Cycling can be beneficial for health, well-being and the environment; however, cycling participation in the UK remains low. Effective and cost-effective strategies are needed to support people in the community to increase cycling. The Cycle Nation Communities randomised controlled trial (RCT) will evaluate whether a 9 week multi-component cycling programme (Cycle Nation) is more effective and cost-effective than an existing national cycle training session on cycling participation, transport use and health and well-being.

This pragmatic, single-blinded, two-arm RCT will recruit ≥268 adults who cycle infrequently. Participants will be randomised to the 9 week multi-component individual/social-level group-based Cycle Nation programme or an existing national standard single group-based cycle training session. Both arms will be delivered by community-based cycling organisations in Glasgow. Participants will complete self-reported measurements at baseline, 12 weeks and 12 months. The primary outcome is the proportion of participants cycling at least weekly at 12 months. Secondary outcomes include proportion of participants cycling at least weekly at 12 weeks; change in weekly number of rides and minutes of cycling and use of private car, taxi, public transport and walking at 12 weeks and 12 months; change in motivation, perceptions of cycling safety, confidence to cycle, self-esteem, vitality, health-related quality of life and perceived general physical health at 12 weeks and 12 months. A within-trial economic evaluation from a National Health Service/personal social service and a broader societal perspective will be undertaken. Pending within-trial results, a long-term model may be developed. An embedded process evaluation will use participant and facilitator interviews, participant acceptability questionnaires, facilitator delivery proforma and session observations.

Ethical approval has been obtained from the University of Glasgow Medical, Veterinary and Life Sciences Ethics Committee (11 April 25). Findings will be published in peer-reviewed journals and communicated to stakeholders and the public.

NCT07005674.

Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5–2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer’s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.

Multicentre, retrospective, observational, new-user, active-comparator cohort study.

Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.

Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.

Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.

The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.

SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.

International guidelines on breast cancer (BC) screening have differing recommendations leading to uncertainty on best practices for primary care providers. The purpose of this study was to create a Canadian best practices document on BC health and screening for primary healthcare providers through multidisciplinary consensus using Nominal Group Technique and Delphi method.

A 9-member multidisciplinary expert group and a patient advocate participated in the consensus methods and voting. Experts included those involved in BC management and two primary care physicians. Twenty-nine experts across BC disciplines participated in external review.

Two study objectives included (1) building consensus on key ‘best practice’ behaviours related to BC-related health and screening and (2) building consensus on specific definitions related to BC screening.

The final consensus document consists of 65 statements grouped in five categories with companion resources to support uptake of all best practices. Categories include identification and work-up for diagnostic imaging, risk factors and identifying individuals eligible for high-risk screening, shared decision-making, decisions and referrals for BC screening and screening outcomes. Special areas of focus were shared decision-making, age to initiate screening, and BC screening in special populations.

We created a comprehensive consensus document distilling the latest evidence to provide practical Canadian consensus-based advice on specific ‘best practice behaviours’ related to BC health and screening to serve as a resource for providers.

Cancer remains a growing public health challenge in India, impacting not only patients but also their caregivers, often family members who bear the emotional, physical and financial burdens of care. These family caregivers face overwhelming stress, anxiety and depression, particularly in rural areas with limited healthcare access. Cultural expectations often lead them to neglect their own well-being. Many are forced to reduce work or quit jobs, worsening financial strain. Despite their vital role, caregivers are largely overlooked in cancer care discourse. There is an urgent need for India-specific, empathetic research and policies that support caregiver health and recognise caregiving as a public health priority.

This study employs a sequential explanatory mixed-methods design to examine the association between caregiver burden and mental health status among informal caregivers of patients with cancer in central rural India. In the quantitative phase, a cross-sectional survey will be conducted using systematic random sampling. Data will be collected via a semistructured questionnaire and standardised tools: the Copenhagen Burnout Inventory to assess burnout levels, and the Depression, Anxiety and Stress Scale-21 to evaluate psychological distress. Statistical analysis will include descriptive statistics and regression analysis.

