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Anti-cancer effect of a novel photodynamic therapy using glucose-linked chlorin e6 conjugated trastuzumab for HER2-positive gastrointestinal cancers

by Makiko Sasaki, Mamoru Tanaka, Akihiro Nomoto, Ryusei Yamasaki, Tomokazu Yoshimura, Shigenobu Yano, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka

Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.
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Association between angiotensin receptor-neprilysin inhibitor use and clinical outcomes in patients with heart failure: a 1-year prospective cohort study from Jordan

Por: Odeh · R. S. · Abdel Jalil · M. · Qudah · M. A. · Al-Makhamreh · H. K. · Saleh · A. · Awwad · O.
Objectives

Heart failure (HF) is associated with complex symptoms and frequent hospitalisation that reduce patients’ quality of life (QoL). This study aims to assess the association between angiotensin receptor-neprilysin inhibitor (ARNI) use and changes in QoL and disease-related outcomes among patients with HF in Jordan.

Design

Prospective observational cohort study.

Setting and participants

The study was conducted among patients with HF attending the outpatient cardiology clinics at Jordan University Hospital, a tertiary care centre in Amman, Jordan. Patients either initiated on ARNI or receiving angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) were included in the study at a 1:2 ratio. All participants were followed up for up to 1 year after recruitment. The study period was from 4 February 2024 to 29 May 2025.

Primary and secondary outcome measures

Data on QoL, New York Heart Association (NYHA) functional class and left ventricular ejection fraction (LVEF) were collected at baseline and after 3 months of treatment. Hospitalisation data were collected for the preceding year and the year following participants’ recruitment. Medication adherence and ARNI side effects were assessed after 3-month of follow-up period.

Results

A total of 227 patients with HF were included; 74 were initiated on ARNI, and 153 were receiving ACEIs/ARBs. At baseline, significantly lower QoL scores and LVEF were observed in the ARNI group compared with the ACEIs/ARBs group. After 3-month, the ARNI group showed improvements in all QoL scores, NYHA functional class and LVEF (p

Conclusions

ARNI use was associated with favourable QoL, NYHA class, and LVEF as well as lower hospitalisation rates among patients with HF in Jordan. The safety profile was consistent with previous studies.

Flow of Medication Information Incidents in the Home Care Setting in Finland: A Qualitative Descriptive Study

ABSTRACT

Aim

To describe the challenges related to the flow of medication information in home care, their contributing factors, and home care registered nurses' and nurse leaders' views on preventing them.

Design

A descriptive qualitative study.

Methods

Six group and one individual semi-structured interview were conducted remotely with 15 home care registered nurses and nurse leaders between 12 February 2023 and 9 November 2023 in Finland. The data were analysed using reflexive thematic analysis.

Results

We identified four main themes related to the challenges of medication information flow: the complexity of home care work in cooperation and the medication process, technology-related challenges, the healthcare professionals' individual factors and client-related challenges. These factors contributed to the challenges: the lack of healthcare professionals' resources, the healthcare professionals' attitudes to work and individual characteristics, the lack of healthcare professionals' uniform practices and client-related factors. Preventing challenges and incidents: strengthening standard healthcare practices, increasing healthcare resources, improving the individual factors of healthcare professionals, and guiding the client in the management of medication.

Conclusion

The medication information flow can be improved by discussing standard practices for the flow of medication information in home care and between home care and hospital teams.

Implications for the Profession and/or Patient Care

It is crucial to identify challenges, contributing factors and prevention in the medication information flow from the home care registered nurses' and nurse leaders' perspective. These elements play an important role in developing medication information flow by collaborating extensively with other healthcare providers, clients, and relatives.

Impact

Healthcare professionals, nurse leaders, and educators can utilise this study's findings to develop the flow of medication information within and between organisations.

Reporting Method

The Standards for Reporting Qualitative Research checklist was used.

Patient or Public Contribution

No patient or public contribution.

Characterising cystic fibrosis in African populations: a scoping review protocol on phenotype, diagnosis, genetics and barriers to care

Por: Ratner · L. · Marangu-Boore · D. · Hamouda · S. · Kwarteng Owusu · S. · Eze · J. · Dakshi · A. · Wordui · S. · Hamdy · A. · Owusu · S. A. · Weldetsadik · Y. · Uluer · A. · Daimi · H. · El Makhzen · N. · Abriel · H. · Nasr · S. · Moosa · S. · Swanson · C. · Cronin · A. E. · Zampoli · M.
Introduction

Cystic fibrosis (CF) is a life-shortening genetic disorder traditionally mischaracterised as affecting only populations of European descent. This framing has contributed to under-recognition of CF in African populations, despite emerging evidence of both common and region-specific cystic fibrosis transmembrane conductance regulator mutations across the continent. Diagnostic barriers, structural inequities and lack of surveillance further exacerbate disparities in care and visibility.

