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Housing environment bilaterally alters transcriptomic profile in the rat hippocampal CA1 region

by Azusa Kubota, Kentaro Kojima, Shinnosuke Koketsu, Takayuki Kannon, Takehiro Sato, Kazuyoshi Hosomichi, Yoshiaki Shinohara, Atsushi Tajima

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.

Cohort study of older adults receiving home-based primary care in South Korea: cohort profile

Por: Lee · J. · Choi · B. · Shin · Y. · Choi · E. · Choi · J. · Kim · C.-O. · Jang · S.-n.
Purpose

The home-based primary care cohort was set up to identify the characteristics of Home-Based Primary Care (HBPC) users across three domains: health-related information, utility of healthcare service and care-related information.

Participants

A total of 407 patients enrolled in five HBPC centres were recruited between January 2023 and March 2024. The baseline survey was conducted among 332 participants who provided informed consent for both study participation and home visits. The second wave of data collection is scheduled to take place 6 months after enrolment, while the third wave will be conducted 12 months post-enrolment. During each home visit, trained interviewers administered structured survey questionnaires. On completion of the 12-month follow-up period, the dataset will include survey data, intervention records from the five participating HBPC centres, home mortality status and institutionalisation risk linked to each participant.

Findings to date

This study examines HBPC in Korea, integrating the Widely Integrated Services in Home model with the long-term care insurance system. Among participants, 30.1% lived alone, and 74.1% were homebound, showing similarities to findings from a US HBPC study. Analysing cohort data, this study evaluates the impact of HBPC on healthcare utilisation, aligning with international findings on reduced hospitalisations and costs. As the first HBPC effectiveness study in Korea, it highlights its role in enhancing care for homebound older adults and shaping national health policies.

Future plans

Data on the number of interventions by profession, institutionalisation and hospitalisation status and duration, and death at home occurrence are being separately collected from five HBPC centres and will be included in the analysis. The analysis will examine associations between these variables to identify risk factors influencing institutionalisation. Additionally, this study plans to link the dataset with the National Health Insurance Service-Senior (NHIS-Senior) customised cohort for further analysis.

Visit-to-visit glycemic variability is associated with lung function variables and lung function impairment in individuals with type 2 diabetes

by Yi-Hua Wu, Chia-Ing Li, Chiu-Shong Liu, Chih-Hsueh Lin, Shing-Yu Yang, Cheng-Chieh Lin, Tsai-Chung Li

Glycemic variability (GV) is an emerging biomarker of glycemic control and may be a predictor for lung function impairment in persons with type 2 diabetes mellitus (T2DM). However, the associations between GV and lung function variables and lung function impairment have not been fully evaluated. The objective of this study was to assess the associations of glycemic variability (GV) with lung function impairment in persons with T2DM. A follow-up study was conducted on the data of 3,108 subjects collected from 2001 to 2020 using the diabetes care management program database in Taiwan. GV in fasting plasma glucose (FPG) was calculated using standard deviation (SD), average real variability (ARV), coefficient of variation (CV), variability independent of the mean (VIM), and slope of 1-year repeated measurements. A ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) less than 0.70 was used to define lung function impairment. Multivariable linear and logistic regression models were applied to explore the relationships of GV with lung function variables and lung function impairment. A total of 359 (11.6%) subjects were defined as having lung function impairment. After multivariable adjustment, FPG‐SD, FPG-CV, FPG-AVR, FPG-VIM and were found to be negatively linked with FEV1, % predicted FEV1, and FVC but not FEV1/FVC. Relative to those for the first tertile, the odds ratios (ORs) of lung function impairment for the second and third tertiles were 1.37 (95% confidence interval [CI]: 1.01, 1.87) and 1.51 (1.10, 2.08) for FPG-CV, respectively; 1.59 (1.16, 2.17) and 1.73 (1.24, 2.40) for FPG‐SD, respectively; and 1.57 (1.15, 2.13) and 1.69 (1.22, 2.33) for FPG-AVR, respectively. GV, measured by CV, SD, VIM, and VIM, is linked with lung function impairment and all lung function variables, except for FEV1/FVC ratio. GV may serve as a useful biomarker for assessing lung function impairment in persons with T2DM.

Clinical impact of prophylactic antibiotics in kidney transplantation: A retrospective observational cohort study with historical comparison

by Sang Ah Lee, Jin-Myung Kim, Hye Eun Kwon, Youngmin Ko, Joo Hee Jung, Sung Shin, Young Hoon Kim, Sung-Han Kim, Hyunwook Kwon

Purpose

Optimal perioperative antibiotic prophylaxis in kidney transplantation remains undefined despite routine antibiotic administration to prevent infections. In this retrospective observational cohort study with historical comparison, we compared the clinical efficacy of 6 days of ampicillin/sulbactam vs. a single dose of cefazolin.

