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° Se han desarrollado muchos modelos de probabilidad de complicaciones en tejidos normales (PCTN) para predecir los efectos no deseados después de la radioterapia en pacientes con cáncer de cabeza y cuello, pero la mayoría de ellos no se han validado lo suficiente de forma externa, es decir, no se han analizado lo suficiente en pacientes que no participaron en el estudio original de desarrollo del modelo, para saber cómo de bien predicen realmente los efectos no deseados.
° Para los modelos analizados en dos o más estudios además de sus estudios originales de desarrollo del modelo, la calidad de las pruebas y el informe de sus resultados fue generalmente deficiente, por lo que es difícil saber su utilidad.
° Se necesitan más estudios mejor diseñados para investigar este tema en el área del cáncer de cabeza y cuello.
La probabilidad de tener efectos adversos como resultado de la radioterapia se puede calcular mediante los denominados modelos de PCTN. Los modelos de PCTN calculan el riesgo de efectos secundarios inducidos por la radiación según la información del paciente, su enfermedad y su tratamiento.
La radioterapia es la base del tratamiento de pacientes con cáncer de cabeza y cuello. Sin embargo, la radioterapia expone a radiación partes sanas, a veces esenciales, de la región de la cabeza y el cuello. Esto puede provocar daños en estos órganos normales, p. ej. alteración de la producción de saliva, que puede tener consecuencias importantes para la calidad de vida de los pacientes con cáncer de cabeza y cuello tratados con radioterapia. Los modelos de probabilidad de complicaciones en tejidos normales (PCTN) podrían ser útiles para lograr un equilibrio óptimo entre el control del tumor y prevenir los efectos secundarios inducidos por la radiación. Estos modelos predicen el riesgo de efectos secundarios inducidos por la radiación a partir de la información del paciente, su enfermedad y su tratamiento. Ha habido un número considerable de modelos de PCTN para pacientes con cáncer de cabeza y cuello. Se quería averiguar cuál es la calidad del diseño, la ejecución y el análisis de los estudios (es decir, el riesgo de sesgo) y la eficacia de estos modelos para predecir el riesgo de efectos secundarios inducidos por la radiación.
Se buscaron estudios que desarrollaran o validaran modelos de PCTN en pacientes con cáncer de cabeza y cuello.
En la mayoría de los 592 modelos desarrollados a partir de 140 767 pacientes en 143 artículos identificados, la calidad de los modelos no fue suficiente; y para el 81% de estos modelos no se ha investigado cómo de bien funcionan en otros pacientes. Del 19% restante de los modelos, se encontraron 152 validaciones externas en 34 304 pacientes de 41 artículos. Solo hubo nueve modelos con dos o más validaciones externas. Los modelos pudieron distinguir bien a los pacientes con y sin el desenlace, pero a menudo no estuvo claro si sus predicciones concordaban con lo observado, porque esto último no siempre se evaluó o se proporcionó. En general, la calidad de la mayoría de estos estudios fue baja.
La evidencia está actualizada hasta el 8 de enero de 2024.
by Abbas Ahmad, Shehzad Khalil, Douglas Law, Patricio R. De los Ríos-Escalante, Mostafa A. Abdel-Maksoud, Saeedah Almutairi, Aljawharah Fahad Alabbad, Waheed Ahmad, Ayaz Ahmad
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial inflammation, progressive joint destruction, and systemic immune dysregulation. Recent findings suggest that disturbed metal homeostasis and regulated cell death pathways, including ferroptosis (iron-dependent lipid peroxidation) and cuproptosis (copper-dependent mitochondrial proteotoxic stress), contribute to RA pathogenesis. In this study, we used an integrative bioinformatic approach combining weighted gene co-expression network analysis (WGCNA), differential expression analysis, functional enrichment, protein-protein interaction (PPI) network construction, and immune cell infiltration deconvolution to identify key metal-dependent cell death regulators in RA. Using bulk RNA-seq data from peripheral CD14+ monocytes (GSE294225) from 15 healthy controls and 9 patients with active RA (DAS28 > 2.7), we identified 1,410 significantly differentially expressed genes (DEGs) (adjusted P < 0.05, log2 fold change > 1). WGCNA revealed an RA-associated module enriched in oxidative stress, mitochondrial dysfunction, and cell death pathways. Overlap analysis of ferroptosis- and cuproptosis-related gene sets distinguished three upregulated hub genes, including FTH1 (ferritin heavy chain 1), SOD2 (superoxide dismutase 2), and CDKN2A (cyclin-dependent kinase inhibitor 2A) as key candidate regulators. These genes showed high module membership, significant differential expression in RA monocytes, and notable associations with immune infiltration patterns, including increased pro-inflammatory monocytes/macrophages and reduced regulatory T cells. Functional enrichment also highlighted oxidative stress response, iron and copper homeostasis, mitochondrial respiration, and cellular senescence. The single-cell analysis further showed that these hub genes are predominantly expressed in the RA synovial macrophages and fibroblasts, two major mediators of joint pathology. Together, these findings indicate that there may be an association between ferroptosis-related pathways and cuproptosis-related pathways in RA and suggest that FTH1, SOD2, and CDKN2A are candidate biomarkers and candidate therapeutic targets.by Odey Bsharat, Michel Hanania, Raed Alkowni, Nisreen Al-Hajj, Eman Elsaid, Nawaf Al-Maharik