Methods and analysis

This scoping review aims to characterise CF in African populations by synthesising evidence on clinical presentation, diagnostic practices, genotypic diversity, prevalence and structural barriers to care. We will include case reports, cohort studies, registry analyses and other primary data sources involving individuals of African descent with suspected or confirmed CF. Key outcomes include clinical phenotype, age at diagnosis, mutation profile, diagnostic testing access and mortality. Data sources include Ovid Medline, Embase, Ebsco Global Health, CAB Abstracts and Web of Science Core Collection. Multiple-reviewer screening and extraction will be conducted. We will use narrative synthesis, thematic analysis and meta-analysis for prevalence where feasible.

Ethics and dissemination

No ethical approval is required as the review uses published data. Results will be shared with clinicians, researchers and CF networks in Africa and globally to inform diagnostic strategies and policy.

‘Something Was Missing’: A Qualitative Study of Parents' Expectations in Weight‐Related Health Care for Children

ABSTRACT

Aim

To explore how parents perceive health care encounters related to their child's higher weight and to interpret these experiences within the broader societal context shaped by cultural norms and representations.

Design

A qualitative design was employed using semi-structured interviews to capture parents' experiences. The study was informed by a conceptual framework that views weight as both a personal and socially constructed phenomenon.

Methods

Eighteen parents from Finland were interviewed between May 2022 and June 2023. The data were analysed using reflexive thematic analysis to identify key themes in parents' experiences and perceptions.

Results

Three main themes were identified. The relational dimension highlighted the importance of individualised care, where health care professionals take time to get to know the family and recognise each member as an individual. The emotional dimension emphasised the need to protect the child, strengthen parental self-efficacy and provide sensitive, skilled support that fosters a sense of safety. The practical dimension focused on the need for active and targeted care, including structured weight-related routines, multidisciplinary collaboration and services that respond to the everyday realities of families.

Conclusion

The study highlights the need for health care encounters that are individualised, emotionally safe and sensitive to the diverse realities of families. Moving beyond weight-centric approaches, care should offer a range of supportive options that reflect parents' varied expectations, concerns and needs.

Impact

This study responds to the need for a deeper understanding of how parents experience health care encounters related to their children's higher weight. The findings highlight the importance of designing care interactions that provide professionals with adequate time, expertise and training to deliver individualised, stigma-sensitive care.

Reporting Method

COREQ.

Patient or Public Contribution

No patient or public contribution.

Azithromycin use in labour to prevent sepsis among pregnant women undergoing vaginal delivery in Nigeria (AZIN-V): a study protocol for a hybrid type 2 effectiveness-implementation trial

Por: Afolabi · B. B. · Makwe · C. C. · Oluwole · E. O. · Obi-Jeff · C. · Mitchell · E. J. · Banke-Thomas · A. · Adeyemo · T. A. · Abioye · A. I. · Eboreime · E. A. · Saidu · A. D. · Okoro · U. A. · Akintan · P. · Osuagwu · C. S. · Chieme · C. F. · Lawanson · T. · Hossain · A. · Walker · K.
Introduction

Nigeria has the highest number of maternal deaths globally, and maternal peripartum sepsis is one of the leading causes of maternal mortality. A single oral dose of azithromycin (AZM; 2 g) is safe and effectively reduces 33%–60% of maternal sepsis during planned vaginal birth in low- and middle-income countries (LMICs). However, the clinical and cost-effectiveness of oral AZM during vaginal birth in Nigeria remains unknown in the context of poor antimicrobial stewardship practices, significant antimicrobial resistance and healthcare financing. Evidence is also lacking on the standard care for the prevention of maternal sepsis among pregnant women undergoing vaginal births in Nigeria. The AZIN-V trial is a hybrid type 2 effectiveness-implementation trial to determine the safety, clinical and cost-effectiveness of intrapartum oral AZM versus usual care in the prevention of peripartum maternal sepsis. The trial will also examine the impact of implementation strategies in enhancing adherence to the oral AZM protocol during planned vaginal births and identify effective strategies to improve adherence (fidelity) to the protocol in real-world LMIC settings.

