The ‘time-limited trial’ for patients with critical illness is a collaborative plan made by clinicians, patients and families to use life-sustaining therapies for a defined duration. After this period, the patient’s response to therapy informs decisions about continuing recovery-focused care or transitioning to comfort-focused care. The promise of time-limited trials to help navigate the uncertain limits and benefits of life-sustaining therapies has been extensively discussed in the palliative and critical care literature, leading to their dissemination into clinical practice. However, we have little evidence to guide clinicians in how to conduct time-limited trials, leading to substantial variation in how and why they are currently used. The overall purpose of this study is to characterise the features of an optimal time-limited trial through a rich understanding of how they are currently shaping critical care delivery.

We are conducting an observational, multicentre, focused ethnography of time-limited trials in patients with acute respiratory failure receiving invasive mechanical ventilation in six intensive care units (ICUs) within five hospitals across the US. Study participants include patients, their surrogate decision makers and ICU clinicians. We are pursuing two complementary analyses of this rich data set using the open-ended, inductive approach of constructivist grounded theory and, in parallel, the structured, deductive methods of systems engineering. This cross-disciplinary, tailored approach intentionally preserves the tension between time-limited trials’ conceptual formulation and their heterogeneous, real-world use.

This study has been reviewed and approved by the University of Wisconsin Institutional Review Board (IRB) as the single IRB (ID: 2022-1681; initial approval date 23 January 2023). Our findings will be disseminated through peer-reviewed publication, conference presentations, and summaries for the public.

NCT06042621.

Inside CKD aims to assess the burden of chronic kidney disease (CKD) and the cost-effectiveness of screening programmes in Belgium.

Microsimulation-based modelling.

Data derived from national statistics and key literature from Belgium.

Virtual populations of ≥10 million individuals, representative of Belgian populations of interest, were generated based on published data and cycled through the Inside CKD model. Baseline input data included age, estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR) and CKD status.

Outcomes included the clinical and economic burden of CKD during 2022–2027 and the cost-effectiveness of two different CKD screening programmes (one UACR measurement and two eGFR measurements or only two eGFR measurements, followed by renin-angiotensin-aldosterone system inhibitor treatment in newly diagnosed eligible patients). The economic burden estimation included patients diagnosed with CKD stages 3–5; the screening cost-effectiveness estimation included patients aged ≥45 years with no CKD diagnosis and high-risk subgroups (with cardiovascular disease, hypertension, type 2 diabetes or aged ≥65 years).

Between 2022 and 2027, CKD prevalence is estimated to remain stable and substantial at approximately 1.66 million, with 69.9% undiagnosed. The total healthcare cost of patients diagnosed with CKD is expected to remain stable at approximately 2.15 billion per year. The one UACR, two eGFR measurement screening programme was cost-effective in all populations, with an incremental cost-effectiveness ratio of 3623 per quality-adjusted life year (QALY) gained in those aged ≥45 years, well below the estimated willingness-to-pay threshold of 43 839 per QALY gained.

Without changes to current practice, the disease burden of CKD in Belgium is predicted to remain substantial over the next few years. This highlights the need for timely diagnosis of CKD and demonstrates that, in line with guideline recommendations, implementing a CKD screening programme involving UACR and eGFR measurements followed by treatment would be cost-effective.

To identify the barriers and facilitators towards deceased organ donation among Pakistanis living globally.

Systematic review using narrative synthesis.

CINAHL, Medline with Full Text, Global Health and PsycINFO via EBSCO; Scopus via Elsevier; Web of Science via Clarivate; and PubMed through the US National Library of Medicine and the National Institutes of Health were searched between 1 January 1995 and 31 July 2024 and limited to English.

We included qualitative and cross-sectional studies involving Pakistani participants aged 18 years and above, conducted both within Pakistan and internationally across settings such as universities, religious venues, hospitals and workplaces.

Four independent reviewers were involved in screening, quality assessment and data extraction. A narrative synthesis method was employed to synthesise and integrate the data from qualitative and cross-sectional studies. The Joanna Briggs Institute tool was used to assess the quality of the included studies.