Coridothymus capitatus (L.) Reichenb. f. (syn. Thymus capitatus) is a Mediterranean aromatic herb esteemed for its essential oil rich in bioactive phenolic compounds. In the current study, essential oils (EOs) were obtained by hydrodistillation from fresh and dried leaves of C. capitatus collected from Hebron and Bethlehem, Palestine, and evaluated for their chemical composition, antioxidant, antibacterial, and antifungal activities. Gas chromatography-mass spectrometry (GC-MS) analysis showed that oxygenated monoterpenes were the leading class (69.03–74.44%), with thymol and carvacrol as the major constituents. A clear chemotypic divergence was observed between the two locations, with thymol-rich oils in Hebron and carvacrol-rich oils in Bethlehem. Antioxidant activity was evaluated using the DPPH radical-scavenging assay over a concentration range of 0.333–33.33 µg/mL. At the highest experimentally tested concentration (33.33 µg/mL), DPPH inhibition ranged from 28.21 ± 0.76 to 34.40 ± 0.85ᵃ% among the EOs, with Hebron-fresh oil showing the highest activity. Antibacterial tests displayed substantial activity against Gram-positive and Gram-negative bacteria, with MICs between 25 and 100 µg/mL, while antifungal tests revealed strong inhibitory effects against phytopathogenic fungi, particularly Botrytis californica and Fusarium species, with MICs as low as 6.25 µg/mL. The geographical origin and post-harvest drying influenced the chemical composition and biological activities of the EOs, demonstrating chemotypic variation among Palestinian C. capitatus populations. This study provides a comprehensive comparison of EOs from C. capitatus populations from two geographically distinct regions of Palestine and evaluates the effects of post-harvest drying on their phytochemical composition and antioxidant, antibacterial, and antifungal activities. These findings contribute to understanding the chemotypic variation of Palestinian C. capitatus and highlight its potential as a natural source of bioactive compounds for food preservation, sustainable crop protection, and related applications. Coridothymus capitatus (L.) Reichenb. f. (syn. Thymus capitatus) is a Mediterranean aromatic herb esteemed for its essential oil rich in bioactive phenolic compounds. In the current study, essential oils (EOs) were obtained by hydrodistillation from fresh and dried leaves of C. capitatus collected from Hebron and Bethlehem, Palestine, and evaluated for their chemical composition, antioxidant, antibacterial, and antifungal activities. Gas chromatography-mass spectrometry (GC-MS) analysis showed that oxygenated monoterpenes were the leading class (69.03–74.44%), with thymol and carvacrol as the major constituents. A clear chemotypic divergence was observed between the two locations, with thymol-rich oils in Hebron and carvacrol-rich oils in Bethlehem. Antioxidant activity was evaluated using the DPPH radical-scavenging assay over a concentration range of 0.333–33.33 µg/mL. At the highest experimentally tested concentration (33.33 µg/mL), DPPH inhibition ranged from 37.50 ± 0.83% to 52.08 ± 0.36% among the EOs, with Hebron-fresh oil showing the highest activity. Antibacterial tests displayed substantial activity against Gram-positive and Gram-negative bacteria, with MICs between 25 and 100 µg/mL, while antifungal tests revealed strong inhibitory effects against phytopathogenic fungi, particularly Botrytis californica and Fusarium species, with MICs as low as 6.25 µg/mL. The geographical origin and post-harvest drying influenced the chemical composition and biological activities of the EOs, demonstrating chemotypic variation among Palestinian C. capitatus populations. These findings contribute to understanding the chemotypic variation of Palestinian C. capitatus and highlight its potential as a natural source of bioactive compounds for food preservation, sustainable crop protection, and related applications.by Hosein Ataei-Goujani, Sarmad Salehi, Pardis Zarepour, Ozra Tabatabaei-Malazy, Nazila Rezaei, Mina Mirzad, Anis Gharajeh, Samaneh Akbarpour, Yosra Azizpour