Materials and methods

We retrospectively analyzed 2322 kidney transplantation recipients at a single center, with the evaluation period spanning from 2015 through 2021. Patients were divided into 2 groups based on the perioperative antibiotic regimen received: 971 patients received ampicillin/sulbactam, and 1351 received cefazolin. This study focused on evaluating the impact of these regimens on postoperative infection incidence and the 6-month acute rejection (AR) rates.

Results

The cefazolin group exhibited a tendency toward higher urinary tract infection rates within 1 month after transplantation (3.4% vs. 2.2%, p= = 0.078). There were no significant differences in surgical site infections between the groups. The 6-month AR rates were significantly lower in the cefazolin group than in the ampicillin/sulbactam group (5.1% vs. 7.9%, p= = 0.009). Cefazolin was also confirmed to be significantly associated with reduced 6-month AR rates in the multivariable logistic regression analysis (odds ratio 0.63, 95% confidence interval [0.45-0.89], p= = 0.009).

Conclusion

In this study, we observed that a single dose of cefazolin as perioperative antibiotic prophylaxis may lead to higher rates of postoperative urinary tract infections, but it could potentially lower the incidence of acute rejection within six months.

Barriers and Facilitators to Implementing a Nurse‐Led Information System for Older Adult Patients' Post‐Discharge Self‐Care: An Exploratory Sequential Mixed‐Methods Study

ABSTRACT

Aim

To explore determinants impacting an Electronic Health Record-based information system implementation and their association with implementation fidelity based on the Theoretical Domains Framework (TDF) from nurses' perspectives.

Design

Exploratory sequential mixed-method design.

Methods

In stage one, semi-structured interviews with 53 purposively selected nurses informed the exploration of TDF domains influencing the implementation of the information system with directed content analysis. In stage two, a cross-sectional survey, informed by the qualitative findings, was conducted among 482 nurses to identify the most relevant and relatively important TDF domains by running generalised linear regression models.

Results

The qualitative interviews generated 13 TDF domains that were identified as major influencing factors, including technology characteristics, knowledge, attitudes, role agreement, self-efficacy, goal-setting, information circulation, and communication among nurses. Quantitative findings showed that 70% of nurses used and printed the written form through the information system, and only 34% offered verbal education consistently. Regression analysis identified nine domains that were relevant and important factors for implementation fidelity, including knowledge, skills, role identity, beliefs in consequences, beliefs in capabilities, intentions, goals, memory and decision processes, and environmental context.

Conclusion

Our findings confirmed previous evidence on determinants of implementing digital health technologies, including knowledge, competencies, perceived effectiveness, role agreement, intentions, decision processes, and environmental context. Additionally, we highlighted the importance of goal-setting for successful implementation.

Impact

This study investigated the relatively important associated factors that can impact the successful implementation of the nurse-led information system for post-acute care based on nurses' perspectives. These results can guide nurse practitioners in implementing similar initiatives and support evidence-based decision-making. Researchers can also further investigate the relationships between the identified determinants.

Reporting Method

Journal Article Reporting Standards for Mixed Methods Research.

Patient or Public Contribution

No patient or public contribution.

Predicting 30-day and 1-year mortality in heart failure with preserved ejection fraction (HFpEF)

by Ikgyu Shin, Nilay Bhatt, Alaa Alashi, Keervani Kandala, Karthik Murugiah

Objectives

To develop and compare prediction models for 30-day and 1-year mortality in Heart failure with preserved ejection fraction (HFpEF) using EHR data, utilizing both traditional and machine learning (ML) techniques.

Background

HFpEF represents 1 in 2 heart failure patients. Predictive models in HFpEF, specifically those derived from electronic health record (EHR) data, are less established.

Methods

Using MIMIC-IV EHR data from 2008−2019, patients aged ≥ 18 years admitted with a primary diagnosis of HFpEF were identified using ICD-9 and 10 codes. Demographics, vital signs, prior diagnoses, and lab data were extracted. Data was partitioned into 80% training, 20% test sets. Prediction models from seven model classes (Support Vector Classifier (SVC), Logistic Regression, Lasso Regression, Elastic Net, Random Forest, Histogram-based Gradient Boosting Classifier (HGBC), and eXtreme Gradient Boosting (XGBoost)) were developed using various imputation and oversampling techniques with 5-fold cross-validation. Model performance was compared using several metrics, and individual feature importance assessed using SHapley Additive exPlanations (SHAP) analysis.