Methods and analysis

This is a multicentre hybrid type 2 trial conducted in six Nigerian states: Ebonyi, Edo, Gombe, Kano, Kwara and Lagos. The study aims to simultaneously test the clinical and cost-effectiveness of AZM (clinical trial) and the impact of implementation strategies (implementation research) in Nigeria’s unique healthcare context. The clinical trial is a two-arm, cluster-randomised controlled trial conducted across 48 health facilities, randomly assigned (1:1) to either intrapartum administration of oral AZM (intervention group) or usual care—the current routine practice (control group). A total of 5040 study participants (2520 in each group) will be enrolled in the clinical trial. The implementation trial is a two-arm cluster non-randomised controlled trial conducted in 12 health facilities (1:1) allocated to either a bottom-up approach using the Plan-Do-Study-Act cycle or a usual top-down approach with a one-time training workshop and distribution of clinical guidelines, with both arms administering oral AZM during vaginal birth while assessing fidelity (primary outcome).

For the clinical trial, data will be analysed using intention-to-treat statistical methods. The cost-effectiveness outcome will be analysed using the Incremental Cost-Effectiveness Ratio. Implementation outcomes will be analysed using descriptive statistics and a thematic approach.

Ethics and dissemination

This study has been approved by the National Health Research Ethics Committee, Nigeria (NHREC/01/01/2007-30/09/2024), the ethics committees of the participating health institutions (Lagos University Teaching Hospital Research Ethics Committee: ADM/DSCST/HREC/APP/6325; University of Ilorin Teaching Hospital Health Research Ethics Committee: ERC/PAN/2025/03/0581; University of Benin Teaching Hospital Health Research Ethics Committee: ADM/E22/A/VOL. VII/483117141; Aminu Kano Teaching Hospital Research Ethics Committee: AKTH/MAC/SUB/12 A/P-3/VI/2509 and Irrua Specialist Teaching Hospital Research Ethics Committee: ISTH/HREC/20241507/605), the Ministries of Health of the six states and the National Agency for Food and Drug Administration and Control. Written informed consent will be obtained from all eligible study participants before enrolment. Results will be shared with communities and policy stakeholders and through peer-reviewed journals and will be presented at conferences.

Trial registration number

ISRCTN16415327.

Enarodustat suppresses thymic stromal lymphopoietin expression via hypoxia-inducible factor-mediated c-Jun N-terminal kinases dephosphorylation

by Ryosuke Segawa, Makiko Yagisawa, Chihiro Miyata, Noriyasu Hirasawa

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that induces type 2 immune responses through dendritic cell activation, and its aberrant regulation is implicated in TSLP-associated inflammatory disorders including atopic dermatitis. We previously demonstrated that hypoxia-inducible factor (HIF) suppresses TSLP expression in human keratinocyte cells; however, the underlying mechanism remained unclear. In this study, we aimed to explore the suppressive mechanism of enarodustat, an HIF-prolyl hydroxylase inhibitor. Enarodustat selectively suppressed TSLP expression induced by the fibroblast-stimulating lipopeptide (FSL-1), a toll like receptor 2/6 agonist in HaCaT, a human keratinocyte cell line. Although both the nuclear factor-κB (NF-κB) and activator protein (AP)-1 contributed to FSL-1-induced TSLP induction, enarodustat preferentially attenuated AP-1 signaling by reducing c-Jun N-terminal kinase (JNK) phosphorylation. This JNK dephosphorylation required both HIF1α and HIF2α and was accompanied by increased expression of dual-specificity phosphatases (DUSPs), which target JNK for dephosphorylation. Collectively, our findings identify a previously uncharacterized HIF–DUSP–JNK axis that negatively regulates TSLP expression. This study provides mechanistic insight into how HIF activation shapes epithelial cytokine responses, offering a basis for understanding the pathogenesis of TSLP-associated diseases such as atopic dermatitis.