Out of 11 944 studies retrieved, 26 studies were included in the current review. Based on the narrative synthesis, the findings are presented under the following five themes: (1) knowledge of deceased organ donation, (2) willingness towards deceased organ donation, (3) collective decision-making overriding individual’s preferences, (4) religious uncertainty and its impact on deceased organ donation and (5) trust and the healthcare systems.

This review shows that decisions about deceased organ donation are shaped by family dynamics, religious beliefs and trust in healthcare. More diverse research is needed to uncover new gaps and improve donor registration and consent rates in Pakistan. A whole-systems approach, considering families, religion and trust, is essential for effective strategies.

CRD42022346343.

An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.

No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.

CRD42025644244.

This study aimed to identify and validate risk factors for suicidal ideation (SI) and non-suicidal self-injury (NSSI) among nursing staff through the development and application of a risk model and nomogram.

A cross-sectional online survey was conducted in Dehong District to collect relevant data.

A total of 1774 Chinese nursing staff members were enrolled in this study.

Multiple factors were independently associated with SI among nursing staff. These included divorce or other non-marital status (OR=2.42, 95% CI 1.07 to 5.44), drinking frequency (OR=1.34, 95% CI 1.001 to 1.79), loneliness (OR=1.26, 95% CI 1.11 to 1.44), depressive symptoms (OR=1.13, 95% CI 1.09 to 1.18), childhood trauma (OR=1.03, 95% CI 1.02 to 1.05) and life quality satisfaction (OR=0.63, 95% CI 0.49 to 0.80). Similarly, for NSSI among nursing staff, independent risk factors were identified, such as smoking frequency (OR=1.37, 95% CI 1.01 to 1.85), drinking frequency (OR=1.42, 95% CI 1.05 to 1.91), loneliness (OR=1.21, 95% CI 1.05 to 1.39), depressive symptoms (OR=1.13, 95% CI 1.09 to 1.18) and childhood trauma (OR=1.03, 95% CI 1.01 to 1.05). A nomogram for assessing SI/NSSI was established and demonstrated good calibration, with a Concordance Index of 0.82 (95% CI 0.79 to 0.86) for SI and 0.81 (95% CI 0.78 to 0.85) for NSSI.

The findings of this study can be used to identify nursing staff at risk of developing SI/NSSI. By using the developed nomograms for self-assessment, individuals might gain a better understanding of their occupational stress levels while performing routine work tasks. However, it should be noted that the study lacks external validation, which limits the generalisability of the findings at this stage.

Countries face challenges in maternal and newborn care (MNC) regarding costs, workforce and sustainability. Organising integrated care is increasingly seen as a way to address these challenges. The evidence on the optimal organisation of integrated MNC in order to improve outcomes is limited.

(1) To study associations between organisational elements of integrated care and maternal and neonatal health outcomes, experiences of women and professionals, healthcare costs and care processes and (2) to examine how the different dimensions of integrated care, as defined by the Rainbow Model of Integrated Care, are reflected in the literature addressing these organisational elements.

We included 288 papers and identified 23 organisational elements, grouped into 6 categories: personal continuity of care; interventions to improve interdisciplinary collaboration and coordination; care by a midwife; alternative payment models (non-fee-for-service); place of birth outside the obstetric unit and woman-centred care. Personal continuity, care by a midwife and births outside obstetric units were most consistently associated with improved maternal and newborn outcomes, positive experiences for women and professionals and potential cost savings, particularly where well-coordinated multidisciplinary care was established. Positive professional experiences of collaboration depended on clear roles, mutual trust and respectful interdisciplinary behaviour. Evidence on collaboration interventions and alternative payment models was inconclusive. Most studies emphasised clinical and professional aspects rather than organisational integration, with implementation barriers linked to prevailing biomedical system orientations.

Although the literature provides substantial evidence of organisational elements that contribute to improved outcomes, a significant gap remains in understanding how to overcome the barriers in sustainable implementation of these elements within healthcare systems. Interpreted through a systems and transition science lens, these findings suggest that strengthening integrated maternity care requires system-level changes aligning with WHO policy directions towards midwifery models of person-centred care.