Results

Among 3,235 hospitalizations for HFpEF, 30-day mortality was 6.3%, and 1- year mortality was 29.2%. Logistic regression performed well for 30-day mortality (Area Under the Receiver operating characteristic curve (AUC) 0.83), whereas Random Forest (AUC 0.79) and HGBC (AUC 0.78) for 1-year mortality. Age and NT-proBNP were the strongest predictors in SHAP analyses for both outcomes.

Conclusion

Models derived from EHR data can predict mortality after HFpEF hospitalization with comparable performance to models derived from registry or trial data, highlighting the potential for clinical implementation.

Relationship between HLA-DRB1 shared epitope alleles and peripheral blood monocyte counts in Japanese patients with rheumatoid arthritis

by Daisuke Hiraoka, Jun Ishizaki, Kenta Horie, Kensuke Oryoji, Shin-ichi Mizuki, Katsuto Takenaka

Objectives

To investigate the relationship between Human Leukocyte Antigen-DR beta 1 (HLA-DRB1) shared epitope (SE) alleles and peripheral blood monocyte counts in disease-modifying antirheumatic drug-naïve patients with rheumatoid arthritis (RA), and also the relationship between specific SE alleles and anti-cyclic citrullinated peptide antibody (anti-CCP Ab) titers.

Methods

This retrospective single-center study included 86 Japanese patients with RA. HLA-DRB1 genotyping was performed, and SE alleles associated with a high risk of developing RA were classified into the S2 (*04:01) and S3P (*01:01, *01:02, *04:04, *04:05, *04:08, and *10:01) categories. Patients were stratified based on monocyte count tertiles. The relationships between monocyte counts at diagnosis and clinical, serological, and genetic factors were analyzed. Logistic regression was used to identify independent factors associated with high monocyte counts.

Results

SE-positive patients, particularly those with S3P alleles, had significantly higher monocyte counts than SE-negative patients. A multivariate analysis revealed that male sex and S3P positivity, particularly HLA-DRB1 *01:01 or *04:05, were independently associated with higher monocyte counts. Patients carrying at least one S3P allele had significantly higher anti-CCP Ab titers, with patients homozygous for HLA-DRB1 *04:05 having the highest levels. A similar relationship was not found with HLA-DRB1 *01:01 despite its strong effect on monocyte counts.

Conclusions

This is the first study to demonstrate a significant association between SE alleles and peripheral blood monocyte counts in RA. The results obtained suggest that specific SE alleles, particularly S3P alleles, contribute to the early pathogenesis of RA by enhancing monocyte-driven immune activation and anti-CCP Ab production.

Association between the central sensitization inventory score and health-related quality of life in community-dwelling middle-aged and older adults

by Naoki Segi, Hiroaki Nakashima, Ryotaro Oishi, Sadayuki Ito, Jun Ouchida, Ippei Yamauchi, Yasuhiro Nagatani, Taisuke Seki, Yasuhiko Takegami, Shinya Ishizuka, Yukiharu Hasegawa, Shiro Imagama

Background

Central sensitization is an important factor associated with impaired health-related quality of life in patients with musculoskeletal disorders and community-dwelling older adults. However, health-related quality-of-life domains strongly associated with central sensitization in the general population remain unclear. This study aimed to examine the association between the Central Sensitization Inventory Part A scores and health-related quality of life using community health checkup data.

Methods

A total of 419 middle-aged and older adults (mean age, 64.4 ± 11.2 years; 59.4% female) were included. Participants completed a questionnaire survey on pain, including visual analogue scales (VASs) for lower-back and knee pain, and the Central Sensitization Inventory Part A. Additionally, participants completed the Short-Form 36-Item Health Survey, and three component-summary scores and eight subscales were calculated. Additionally, participants completed the 5-level EuroQol 5 dimensions, and health-state utility values were calculated. The correlation between the Central Sensitization Inventory Part A scores and these health-related quality-of-life measures was investigated.

Results

Central Sensitization Inventory Part A score ≥40 was observed in 2.6% participants. Significant moderate negative correlations were observed between the Central Sensitization Inventory Part A scores and EuroQol 5 dimensions health-state utility values (r = −0.631, P r = −0.550, P r = −0.556, P r = −0.556, P r = −0.610, P r = −0.556, P  Conclusions

In community-dwelling middle-aged and older adults, Central Sensitization Inventory Part A scores were negatively correlated with health-related quality-of-life scores, even in participants with Central Sensitization Inventory Part A scores

Impact of COVID‐19 on Telephone‐Triage Nurses' Emotional Well‐Being: A Qualitative Study

ABSTRACT

Aims

To describe telephone-triage nurses' perceptions of their well-being and the system factors that influenced their well-being while conducting telephone-triage for COVID-19 during the pandemic.

