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.

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.

About 30% of depressed patients suffer from a protracted course in which the disorder continues to cause significant burden despite treatment efforts. While originally developed for relapse prevention, mindfulness-based cognitive therapy (MBCT) has increasingly been investigated in depressed patients with such ‘difficult-to-treat’ courses. This is a protocol for an individual participant data (IPD) meta-analysis aiming to determine efficacy and potential moderators of MBCT treatment effects in this group based on evidence from randomised controlled trials.

Systematic searches in PubMed, Web of Science, Scopus, PsycINFO, EMBASE and the Cochrane Controlled Trials Register for randomised controlled trials were completed on 17 June 2024. Authors of identified studies have contributed IPD, and data extractions have been completed. An update search will be conducted immediately before the start of data analyses. We will investigate the following outcomes: (a) self-reported and observer-reported severity of depression symptomatology, (b) remission and (c) clinically meaningful improvement and deterioration. One-stage and two-stage IPD-MA will be conducted with one-stage models using the observed IPD from all studies simultaneously as the primary approach. One-stage IPD models will include stratified study intercepts and error terms as well as random effects to capture between-study heterogeneity. Moderator analyses will test treatment-covariate interactions for both individual patient-level and study-level characteristics.

The results will inform understanding of the use of MBCT in patients with current ‘difficult-to-treat’ depression and will contribute to arguments in favour of or against implementing MBCT as a treatment for this group. They will be published in a peer-reviewed journal and made available to stakeholders in accessible formats. No local ethical review was necessary following consultation with the Ethics and Governance Board of the University of Surrey. Guidance on patient data storage and management will be adhered to throughout.

CRD42022332039.

Inguinal hernia repair is one of the most frequently performed operations in the paediatric population and can be performed according to two approaches: open or laparoscopic. At present, decisive evidence about the best treatment strategy is lacking and consequently, there is an ongoing debate about the most (cost-)effective treatment for the paediatric inguinal hernia. The aim of the Hernia Endoscopic oR opeN repair In chIldren Analysis—trial (HERNIIA2-trial) is to estimate the (cost-)effectiveness of the laparoscopic percutaneous internal ring suturing (PIRS) technique compared with open repair in children aged 0–16 years with a primary unilateral inguinal hernia.

A national multicentre randomised controlled trial will be performed including 464 children aged 0–16 years with a primary unilateral inguinal hernia. Patients will be randomised between the open or PIRS technique. The primary outcome is the number of reoperations within 2 years after primary surgery. Secondary outcome measures are: operative and postoperative complications, total duration of surgery, postoperative pain, length of admission, time to normal daily activities, cosmetic appearance of the scar, social and healthcare costs and health-related quality of life. Furthermore, cost-effectiveness will be assessed from a societal and healthcare perspective.

The protocol was approved by the ethics committee of the Amsterdam University Medical Hospital. Informed consent will be obtained by parents and, if possible, according to age, by patient. The study will be conducted according to the principles of the Declaration of Helsinki (2013) and in accordance with the Medical Research Involving Human Subjects Act (WMO) and Good Clinical Practice. Study findings will be disseminated through scientific publications, conferences and patient-friendly materials. The national study network of participating centres will facilitate rapid dissemination and implementation within the Netherlands and potentially abroad.

ClinicalTrials.gov PRS (ID NCT06451432).

This study aimed to assess construct validity against commonly used patient-reported outcome measures (PROMs), test–retest reliability and responsiveness of seven Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) computerised adaptive testing (CATs) in Dutch adults with type 2 diabetes (T2D), and assess their acceptability in healthcare providers and people with T2D.

A cross-sectional observational study in people with T2D and qualitative study involving both people with T2D and healthcare professionals.

Participants with T2D were recruited from the ongoing Hoorn Diabetes Care System cohort in the West-Friesland area of the Netherlands. Additionally, people with T2D and advanced chronic kidney disease were recruited at the outpatient clinics of Amsterdam University Medical Centre and ‘Niercentrum aan de Amstel’, both in the Amsterdam area of the Netherlands. The healthcare professionals involved in the qualitative part were recruited at the Amsterdam University Medical Centre.

314 people with T2D (age 64.0±10.8 years, 63.7% men).

Participants completed seven PROMIS CATs (assessing (1) Physical Function, (2) Pain Interference, (3) Fatigue, (4) Sleep Disturbance, (5) Anxiety, (6) Depression and (7) Ability to Participate in Social Roles and Activities), and PROMs measuring similar constructs. After 2 weeks and 6 months, participants completed the CATs measures again, together with seven Global Rating Scales (GRS) on perceived change in each domain. Construct validity was assessed using Pearson’s correlations. Test–retest reliability was assessed by the intraclass correlation coefficient (ICC). Measurement error was assessed by the standard error of measurement (SEM) and minimal detectable change (MDC). Responsiveness was assessed by correlations between change scores on the PROMIS CAT and GRS. Acceptability was assessed through focus groups and interviews in healthcare providers and people with T2D.