Effect of returning home on university student hunger during South African COVID-19 lockdown

by Fezile Wagner, Unathi Kolanisi, Ryan G. Wagner, Lerato P. Makuapane, Mxolisi Masango, Francesc Xavier Gómez-Olivé

The COVID-19 pandemic exacerbated hunger levels in South Africa, with an increase from 10% pre-pandemic to 23% during the pandemic. Pre-pandemic national and global research identified university students to be more vulnerable to hunger compared to the general population. This elevated risk is commonly associated with prevalent financial mismanagement in this group. However, research investigating the prevalence of hunger during the pandemic among this at-risk group is limited. This cross-sectional study aimed to assess the prevalence and determinants of hunger among students at a South African university during the COVID-19 lockdown, with particular focus on the effect of returning home. An online, self-administered survey produced a sample of 596 students. The Household Hunger Scale (HHS) was used to assess hunger. Most students (84%) who resided in on- or off-campus residences before the lockdown returned home during the lockdown. The weighted prevalence of hunger during lockdown was 16.4% (95%CI 13.6%, 19.6%). Bivariate analyses found living alone to be significantly associated with hunger, while multivariate analyses found that first-generation students (adjusted odds ratio (aOR) = 1.78; 95%CI: 1.04, 3.07, p = 0.015), financial aid recipients (aOR = 2.69; 95%CI: 1.47, 4.91, p = 0.001), and those experiencing financial stress/worry (aOR = 3.38; 95%CI: 1.85, 6.18, p 

<i>Clostridioides difficile</i> infection in Saudi Arabia: Prevalence, risk factors, and outcomes in a tertiary hospital setting

by Abdullah M. Aldhaif, Mohammed A. Al-Garni, Ahmed A. Muyidi, Mohammed H. Makkawi

Background

Clostridioides difficile infection (CDI) remains a major healthcare-associated infection with limited contemporary data from Saudi Arabia. This study evaluated CDI prevalence, risk factors, recurrence predictors, and treatment patterns in hospitalized patients at a tertiary teaching hospital.

Methods

Retrospective analysis of 1,054 hospitalized patients screened between March 2023 and February 2024. CDI was confirmed by positive toxin assay and/or nucleic acid amplification test (NAAT). Demographic, clinical, antibiotic, acid-suppressant, and treatment data were collected. Bivariate associations and multivariable logistic regression were used to identify predictors of recurrence.

Results

CDI prevalence was 10.8% (114/1,054). Median age was 37 years (IQR 51.25); 32.5% had malignancy. Antibiotic exposure preceded CDI in 59.6% (meropenem 24.7%, ceftriaxone 16.5% of courses), and acid suppressants were used in 57.0% (omeprazole 92.3%). Recurrence occurred in 11.4% (13/114). On bivariate analysis, acid-suppressant use was significantly associated with recurrence (p = 0.041). In multivariable logistic regression, only metronidazole plus vancomycin combination therapy independently predicted recurrence (OR 11.29, 95% CI 1.13–112.42, p = 0.039). Trends were observed for malignancy (OR 2.94, p = 0.112) and acid-suppressant use (OR 1.85, p = 0.440), limited by the small number of recurrent events. Metronidazole monotherapy dominated treatment (64.8%).

Conclusion

CDI prevalence reached 10.8% with an 11.4% recurrence rate. Acid-suppressant exposure and combination therapy were key recurrence signals, while metronidazole remains overused despite international guideline shifts. Enhanced antibiotic and acid-suppressant stewardship, alongside improved access to guideline-recommended therapies, are critical to reducing CDI burden in Saudi tertiary hospitals.

Exploring what works, for whom, under what circumstances to transform systems: realist synthesis protocol of four ongoing studies and literature addressing health inequalities

Por: Horck · S. S. · Crone · M. · Kamphuis · C. B. M. · Stevens · G. W. J. M. · Dedding · C. · Bussemaker · J. · van der Pas · S. · van Berkel · J.
Introduction

Health inequalities remain resistant to interventions that primarily target individual behaviour. Although systems approaches are increasingly promoted, their application in practice is often not well grounded in real-world settings. In this protocol paper, we present the approach we will take in an overarching project that synthesises the combined insights of four ongoing systems-based research projects on system-based approaches for reducing health inequalities in the Netherlands. By bringing together and comparing findings across diverse contexts, populations and interventions, we aim to generate an empirically grounded understanding of what works, for whom, in what contexts and why, and to derive actionable strategies for systemic change to reduce health inequalities.

Methods and analysis

We use a realist approach to synthesise insights from the four ongoing projects. The design involves four iterative steps: (1) Identifying cross-cutting themes from project proposals and literature, (2) Developing and refining context–mechanism–outcome (CMO) configurations through literature review and Slow Science meetings, (3) Engaging Critical Friends to co-develop actionable strategies and (4) Assessing and validating these strategies across diverse contexts. Iterative feedback loops ensure continuous refinement, integration of stakeholder perspectives and exploration of emergent challenges. This design enables theory-informed, practice-based strategies to support sustainable system change in reducing health inequalities.