Many patients receive oral anticoagulation for reduced stroke risk in atrial fibrillation or as treatment or prevention of venous thromboembolism. Oral factor Xa inhibitors (oral FXaI, eg, apixaban, edoxaban or rivaroxaban) are commonly prescribed for this indication. Dabigatran, an oral direct thrombin inhibitor, is similarly approved. In vitro and animal model evidence suggests that dabigatran also has direct effects on Staphylococcus aureus virulence and infection. Observational data have shown that dabigatran users are less likely to develop S. aureus bacteremia (SAB), and a small randomised controlled trial showed that dabigatran has anti-S. aureus effects when compared with low molecular weight heparins during bloodstream infection. We seek to answer whether dabigatran is superior to the oral FXaIs in achieving better SAB outcomes among patients who independently require oral anticoagulation. We report the intervention-specific protocol, embedded in an adaptive platform trial.

The S. aureus Network Adaptive Platform (SNAP) trial [NCT05137119] is a pragmatic, randomised, multicentre adaptive platform trial that compares different SAB therapies for 90-day mortality rates. For this intervention (‘Dabi-SNAP’), patients receiving therapy with an oral FXaI will be randomised to continue as usual or to change to dabigatran as of the next scheduled dose. All subjects will receive standard of care antibiotics and/or antibiotics allocated through other active domains in the platform. As the choice of anticoagulant may not demonstrate large differences in mortality, a ranked composite of death and adverse outcomes (Desirability of Outcome Ranking, or DOOR) was chosen as the primary outcome.

The study is conditionally approved by the research ethics board of the McGill University Health Centre: identifier 2025-10900. Trial results will be published open access in a peer-reviewed journal and presented at a global infectious disease conference. The trial is registered at clinicaltrials.gov with the identifier NCT06650501.

NCT0665050.

To assess how preoperative anaemia affects surgical outcomes in elderly patients within a resource-limited setting.

Prospective cohort study.

Two comprehensive specialised hospitals in Ethiopia.

Participants consisted of 224 patients aged 65 years and older who underwent surgery between 1 December 2024 and 29 March 2025.

Perioperative blood transfusions were the primary outcome. Secondary outcomes included intensive care unit (ICU) admission, risk of postoperative complications, prolonged hospitalisation, poor recovery quality and in-hospital mortality.

The anaemic group required transfusions of three or more units more frequently than the non-anaemic group (10.5% vs 2.6%; absolute risk difference 8.0%). Their perioperative transfusion rates were significantly higher (42.3% vs 18.4%; p

Preoperative anaemia significantly increases the risk of transfusion, poor recovery, ICU admission, prolonged hospitalisation and in-hospital mortality in older patients who underwent surgery. In resource-limited settings, improving perioperative outcomes should prioritise the early detection and treatment of anaemia.

Persistent somatic symptoms and functional disorders are conditions requiring a biopsychosocial approach to care, often from multiple professionals. The fragmentation of care common in most health systems results in unsatisfactory and challenging care experiences. Collaborative care networks form an important route towards improving outcomes and the overall experience of care for patients and professionals. While we have a good idea of what such collaborative care networks can look like, we lack knowledge on the practicalities of implementing change in such networks.

The core objective of this study is to implement change in a collaborative care network for persistent somatic symptoms and functional disorders care. Our questions were twofold: first, what are examples of realistic action processes to improve such collaborative care networks? Second, what are, in our experience, conditions for an effective change process in such a collaborative care network?

Participatory action research approach embedded within an active regional network between May 2023 and May 2024. The process was led by an action group who selected objectives and related actions with the aim of improving the network, leading to better care for people with persistent somatic symptoms and functional disorders as well as improving satisfaction among professionals.

ALK Netwerk Salland, a regional network of professionals and experts-by-experience, focused on care of persistent somatic symptoms. This network is based in the Salland region in the east of the Netherlands, centred around the city of Deventer.

The action group was made up of local stakeholders including experts-by-experience and health and social care professionals, facilitated by a researcher-in-residence. Other participants included members of the regional network who provided input towards the different objectives.