Design

This descriptive, qualitative study applied both inductive and deductive analysis to generate themes.

Methods

We interviewed a convenience sample of 27 nurses from two health systems about their perceptions of well-being when triaging patient calls about COVID-19 and reasons for those perceptions. Data collection occurred between November 2020 and June 2021. Themes were organised using the National Academies of Science, Engineering and Medicine framework.

Results

Telephone-triage nurses' well-being was significantly impacted by COVID-19. Uncertainty regarding evolving COVID-19 guidance, increased call volumes and difficult patient responses were some of the key work system challenges that impacted nurses' well-being.

Conclusions

Our findings suggest the need to revisit work system factors that impact the well-being of telephone-triage nurses and develop organisational interventions to support nurses to provide optimal care during crisis situations.

Practice Implications

Organisational information infrastructure should be bolstered for future pandemic responses to minimise impacts on nurses' well-being. Additionally, leaders need to realign tasks, workflows and workload of telephone triage during pandemic surges to prevent excessive demands on nurses.

Impact

This work contributes to understanding telephone-triage nurses' well-being during COVID-19. The increased demands they faced and impact on their well-being point to opportunities for organisational well-being interventions and development of crisis standards for tele-triaging to support nurses during high-stress, crisis situations.

Reporting

The authors have adhered to COREQ guidelines for reporting.

Patient or Public Contribution

No patient or public contribution.

Descriptive study of cholera-related deaths in communities during Zambias 2023-2024 outbreak: key insights

Por: Mweso · O. · Shula · A. · Sialubanje · C. · Chanda · S. L. · Shinjeka · T. · Mwangilwa · K. · Chirwa · L. · Kabwe · D. · Mwanza · J. · Mbewe · N. · Fwoloshi · S. · Sinyange · N. · Kapina · M. · Gebregiorgis · A. · Shikanga · O. · Mwale · M. · Nyirenda · M. · Lisulo · P. · Chipimo · P. · Mube
Objectives

The study sought to understand the characteristics of community deaths due to cholera in Zambia. We sought to examine the drivers of mortality from cholera among communities in Zambia’s 2023–2024 outbreak.

Design/setting

This is a descriptive study of the characteristics of community deaths due to cholera in three provinces in Zambia. Routine surveillance data collected between 14 October 2023 and 16 April 2024, comprising a national line list of cholera deaths, were used for this study.

Participants

178 participants were included in the study and completed it. All community deaths on the line list were eligible for inclusion. This comprised: deceased individuals whose death was associated with cholera or who met the national cholera case definition (suspected or confirmed); death occurring in the community, en route or on arrival to a health facility prior to admission; and death must have occurred between 14 October 2023 and 16 April 2024. Deceased individuals whose family members could not be traced or did not consent to participate in the interview were excluded.

Primary and secondary outcome measures

The primary outcome was identifying characteristics of cholera-related community deaths. There were no secondary outcomes measured.

Results

Among 178 community deaths due to cholera, the majority were males (61.8%), with the highest mortality in adults aged 35–49 years (22.5%). Over half of the deaths occurred on arrival at healthcare facilities due to delays influenced by socioeconomic barriers. Comorbidities such as HIV/AIDS and hypertension were present in 23% of cases.

Conclusions

The study found that males, death on arrival at healthcare facilities, delays in seeking healthcare and comorbidities such as HIV/AIDS and hypertension were more frequently observed among those who died due to cholera in the community. These findings highlight the need for enhanced early care-seeking behaviours, improved access to timely treatment and targeted interventions for individuals with comorbidities to potentially reduce cholera mortality.

Six‐Month Outcomes After Transmetatarsal Amputation in Diabetic Patients: Predictive Utility of the SINBAD Classification

ABSTRACT

This study retrospectively reviewed 46 patients undergoing transmetatarsal amputation (TMA) between January 2017 and January 2023 to evaluate complication rates within 6 months and assess the predictive value of the SINBAD classification for re-amputation risk. Patients were categorised based on re-amputation occurrence, and clinical and demographic data were collected. Each case was evaluated using the SINBAD scoring system, with logistic regression used to assess associations. Among the patients, 28 (60.9%) experienced no re-amputation, while 18 (39.1%) underwent re-amputation. Baseline demographics and laboratory findings did not significantly differ between groups. The mean SINBAD score was significantly higher in the re-amputation group (3.67 vs. 2.29; p < 0.001), with logistic regression identifying SINBAD score as an independent predictor (OR 6.76; 95% CI: 2.18–21.02; p < 0.001). A SINBAD score of ≥ 4 was associated with a re-amputation rate of 90.9%. In conclusion, the SINBAD classification proves to be a simple and effective tool for predicting re-amputation post-TMA, facilitating risk stratification and surgical planning for diabetic foot ulcer patients.

