Despite implementation of the National Programme for Prevention and Control of Non-Communicable Diseases (NP-NCD), screening coverage for oral, breast and cervical cancers remains below 2%. Screening quality is inadequately addressed and delays in diagnosis and treatment initiation continue to persist. This multisite implementation research aims to improve district-level coverage and quality of screening, early diagnosis and timeliness of treatment initiation through a model co-developed within the NP-NCD context.

The study will be conducted in three phases across seven districts in diverse regions of India. In phase I (formative), the current status, barriers and facilitators of cancer screening, diagnosis and treatment initiation under NP-NCD will be assessed. In phase II (optimisation), a model (package of implementation strategies) will be co-developed and iteratively optimised with multistakeholder engagement at the subdistrict level to improve screening coverage and quality and strengthen the referral system for early diagnosis and treatment initiation. In phase III (scale-up and evaluation), the model will be implemented at the district level and evaluated for improvements in screening, early diagnosis and treatment initiation. A convergent mixed-methods design will be used, incorporating household surveys, facility assessments and stakeholder interviews. Implementation Research Logic Model will guide planning, execution and evaluation in the present study. Determinants of screening coverage and quality, early diagnosis and treatment initiation will be assessed using the Consolidated Framework for Implementation Research. Implementation strategies for the model will be finalised using the Expert Recommendations for Implementing Change framework. Implementation and service outcomes will be evaluated using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework.

Ethical approval has been obtained from all study sites. The study findings will be disseminated at the state, national and global levels through meetings and conferences and submitted to a peer-reviewed journal for publication.

CTRI/2025/08/092672.

Asthma, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent chronic respiratory diseases associated with increased comorbidity, mortality and healthcare costs. Physical activity and exercise are widely recommended as part of treatment for these conditions, yet the specific effects of Nordic walking (NW) remain underexplored. The aims of this randomised controlled trial (RCT) are to improve physical fitness, functional capacity and respiratory health and increase regular physical activity and quality of life of older adults with asthma and/or COPD and/or OSA through a supervised 3-month group-based NW intervention combined with resistance, balance and mobility training.

This single-blinded, parallel-group RCT will recruit 100 adults aged 55–80 years diagnosed with asthma and/or COPD and/or OSA in the Northern Savo region of Finland. Participants will be randomly allocated to either an intervention group or a control group.

The intervention group will participate in a 12-week supervised exercise programme consisting of progressive NW sessions twice per week and resistance, balance and mobility training once per week. The primary outcome is a change in cardiorespiratory endurance. Secondary outcomes include functional capacity, physical activity level, spirometry parameters and quality of life. The control group will continue their usual physical activity and receive physical activity guidance after 12 weeks. Measurements were conducted at baseline, three and 9 months. Data will be analysed according to the intention-to-treat principle. Group differences over time will be examined using appropriate parametric or non-parametric methods depending on data distribution.

Ethical approval was obtained from the Regional Medical Research Ethics Committee of Eastern Finland Collaborative Area (892/13.00/2023). Findings will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.

The trial is registered at ISRCTN12097135, registration date: 7 June 2024.

The incidence of depression among children and adolescents has been increasing in recent years, posing significant challenges to public health and clinical care. A variety of treatments, including pharmacotherapy, psychotherapy and physical interventions, are widely used in clinical practice. However, a comprehensive synthesis of the evidence on the efficacy and acceptability of all these treatment modalities is currently lacking. This study aims to use network meta-analysis (NMA) to compare the efficacy and acceptability of all available treatments for depression in children and adolescents, offering valuable insights to inform clinical decision-making and guide future research in this critical area.