Over the course of a year, three objectives were selected and enacted, including assessing the resources of the network, improving knowledge of treatment options and improving the shared vision of care. The process faced some challenges, such as changes in action group members and a lack of resources and time to enact changes. However, by having a trusted and engaged team, working with an active network, we were able to enact significant changes to the network, which may be sustained and built on through the ongoing action group.

Future participatory action research studies would benefit from a trusted and embedded researcher-in-residence, meaningful involvement early in the process of experts-by-experience, and serious consideration of realistic outcome measures to monitor for evaluation of changes made.

Post-COVID syndrome manifests with a diverse array of symptoms for which no standard care plan currently exists. Many questions were raised by patients, which underscored the need for a validated patient-reported outcome measure (PROM). Therefore, a post-COVID module was developed to be included in the Assessment of Burden of Chronic Conditions (ABCC-) tool. The ABCC-tool evaluates and visualises the perceived physical, emotional and social burden of one or multiple chronic disease(s) using a balloon diagram and aims to facilitate person-centred care and structured discussions between patients and healthcare professionals. This study explores the patients’ perspective on the content of the ABCC-tool for post-COVID and the tool’s usability in a home-based setting.

All patients who completed the ABCC-tool for post-COVID were invited for an online semi-structured interview. We selected post-COVID patients who had used the tool in the past three months. Interviews were audio recorded and analysed using a thematic approach with Atlas.ti version 23.

Nineteen post-COVID patients (10 males, mean age 56) were interviewed between May and August 2024. The tool was regarded as user-friendly, and patients indicated they would use the tool again in the future. Patients valued the tool’s broad range of topics, some of which are often overlooked in standard healthcare consultations. The tool was comprehensible and relevant according to all patients. The balloon diagram was easy to understand, but a legend explaining the colours of the balloons was preferred. Other suggestions for improvement included adding open-text fields and periodic reminders to increase usability and adding long-term data.

The ABCC-tool is a promising instrument for post-COVID patients, offering a structured way to monitor and communicate experienced burden in addition to standard healthcare consultations. Refinements addressing usability and comprehensiveness are recommended to facilitate its integration into clinical practices.

Asthma is a chronic respiratory disorder requiring ongoing medical management. This ecological study investigated the spatial and temporal patterns of notification rates for asthma from clinic visits and hospital discharges and identified demographic, meteorological and environmental factors that drive asthma in Bhutan.

Monthly numbers of asthma notifications from 2016 to 2022 were obtained from the Bhutan Ministry of Health. Climatic variables (rainfall, relative humidity, minimum and maximum temperature) were obtained from the National Centre for Hydrology and Meteorology, Bhutan. The Normalised Difference Vegetation Index (NDVI) and surface particulate matter (PM2.5) were extracted from open sources. A multivariable zero-inflated Poisson regression (ZIP) model was developed in a Bayesian framework to quantify the relationship between risk of asthma and sociodemographic and environmental correlates, while also identifying the underlying spatial structure of the data.

There were 12 696 asthma notifications, with an annual average prevalence of 244/100 000 population between 2016 and 2022. In ZIP analysis, asthma notifications were 3.4 times (relative risk (RR)=3.39; 95% credible interval (CrI) 3.047 to 3.773) more likely in individuals aged >14 years than those aged ≤14 years, and 43% (RR=1.43; 95% CrI 36.5% to 49.2%) more likely for females than males. Asthma notification increased by 0.8% (RR=1.008, 95% CrI 0.2% to 1.5%) for every 10 cm increase in rainfall, and 1.7% (RR=1.017; 95% CrI 1.2% to 2.3%) for a 1°C increase in maximum temperature. An increase in one unit of NDVI and 10 µg/m³ PM2.5 was associated with 27.3% (RR=1.273; 95% CrI 8.7% to 49.2%), and 2.0% (RR=1.02; 95% CrI 1.0% to 4.0%) increase in asthma notification, respectively. The high-risk spatial clusters were identified in the south and southeastern regions of Bhutan, after accounting for covariates.

Environmental risk factors and spatial clusters of asthma notifications were identified. Identification of spatial clusters and environmental risk factors can help develop targeted interventions that maximise impact of limited public health resources for controlling asthma in Bhutan.