Dose-averaged LET escalation with multi-ion therapy for head and neck cancers: a phase I study protocol for a prospective, open-label, single-arm, single-centre trial (MULTI-ION-HN-I)

Por: Ikawa · H. · Shinoto · M. · Koto · M. · Masuda · T. · Inaniwa · T. · Takiyama · H. · Isozaki · T. · Yamada · S. · Ishikawa · H.
Introduction

The standard treatment for unresectable head and neck cancer typically involves radiotherapy (RT) alone or chemoradiotherapy (chemo-RT). Non-squamous cell carcinomas exhibit relatively low radiosensitivity, limiting the efficacy of conventional photon RT. Carbon-ion (C-ion) RT, characterised by high linear energy transfer (LET) and high relative biological effectiveness (RBE), has shown promising outcomes in treating radioresistant head and neck cancers. However, local recurrences still occur, and further improvements in treatment outcomes are needed. To enhance the local control rate, an increase in dose-averaged LET (LETd) to the tumour was considered.

Following a simulation study, a clinical trial was conducted to optimise LETd using only C-ion therapy, and its safety was confirmed. However, in this clinical trial, LETd could only be increased to approximately 70 keV/μm. To further escalate LETd, multi-ion therapy using ions heavier than carbon was developed. Simulation studies demonstrated that multi-ion therapy incorporating carbon, oxygen and neon ions could increase LETd up to 90 keV/μm, regardless of tumour size, while maintaining high-dose uniformity within the tumour. Based on these results, a clinical study was planned to evaluate the safety of escalating LETd from 70 keV/μm to 90 keV/μm using multi-ion therapy. The primary objective of this study is to evaluate the safety of escalating LETd to the tumour using multi-ion therapy for head and neck cancer, with the secondary goal of identifying the maximum tolerated LETd.

Methods and analysis

This is a non-randomised, open-label, phase 1 study focused on LETd escalation. A maximum of 18 patients with histologically confirmed inoperable head and neck malignancies will be enrolled. All patients will receive multi-ion therapy using helium, carbon, oxygen or neon ions, either alone or in combination, at an RBE-weighted dose ranging from 57.6 to 70.4 Gy, delivered in 16 fractions (4 fractions per week) over 4 weeks. The specific dose will be determined according to histology. LETd escalation will begin at 70 keV/μm and will increase by 10 keV/μm increments, reaching a maximum of 90 keV/μm. The safety of multi-ion therapy will be assessed based on the frequency and severity of dose-limiting toxicities, monitored up to 90 days after the initial irradiation. Patients will be followed up according to the protocol for 180 days after the initial multi-ion therapy irradiation.

Ethics and dissemination

The study protocol has been approved by the National Institutes for Quantum Science and Technology Certified Review Board (#L24-002). The results will be published in a peer-reviewed journal and presented at a scientific conference.

Trial registration number

jRCTs032240451.

Feasibility of implementing a non-invasive self-sampling method for saliva specimens that can be used for the diagnosis of respiratory infections among paediatric patients in the Tshwane District, South Africa: a study protocol

Por: Nxele · S. · Dlangalala · T. · Gxekwa · N. V. · Ramatsokotla · S. · Musekiwa · A. · Kgatle · M. M. · Hatchett · D. B. · Shin · A. · Tu · W.-c. · Robertson · I. H. · Su · X. · Berthier · E. · Thongpang · S. · Theberge · A. B. · Mashamba-Thompson · T. P.
Introduction

Effective community-based disease management is essential for public health. In low- and middle-income countries, sustainable strategies for timely diagnosis and treatment are a research priority. This study aims to assess the feasibility of a non-invasive saliva self-sampling method, paired with digitally linked molecular point-of-care diagnostics, for detecting respiratory infections among paediatric patients in the Tshwane District, South Africa.