We will include randomised controlled trials evaluating active interventions for depressive disorders in children and adolescents. Seven electronic databases (PubMed, Embase, the Cochrane Library, Web of Science, PsycINFO, Scopus and ClinicalTrials.gov) were searched from inception to 2 July 2024 and updated on 2 November 2025. Two of four investigators will independently screen studies, extract data from eligible articles and assess the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome will be the change in depressive symptoms. Secondary outcomes will include acceptability (all-cause discontinuation), response rate, remission rate and overall functioning. Pairwise and Bayesian NMA will be conducted. Small-study effects and publication bias will be assessed. The certainty of the evidence will be evaluated according to the Confidence in Network Meta-Analysis approach.

As this review involves secondary analysis of previously published studies, ethical approval is not required. The findings will be disseminated through publication in peer-reviewed journals.

PROSPERO-ID CRD42024557384.

In kidney transplantation, immunosuppressive therapy is essential to control alloimmune reactions, prevent graft rejection and improve patient survival rates. However, commonly used drugs like tacrolimus (TAC) and mycophenolate mofetil (MMF) have a narrow therapeutic window and exhibit significant inter- and intra-individual variability in pharmacokinetics (PK) and dose-response relationships. Recent pilot studies suggest that the gut microbiome may influence this variability.

ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiome modulations After kidney transplantation (ENIGMA) is a prospective, low-interventional, naturalistic longitudinal trial designed to identify biomarkers of TAC and MMF PK variability by examining gut microbiome changes and modulations after kidney transplantation and their link with TAC and MMF PK. Biological samples from 50 patients will be collected at nine specific timepoints pre- and post-transplantation using a rich PK and biological sampling strategy. This approach will enable the derivation of PK parameters for the investigated drugs and the creation of a biobank for future hypothesis testing.

The ENIGMA trial has received ethical approval from the European Medicines Agency (EMA). The reference number of our project is R&D/1325226 and is registered on the Clinical Trial Information System (CTIS) platform with European Union Clinical Trial number 2023–5 08 335-31-00. Results of the trial will be published in scientific journals and presented at different (inter)national conferences.

2023–5 08 335-31-00 EMA.

In individuals at-risk of rheumatoid arthritis (RA), to investigate how joint tenderness and patient-reported joint pain (PRJP) relate to ultrasound abnormalities and assess whether these exploratory results could be used to assist future evaluation of symptom/signs-guided ultrasound scanning approaches in this population.

This is a cross-sectional analysis from a Leeds (UK) cohort of anti-cyclic citrullinated peptide (anti-CCP) positive individuals with new musculoskeletal complaints and no clinical arthritis. Assessments included physical examination, a mannequin where participants ticked joints that were painful and ultrasound scans of wrists, metacarpo-phalangeal joints 1–5 (MCPs1-5), proximal interphalangeal joints 1–5 (PIPs1-5), elbows, knees, ankles, metatarso-phalangeal joints 1–5 (MTPs1-5), finger flexor tendons (2-5) and extensor carpi ulnaris. Grey scale (GS), power Doppler (PD), tenosynovitis and erosions were assessed. A generalised estimating equations model was used to evaluate potential associations between tenderness/PRJP and ultrasound findings at the joint-level, adjusting for age and sex. Positive and negative predictive values for ultrasound changes were calculated.

323 participants were analysed. Joint tenderness was associated with ultrasound abnormalities, predominantly PD in wrists, MCPs, PIPs, elbows, knees and MTPs. GS and erosions were also associated with tenderness, but to a lesser degree. Association of PRJP with ultrasound abnormalities was more inconsistent and mostly for GS in the feet (all p≤0.05). Absence of symptoms and signs had a negative predictive value between 97% and 100% in all joints, except in wrists; which was slightly lower.

In anti-CCP positive individuals at risk of RA, tenderness, predominantly in the small joints, was associated with local inflammatory changes on ultrasound. The association of PRJP and ultrasound was limited. In the absence of tenderness, the presence of PD, tenosynovitis or erosions was uncommon. These findings may inform future studies evaluating symptom/sign-guided ultrasound assessment approaches in at-risk populations.

NCT02012764.

To examine whether the use of a venous access-site closure device is associated with the occurrence of postoperative nausea and vomiting (PONV) after atrial fibrillation (AF) ablation under propofol sedation.