Ethics and dissemination

Ethical approval for the four underlying projects has been obtained from the relevant institutional review boards, and the way their data is used for this overarching project falls within their approved scope. Dissemination will be ongoing and co-created with stakeholders, including policy briefs, factsheets, educational tools and academic publications, to support uptake of strategies for systems change.

Challenges and coping practices of frontline health workers in newly created districts in Uganda: an exploratory qualitative study

Por: Mutebi · A. · Mukuru · M. · Kiwanuka · S. N. · Makumbi · F. · Rutebemberwa · E.
Objective

This paper examines the challenges frontline health workers face, as well as their coping practices following district splitting. It also has ramifications for the need to take into account the nexus between district splitting and subnational health system functioning.

Design

A qualitative cross-sectional study employing an exploratory design. Data were collected using an in-depth interview guide for individual interviews. We used a deductive thematic analysis to identify and structure challenges faced and coping mechanisms by health workers in new districts. The data were analysed deductively using Braun and Clarke’s six-step thematic analysis.

Setting

Frontline health workers from four randomly selected regions with one parent district selected randomly from each region and a respective child district that had been split from it between 2005 and 2015. Interviews were conducted between June and November 2018.

Participants

In-depth interviews were conducted with 24 frontline health workers whose age ranged from 33 to 51 years and these had changed locations between districts after district splitting occurred.

Results

The challenges frontline health workers faced included work-related role changes, social demands, team integration and health system inadequacies. Health workers switched roles across districts, adapting to leadership while balancing clinical and administrative duties. Overall, five themes emerged during analysis. Newly promoted staff faced knowledge gaps in facility management. Social demands included accommodation issues and family/community pressures. Team integration impacted daily work, requiring newcomers to navigate hierarchy and culture. Health system issues, such as understaffing, poor infrastructure, drug shortages and strained work relations, worsened working conditions. Coping practices included induction, leadership training, staff appraisals, duty rosters, supervision, team building, partner support and financial/community planning.

Conclusions

District splitting worsens challenges for frontline health workers. While they show resilience through coping strategies, systemic improvements remain essential. Addressing root causes like better resource distribution, expanded training and stronger administrative support is crucial to achieving the district splitting goal of improving healthcare delivery in newly formed districts in Uganda.

CONsensus-based Process evaluation reporting guideline for public HEalth intervention Studies (CONPHES) conducted alongside an effectiveness trial: an e-Delphi study

Por: van Nassau · F. · Cillekens · B. · Jelsma · J. G. M. · Vis · C. · Mokkink · L. B. · Treweek · S. · van der Ploeg · H. P. · e-Delphi panel members · Anema · Baker · Bakker · Baranowski · Boendermaker · Burke · Chalkley · Chambers · Drozd · Edney · Engell · Finch · Fynn · Goense · Gra
Objectives

Many researchers conduct a process evaluation alongside an effectiveness trial of a public health intervention to better understand mechanisms behind observed effects. Yet, there is no standardised, scientifically accepted guideline for reporting such process evaluations, which impedes interpretation and comparison of study results. The aim of this project was to develop a consensus-based and expert-based guideline for reporting process evaluations of public health interventions conducted alongside an effectiveness trial.

Design and setting

We conducted an e-Delphi study with a large panel of international experts.

Participants

Based on purposive sampling, we invited 137 international experts that had been involved in the design of process evaluations, researchers who published high-profile process evaluations or frameworks, editors of journals that publish process evaluations, and authors of other reporting guidelines.

Results

Based on a literature search, a first draft of the reporting guideline included 32 items, which was proposed to panel members during the first round. Of the invited 137 invited international experts, 73 (53%) participated in at least one round of the e-Delphi study. Participants rated the inclusion and comprehensibility of the proposed items on a 5-point Likert scale and provided comments and suggestions for relevance and definitions of the items. Adjustments to the items and descriptions were proposed to the e-Delphi panel until consensus of ≥67% for each individual item was reached. In total, 64 (88% of 73) completed round 2, and 55 (76% of 73) completed round 3. This resulted in 19 items that are included in the consensus-based process evaluation reporting guideline for public health intervention studies (CONPHES) guideline. The items cover a detailed description of the intervention that is evaluated, the implementation strategies applied, and underlying causal pathways, and the role of the delivery and support team. The guideline also requires describing the evaluation framework and how evaluation outcomes were assessed. Lastly, the guideline includes items on providing a detailed description of applied analyses (both quantitative and qualitative) and measures for assuring quality. The guideline is accompanied by an Explanation and Elaboration document, with a more detailed explanation of each item.