Non-communicable diseases (NCDs) account for more than 81% of all deaths in Iran and impose a substantial burden on the national health system. Although Iran has implemented multiple initiatives, including the World Health Organization’s STEPwise Approach to NCD Risk Factor Surveillance (STEPS), to monitor NCD risk factors, critical gaps remain in longitudinal outcome assessment, particularly in the post–COVID-19 period, for which national data are limited. Moreover, in the context of declining fertility rates and demographic challenges in Iran, emerging evidence suggests that metabolic and lifestyle-related NCD risk factors are associated with impaired reproductive health, fertility potential, and childbearing behaviors. Therefore, the assessment of reproductive outcomes within population-based NCD surveillance frameworks addresses an important knowledge gap in Iran. The Iran STEPS Follow-Up Cohort (ISFUC) is established to evaluate mortality, health outcomes related to NCD risk factors, and fertility related outcomes using population-based data from the 2021 STEPS survey. The ISFUC is a population-based cohort study established through follow-up of participants from the nationally representative 2021 Iranian STEPS survey. The 2021 STEPS survey constitutes the baseline assessment, whereas ISFUC represents the subsequent follow-up phase. Baseline assessments were collected through interviewer-administered questionnaires, standardized physical measurements, and laboratory analyses of blood and urine biomarkers. Follow-up began in 4 April 2025, a five-years interval after baseline, and is ongoing. It will be conducted through structured telephone interviews by trained staff after renewed verbal consent. Study outcomes include all-cause mortality, healthcare utilization, injuries, reproductive health indicators, fertility-related behaviors and attitudes, and use of governmental childbearing support policies. Mortality outcomes are validated through linkage with the national death registry. Questionnaire validity was ensured using expert review, the Content Validity Ratio, and the Content Validity Index methods. By linking comprehensive 2021 STEPS baseline data with follow-up information on health, healthcare utilization, mortality, and reproductive outcomes, ISFUC provides a national platform for investigating Iran’s evolving epidemiological and demographic health challenges.To examine the geographical and temporal distribution of safeguarding concerns and enquiries among older adults living with dementia in England, and to assess variation by sex, age and region.
Population-based, repeated cross-sectional study.
England, using national administrative datasets.
Older adults living with dementia in England, identified using national dementia prevalence estimates; safeguarding activity was analysed at local authority and regional level.
Primary outcomes were the number of safeguarding concerns and Section 42 safeguarding enquiries recorded by local authorities. Secondary outcomes included other safeguarding enquiries and variation by age, sex and geographic region.
Safeguarding concerns more than doubled between 2015 and 2022 across the adult population. Among adults with dementia, safeguarding concerns increased by 55.5% between 2015/2016 and 2019/2020, with a temporary decline during the COVID-19 pandemic. Women with dementia, particularly those aged 85 and older, had higher rates of safeguarding concerns and enquiries than men. Spatial analysis revealed substantial variation across England, with higher safeguarding activity in urban and more deprived regions, such as parts of the North West (eg, Manchester, Liverpool), Yorkshire and the Humber, and the Midlands, while lower activity was observed in more rural and less deprived areas such as the North East and South West.
This study provides the first national analysis of safeguarding patterns for people living with dementia in England. The findings found demographic and geographic disparities in safeguarding activity, highlighting the need for more detailed and individual-level data to inform responsive, dementia-sensitive safeguarding policies.
Walk-and-talk therapy integrates psychological support and physical activity conducted in outdoor environments, and has potential to better align with men’s preferences and masculine norms around emotional communication. Conventional indoor psychotherapy is effective for treating depression but can be less engaging for men, leading to less satisfaction and high rates of dropout. This trial aims to determine whether walk-and-talk therapy offers men with depressive symptoms clinically meaningful benefits over conventional indoor therapy.
This assessor-blinded, parallel group randomised controlled trial is comparing the efficacy of walk-and-talk therapy to conventional indoor therapy for men with depressive symptoms. After randomisation, all participants receive 10 fortnightly 1-hour individual psychotherapy sessions over 20 weeks as either: (1) conventional indoor therapy (sitting down indoors) or (2) walk-and-talk therapy (walking outdoors). Participants are assessed at ‘pre-intervention’ (baseline), ‘post-intervention’ (5 months post baseline) and ‘follow-up’ (12 months post baseline) time points. The primary outcome is change in overall psychological distress (21-item version of the Depression, Anxiety and Stress Scale (DASS-21)) at post-intervention. Secondary outcomes include male-type depression symptoms, mental well-being, suicidal ideation and quality of life. Costing data is being collected for cost-effectiveness analysis. Linear mixed models will be used to examine the impact of group (conventional indoor vs walk-and-talk), time (baseline, 5-month and 12-month) and the group-by-time interaction for primary and secondary outcomes.