Methods and analysis

A field study will be conducted at Steve Biko Academic Hospital to compare saliva collection using the CandyCollect lollipop device and standard mouth swabs. The spiral groove of the lollipop device captures pathogens, which are stored in DNA/RNA preservation media and later analysed using quantitative PCR and commercially available rapid antigen tests. The multiplex respiratory pathogen panel, based on TaqMan real-time PCR technology, targets key paediatric pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, respiratory syncytial virus (RSV) and influenza A/B. Nucleic acids will be extracted using standard viral extraction kits and analysed following manufacturer protocols. Internal controls will be included in each qPCR run, and samples with CT values below defined thresholds will be considered positive. Rapid antigen tests will detect common pathogens such as influenza A/B, RSV and SARS-CoV-2 for comparative analysis. User experience and acceptability will be assessed via child-friendly and caregiver surveys following sample collection. The study will be implemented in two phases: diagnostic performance evaluation and user feedback assessment. The protocol is aligned with the Standard Protocol Items: Recommendations for Interventional Trials 2013 checklist.

Ethics and dissemination

Ethical approval has been granted by the University of Pretoria (509/2023) and the Gauteng Department of Health (GP_202406_032). The study is registered in the Pan African Clinical Trial Registry (PACTR202411743094783). Findings will be disseminated through peer-reviewed journals, conferences and stakeholder briefings. The study complies with South Africa’s Protection of Personal Information Act. Data collection is scheduled from November 2024 to February 2025, with project completion expected within 1 year.

Trial registration number

Pan African Clinical Trial Registry (PACTR202411743094783).

Prospective, multicentre trial on preoperative biliary drainage by endoscopic ultrasound-guided hepaticogastrostomy for resectable/borderline resectable pancreatic cancer with biliary obstruction: the PROLOGUE study - a study protocol

Por: Yagi · S. · Hijioka · S. · Nagashio · Y. · Harai · S. · Agarie · D. · Yamashige · D. · Okamoto · K. · Fukuda · S. · Kuwada · M. · Komori · Y. · Kurita · Y. · Hasegawa · S. · Kubota · K. · Ishida · Y. · Ushio · J. · Takeshita · K. · Yoshino · K. · Ishiwatari · H. · Okusaka · T.
Introduction

Preoperative biliary drainage (PBD) is often required for patients with pancreatic cancer accompanied by biliary obstruction to ensure the safe administration of neoadjuvant chemotherapy or to manage cholangitis and jaundice. Although endoscopic retrograde cholangiopancreatography (ERCP) is the standard approach for PBD, it carries a significant risk of post-ERCP pancreatitis. Endoscopic ultrasound-guided biliary drainage (EUS-BD), particularly via hepaticogastrostomy (EUS-HGS), offers a promising alternative that avoids papillary manipulation. However, the clinical utility of EUS-BD as primary drainage for PBD remains unclear due to a lack of prospective studies. This multicentre prospective trial aims to evaluate the safety and efficacy of EUS-HGS as primary drainage for PBD in patients with resectable or borderline resectable pancreatic cancer.

Methods and analysis

This multicentre prospective study involves seven institutions in Japan. Eligible patients will undergo EUS-HGS using a 7Fr plastic stent. The primary endpoint is clinical success, defined by improvements in bilirubin or liver enzyme levels within 14 days postprocedure. Secondary endpoints include technical success rate, adverse event incidence, stent patency and surgical outcomes. A total of 30 patients will be enrolled, considering an expected clinical success rate of 90% and a 10% dropout allowance.

Ethics and dissemination

This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2024-084). The results of this study will be reported at an international conference and published in an international peer-reviewed journal.

Trial registration number

UMIN ID: 000055173.

Identifying mood disorder subgroups at early risk of metabolic dysfunction: a cross-sectional cohort study in young people at early intervention services

Por: McKenna · S. · Shin · M. · Park · S. H. · Nichles · A. · Zmicerevska · N. · Crouse · J. · Janiszewski · C. · Park · M. · Phung · E. · Iorfino · F. · Varidel · M. · Scott · E. M. · Carpenter · J. S. · Hickie · I. B.
Background

Severe mental disorders are associated with increased risk of metabolic dysfunction. Identifying those subgroups at higher risk may help to inform more effective early intervention. The objective of this study was to compare metabolic profiles across three proposed pathophysiological subtypes of common mood disorders (‘hyperarousal-anxious depression’, ‘circadian-bipolar spectrum’ and ‘neurodevelopmental-psychosis’).

Methods

751 young people (aged 16–25 years; mean age 19.67±2.69) were recruited from early intervention mental health services between 2004 and 2024 and assigned to two mood disorder subgroups (hyperarousal-anxious depression (n=656) and circadian-bipolar spectrum (n=95)). We conducted cross-sectional assessments and between-group comparisons of metabolic and immune risk factors. Immune-metabolic markers included body mass index (BMI), fasting glucose (FG), fasting insulin, Homeostasis Model Assessment-Insulin Resistance (HOMA2-IR), C reactive protein and blood lipids.