The qualitative phase will involve in-depth interviews with purposively selected caregivers to explore lived experiences, coping mechanisms and emotional challenges. Interviews will be transcribed and analysed using thematic content analysis. Integration of quantitative and qualitative findings will provide a comprehensive understanding of caregiver burden and mental health, reflecting both measurable patterns and the human experience of caregiving in a rural setting.

Ethical clearance for this study protocol was obtained from the Institutional Ethics Committee of Datta Meghe Institute of Medical Education and Research, Sawangi (Meghe), Wardha (Approval No. DMIHER(DU)/IEC/2025/436). Permission for data collection was further granted by both the institutional ethics committee and Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe), Wardha. The findings of this research will be disseminated through publications in peer-reviewed scientific journals and by engaging relevant stakeholders through appropriate channels of communication.

CTRI/2025/08/093357.

Gastrointestinal bleeding (GIB) is a common cause of hospitalisation and decompensation in the hospital, is routinely managed by a wide variety of subspecialties, and requires a host of both technical and non-technical skills (NTS). Simulation-based training (SBT) exercises are an excellent means of training physicians and other healthcare professionals in both technical skills and NTS and are frequently used to teach and assess management of high-stress situations such as cardiopulmonary resuscitation and trauma situations. The manner in which SBT is used to train other types of clinical situations—and at what frequency—is less clear. The extent to which such training programmes are evaluated is also not clear. Here, we intend to characterise the body of literature describing SBT programmes for bedside management of GIB. In doing so, we will gain valuable insight into the current state of SBT as it relates to training healthcare professionals to handle complicated clinical situations.

Our review will follow the six-stage framework outlined by Arksey and O’Malley while considering elaborations and guidance made by Levac et al and the Joanna Briggs Institute. The protocol and review will be created in alignment with the preferred reporting items for systematic reviews and meta-analyses—scoping review checklist and explanatory paper. Using a carefully constructed search strategy, the following databases will be queried from their inception through 31 December 2025: PubMed, Embase, Scopus, Web of Science and ERIC. Following the initial database query and two-step screening process, included articles will be systematically examined and will serve as our data source. Our efforts will ultimately answer the following research question: How is simulation-based training currently used to teach bedside management of GIB to physicians (residents, fellows and attending physicians), and how are these simulation-based training exercises studied and evaluated?

Ethical approval from the Institutional Review Board is not required for this study since all investigations are being carried out on previously published manuscripts. Final results will be compiled and submitted for publication once the study has been completed and all data has been charted/analysed.

To identify predictors of treatment changes and to evaluate the effectiveness and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) initiating tofacitinib in a real-world setting.

The non-interventional study ESCALATE-RA included 1518 patients with RA from Germany. RA treatment, including all changes in therapy, was documented for 24 months starting from the initial intake of tofacitinib.

All patients started with tofacitinib therapy, either as monotherapy or in combination with methotrexate (MTX).

The impact of several factors of interest on the number and timing of treatment changes was assessed as primary outcome using Cox proportional hazards models. Further outcomes were tofacitinib drug survival and the use of follow-up disease-modifying antirheumatic drugs after first treatment change. We also assessed the effectiveness, concomitant glucocorticoid (GC) use, PROs (such as functional ability, patient satisfaction, pain and quality of life) and safety. Analyses were based on observed data.

‘Lack of efficacy’ (HR 3.30) and ‘intolerance’ (HR 4.43) leading to termination of tofacitinib were key factors favouring therapy changes. Higher patient satisfaction was significantly associated with a reduced likelihood of treatment changes (HR 0.82). Increasing GC doses were associated with a higher probability of step-up/switch changes (HR 1.21). The estimated tofacitinib drug survival was 48% at the end of study. Proportions of patients achieving low disease activity (both Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) 62%) and remission (SDAI 25%, CDAI 28%) increased from baseline under tofacitinib and were comparable between monotherapy and combination therapy with MTX. Mean concomitant GC dose decreased (2 mg/day). PROs indicated reduced pain and fatigue, while functional ability and quality of life improved. 63.9% of the patients experienced a treatment-emergent adverse event (AE), 8.8% a treatment-emergent AE of special interest and deaths occurred in 0.5%.