China has continued to improve tuberculosis (TB) control in the past decade; however, the sudden outbreak of COVID-19 hindered this progress. As a province with a large population and frequent international exchanges, Guangdong has been seriously affected by COVID-19. This study aimed to understand the effect of COVID-19 on TB detection in Guangdong based on the autoregressive integrated moving average (ARIMA) model.

Time-series study.

Guangdong, China.

We used the ARIMA model to quantify the effect of COVID-19 by comparing reported cases during the COVID-19 pandemic with predicted cases under a counterfactual scenario of no COVID-19 pandemic. After model evaluation, we chose ARIMA (0,1,2)(0,1,1)₁₂ as the prediction model. We also highlighted that there were three emergency response periods in which the responses and public responses to COVID-19 varied.

During the pandemic period, the average annual TB notification rate was 57.95/100 000, which decreased by 27.97% compared with the pre-pandemic period. Although it decreased by 6.17% on average annually in the pre-pandemic period, it decreased by 14.92% in 2020 as compared with 2019, but only decreased by 0.34% in 2021 as compared with 2020. The results of the ARIMA model showed that the number of reported cases in 2020 decreased by 6.62% compared with that of the predicted cases, but this decreased by 0.42% only in 2021. The most seriously affected period was the second-level emergency response period in 2020, when the relative difference between reported and predicted cases reached the peak (–16.43%). The least affected period was the third-level emergency response period of 2021, the reported cases recovered and exceeded the predicted cases, with a gap of 0.77%.

TB detection in Guangdong had generally declined during the COVID-19 pandemic, which might be related to the movement restrictions, diverted resources and patients’ concerns. This decline would lead to the delay or even interruption of diagnosis and treatment, which would cause the regression of TB control. To improve TB detection, it is important for stakeholders to take consorted effort during public health emergencies.

The study aimed to assess the prevalence of financial catastrophe and explore patients’ perceived effectiveness of the government support programme related to chronic kidney disease.

Cross-sectional mixed-method study.

A total of 120 patients receiving free regular haemodialysis under the government’s Deprived Citizen Support Programme for at least 6 months were included in the quantitative study, and 9 patients participated in the qualitative study.

Prevalence of financial catastrophe and factors associated with financial catastrophe among chronic kidney disease patients undergoing haemodialysis.

A convergent parallel mixed-method approach was carried out from 15 June to 15 December 2024, among chronic kidney disease patients undergoing haemodialysis at the National Kidney Center. Quantitative data were collected through face-to-face interviews using a semi-structured questionnaire. Financial catastrophe was defined as out-of-pocket (OOP) healthcare payments ≥40% of a household’s disposable income, following the WHO-recommended threshold for severe financial burden. OOP expenditures were assessed over 6 months, and associations were tested using ² and binary logistic regression at a 95% CI in SPSS V.25.0. For the qualitative arm, in-depth interviews were conducted with nine purposively selected patients, and inductive thematic analysis was applied to explore the perceived effectiveness of the government support programme. The quantitative and qualitative findings were then integrated to achieve convergence and divergence, allowing for a comprehensive understanding of the extent and context of financial hardship among patients.

The prevalence of financial catastrophe was 72.5%. The factors associated with financial catastrophe were the presence of complications (adjusted OR (AOR): 3.67, 95% CI 1.019 to 13.27), patients without financial support (AOR: 2.77, 95% CI 1.016 to 7.56) and reduction in food expenses (AOR: 0.313, 95% CI 0.109 to 0.896). Qualitative findings on awareness regarding government subsidies, financial strain, barriers to receiving treatment and perceived effectiveness of the programme revealed key aspects of utilisation and effectiveness of the government support programme.

The prevalence of financial catastrophe was substantially high, which highlights the importance of addressing economic challenges in chronic kidney disease care. The study emphasised the need to strengthen financial protection through the expansion of government subsidies and improved insurance coverage.

The Communication and Symbolic Behaviour Scales Developmental Profile Infant–Toddler Checklist (CSBS DP ITC) is a screening tool designed to identify early deficits in social communication, expressive speech/language and symbolic functioning in children aged 6–24 months. This study aimed to translate and content validate the CSBS DP ITC into Modern Standard Arabic.