Except for Fatigue, all PROMIS CAT domains demonstrated sufficient construct validity, since ≥75% of the results was in accordance with a priori hypotheses. All seven PROMIS CATs showed sufficient test–retest reliability (ICCs 0.73–0.91). SEM and MDC ranged from 2.1 to 2.7 and from 5.7 to 7.4, respectively. Responsiveness was rated as insufficient in this study design as there was almost no change in participants’ own rating of their health compared with 6 months ago according to a global rating of change.

During the focus groups and interviews, healthcare providers and people with T2D agreed that CATs could serve as a conversation starter in routine care, but should never replace personal consultations with a doctor. If implemented, participants would be willing to spend 15 min to complete the PROMIS CATs.

The PROMIS CATs showed sufficient construct validity and test–retest reliability in most domains in people with T2D. Responsiveness needs to be evaluated in a population with poorer diabetes control or in a study design with longer follow-up. The CATs are well accepted to be used in care to identify relevant topics, but should not replace personal contact with the doctor.

To determine age-specific and age-standardised incidence trends of acute rheumatic fever (ARF) or rheumatic heart disease (RHD) among Indigenous Western Australians aged less than 35 years of age.

A population-based retrospective cohort study with linked data analysis.

Western Australian hospital admissions (1996–2022) and RHD notifications to the state-based register (2011–2015).

Patients, both Indigenous and non-Indigenous aged

Of 1746 incident ARF/RHD cases, 1526 (87%) were Indigenous peoples, with the highest rates observed in patients aged 5–14 years, with an annual estimated increase of 4.3% (95% CI 3.2% to 5.2%). The 0–4 years age group experienced an annual increase in incidence rates of 4.8% (95% CI 1.4% to 8.2%). Overall, Indigenous patients experienced an annual increase of 1.9% (95% CI 1.3% to 2.6%) from 1996 to 2022. However, most cases (n=894) were identified after multiple significant policy developments (2011–2022) with an annual increase of 5.7% (95% CI 3.7% to 7.5%) for this period.

Increasing trends of incident ARF/RHD were observed in Indigenous patients aged under 15 years, with the greatest annual increments observed after policy implementation for disease reporting and awareness in the period from 2011 to 2022. Improvement in case ascertainment of ARF/RHD may be contributing towards increasing trends with improved reporting and monitoring of incident cases in very young Indigenous Australians more recently.

People without access to recognised and understood speech and/or written communication methods can experience exceptional disadvantage in health settings. This can result in poor health outcomes, lengthier hospital admissions and adverse events, including preventable deaths. Despite numerous attempts to integrate augmentative and alternative communication into health settings, the first-person ‘voice’ of the patient is often not accessible or prioritised, deferring instead to others, such as parents or carers, or the ‘best guess’ by healthcare professionals. The Talking Scrubs project aims to form a bridge to augmentative and alternative communication by locating key communication icons on scrubs (and scrubs/vest) to be used with patients (in and of themselves) and/or to prompt the use of patient individualised communication methods. The paper describes the methodological process for Stage 4 of the project. Prior stages involved investigating the concept, developing and validating instrument measures and co-designing and feasibility pilot testing the scrubs/vests. Stage 4 (this protocol) aligns with the diagnostic process, to test the feasibility and effectiveness of the scrubs intervention at two large, metropolitan medical centres with 5–10 general practitioners, approximately 30 patients and up to 10 flow-on diagnostic screening clinicians such as nurses and phlebotomists. Stage 4 is the first time the instrument measures will be applied and re-tested post-validation.

Using mixed methods, Stage 4 will apply the communication self-efficacy instruments co-designed in Stage 2 and validated in Stage 3 to measure effectiveness of the scrubs intervention by comparing pre-intervention and post-intervention changes in both clinician and patient population groups. Qualitative interviews, agency recorded data and participant journal recordings (optional) will be used to identify feasibility. SPSS V.29 (IBM, Chicago, Illinois, USA) will be applied to analyse participant communication self-efficacy measures and NVIVO V.10 (Lumiverso, Denver, Colorado, USA) to the retrieved qualitative data.

Stages 3 and 4 have ethics approval from the University of South Australia Ethics Committee identification number 206 930 and are registered as a clinical trial with Australia and New Zealand Clinical Research Trials (ANZCRT) with registration number 12625000490471p. Stage 1 (national survey) and Stage 2 (stakeholder focus groups) received ethics approval from Flinders University. Findings will be disseminated through national and international health translation platforms, publications, media and on the Talking Scrubs website.