Key factors for therapy changes in patients with RA treated with tofacitinib were lack of efficacy and intolerance. Higher patient satisfaction was associated with a reduced probability of treatment changes, while increased GC doses led to a higher likelihood of step-ups/switches. Patients demonstrated a marked reduction in disease activity for up to 24 months, along with improvements in functional ability, pain and quality of life. Observed AEs were consistent with the known safety profile of tofacitinib.

NCT03387423.

Multimorbidity, defined as two or more chronic medical conditions, leads to the use of multiple medicines, including for cardiovascular conditions. This is associated with frailty and an increased risk of medication-related harm. Hospitalised adults have higher rates of multimorbidity and frailty compared with non-hospitalised adults. The aim of this study was to examine the use of medicines for hypertension, ischaemic heart disease and atrial fibrillation among patients with multimorbidity and frailty, who are generally not well represented in clinical trials.

A cross-sectional study was performed of adults aged ≥45 years with inpatient admissions during an 18-month period. Regular medications prescribed at discharge and coding data were obtained from the electronic medical record and hospital datasets.

The prevalence of multimorbidity (using coded chronic medical conditions or the RxRisk pharmaceutical comorbidity index), frailty (using hospital frailty risk score) and polypharmacy (defined as ≥5 medicines) were calculated. The uptake of medicines recommended by the Australian Therapeutic Guidelines for patients with coded hypertension, ischaemic heart disease and atrial fibrillation was also assessed.

Two large acute care, teaching hospitals in Adelaide, South Australia.

23 980 unique patients were identified.

69% (n=16 637) of patients had multimorbidity using the coding definition compared with 94% (n=22 620) using the pharmaceutical comorbidity score. 81% (n=19 366) had polypharmacy and 46% (n=11 091) had frailty. More than 85% of patients with hypertension were taking an antihypertensive. More than 75% of patients with ischaemic heart disease were taking an antithrombotic or a lipid-lowering agent and more than 50% were taking an agent acting on the renin-angiotensin system. Over 70% of patients with atrial fibrillation without a contraindication to anticoagulation were taking an anticoagulant. Patients with multimorbidity were 11–51% more likely to be taking an antihypertensive, antithrombotic or lipid-lowering medicine for the respective cardiovascular conditions, whereas those with frailty were 31–48% less likely to be taking guideline-directed medicines for all conditions studied.

Over two-thirds of hospitalised patients with these cardiovascular conditions were taking at least one guideline-directed medicine. Medication use was generally more common in multimorbidity and less common in frailty. Outcomes studies are needed to quantify the risks and benefits of cardiovascular medicines in these patients.

Some intensive care unit (ICU) patients develop an extremely deep and sustained immunosuppression that increases the risk of secondary infections and can ultimately compromise survival. Thanks to an easily accessible and simplified immune monitoring to identify immunological failure, a personalised immune restoration approach is now feasible. Among the different therapeutic strategies in this field, interferon gamma (IFN-) is probably the most interesting drug to reduce the burden of secondary infections in the ICU.

This is a two parallel group multicentre blinded add-on randomised trial comparing immunorestoration by subcutaneous injection of IFN- to standard of care in targeted ICU patients. The study will be performed in 23 ICUs in France. Patients hospitalised in the ICU for a week, with multiple organ failure defined by a sequential organ failure assessment score ≥6 during this first week, will be enrolled. If within 96 hours after inclusion, these patients express immunosuppressed features defined by a low absolute lymphocyte count (x10⁹/L) and low expression of human leucocyte antigen-DR (HLA-DR) on monocytes (13 500 antibodies bound per cell and an absolute lymphocyte count >1200 x10⁹/L) at day 10, healthcare costs at day 90 and rate of serious adverse reactions and suspected unexpected serious adverse reaction at day 90. We plan to randomise 326 patients.

The study will be implemented in accordance with European regulations and was independently reviewed and approved by the French Ethics Committee Comité de Protection des Personnes Ile de France III (EUCT number: 2024-516780-93-00). The results will be reported in international peer-reviewed journals and presented at international and national conferences.