Observational study.

A single-centre retrospective observational study in Okayama, Japan.

We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303).

Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis.

The primary outcome was the occurrence of PONV following AF ablation.

All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference –14.7 hours, 95% CI –15.2 to –14.0).

PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of –3.2% (95% CI –6.0% to –0.5%).

In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV.

In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design.

The establishment of an effective strategy for recurrence prevention following curative treatment for hepatocellular carcinoma (HCC), including radiotherapy, remains a critical unmet clinical need. Despite favourable local control and safety profiles, recurrence after particle therapy remains a major challenge, highlighting the need for effective adjuvant strategies to improve long-term outcomes. The present phase Ib/II trial is designed to evaluate the safety and efficacy of atezolizumab plus bevacizumab (Atezo+Bev) administered after carbon-ion radiotherapy (C-ion RT) in patients with unresectable non-metastatic large HCC. This study aims to explore the potential of this multimodal approach as a novel adjuvant strategy to improve outcomes in patients at high risk of recurrence.

This is a phase Ib/II, single-arm clinical trial designed to evaluate the safety and efficacy of adjuvant Atezo+Bev following C-ion RT in patients with HCC. Eligible patients will be enrolled in the first registration phase. C-ion RT (60 Gy) will be administered over four consecutive treatment days ideally within one calendar week. Patients will receive a combination of atezolizumab (1200 mg) and bevacizumab (15 mg/kg) administered intravenously every 21 days for one treatment cycle. The primary endpoint of the phase Ib part is the proportion of patients with dose-limiting toxicity (DLT). DLT is defined as prespecified toxicities associated with the investigational drug among the adverse events that occurred from the start date of the investigational drug (Day 1) to Day 21. If there is one or fewer cases of DLT out of six cases, the trial will proceed to the phase II part. The primary endpoint of the phase II part is the 1-year recurrence-free survival rate.

This study was approved by the ethics committee of two participating institutions (Chiba University Hospital (approval No. 2024021) and National Institute for Quantum and Radiological Science and Technology, QST Hospital (approval No. C24-001)). Trial results will be reported in a peer-reviewed journal publication.

jRCT2031240284.

Maternal anaemia remains a pressing global health challenge, with a notable burden in low- and middle-income countries. Existing studies in sub-Saharan Africa have largely relied on average associations, thereby concealing key variation among women and failing to account for heterogeneity.

To assess the association between completing at least eight antenatal care (ANC) contacts and maternal anaemia in Ghana and to explore heterogeneity in this association using causal machine learning.

An institution-based cross-sectional study was conducted using a retrospective review of medical records and causal machine learning analysis.

Juaben Government Hospital.

Of 2326 women who delivered at the hospital, 2114 with complete data on the main exposure and outcome variables were included in the analysis.

Completion of at least eight ANC contacts. ANC contact was defined as the in-person visit to the clinic with a healthcare professional for routine ANC services and follow-up.

Maternal anaemia, defined as a haemoglobin level below 11 g/dL in the last ANC before delivery.

A causal forest model was used to estimate the association between completing at least eight ANC contacts and maternal anaemia. Conditional average treatment effects were used to explore individual-level variation in these associations, providing policy-relevant insights.

Completing ≥8 ANC contacts was associated with a 6 percentage-point lower probability of maternal anaemia compared with having fewer visits (average treatment effect: -0.06, 95% CI –0.11 to –0.02). Predicted individual-level effects ranged from –0.21 to 0.09. Participants’ age, malaria prophylaxis, marital status, parity and educational level were the five most important contributors to the observed heterogeneity.

This study demonstrated that completing ≥8 ANC contacts is associated with a lower probability of maternal anaemia, with heterogeneity across subgroups. We recommend differentiated, context-specific ANC interventions that focus on high-impact subgroups while strengthening the effectiveness and quality of care delivered at each visit.