Results

Individuals in the circadian-bipolar spectrum subgroup had significantly elevated FG (F=5.75, p=0.04), HOMA2-IR (F=4.86, p=0.03) and triglycerides (F=4.98, p=0.03) as compared with those in the hyperarousal-anxious depression subgroup. As the larger hyperarousal-anxious depression subgroup is the most generic type, and weight gain is also a characteristic of the circadian-bipolar subgroup, we then differentiated those with the hyperarousal-anxious subtype on the basis of low versus high BMI (2 vs ≥25 kg/m2, respectively). The ‘circadian-bipolar’ group had higher FG, FI and HOMA2-IR than those in the hyperarousal-anxious-depression group with low BMI.

Conclusions

Circadian disturbance may be driving increased rates of metabolic dysfunction among youth with emerging mood disorders, while increased BMI also remains a key determinant. Implications for assessment and early interventions are discussed.

eHealth Literacy Mediating Social Support and Technology Acceptance Among Patients With Chronic Illnesses: A Cross‐Sectional Study

ABSTRACT

Aim

To examine the relationships among social support, eHealth literacy and eHealth technology acceptance among patients with chronic illnesses, and investigate whether eHealth literacy plays a mediating role.

Design

A cross-sectional correlational study.

Methods

A total of 202 patients with chronic illnesses were recruited from outpatient clinics and communities in Taiwan. Data were collected via structured questionnaires and analysed using SPSS and PROCESS macro with 1000 bootstrap samples.

Results

eHealth literacy was the strongest predictor of technology acceptance. Although social support was positively associated with eHealth literacy, it did not directly predict technology acceptance after controlling for eHealth literacy, indicating a full mediation effect.

Conclusions

eHealth literacy is a crucial mechanism through which social support influences health technologies acceptance. Interventions to improve eHealth literacy, particularly those integrated with social support strategies based on different cultural backgrounds, enhance digital engagement among chronic illnesses.

Implications for Profession and/or Patient Care

Healthcare professionals and policy-makers should design literacy-sensitive interventions that leverage social networks and involve significant others to promote meaningful eHealth engagement in disease management.

Impact

eHealth literacy fully mediates the relationship between social support and eHealth technology acceptance, proving that social support alone does not directly increase adoption without improving eHealth literacy. eHealth literacy is the strongest predictor of eHealth technology acceptance, emphasising its central role in bridging the gap between social support and eHealth engagement.

Reporting Method

This study followed the STROBE checklist guideline.

Patient or Public Contribution

No patient or public involvement.

Multifaceted analysis of presenteeism: contributions of pain, psychological factors and daily functioning - a cross-sectional study in Japan

Por: Yoshino · A. · Ushio · K. · Nakamura · R. · Shiota · S. · Katagiri · T. · Nishihara · K. · Moriwaki · K. · Anno · K. · Mikami · Y. · Tsutsumi · Y.
Objective

Presenteeism, defined as reduced work efficiency due to health issues despite attending work, accounts for a substantial proportion of labour productivity loss. Although pain significantly impacts presenteeism, the relationship between pain and presenteeism remains poorly understood due to the multifaceted nature of pain, encompassing psychosocial factors and daily functioning. This study aimed to identify which of these factors are significantly associated with presenteeism among employees.

Design

Cross-sectional study using self-administered questionnaires and generalised additive model analysis.

Setting

Multiple workplaces (including a university and hospitals) in Japan.

Participants

Employed individuals (n=212, age range: 20–65 years; 59 males and 153 females) participated. They were recruited through workplace bulletin boards, email announcements and direct invitations. Participants with and without chronic pain were included.

Primary and secondary outcome measures

Participants completed self-report measures, including the Health and Work Performance Questionnaire (HPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Pain Catastrophising Scale (PCS), Beck Depression Inventory-second edition (BDI-II), State-Trait Anxiety Inventory (STAI) and WHO Disability Assessment Schedule 2.0 (WHODAS 2.0).

Results

The results indicated that absolute HPQ was significantly associated with BDI-II scores (F=4.51, p=0.035). On the other hand, relative HPQ was influenced by SF-MPQ (F=3.76, p=0.005), PCS (F=4.16, p=0.014), STAI (F=5.62, p=0.019) and limited daily activities (F=13.25, p=0.00035).

Conclusions

These findings suggest that presenteeism is multifactorial, with pain, psychosocial factors and daily functioning playing critical roles. Moreover, the impact of depression on presenteeism differs from that of pain and anxiety. Therefore, tailored intervention approaches may be required for each factor, ultimately improving workplace productivity.