Methodological study involving translation and content validation.

The study was conducted in the United Arab Emirates.

The translation process involved five bilingual translators and one monolingual Arabic language expert. Ten experts participated in the content validation phase, and 10 parents of young children participated in the face validity assessment.

Content Validity Indices (CVIs), including the Item-level CVI (I-CVI), the Scale-level CVI by Average (S-CVI/Ave) and the S-CVI by Universal Agreement (S-CVI/UA), along with modified kappa statistics, were calculated to assess item-level and scale-level clarity, relevance and comprehensiveness.

Expert panel ratings showed high clarity (I-CVI: 0.8–1, S-CVI/Ave: 0.98, S-CVI/UA: 0.88) and similar relevance scores. Face validity assessments yielded clarity I-CVI scores of 0.9–1, with S-CVI/Ave at 0.98 and S-CVI/UA at 0.8. The modified kappa statistic ranged from 0.89 to 1, indicating strong agreement among parents.

The CSBS DP ITC was effectively translated and content validated into Modern Standard Arabic. The calculated CVI values ranged from excellent to acceptable. This step establishes a foundation before proceeding to full psychometric testing of the instrument, paving the way for a reliable and culturally appropriate tool to identify early communication delays for use across the Arab-speaking population.

This systematic review and meta-analysis aims to provide an overview of the effectiveness of digital physiotherapy interventions on pain, physical functions and quality of life for patients with knee osteoarthritis.

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

A systematic search of electronic databases, including MEDLINE, EMBASE, Web of Science, PsycInfo, CINAHL, Scopus and Cochrane Library, was conducted on 19 February 2025.

We included randomised controlled trials which compared digital physiotherapy interventions to standard physiotherapy care for patients with knee osteoarthritis. Main outcomes included pain, physical functions and quality of life.

25 studies met the inclusion criteria, and 18 studies were eligible for meta-analysis. The primary author conducted the initial search, selected articles and extracted data from eligible studies, which were independently checked by a second reviewer. Risk of bias (ROB) was assessed by Cochrane ROB-2 tool. Quality of evidence was evaluated by the GRADE approach.

Overall, digital physiotherapy was associated with a small but statistically significant improvement in physical function (SMD=0.24, 95% CI 0.13 to 0.35); an overall meta-analysis was not performed for pain and quality of life due to considerable heterogeneity. Subgroup analyses revealed both video-conferencing and app- or web-based physiotherapy significantly reduced pain (SMD=–0.53, 95% CI –1.06 to –0.01 and SMD=–0.47, 95% CI –0.70 to –0.25, respectively) and physical function (SMD=0.32, 95% CI 0.10 to 0.54 and SMD=0.30, 95% CI 0.09 to 0.50 respectively). Digital physiotherapy interventions with individualised exercise components also reduced pain (SMD=–0.43, 95% CI –0.66 to –0.21) and improved physical function (SMD=0.30, 95% CI 0.17 to 0.43), when compared with non-exercise interventions.

There was moderate-quality evidence to support the use of digital physiotherapy interventions in improving pain and function in patients with knee osteoarthritis. Subgroup analyses revealed low-to-moderate quality evidence in using video-conferencing and app-/web-based physiotherapy and interventions with exercise components to treat patients with knee osteoarthritis. Overall, there were limited high-quality trials in drawing a robust conclusion. High ROB and huge heterogeneity were observed across studies. Further research should minimise the ROB and investigate the effect of different digital modalities, intervention components and length of follow-up.

Approximately 53 million family caregivers (FCGs) support and provide home-based care for patients with chronic and life-limiting conditions. Caregiving at the end of life is an emotionally, cognitively and physically demanding role, and FCGs are often unpaid and receive little training. FCGs in remote, rural areas experience adverse social determinants of health (SDOHs), such as limited access to healthcare services and are often financially vulnerable, affecting their healthcare coverage, placing them at higher risk for poor emotional health. Adequate health literacy, a key SDOH, may be a protective factor. The purpose is to present the protocol of an explanatory sequential mixed-method study aiming to examine rural-dwelling FCGs’ emotional health, relationships among FCG characteristics (demographics, co-morbidities) and SDOH and health literacy as a potential mediator.