To develop a simple screening scale to predict depression after discharge in patients with acute coronary syndrome after percutaneous coronary intervention (ACS-PCI) and to verify its reliability, validity and cutoff value.

Prospective longitudinal study was conducted 1 week and 3 months after discharge.

Two hospitals where PCI is performed in Japan.

A total of 183 patients were potential candidates for the survey, of whom 42 provided valid responses (response rate: 23.0%).

The number of items was reduced from 14 to 12 with item-total correlations and principal component analysis. Cronbach’s alpha coefficient was 0.832 and the intraclass correlation coefficient (1, 2) was 0.811 (95% CI 0.650 to 0.898). Significant correlations were observed for concurrent validity (r=0.699, p

This study developed a simple screening scale for predicting postdischarge depression in patients with ACS-PCI (SDACS-12) and demonstrated its reliability, validity and predictive ability with 12 items. Nevertheless, its results should be interpreted cautiously given the moderate variance explained by PCA and the low specificity and PPV.

While compassion is widely recognised as an essential component of high-quality patient care, the compassion needs of clinicians often go unrecognised and unmet. Clinicians face multifaceted sources of workplace suffering, both sources inherent to working with the sick and avoidable sources due to healthcare systems and leadership challenges. Organisational compassion, defined as the continuous and systematic identification, prevention and alleviation of sources of suffering for healthcare workers, offers a paradigm shift in mitigating and preventing clinician suffering and burnout. Yet little is known about how clinicians experience suffering and compassion from their organisations, teams and leaders.

Our overarching goal is to develop a clinician-reported experience measure of organisational compassion. The purpose of this study was to explore how clinicians experience suffering and compassion in healthcare organisations.

This qualitative study used semistructured interviews of interdisciplinary paediatric hospice and palliative care clinicians from across the USA. A moderator’s guide was developed based on the literature of organisational compassion in management and healthcare and validated through practice interviews with clinicians. 22 participants were recruited via national paediatric hospice and palliative care email list serves. Video interviews were conducted via Zoom. Transcripts were analysed using a hybrid grounded theory-thematic analysis methodology to identify themes and to construct a theoretical framework of compassion experiences.

Five major themes of experiencing compassion emerged: (1) Feeling cared about, characterised by authentic, empathetic responses to clinician distress; (2) Dignity, encompassing being valued, respected and recognised as a whole person and professional; (3) Proximal (team) compassion, including camaraderie, shared workload and mutual support within teams; (4) Structural (organisational) compassion, reflecting policies, practices and benefits that alleviate or exacerbate suffering and (5) Compassionate leadership behaviours, such as presence, empathy and connection to frontline staff needs.

Healthcare work includes sources of both inherent and avoidable suffering for clinicians. In this study, we sought to understand how clinicians experience compassion from their organisations, leaders and team members during times of distress. We found five themes of experiencing compassion in healthcare organisations: feeling cared about; dignity; proximal (team) compassion; structural (organisational) compassion and compassionate leadership behaviours. These qualitative data and results will provide an empiric foundation for the development of a clinician-reported experience measure of compassion for use in healthcare settings. Such a measure will enable future research examining how compassion experiences in healthcare may predict workforce outcomes such as burnout, satisfaction, engagement and thriving. Ultimately, this work may support the design of interventions aimed at strengthening compassionate organisational cultures and improving conditions for the healthcare workforce and both experiences and outcomes of the patients they serve.

Tanzania carries a dual burden of communicable and non-communicable diseases while remaining vulnerable to emerging pandemics of public health concern. Since its independence in 1961, Tanzania has implemented successive health reforms aimed at expanding access and moving towards universal health coverage (UHC). Despite notable progress, inequities in access, quality and financial protection persist. This review examined how policy evolution (1961–2025) addressed or reinforced inequities and the lessons for building resilience and equity in UHC.