NCT06774235.

Falls are a significant health concern and associated with cancer survivorship. Falls can result in negative psychosocial consequences for cancer survivors and economic sequelae for healthcare delivery. There are cancer-specific fall risk factors relevant to cancer survivors which can contribute to increased fall risk. However, fall prevention may not be addressed in standard care for cancer survivors. This review aims to synthesise the findings from published research to explore the intervention characteristics and the effectiveness of fall prevention interventions on the incidence of falls and risk factors for falls in cancer survivors.

This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search in CINAHL Ultimate, PubMed, Scopus, Embase and supplementary search Google Scholar will be conducted in November 2025. We will include randomised controlled and controlled trials that describe the characteristics of the programme and report falls or risk factors for falls as outcomes. Title, abstract and full-text screening will be performed independently by two reviewers. The Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX), Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials (ROBUST-RCT) and Grading of Recommendations Assessment, Development and Evaluations (GRADE) tools will be used to assess the quality and certainty of evidence. We will provide a summary of the intervention characteristics and perform a meta-analysis or narrative synthesis of the findings as appropriate.

Ethics approval is not required for this systematic review as we will include papers published in peer-reviewed journals and original data will not be collected. The findings of this systematic review will be disseminated in a peer-reviewed publication and presented at relevant conferences.

ID 1240723.

Women experiencing infertility employed various coping strategies to overcome the diverse stressors encountered. These coping strategies had their peculiar consequences or outcomes. This study aimed to explore the outcomes deduced from the coping strategies employed by women with infertility.

The study employed a qualitative descriptive research design to gain an in-depth understanding of the outcomes of coping strategies used by women with infertility. In-depth interviews were conducted using a semi-structured interview guide.

The study was carried out at a private fertility and specialist hospital within the Kumasi Metropolitan Assembly, where 15 women diagnosed with primary infertility were interviewed for 45 min to 1 hour each. With all participants completing the study, interviews were audiotaped with consent, transcribed verbatim and analysed using content analysis.

The findings revealed that women with infertility used various coping strategies to mitigate the psychosocial stressors encountered. The coping strategies employed had a varying impact on the well-being of women with infertility, from long-term (physical health, mental health and life satisfaction) to short-term (composure and reduced state anxiety) coping outcomes. The result of the coping strategy employed had a varying impact on the well-being of women with infertility.

Women with infertility shared how they experienced good physical health, mental health and life satisfaction after employing adaptive coping strategies like seeking social support. They also shared how they exercised composure and had reduced state anxiety after using some maladaptive coping strategies, such as self-control and avoidance.

Metabolic bariatric surgery (MBS) can lead to substantial fat-free mass loss (FFML) due to malnutrition, decreased protein intake and insufficient physical activity. Disproportional FFML has been associated with an increased risk for adverse health outcomes. Resistance training (RT) combined with protein intake contributes to maintenance and increase of fat-free mass (FFM) in healthy individuals. However, it is unclear whether RT and protein supplementation can prevent FFML after MBS.

In the EffectiveNess of pRotein supplementatIon Combined witH resistance Exercise training to counteract Disproportional fat-free mass loss following metabolic bariatric surgery (ENRICHED) randomised controlled trial, 400 patients scheduled to undergo MBS will be randomised in a 1:1 ratio to the ENRICHED perioperative care programme (intervention group) or the standard perioperative care programme of the Dutch Obesity Clinic (control group). The study is currently recruiting participants at two centres in the Netherlands: Nieuwegein and Amsterdam. The postoperative standard programme consists of 13 group sessions spread over a period of 18 months. As part of the ENRICHED programme, RT and protein supplementation will be added 3 weeks after MBS. Additional whole-body RT consists of home-based training sessions two to three times a week, and supervised RT sessions of 45–60 min once weekly, performed at 60–75% of one-repetition maximum (1-RM). Protein supplementation will start by adding 20 g of whey protein to the daily intake. The supplementation will be gradually increased with 20 g every 4 weeks until a total of 60 g whey protein a day is reached. After 12 weeks of protein supplementation, the focus shifts towards incorporating protein-rich food products into the daily dietary intake. The primary endpoint is the prevalence of disproportional FFM loss, defined as FFML/total weight loss ≥30%, at 3 months post-MBS. Secondary endpoints are differences in body composition, muscle strength and function, cardiorespiratory fitness, (cardio)metabolic health, health-related quality of life, gastrointestinal discomfort, cost-effectiveness of the intervention and treatment satisfaction. Outcomes will be assessed preoperatively and at 3, 6 and 12 months postoperatively.