Conclusions

We expect that the CONPHES reporting guideline for process evaluations of public health interventions can improve the reporting of process evaluations of interventions aimed at promoting public health. This can potentially facilitate more effective translation of public health research into practice and contribute to improving both individual and population health outcomes.

Associations between oral health behaviours, oral health, salivary biomarkers and clinical phenotype in individuals with alcohol use disorder: protocol for a longitudinal observational study

Por: Maki · K. A. · Xu · S. · Wallen · G. R. · Gerrard · C. · Sung · C. · Papneja · S. · Tuason · R. T. S. · Ramchandani · V. A. · Diazgranados · N. · Barb · J. J.
Introduction

Binge drinking in the previous month was reported in 23.5% of US adults, and 28.1 million adults met criteria for Alcohol Use Disorder (AUD) in 2023. Individuals with AUD face increased risks of oral health problems, including caries, periodontal disease and mucosal lesions. Poor oral hygiene, nutrition and dental care all contribute to these conditions, but individuals with AUD are often under-represented in oral health surveys. Understanding relationships between oral health behaviours, attitudes and general health is crucial for designing future interventions. This pilot aims to explore the relationship between oral and systemic health in subjects with AUD, focusing on oral health behaviours, salivary biomarkers and clinical phenotype, including systemic biomarkers of inflammation, to inform future research on oral–systemic interactions in AUD.

Methods and analysis

This protocol has two parts. Part 1 involves cognitive interviews to assess the content validity and interpretability of the Oral Health Behaviours Assessment (OHBA) questionnaire. Part 2 will collect biological and behavioural data from treatment-seeking patients with AUD and matched controls (age, sex and smoking status), including saliva, blood, dental exams, and health behaviour and symptom measures. Inpatients with AUD will provide biospecimens and answer symptom severity questionnaires at admission and again at the dental exam visit (7–12 days later), while controls will provide a single set of measures at their dental exam visit. Oral health will be assessed through structured dental and periodontal examinations, radiographs and validated questionnaires (including the OHBA). Additional data will include alcohol use history, psychiatric and medical history assessments, dietary recall, and measures of stress, sleep and mood to capture potential moderators of oral–systemic relationships. Biomarkers of inflammation and stress will be quantified from saliva and blood using immunoassays. Primary outcomes will compare oral health, salivary biomarkers and clinical measures between AUD and controls, while secondary outcomes will evaluate within-subject changes in patients with AUD during inpatient treatment and early abstinence.

Ethics and dissemination

This clinical protocol was approved by the National Institutes of Health Institutional Review Board (IRB #002005). Prior to enrolling, participants will be informed of the study purpose, risks and benefits, and study procedures, and evaluated for understanding prior to signing consent. Part 1 of the protocol is currently active and recruiting participants for cognitive interviews. The study findings will be disseminated through journals and conferences related to addiction medicine, psychology, immunology, neuroscience and dentistry. We expect the results of the pilot study will inform future research on oral health and salivary bioscience while also providing treatment-seeking patients with AUD targeted information on the importance of oral health behaviours for maintaining oral and systemic health.

Trial registration number

NCT06684483; preresults.

Causes of community deaths by verbal autopsy among persons with HIV in 33 districts in Zambia, 2020–2023

by Priscilla Kapombe, Choolwe Jacobs, Mark W. Tenforde, Kashala Kamalonga, Diane Morof, Terrence Lo, Mweene Cheelo, Lloyd Mulenga, Sombo Fwoloshi, Cordilia M. Himwaze, Patrick Musonda, Mpundu Makasa, Jonas Z. Hines

Zambia has achieved improvements in life expectancy among persons living with HIV (PLHIV) because of high antiretroviral therapy (ART) coverage, which should improve survival due to reductions in AIDS-defining conditions. However, recent estimates of the most common causes of death are not widely available. We utilized mortality surveillance data to report on common causes of death among persons with HIV who died in community settings in Zambia. The Zambian Ministry of Health conducted sentinel mortality surveillance of community deaths in 45 hospitals in 33 of 116 districts from January 2020 through December 2023. Verbal autopsies (VA) were conducted through interviews with relatives or close associates of deceased persons using the 2016 World Health Organization tool. HIV status was reported. A probable cause of death was assigned by a validated computer algorithm (InterVA5). We describe the top assigned causes of death stratified by HIV status. Verbal autopsies were conducted for 67,079 community deaths, of which 11,475 (17.1%) were persons with HIV. The mean age at death was 45 years among persons with HIV and 48 years for persons without HIV (T-test p 

Clinical Nurses' Attitudes and Self‐Reported Practices of Family Nursing in Japan Following COVID‐19 Visitation Restrictions: A Cross‐Sectional Study

ABSTRACT

Aim

To examine clinical nurses' attitudes towards and self-reported experiences of family nursing in Japan following the relaxation of COVID-19 visitation restrictions. Particular attention is paid to early career nurses whose formative training occurred during visitation bans. The study focused on nurses' negative perceptions and emotional burdens associated with family involvement.