We conducted a scoping review of national health policies, strategies, legislation and the related literature (1961–2025), following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Eligible sources included government reports, strategic plans, evaluation reports and peer-reviewed or grey literature. Data were analysed using the Walt and Gilson Policy Triangle and mapped against the WHO Health Systems Building Blocks.

Out of 10 435 records identified, 60 documents met the inclusion criteria. Policy evolution reflected five broad reform episodes, ranging from postindependence centralisation to primary healthcare, structural adjustment and cost-sharing, sector-wide reforms and recent UHC-focused financing strategies. Reforms shifted from politically driven, top-down policies to participatory and evidence-informed approaches. Mapping showed progressive but uneven gains across service delivery, workforce, financing, governance, medicines and information systems. Six thematic shifts towards UHC were identified: fragmented to pooled financing, routine delivery to resilient systems, paper to digital systems, workforce numbers to distribution and skills-mix, state-only to mixed providers and expansion to effective coverage.

Tanzania’s reform trajectory illustrates adaptive progress, but persistent inequities in financing, workforce distribution and service access remain. Achieving equitable and resilient UHC will require stronger domestic financing, governance and primary care, with transferable lessons for other low- and middle-income countries.

The Healthy Lifestyle Index (HLI) integrates key behaviours to assess their cumulative impact on health. While higher HLI adherence is linked to lower disease and mortality risk, its long-term trajectory association remains understudied. This study aims to examine the dose-response relationship and long-term association of HLI on mortality risks.

Systematic review and dose-response meta-analysis using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach.

PubMed, Scopus and Web of Science were searched until June 2024.

We included observational cohort studies that assessed the relationship of HLI or its trajectories with all-cause, cardiovascular disease (CVD)-cause or cancer-cause of mortality.

Analysis of 13.7 million participants demonstrated that higher adherence to the HLI is linked to lower risk of all-cause (HR: 0.48; 95% CI 0.46 to 0.53; GRADE: moderate), CVD-cause (HR: 0.49; 95% CI 0.44 to 0.51; GRADE: moderate) and cancer-cause mortality (HR: 0.55; 95% CI 0.49 to 0.61; GRADE: low). These associations were further confirmed in a dose-response manner. Moreover, compared with maintaining an unhealthy lifestyle, a decline in HLI adherence was associated with a 14% higher risk of all-cause and a 19% higher risk of cancer-related mortality. In contrast, an improvement in HLI adherence was linked to a 20% lower risk of all-cause and a 13% lower risk of cancer-related mortality.

Adherence to HLI and its long-term patterns are associated with lower mortality risk. These findings emphasise the importance of lifestyle-based prevention and intervention strategies in reducing mortality.

CRD42024500538.

To update the rurality index for Japan (RIJ) using the most recent national data and to test and evaluate the updated RIJ variants that incorporate alternative distance metrics and a modified classification of remote islands, thereby providing methodological guidance for their use in research and health policy.

Nationwide methodological study.

Japan.

All postal code areas in Japan; analyses were aggregated into municipalities and secondary medical care areas for evaluation.

Six RIJ variants (‘RIJ family’) constructed by combining three distance metrics (direct distance, road-based distance and travel time by car) and two island classifications (original RIJ and modified RIJ), standardised to a continuous 0–100 scale using percentile ranks.

Concordance among RIJ variants was assessed using Spearman’s rank correlation coefficients, quintile reclassification matrices and rank-difference analyses; convergent validity was evaluated using the national physician distribution index. Criterion-related validity was assessed using municipal-level life expectancy for men and women.

All RIJ variants had extremely high concordance (Spearman’s ≥0.99 across all pairwise comparisons). Compared with the previous RIJ classification, >98% of the geographic units remained in the same rurality quintile and

Despite differences in distance metrics and island classification, all RIJ variants captured highly similar underlying dimensions of rurality and demonstrated comparable validity. These findings indicate that rurality measurement in Japan is stable regardless of methodological refinements, allowing RIJ variants to be flexibly selected according to specific research or policy purposes without materially affecting conclusions.