With 80% power to detect a mediation effect of at least 0.11 when the two-sided alpha is 0.05, an anticipated 108 adult rural FCGs who are providing palliative end-of-life care (PEOLC) will be recruited. Rigorous remote, digital- and community-based recruitment strategies will be employed to increase access to FCGs from under-represented rural communities. Self-report surveys include demographic and health characteristics, SDOH (health literacy, education level, employment status, annual income level, healthcare access and insurance) and anxiety/depressive symptoms. Descriptive statistics will be used to characterise the sample. Correlation analysis and one-way Analysis of variance (ANOVA) will be used to study the relationships between FCG characteristics, SDOH and anxiety/depressive symptoms. Hayes’ PROCESS Macro for IBM SPSS Statistics will be used to test mediation effects of health literacy between FCG characteristics/SDOH and anxiety/depressive symptoms. Indirect effects will be tested using bootstrapped CIs. Semistructured interviews will be conducted with a representative sample to elicit FCG perceptions relative to how SDOH affect their care provision and emotional health, then analysed using content analysis. Quantitative and qualitative strands will be examined and compared for convergence and divergence, then integrated for final interpretations.

Michigan State University’s Institutional Review Board has reviewed and approved the study. Written informed consent will be obtained from each participant. Study findings will be disseminated through publications in peer-reviewed journals and presentations at academic conferences.

Study outcomes will inform the role of SDOHs, particularly health literacy, for the development of interventions to emotionally support rural FCGs.

Achieving physical activity recommendations for health as part of mental healthcare for adults with severe mental illness (SMI) could enhance clinical, functional and quality of life outcomes. We have co-designed a protocol to evaluate the impact of an intervention which combines High Intensity Interval Training (HIIT) and Vigorous Intermittent Lifestyle Physical Activity (VILPA) on clinical, functional and quality of life outcomes in people who have SMI.

Pragmatic clinical trial with an intervention and control arms. Participants will be recruited from two mental health services in two different cities in the same geographical area. Participants who meet the inclusion criteria (>18 years, SMI diagnosis, not at medical risk to practise vigorous physical activity, living in the community) will be included. Those from one service will be assigned to the intervention group and those from the other to the control group. The intervention will take place in the mental healthcare centre and will comprise 16 weeks of group-based HIIT, with transition to an individual lifestyle intervention VILPA over the next 12 weeks—for a total intervention period of 28 weeks. Primary outcome (clinical and functional and quality of life) measures and secondary (self-perception and device-measured fitness, physical activity and sedentary behaviour, and experience) measures will be assessed at baseline and at 16-week, 28-week and 40-week follow-ups. Group differences in change scores will be assessed using linear mixed-effects models with time, group and their interaction as fixed effects, accounting for within-subject correlations.

The study was approved by the Human Ethics Committee of the Institute for Research and Innovation in Life and Health Sciences in Central Catalonia (Spain, CEIm code: 24/007). Data will be shared following publication of results with no end date. Results will be disseminated in peer-reviewed journals and at national and international conferences and will inform the development of recovery protocols for people with SMI.

ClinicalTrials.gov NCT06338917.

To assess the feasibility of conducting a cluster randomised controlled trial comparing the effects of Advanced Trauma Life Support (ATLS) and Primary Trauma Care (PTC) with standard care on patient outcomes.

This was a pilot pragmatic three-armed parallel, cluster randomised, controlled trial conducted between April 2022 and February 2023. Patients were followed up for 30 days.

Tertiary care hospitals across metropolitan areas in India.

Adult trauma patients and residents managing these patients were included.

ATLS or PTC training was provided for residents in the intervention arms.

The outcomes were the consent rate, loss to follow-up rate, missing data rates, differences in the distribution between observed data and data extracted from medical records, and the resident pass rate.

Two hospitals were randomised to the ATLS arm, two to the PTC arm and three to the standard care arm. We included 376 patients and 22 residents. The percentage of patients who consented to follow-up was 77% and the percentage of residents who consented to receive training was 100%. The loss to follow-up rate was 14%. The pass rate was 100%. Overall, the amount of missing data for key variables was low. The data collected through observations were similar to data extracted from medical records, but there were more missing values in the extracted data.