Design

A quantitative-dominant mixed-methods cross-sectional study reported in accordance with the STROBE guideline.

Methods

Using a convenience sampling approach, a self-administered, paper-based questionnaire was distributed to clinical nurses in four general hospitals in Japan between January and May 2024. The questionnaire consisted of four parts: demographic and professional background, learning methods related to family nursing, 17 items including negatively valenced statements adapted from the Families' Importance in Nursing Care–Nurses' Attitudes (FINC-NA) scale, and one open-ended question. Quantitative data were analysed using descriptive statistics and t-tests, and qualitative responses were thematically analysed.

Results

Of 1921 nurses invited, 957 responded (response rate: 49.8%), and data from 892 valid responses were analysed. Overall, the nurses demonstrated positive recognition of family nursing as a professional value but also reported lingering emotional burdens and practical challenges when interacting with families. Early-career nurses who began practice during the pandemic showed greater uncertainty and lower affective engagement. Thematic analysis revealed five key themes: relational disruption, emotional stress, moral conflict, reappraisal of family engagement and ongoing barriers.

Conclusion

The findings underscore the need to structurally and educationally reintegrate families into nursing care. Simulation-based training, clear institutional policies and hybrid communication models are essential to rebuild relational continuity and support nurses' emotional and ethical capacity for family nursing.

Implications for the Profession and/or Patient Care

The findings highlight the need to structurally and educationally reintegrate families into clinical care to address the emotional burden and ambivalence reported by nurses. Organisational support—such as clear visitation policies, simulation-based education and reflective opportunities—can help rebuild nurses' relational competence and confidence in engaging with families. Creating supportive learning environments, including on-the-job mentoring and team-based reflection, may further facilitate the restoration of family nursing.

Impact

This study addressed how prolonged COVID-19 visitation restrictions disrupted family nursing practice in Japan, created generational differences in nurses' competencies, and shaped nurses' perceptions of family involvement. Nurses reported emotional strain, feelings of being monitored and lack of time when families were present. Early career nurses showed lower relational engagement, while experienced nurses expressed moral distress. ‘Latent indifference’ was also noted. The findings provide valuable insights for healthcare organisations, nurse educators and policymakers by informing strategies to reintegrate families into patient care, improve discharge planning and strengthen training models.

Reporting Method

The STROBE checklist.

Patient or Public Contribution

No patient or public contribution.

CRE-Ter enhances murine bone differentiation, improves muscle cell atrophy, and increases irisin expression

by Sompot Jantarawong, Wipapan Khimmaktong, Pharkphoom Panichayupakaranant, Yutthana Pengjam

Ternary complex of curcuminoid-rich extract (CRE-Ter) is a developed water-soluble Curcuma longa extract containing 14% w/w curcuminoids, hydroxypropyl-β-cyclodextrin, and polyvinylpyrrolidone K30. This study aimed to investigate the biomolecular effects of CRE-Ter on differentiation of bone cells (murine MC3T3-E1 preosteoblasts), muscle cells (murine dexamethasone-treated C2C12 myotubes) atrophy and irisin expression. In MC3T3-E1 preosteoblasts, CRE-Ter treatment increased alkaline phosphatase activity, calcium deposition, and expression of Bmp-2, Runx2, and collagen 1a significantly and dose-dependently. 5, 10, and 20 µg/mL CRE-Ter upregulated β-catenin expression significantly. CRE-Ter improved the atrophy of dexamethasone-treated C2C12 myotubes. CRE-Ter decreased proinflammatory cytokine (TNF-α and IL-6) expression but increased FNDC5 and irisin expression and nitric oxide production in dexamethasone-treated C2C12 myotubes significantly and dose-dependently. Dexamethasone promoted β-catenin and total p38 expression in C2C12 myotubes. CRE-Ter at 2.5–20 µg/mL reversed the increase in β-catenin expression, whereas 2.5 µg/mL reversed total p38 expression. Crosstalk experiments further revealed that conditioned medium from C2C12 myotubes enhanced osteocalcin expression in MC3T3-E1 osteoblasts. Molecular docking simulations using CB-Dock2 showed strong interactions between each curcuminoid molecule and irisin. Therefore, CRE-Ter may stimulate osteoblast differentiation, ameliorate myotube atrophy, and increase irisin expression, indicating its therapeutic potential in osteoporosis, sarcopenia, and osteosarcopenia.