The study protocol V.2.0 was approved by the Medical Research Ethics Committee Oost-Nederland (NL-OMON57119) on 9 April 2025. All participants will provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and conference presentations. Insights gained in this study will provide evidence for a patient-tailored intervention that could be implemented in clinical practice.

NCT07156552.

This study aimed to assess the associations between childhood adverse socioeconomic conditions and intrinsic capacity in older adults using an integrative approach to ageing.

A cross-sectional study.

We used data from the Lausanne Cohort 65+, a population-based longitudinal study that has been conducted in Lausanne, Switzerland, since 2004.

Lausanne citizens aged 67–71 years old.

Intrinsic capacity was assessed in 2015 using validated self-reported measures and performance tests. Partial Least Squares Structural Equation Modelling was used in a formative approach to calculate the global score of intrinsic capacity and the scores of its domains. Adverse socioeconomic conditions in childhood were retrospectively assessed in 2014 using self-reported measures of financial strain, dietary restrictions and child labour.

The study sample included 1328 individuals. Multivariable regressions revealed that the global score of intrinsic capacity was lower in individuals who reported financial strain (B=–0.15, p=0.029) and dietary restrictions (B=–0.314, p=0.004) in childhood. They further showed an association between financial strain and lower locomotor and sensory capacities (B=–0.173, p=0.011 and B=–0.153, p=0.027, respectively), and between child labour and a lower score on cognition (B=–0.342, p

Our results emphasise the critical role of early life conditions in healthy ageing. They highlight the importance of financial support for families and access to nutrition.

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

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

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

Long-term brain health profiles following exposure to repetitive head impacts and/or concussions in contact sports are a public health focus and the subject of a national debate. The true prevalence rates of mild cognitive impairment (MCI) or neurobehavioural dysregulation are unknown in the nearly 20 000 current/living former professional football players. Here, we describe the procedures and methodology of the prevalence study of cognitive function in former professional football players from the Brain Health Initiative at the University of Pittsburgh. The objective is to define the prevalence of normal cognitive function versus neurodegeneration in former professional football players through clinical, neuroimaging and biomarker assessments.

Participants include former professional football players aged 29–59 years at study onset who played a minimum of three professional football games in three professional seasons and non-exposed controls. Participants are recruited by two mechanisms, a random and non-random sample. The full study protocol includes a 3–4-day, multidomain assessment (eg, neurological, neurocognitive, psychiatric, sleep, vestibular, orthopaedic and cardiovascular) for neurodegenerative disease and overall health and function, including MRI, positron emission tomography scans, analysis of blood plasma and cerebrospinal fluid, neurocognitive assessments, applanation tonometry, overnight sleep study and informant interview. A multidisciplinary clinical panel conducts a blinded diagnostic consensus conference to adjudicate the presence of MCI and/or traumatic encephalopathy syndrome, which serve as the study’s primary and secondary outcomes, respectively. Point prevalence of these for both the exposed and unexposed cohorts will be calculated as the primary statistical analysis.

The University of Pittsburgh Institutional Review Board approved the study prior to recruiting human subjects (protocol numbers STUDY19010008: sIRB - Brain Health Initiative (Part 1) and STUDY19030211: sIRB - Brain Health Initiative (Part 2)). The results will be disseminated in peer-reviewed journals and as presentations at national and international scientific conferences.

In-hospital cardiac arrest (IHCA) is associated with high mortality and serious neurological sequelae. Although medical alert systems have evolved, the ability of these systems to influence changes in IHCA incidence and aetiology remains limited.

Retrospective observational cohort study.