This study is approved by the University of Newcastle Human Research Ethics Committee (H-2024-0090). Results will be published in an open access peer-reviewed journal and disseminated through conference presentations.
ACTRN12624000794505.
Potentially inappropriate prescribing (PIP) in the elderly is associated with adverse outcomes and increased healthcare use. We aimed to estimate its prevalence and pattern among the elderly population of Iran using the Screening Tool of Older Persons’ Prescriptions (STOPP) criteria.
Retrospective, population-based observational study.
Nationwide data of Iran Health Insurance Organization (IHIO) prescription claims from 24 provinces (21 March 2014 to 19 March 2017).
Adults aged ≥60 years with at least one prescription in the dataset were included. The study comprised 2 696 300 older adults who received 28 575 400 prescriptions.
Not applicable.
Using a two-stage curation process, we selected STOPP version 3 criteria that could be operationalised from dispensing data alone (age, Anatomical Therapeutic Chemical code, dose, duration and concurrent use). For each criterion, we calculated prescription and patient level PIP prevalence overall and among at-risk prescriptions.
Across the curated STOPP criteria, 313 315 prescriptions issued to 131 012 patients met at least one PIP criterion. The most frequent PIPs were concurrent beta blocker and diltiazem use (99 027 prescriptions; 1.26% of patients), benzodiazepine therapy ≥4 weeks (89 240 prescriptions; 1.60% of patients), ≥2 anticholinergic drugs (47 079 prescriptions; 0.78% of patients) and concomitant non-steroidal anti-inflammatory drug plus anticoagulant (25 685 prescriptions; 0.38% of patients). PIPs involving acetylcholinesterase inhibitors, ticlopidine, clonidine and methyldopa were rare.
In this nationwide claims-based study, about 5% of elderly Iranians were exposed to PIPs, particularly chronic benzodiazepine use, excessive anticholinergic burden and high-risk cardiovascular and antithrombotic combinations. Our findings provide concrete targets for claims-based surveillance and interventions to improve prescribing safety in Iran’s ageing population.
Long-term sickness absence represents a major public health challenge with far-reaching consequences for both individuals and society. Musculoskeletal disorders (MSDs) are among the leading causes of sickness absence. Although mobile apps show promise for supporting self-management of MSDs, high-quality evidence remains limited, and outcomes related to work participation are rarely examined. This trial aims to evaluate whether an individually tailored, app-based self-management intervention (SmaRTWork), provided in addition to usual care, improves return-to-work compared with usual care alone among individuals on sick leave due to MSDs.
We will conduct a randomised controlled trial with two parallel arms: 1) SmaRTWork in addition to usual care and 2) usual care alone. Individuals 20–59 years old who have been sick-listed for
The trial is approved by the Committees for Clinical Trials of Pharmaceuticals and Medical Devices (Ref. 563919). Results will be published in peer-reviewed journals and presented at national and international conferences.
Cross-border collaboration in healthcare has become increasingly important in the context of European integration, particularly in border regions where institutional and health system interactions are most pronounced. These regions offer opportunities for joint healthcare provision, patient and workforce mobility and shared use of resources. However, healthcare governance largely remains a national responsibility, introducing administrative, legal and institutional barriers to coordinated care. This review will examine the structures and mechanisms in place for cooperation and will map the available evidence relevant to the functions of cross-border healthcare in Europe using the Health System Performance Assessment framework.
This scoping review will follow the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Eligibility will be determined using the Population–Concept–Context approach. A three-step search strategy will include an initial limited search, comprehensive searches across six databases (PubMed, Web of Science, Medline, Embase, Global Health, Scopus) and grey literature searching. Two reviewers will independently screen studies via Covidence. Data will be extracted using a standardised form and synthesised descriptively. AI tools can assist with specific steps in the Responsible AI in Evidence Synthesis framework, provided they are supplemented by manual verification.
Ethical approval is not required as this review uses publicly available literature. Findings will be disseminated through an open-access publication, conferences and policy briefs targeting cross-border healthcare stakeholders.
Methadone is a long-acting opioid used to treat opioid use disorder, cancer pain and provide perioperative analgesia. Methadone administration has been associated with QTc interval prolongation and consequently an increased risk of ventricular arrhythmias. This mechanism appears to be mediated by HERG channel inhibition, drug–drug interactions and genetic susceptibility. This protocol describes the methodology for a systematic review and meta-analysis aiming to evaluate the association between methadone administration and QTc prolongation and estimate the odds of major cardiac events. Our leading hypothesis is that methadone exerts a dose-dependent and time-dependent effect on QT prolongation.