Conducting a full-scale cluster randomised controlled trial comparing the effects of ATLS, PTC and standard care on patient outcomes appears feasible, especially if such a trial would use data and outcomes available in medical records.

NCT05417243.

Delays in cancer diagnosis for patients with non-specific symptoms (NSSs) lead to poorer outcomes. Rapid Diagnostic Clinics (RDCs) expedite care, but most NSS patients do not have cancer, highlighting the need for better risk stratification. This study aimed to develop biomarker-based clinical prediction scores to differentiate high-risk and low-risk NSS patients, enabling more targeted diagnostics.

Retrospective and prospective cohort study.

Secondary care RDC in London.

Adult patients attending an RDC between December 2016 and September 2023 were included. External validation used data from another RDC.

The primary outcome was a cancer diagnosis. Biomarker-based risk scores were developed using Latent Class Analysis (LCA) and Least Absolute Shrinkage and Selection Operator (LASSO). Model performance was assessed using logistic regression, receiver operating characteristic curves (AUROC) and decision curve analysis.

Among 5821 RDC patients, LCA identified high white cell count, low haemoglobin, low albumin, high serum lambda light chain, high neutrophil-to-lymphocyte ratio, high serum kappa light chain (SKLC), high erythrocyte sedimentation rate (ESR), high C-reactive protein (CRP) and high neutrophils as cancer risk markers. LASSO selected high platelets, ESR, CRP, SKLC, alkaline phosphatase and lactate dehydrogenase. Each one-point increase in score predicted higher odds of cancer (LCA: AOR 1.19, 95% CI 1.16 to 1.23; LASSO: AOR 1.29, 95% CI 1.25 to 1.34). Scores ≥2 predicted significantly higher cancer odds (LCA: AOR 3.79, 95% CI 2.91 to 4.95; LASSO: AOR 3.44, 95% CI 2.66 to 4.44). Discrimination was good (AUROC: LCA 0.74; LASSO 0.73). External validation in 573 patients confirmed predicted increases in cancer risk per one-point LASSO score rise (AOR 1.28, 95% CI 1.15 to 1.42), with a borderline increase for LCA (AOR 1.16, 95% CI 1.06 to 1.27).

Biomarker-based scores effectively identified NSS patients at higher cancer risk. LCA captured a broader biomarker range, offering higher sensitivity, while LASSO achieved higher specificity with fewer markers. These scores may also help detect severe benign conditions, improving RDC triage. Further validation is needed before broader clinical implementation.

To identify enablers and barriers for scaling up non-communicable disease (NCD) interventions across diverse global contexts and to map these factors to the WHO’s health system building blocks.

A multi-method qualitative study applying the Consolidated Framework for Implementation Research to analyse data from multiple projects nearing or completing scale-up.

Global Alliance for Chronic Diseases-funded implementation research projects conducted across 18 low- and middle-income countries and high-income settings.

Data was derived from documents (n=77) including peer-reviewed publications, policy briefs, and reports and interviews with stakeholders (n=18) (eg, principal investigators, medical professionals, public health workers).

Various context-specific interventions targeting sustainable scale-up of NCD (eg, diabetes, hypertension, cardiovascular disease) interventions at the community, primary care or policy levels.

The primary outcome was identifying contextual enablers and barriers to intervention scale-up. Secondary outcomes included exploring how these factors aligned with health system building blocks (eg, leadership/governance, healthcare workforce).

Twenty enablers (eg, intervention adaptability, strong stakeholder engagement, local empowerment) and 25 barriers (eg, resource limitations, intervention complexity, stakeholder burnout) were identified. Contextual alignment, supportive governance and capacity building were critical for sustainability, while cultural misalignment and socio-political instability frequently hampered scaling efforts.

Tailoring interventions to local health systems, ensuring stakeholder co-ownership and incorporating strategies to mitigate stakeholder burn-out are essential to achieving sustainable, scalable NCD solutions. Future research should focus on integrating systematic cultural adaptation, sustainable financing and workforce capacity building into scale-up planning.