Trial registration number

This study was preregistered at UMIN-CTR (UMIN000054797).

Lay health worker-delivered and technology-based interventions for sexual and reproductive health among adolescents and young adults in low- and middle-income countries: protocol for a scoping review

Por: Kern · M. · Neumann · C. · Bosompim · B. · Ann · D. · Kurniawan · A. L. · Dlamini · N. · Nabukeera · S. · Machanyangwa · S. · Tewahido · D. · Shinde · S. · DASH Collaborators · Bukenya · J. · Laxy · Burns · Fawzi · Sando · Moshabela · Oduola · Guwatudde · Sie · Berhane · Manu · Bärnig
Background

Adolescents and young adults (AYAs) in low- and middle-income countries (LMICs) are at high risk of harmful sexual and reproductive health (SRH) practices due to limited knowledge, low availability or acceptability of modern contraceptives, gender inequality and cultural practices like child marriage. Preventive and educational interventions by lay health workers or through technological means are a cost-effective and scalable solution. Unfortunately, too little is currently known about the scope, content and conditions of the effectiveness and sustainability of these approaches and synthetic evidence on this topic is scarce. To help fill this knowledge gap and to identify where further research is needed, we will conduct a scoping review of technology-based or lay health-worker delivered preventive and educational SRH interventions targeting AYAs in LMICs. This information is valuable to both policymakers and researchers as it provides a synthesis of existing interventions, highlights best practices for their implementation and identifies potential avenues for future research.

Methods

This review will include studies on SRH preventive and educational interventions targeting AYAs aged 10–24 years in LMICs. It encompasses interventions delivered by lay health workers or via technological means, assessing various outcomes including but not limited to SRH literacy, sexual risk behaviours, pregnancies, sexually transmitted infections and gender-based violence. Key databases, including PubMed via MEDLINE and Embase, will be searched from 1 January 2000 up to 23 January 2024, using a comprehensive search strategy. Screening will be conducted using Covidence software. Data extraction will cover study details, methods, intervention strategies, outcomes and findings. A narrative synthesis will be conducted following synthesis without meta-analysis guidelines.

Ethics and dissemination

The scope of this scoping review is limited to publicly accessible databases that do not require prior ethical approval for access. The findings will be disseminated through peer-reviewed journal publications, as well as presentations at national and international conferences and stakeholder meetings in LMICs.

Scoping review registration

The final protocol is prospectively registered with the Open Science Framework on 7 May 2024 (osf.io/vna2z).

Analysis of the utilisation of Chuna manual therapy for musculoskeletal disorders after its coverage under national health insurance in Korea: a retrospective analysis

Por: Baek · G. G. · Ha · I.-H. · Lee · Y. J. · Shin · Y.-J. · Shin · B.-C.
Objective

To examine trends in Chuna manual therapy utilisation for musculoskeletal disorders (MSDs) following its inclusion in the National Health Insurance (NHI) system in Korea in 2019 using claims data from the Health Insurance Review & Assessment Service (HIRA).

Design

Retrospective analysis of NHI claims data.

Setting

Nationwide medical institutions, based on HIRA claims data from April 2019 to December 2021.

Participants

All patients who received at least one Chuna therapy session during the study period.

Primary and secondary outcome measures

Primary outcome: Annual trends in Chuna manual therapy claims. Secondary outcome: Patient demographics, therapy frequency, MSD diagnoses and concurrent therapies.

Results

A total of 12 729 625 Chuna therapy claims were analysed, showing a gradual annual increase in utilisation from 2019 to 2021. The most common age group was 45–54 years (22.3%), with female patients comprising a higher proportion (55.8%) than male patients.

Low back pain (M54.5), lumbar sprain and strain (S33.5) and cervicalgia (M54.2) were the most common diagnoses. Patients receiving Complex Chuna (50% co-payment) had more treatment sessions than those receiving Simple Chuna or Complex Chuna (80% co-payment), with spinal disorders such as spinal stenosis (M48.0) and intervertebral disc disorders (M51.1, M50.1) associated with higher treatment frequency. Acupuncture was the most common concurrent therapy (97.4%).

Conclusions

This study is the first to comprehensively analyse Chuna therapy utilisation using nationwide NHI claims data. The findings confirm that Chuna therapy is widely used for MSDs, particularly among middle-aged and elderly patients with spinal or muscle-related conditions. Patients with severe or chronic spinal diseases were more likely to receive frequent Chuna therapy sessions. These results provide insights into the utilisation patterns of Chuna therapy and highlight the need for further research to refine reimbursement policies based on disease severity and patient characteristics.

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.

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