We will conduct a systematic literature search of randomised controlled trials, prospective and retrospective cohort studies and case–control studies involving adult or paediatric patients receiving oral or intravenous methadone for opioid use disorder, cancer-related pain and surgical pain. Searches will be performed in Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, Web of Science and ClinicalTrials.gov. The primary outcome will be QTc interval length (in milliseconds). Secondary outcomes will include odds of clinically significant QTc prolongation and major adverse cardiac events. Comparator groups will include baseline pre-methadone QTc measurements and an external control group not exposed to methadone. Random-effects meta-analyses will be conducted, reporting mean differences with 95% CIs. Prespecified subgroup analyses based on methadone dose and duration of exposure will be performed when feasible. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool for randomised studies and Risk Of Bias In Non-Randomised Studies-of Interventions for non-randomised studies. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
Ethical approval is not required. We will include data obtained exclusively from previously published peer-reviewed studies available in reputable databases. The results of this study are intended for dissemination via publication in a peer-reviewed journal.
CRD420251143441.
Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is diagnosed, current recommendations for clinical care are based primarily on expert consensus with a ’one size fits all’ approach to management. Detailed knowledge of genotype-phenotype associations and the impact of genetic modifiers is lacking, and due to strong ascertainment bias of children already diagnosed with cancer predominantly being tested for a CPS, the true cancer risk is likely overestimated.
The Childhood Cancer Predisposition Study (CCPS) is a multi-centre registry and biorepository for children and adolescents aged 0–21 years with a clinical or molecularly confirmed CPS and their family members (NCT04511806). The study objectives are to characterise the natural history of each CPS, correlate the natural history phenotype with CPS genotype, evaluate the efficacy of standard surveillance strategies and allow future investigation into the feasibility and effectiveness of novel surveillance strategies. The principal study question is whether adherence to recommended tumour surveillance guidelines is associated with earlier detection of tumours and/or improved survival. We will also address what barriers exist that prevent adherence to surveillance guidelines. Data collected from primary subjects includes detail about the CPS, genomic data, cancer history and family cancer history, as well as information about tumour surveillance. Required biospecimen collection includes germline DNA samples, with optional collection of serial blood and stool samples. Planned enrolment is 1050 primary subjects.
CCPS was reviewed and approved by a central IRB (WCG IRB 2020P002450) and the Research Ethics Board at The Hospital for Sick Children in Toronto (1000072286). Written informed consent is obtained from all participants. Data and specimens are available to qualified investigators by request to address specific research questions through a standardised research application process. In addition, de-identified data are available through the Pediatric Cancer Data Commons for exploration. Analysed data will be disseminated in peer-reviewed publications and at conferences including meetings inclusive of patient and family advocacy groups.
To identify and describe the medication information needs and preferences of caregivers of children with cancer, and the factors that support or impede those needs being met.
Qualitative descriptive study guided by reflexive thematic analysis.
Between November 2024 and July 2025, semi-structured interviews were conducted with 13 caregivers purposively recruited from a tertiary paediatric oncology centre in Australia. Data collection and analysis proceeded concurrently using reflexive thematic analysis.
Caregivers described receiving supportive medication information, yet their information needs persisted as responsibility for medication management shifted to families. Needs reflected the practical, emotional, and cognitive demands of translating clinical instructions into safe home-based care. Caregivers relied on visual tools, written schedules, and trusted clinicians to support medication management. High satisfaction with medication information coexisted with vigilance and uncertainty, highlighting a gap between information provision and the realities of home-based medication management.
Medication information needs in paediatric oncology are dynamic and linked to the transfer of responsibility to families. Phased, system-integrated approaches that support caregivers during care transitions and treatment are required.
Reconceptualising medication information as an iterative process rather than a discrete event is recommended. Transition support, decision aids, and standardised visual medication tools may reduce cognitive burden and enhance medication safety.
This study addresses the gap between providing medication information and how caregivers manage complex home-based regimens. Unmet needs stem from the demands of medication administration during care transitions and when managing ‘as required’ medicines. Findings offer practical insights for paediatric oncology nurses, pharmacists, and policymakers designing transition processes and medication safety strategies in family-managed cancer care.
Consolidated Criteria for Reporting Qualitative Research 32-item checklist.
Caregivers reviewed the interview guide prior to interviews and were invited to provide feedback; no changes were required.
