outpatients and 200 inpatients were enrolled in the study. Most inpatients were children under 5 years of age and experienced longer illness durations and higher costs, with almost all patients receiving antibiotics. The rate of antimicrobial prescription for ILIs was 79.3% for outpatients and 99.5% for inpatients. The median health-related quality of life score of participants aged ≥18 years during illness was 0.796 (IQR 0.674–0.922). Logistic regression analysis indicated a negative association between a definite diagnosis of viral infection by rapid diagnostic test and outpatient antibiotic prescription (OR: 0.20, p=0.006).

Conclusions

This study underscores the widespread inappropriate antimicrobial use for ILIs in a community in Vietnam, which contributes to an avoidable economic and health burden. The results of this study suggest that implementing diagnostic tools may support antimicrobial stewardship efforts.

Multicentre, prospective, single-arm, non-controlled, open-label trial to evaluate the safety and efficacy of live attenuated influenza vaccine in paediatric patients with atopic dermatitis undergoing dupilumab therapy: a protocol

Por: Kobayashi · T. · Sato · H. · Nagasawa · K. · Hayata · E. · Tanaka · S. · Kurihara · E. · Yamamoto · T. · Nakano · T. · Ozawa · Y. · Yamaide · F. · Inoue · Y. · Suzuki · S. · Arima · T. · Tomiita · M. · Hamada · H. · Ishiwada · N.
Introduction

Atopic dermatitis (AD) is a chronic inflammatory skin condition that impairs the quality of life of affected paediatric patients and their families. Dupilumab, an antagonist of the shared alpha chain subunit of the cytokines interleukin-4 and interleukin-13, has revolutionised the management of moderate-to-severe AD by effectively targeting type 2 inflammation. However, live attenuated vaccines, including live attenuated influenza vaccines (LAIVs), are contraindicated during dupilumab therapy owing to limited safety data. This restriction poses challenges to immunisation strategies, particularly in paediatric populations. This study aims to evaluate the safety and efficacy of LAIV in paediatric patients with AD undergoing dupilumab therapy.

Method and analysis

This multicentre, prospective, single-arm, open-label trial will enrol 50 paediatric patients aged 2–18 years with AD undergoing dupilumab treatment. The participants will receive intranasal LAIV, followed by a 25-week observation period after vaccination. The primary outcome is the proportion of participants with a four-fold or greater increase in haemagglutination inhibition titres against influenza strains A(H1N1), A(H3N2) and B at 4 weeks post vaccination. The secondary outcomes include the incidence of influenza and systemic or local adverse events, such as injection site reactions, fever and other influenza-like symptoms observed within 4 weeks of vaccination. Exploratory endpoints include the evaluation of immunosuppressive markers such as neutrophil counts, lymphocyte subsets and serum immunoglobulin G levels. Safety analyses will assess the frequency of each adverse event, whereas efficacy analyses will focus on immunogenicity and influenza incidence during the 25-week follow-up period. This study aims to provide critical safety and immunogenicity data to guide immunisation strategies in biologically treated paediatric patients with AD.

Ethics and dissemination

This study complies with the principles of the Declaration of Helsinki and received ethics approval from the Institutional Review Board of Chiba University Hospital as a specified clinical trial. Informed consent and assent will be obtained as appropriate based on the participants’ ages. These findings will be disseminated through peer-reviewed journals and scientific conferences to inform clinical vaccination strategies for biologically treated populations.

Trial registration number

jRCTs031240442.

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