A single tertiary hospital in South Korea, covering tertiary care levels.

A total of 1994 adult patients (≥18 years) who experienced 2121 episodes of IHCA between January 2011 and December 2019. Patients with out-of-hospital cardiac arrest, those aged ≤18 years and those with do-not-resuscitate orders were excluded. The mean age of patients was 63.0 years (SD, 14.6); 64.1% were male.

Not applicable.

The incidence and temporal trends of IHCA were stratified by aetiology (cardiac vs non-cardiac). Additional analyses examined changes in arrhythmic versus non-arrhythmic causes over time using Poisson regression.

Cardiac arrhythmia was the most common cause of IHCA (314 of 2121, 14.8%; incidence: 0.42/1000 admissions), including ventricular tachycardia (n=86), ventricular fibrillation (n=87) and Torsades de Pointes (n=79). Respiratory failure was the second most common cause (266 of 2121, 12.5%; incidence: 0.36/1000 admissions). The incidence of IHCA due to respiratory failure in 2011 was 0.63/1000 admissions, which decreased to 0.20/1000 admissions by 2019 (β=0.883, 95% CI 0.842 to 0.926, p for trend 0.007; Poisson p

IHCA causes have shown significant temporal shifts. Arrhythmia has become the leading cause of IHCA, with incidences remaining stable, whereas a marked decrease has been observed in respiratory-related IHCA. Therefore, enhanced in-hospital cardiac monitoring systems are required for early detection.

Total mesorectal excision (TME) is highly effective for early-stage rectal cancer, but is associated with considerable morbidity, which can substantially impair the quality of life (QoL) of patients. For very early tumours (low-risk cT1), local excision (LE) offers the possibility of organ preservation (OP) with reduced morbidity; however, its application is limited to a selected group. For early tumours where upfront LE is not feasible, primary OP with (chemo)radiotherapy as an alternative to TME surgery has been evaluated in the STARTREC phase II/III studies, which reported promising 1-year OP rates.

The STARTREC-3 trial aims to increase the 2-year OP rate from 60% to 80% in early rectal cancer (cT1–3abN0) and from 30% to 60% in early-intermediate rectal cancer (cT1–3abN1, ≤3 mesorectal nodes measuring ≤8 mm) by intensifying neoadjuvant treatment in different study arms.

STARTREC-3 is embedded in the STARTREC master trial protocol, which uses an adaptive platform study design allowing early termination of inferior treatment arms and the addition of novel arms. The multicentre STARTREC-3 trial investigates three parallel, non-comparative treatment strategies for patients with early and early-intermediate rectal adenocarcinoma who prefer OP over primary TME surgery. All arms start with 5x5 Gy radiotherapy, followed by: an endoluminal boost via contact X-ray brachytherapy (arm 1), an external beam radiotherapy (EBRT) boost by MR-guided EBRT (arm 2) or three cycles of capecitabine oxaliplatin systemic treatment chemotherapy (arm 3). Treatment allocation is predefined and centre-dependent. Response evaluations (MRI and endoscopy) are planned at 14–16 weeks and 26 weeks after onset of radiotherapy. The primary endpoint is the proportion of patients with successful OP at 24 months from onset of therapy. Secondary endpoints include toxicity, QoL, functional and oncological outcomes. Data will be analysed separately for early (cN0) and early-intermediate (cN1) disease. The total planned sample size is 210 patients across the three arms. Interim analyses will be performed for each study arm to determine early failures and discontinue ineffective arms.

The trial was approved by the medical ethics committee NedMec of the Netherlands and is registered in the EU Clinical Trials Information System (CTIS). The results will be published in an international peer-reviewed journal.

CTIS EU 2024-514620-17-00

Children sometimes have subtle illness presentations and symptom overlap with non-serious conditions.1 Young age also presents a communication barrier. The combination of these factors can lead to diagnostic delays and sometimes misdiagnosis, particularly in emergency department (EDs) that do not see high volumes of children. In the USA, one in three EDs sees fewer than five children daily. A prior study linked low-paediatric ED volume to diagnostic delays in...

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.

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.