Specialization in nursing is essential to enhance effectiveness, quality, and accessibility of healthcare. Barriers to implementing advanced practice nurses and specialist nurses have been widely reported to limit advanced practice roles in many countries. Identifying these barriers and promoting integration of the role requires an understanding of stakeholders' perspectives. The current study aimed to explore barriers to implementing specialist and advanced specialist nursing roles in Jordan from the perspective of nursing regulators, nursing leaders, and nursing educators.
A qualitative descriptive design was used to collect data from a purposive sample of 23 nursing stakeholders from the private and public sectors. Data were collected through in-depth semi-structured interviews using an interview guide developed specifically for this study. Sample adequacy was guided by data saturation. Inductive thematic analysis following Braun and Clarke's 6-step approach was used.
Based on the participants' narratives, findings were classified into four main themes and six sub-themes: (1) Policy and Regulatory Constraints, with two sub-themes: Scope of Practice limitations and Role Ambiguity, (2) Knowledge and Skill Gaps with two sub-themes: Incompetent Graduates and the Nature of Educational Programs, (3) Organizational and Administrative Obstacles with two sub-themes: Inefficient Management Structures and Burdens, and (4) the Reluctance to Implement. In addition, participants proposed recommendations and approaches such as clarifying scope of practice, defining roles, curricular reforms, and creating a supportive organization to facilitate effective role implementation.
This study demonstrates that implementation of specialist and advanced specialist roles in Jordan is constrained by educational, regulatory organizational structure gaps, and absence of coordinated policy alignment across all levels. Establishing a collaborative implementation model supported by effective policies is crucial to assist healthcare institutions in overcoming obstacles and barriers and to support the specialized roles in Jordan.
by Hirotaka Eguchi, Kiyohito Hosokawa, Ryota Kawano, Yukinori Takenaka, Hiroshi Kato, Toshihiro Kishikawa, Masami Suzuki, Motoyuki Suzuki, Takeshi Tsuda, Ryohei Oya, Hidenori Inohara
BackgroundReduced skeletal muscle mass may impair outcomes of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma. We evaluated whether temporal muscle thickness (TMT) on routine head computed tomography was associated with treatment response and survival.
MethodsWe retrospectively analyzed 109 patients treated with nivolumab or pembrolizumab between 2017 and 2023 (89 men [81.7%], 20 women [18.3%]; median age 69 years [range 21–88]). TMT was measured on CT images at the level where the Sylvian fissure was most clearly visualized, perpendicular to the temporalis muscle long axis, on both sides, and the mean of the bilateral values was used. Sex-specific cutoffs were defined by time-dependent receiver operating characteristic analysis for 12-month overall survival (5.53 mm for men; 3.92 mm for women). Associations with objective response and survival were assessed using logistic regression and Cox proportional hazards models.
ResultsObjective response was evaluable in 105 patients (complete response 12, partial response 30, stable disease 18, progressive disease 45), yielding a response rate of 40.0% and a disease control rate of 57.1%. High temporal muscle thickness was associated with response (univariable odds ratio 2.64, 95% confidence interval 1.18–5.90; p = 0.018) and remained significant after adjustment for chemotherapy (adjusted odds ratio 2.42, 95% confidence interval 1.05–5.58; p = 0.038). One-year progression-free survival was 36.5% in the high group versus 15.8% in the low group (absolute difference 20.7%; p = 0.010; adjusted hazard ratio 0.57, 95% confidence interval 0.36–0.90; p = 0.017). One-year overall survival was 73.1% versus 47.4% (absolute difference 25.7%; p = 0.001; adjusted hazard ratio 0.54, 95% confidence interval 0.34–0.86; p = 0.010).
ConclusionTemporal muscle thickness, obtainable from routine head computed tomography, was independently associated with response and survival in patients receiving immune checkpoint inhibitors and may serve as a practical host-related imaging marker for prognostic risk stratification.