Implementation of an Australian helpline for low back pain: protocol of a type 2 hybrid effectiveness-implementation trial

Por: Zouch · J. · Roberts · K. · Bauman · A. · Jentz · H. · Ho · E. K. · Hodges · P. · Maher · C. · Baysari · M. T. · Thompson · J. · Calder · R. · Luscombe · G. · Ceprnja · D. · Maka · K. · Tian · Y. · Chen · Y. · Chen · M. · Mork · P. J. · Li · Q. · Wise · S. · Gilbert · M. · Hall · M. · Ferreira
Introduction

Low back pain (LBP) is the leading contributor to disability globally. It has a substantial impact on the lives of those who experience it, and places considerable economic burden on healthcare systems. Despite these impacts, and the consistency of guideline recommendations, many individuals do not receive recommended LBP management. Structural barriers to accessing timely, evidence-based care, as well as public uncertainty about where to seek appropriate management, can influence the care individuals receive. Telephone and digitally based helplines assist to overcome many traditional barriers to accessing care and offer a scalable platform to improve the delivery of guideline recommended management for LBP. However, uptake of such services can be limited without targeted promotion and patient-centred design. This project aims to codesign, implement and evaluate an upgraded component of an existing Australian helpline service, tailored for people with back pain and supported by a media awareness campaign. This protocol outlines the codesign process, implementation and planned evaluation of the helpline.

Methods and analyses

This protocol uses three complementary frameworks—an iterative codesign process, the Practical Robust Implementation Sustainability Model, and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework—to guide the codesign and development, implementation and evaluation of an upgraded helpline for people with LBP. The codesign process involves key stakeholders, including consumers and clinicians, to inform the development and implementation of both the upgraded helpline service and the media campaign to raise awareness and uptake of the helpline. Data sources will include a pre–post cohort of helpline service users, routinely collected service data (eg, monthly call rate) and health system data to evaluate the broader population level impact (eg, rates of emergency department presentations for LBP in the Australian region targeted by the media campaign). Implementation evaluation will include Reach, Effectiveness, Adoption, Implementation and Maintenance as well as internal and external environmental factors that influence the success of these outcome measures.

Ethics and dissemination

The project was approved by the University of Sydney’s Human Research Ethics Committee (HE001081). This project involves collaboration with consumers, clinicians and other stakeholders to interpret, translate and disseminate research findings to relevant audiences.

Annual U.S. healthcare expenditures attributable to cigar smoking between 2001 and 2018, overall and by payer

by Xin Xu, Ghada Homsi, Sherry T. Liu, Jennifer M. Gaber, Naa A. Inyang, Brian L. Rostron, Caryn F. Nagler, James Nonnemaker

Background

In 2022, 3.7% of U.S. adults currently smoked cigars. This study assesses cigar-smoking-attributable fractions in U.S. healthcare expenditures and associated annual healthcare expenditures overall and by payer, including publicly funded healthcare programs.

Methods

Data were obtained from the 2000, 2005, 2010, and 2015–2017 National Health Interview Survey linked with corresponding panels from the Medical Expenditure Panel Survey data through 2018. The final sample (n = 53,733) was restricted to adults aged 25 + . Estimates from four-part models and data from the Personal Health Care component of the 2001–2018 National Health Expenditures Accounts were combined to estimate fractions of and annual healthcare expenditures attributable to cigar smoking. All models controlled for sociodemographic characteristics and health-related behaviors.

Results

During 2001–2018, an estimated 1.8% (95% CI = 0.9%–3.4%) or $29.7 billion annually of U.S. healthcare expenditures could be attributed to cigar smoking. Most of this was funded by other third-party health insurance programs, a mix of private and public payers (e.g., Department of Veterans Affairs).

Conclusions

Cigar smoking creates a preventable financial burden on the U.S. healthcare system. Health consequences associated with cigar smoking may remain after successful quitting. The findings underscore the importance of preventing initiation of cigar smoking and providing evidence-based cessation methods to reduce the health and economic burden of cigar smoking.

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