by Kittipan Tharakhet, Eakachai Prompetchara, Chirayus Khawsang, Supichcha Saithong, Papatsara Kaewpang, Nongnaphat Yostrerat, Pachara Wangsoontorn, Jenjira Sontikun, Sawaros Tantratorn, Thidarat Khotprathum, Kieu Lam, James Heyes, Drew Weissman, Kiat Ruxrungtham, Chutitorn Ketloy
Dengue virus (DENV) remains a major global health burden, with four antigenically distinct serotypes (DENV-1–4) posing a significant challenge for vaccine development. Dengue non-structural protein 1 (NS1) has been associated with additional protection and reduced disease severity, supporting its inclusion in vaccine design. In this study, we designed a consensus NS1 (cNS1) antigen by integrating sequence elements from all four DENV serotypes (78–89% amino acid identity) to enhance cross-serotype antigenic coverage. The cNS1 sequence was encoded as a nucleoside-modified mRNA and formulated in lipid nanoparticles (mRNA–LNPs). Immunization of BALB/c mice with a low dose (0.2 µg) of cNS1 mRNA–LNP induced broadly reactive NS1-specific IgG responses that recognized NS1 proteins from all four serotypes. In addition, the vaccine elicited interferon-γ (IFN-γ)–producing T cell responses against peptide pools derived from multiple DENV serotypes, indicating the activation of cross-reactive cellular immunity. While broad immune recognition was achieved, this was accompanied by lower serotype-specific response magnitudes as a trade-off. In conclusion, the cNS1 mRNA vaccine induces cross-serotype humoral and cellular immune responses in mice, highlighting the potential of consensus antigen design to broaden immune recognition of DENV NS1. These findings support the further development of NS1-based immunogens as complementary components of next-generation dengue vaccines aimed at achieving broad and effective protection.by Dan Kambayashi, Shota Suzuki, Masayoshi Hirohara
BackgroundPharmacists are expanding their participation in veterinary healthcare teams and assuming roles beyond traditional dispensing duties. However, the scope of these collaborative practices and the degree of mutual recognition vary substantially across regions.
ObjectivesThis scoping review aimed to organize the existing literature on collaboration between veterinarians and pharmacists, clarifying current roles, practical applications, and professional perceptions within the veterinary field.
MethodsA scoping review was conducted to examine the roles, practices, and perceptions associated with veterinarian–pharmacist collaboration in veterinary medicine and related fields. Two researchers independently searched PubMed, Web of Science, the Cochrane Library, and Ichushi-Web, and additionally screened Google Scholar to identify gray literature (from database inception to August 2025, in English or Japanese). Records were independently screened at the title/abstract and full-text levels using predefined eligibility criteria, and relevant studies were identified.
ResultsThe search yielded 239 records, of which 16 studies published between 2007 and 2024 were included. Studies were conducted primarily in the United States (n = 7), New Zealand (n = 3), and Japan (n = 3); one study collected data from both Japan and Taiwan. Most studies employed cross-sectional survey designs. Pharmacist roles most frequently involved compounding and dispensing for animal patients (62.5%), followed by drug information (DI) and consultation (37.5%), inventory and supply management (25.0%), client education (18.8%), and safety and exposure control (12.5%).
ConclusionsThis scoping review demonstrates that veterinarian–pharmacist collaboration is described within a limited and regionally variable evidence base, with pharmacists most often contributing through compounding/dispensing and drug information support. Sustained and scalable implementation will require improved mutual understanding of professional roles, strengthened veterinary-specific education for pharmacists, and more robust empirical research to inform collaborative practice models.
The prevalence of pre-diabetes mellitus (pre-diabetes, pre-DM) is increasing globally, with 5%–10% of adults with pre-DM progressing to type 2 DM (T2DM) annually. Despite the availability of national screening programmes and lifestyle interventions, uptake remains suboptimal and the lived experiences of individuals navigating pre-DM diagnosis and care in Singapore remain poorly understood. Understanding these experiences is critical, as patient perspectives can reveal gaps in care delivery, particularly in a multiethnic population where cultural, social and systemic factors intersect in complex ways. The current study explores the barriers and facilitators in detecting and managing pre-DM in Singapore’s multiethnic population.
This qualitative study employed purposive sampling and a phenomenological approach to capture the experiences of those living with pre-DM (n=13). Participants were recruited from National Healthcare Group polyclinics through clinician referrals and through self-referrals. Eligible participants were aged 21 and above, Singapore citizens or permanent residents, diagnosed with pre-DM and conversant in at least one local language, while those with T2DM or type 1 DM were excluded. One-to-one in-depth interviews were conducted between August 2023 and February 2024, which were audio-recorded, transcribed verbatim and analysed through reflexive thematic analysis.
Six overarching themes were identified: a) pathways to pre-DM diagnosis (detection during management of chronic conditions, self-initiated detection through health screening (HS)), b) dealing with diagnosis: navigating shock, acceptance and worry about the future, c) life before diagnosis: living in comfort and the absence of consequences (dietary habits and lifestyle choices before diagnosis, when not knowing felt safer: the reasons for not doing HS), d) life after diagnosis: reconfiguring daily life (lifestyle changes: renegotiating diet and exercise habits, alternative therapies: integrating traditional approaches), e) pre-DM care (challenges and enablers of pre-DM management) and f) reimagining care: suggestions for improving pre-DM care. The main barriers were i) personal factors: the struggle to sustain behavioural changes (such as lack of awareness, difficulty with dietary and physical activity changes, lack of self-discipline), ii) navigating social and environmental barriers to lifestyle change, iii) the financial burden of lifestyle changes, iv) work-related factors: competing priorities and time constraints,v) feeling unheard: the healthcare team-related barriers to care and vi) gaps in the systems: structural barriers to care (such as long waiting times, clinician rotation, short consultations). Enablers included i) fear to action: personal drivers of pre-DM self-management (such as personal factors including fear of developing T2DM), ii) family, peers and domestic help as daily support, iii) feeling heard and cared for: healthcare team-related factors, iv) seamless care through operational excellence and v) knowledge about pre-DM: sources and information seeking.
Our findings suggest the need for multilevel collaboration to promote effective strategies to manage pre-DM in the community. This requires interventions to promote early screening, healthcare reforms to reduce waiting times and clinician rotation, and sustaining lifestyle modifications. Interventions should leverage the enablers identified in the study while addressing the barriers to ensure healthcare reforms. The insights derived from this study can directly inform locally contextualised interventions and policy reforms to strengthen pre-DM care delivery within a multiethnic healthcare setting.
To identify and examine evaluation methods and metrics used for specialist cancer nursing.
A scoping review of published and grey literature on evaluation approaches for specialist cancer nursing roles and models of care.
Comprehensive searches were conducted across CINAHL, Cochrane Library, Medline, PsycINFO and Google Scholar for English-language published and grey literature published between January 2014 and November 2025. Two reviewers independently screened and extracted data. Findings were synthesised narratively and mapped to the Strong Model of Advanced Practice Nursing and Quintuple Aim.
Of 3360 records screened, 23 sources met the inclusion criteria: 14 published articles, and 9 grey literature sources (conference abstracts, theses, textbooks). Most sources originated from the USA (n = 12, 52%) or high-income countries (n = 22, 96%), and focused on nurse navigator roles (n = 9, 39%). Five themes emerged in the sources: (1) purpose of evaluation; (2) development of methods and metrics; (3) selection and implementation; (4) data collection approaches; and (5) challenges and considerations. Evaluation was primarily used to demonstrate value and drive quality improvement through pragmatic methods. Metrics varied widely and were concentrated in the Strong Model domains of Direct Comprehensive Care and Support of Systems, with fewer addressing Education, Research and Professional Leadership. Key challenges to evaluation included role variability and lack of standardised tools.
Despite the lack of standardised evaluation practices for specialist cancer nursing, the five themes synthesised in this review can guide evaluation of specialist cancer nursing roles and models of care in real-world settings. Opportunity exists for international collaboration to develop a comprehensive, context-sensitive set of metrics, relevant in diverse healthcare settings, that capture both excellence in service delivery and nursing scholarship.
What problem did the review address? ○
Specialist cancer nurses perform a diverse range of interventions and roles that are complex in nature, leading to challenges in their accurate evaluation.
○Effective and efficient approaches to evaluation of specialist cancer nursing roles are crucial to demonstrate their value.
○A significant body of literature has demonstrated the efficacy of specialist cancer nursing roles and models of care in a research framework; however, evaluation is needed to better understand the impact of translating this evidence into real-world settings.
What were the main findings? ○
A scoping review exploring evaluation methods and metrics of specialist cancer nursing revealed five key themes: (1) purpose of evaluation; (2) development of evaluation methods and metrics; (3) selection and implementation of evaluation methods and metrics; (4) methods of data collection; and (5) challenges and considerations.
○Evaluation of specialist cancer nursing is important, however variation in nurses' roles and responsibilities and lack of standardised measurement tools were key challenges.
○Evaluation metrics varied widely and were specific to specialist cancer nursing roles; predominantly reported under the domains of Direct Comprehensive Care and Support of Systems, with fewer reported under Education, Research and Professional Leadership.
Where and on whom will the research have an impact? ○
Nursing and health service leaders can use the identified themes and subthemes as a framework to guide evaluation of specialist cancer nursing. The predominance of English-language and high-income country evidence limits the global applicability of these findings.
○Gaps in knowledge can drive the future work of cancer nursing organisations to collaboratively develop a comprehensive list of evaluation metrics that can be contextualised for specific roles across diverse health care settings.
○Specialist cancer nurses in all roles and models of care should have metrics for Research, Leadership and Professional Leadership to support the scholarship of nursing.
○Consistent national role definitions, shared competency frameworks and standardised outcome measures should be embedded in policy and commissioning to enable systematic evaluation, appropriate resourcing, and integration into workforce and service planning of specialist cancer nurses.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews PRISMA-ScR checklist.
Employees of a cancer patient advocacy group were involved in the design of the study, interpretation of the data and the preparation of the manuscript. No patients were involved in the conduct of this scoping review.
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