ANZCRT with the registration number ACTRN12625000490471p.

Upper limb task-oriented training (UL-TOT) is a complex intervention in which practice conditions related to motor learning principles are applied to enhance upper limb motor recovery after stroke. The Template for Intervention Description and Replication guidelines suggest that detailed reporting of a complex intervention is essential in published studies. Therefore, this review aimed to determine the extent to which practice conditions related to motor learning principles were reported in UL-TOT stroke clinical trials.

A comprehensive search was done using appropriate keywords in PubMed, CINAHL, Web of Science, Scopus and Cochrane databases from 2000 to 2024. Two reviewers independently conducted title screening, abstract screening and full-text evaluation based on the inclusion and exclusion criteria. A third reviewer resolved the conflicts between the two reviewers during the screening process. Finally, the articles that fulfilled the criteria were included for data extraction.

23 802 studies were retrieved, and 166 studies were retained. Practice conditions such as practice variability (98%), dosage (97%) and movement complexity (96%) were reported more frequently, task selection for practice (75%), challenging and progressive task practice (76%) were reported frequently, practice order (57%), practice distribution (51%), feedback type (44%) and timing (44%) were reported occasionally. Feedback frequency (37%) was reported rarely.

Practice conditions such as practice variability, dosage, movement complexity, task selection, challenging and progressive task practice were reported consistently, while practice distribution, order and feedback were reported inconsistently. Developing a standard checklist for practice conditions related to motor learning principles can improve detailed reporting of practice conditions in future UL-TOT stroke clinical trials. This can help researchers replicate and reliably implement the intervention in specific populations and build on and create more effective interventions.

To develop and validate a polycystic ovary syndrome (PCOS) case definition using administrative health data sources.

A validation study.

Secondary care centre outpatient gynaecology clinic in Calgary, Alberta, Canada.

3951 electronic health records of women aged 18–45 years who presented to a gynaecology clinic in Calgary, Canada, between January 2014 and December 2019 were reviewed. We identified 180 patients with PCOS using the Rotterdam criteria. Participants were excluded if they were biologically male, pregnant at the time of the consultation, did not meet the date criteria or if their consultation note was missing. The chart data were connected to the Practitioner Claims and the Discharge Abstract Database by personal health number.

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 68 case definitions for PCOS were estimated. Case definition performance was graded.

Of the 68 case definitions tested, none had high validity. The best performing case definitions were: (1) ≥3 instances of International Classification of Diseases-9 code 256.4 (polycystic ovaries) with exclusion codes (sensitivity 23.89%, specificity 99.59%, PPV 74.14%, NPV 96.35%) and (2) 626.X (irregular menstruation), 704.1 (hirsutism) and ≥3 instances of code 256.4 with exclusion codes (sensitivity 2.78%, specificity 99.97%, PPV 83.33%, NPV 95.40%).

We identified several case definitions for PCOS of moderate validity with high PPV (>70%) for case ascertainment in PCOS research in jurisdictions with similar administrative health data. These case definitions are limited by low sensitivity, which should be considered when interpreting research findings.

The currently available immunotherapies have failed to meet expectations in inducing durable responses in patients with advanced epithelial ovarian cancer (EOC). The low number of somatic missense mutations in EOC necessitates highly potent neoantigen-directed approaches. To this end, we have developed a novel dendritic cell (DC) product that consists of a specialised cross-presenting subset of DC, conventional DC type 1 (cDC1).

We will conduct the NEODOC study, an investigator-initiated first-in-human phase I/II trial. This study will assess the immunogenicity, safety and feasibility of a cDC1-based, autologous tumour lysate-loaded, DC product. 10 patients with previously untreated advanced EOC (stage IIIb-c, IVa or stage IVb if only supradiaphragmatic or inguinal lymph nodes

Ethical approval for this trial was granted by the Netherlands Central Committee on Research Involving Human Subjects. The results will be disseminated through publications in international, open-access scientific journals and presentations at scientific conferences.

NCT05773859; EUCT number 2024-512353-24-01.

Cardiovascular events (CVEs), in particular acute coronary syndrome (ACS), complicate the course of a significant number of patients hospitalised for community-acquired pneumonia (CAP) or influenza. Emerging evidence suggests that this increased risk of CVEs could be mitigated by the use of acetylsalicylic acid (aspirin). The ASCAP study investigates whether the addition of aspirin to standard therapy in hospitalised patients with moderate-to-severe CAP or influenza can reduce the incidence of CVEs.

The ASCAP study is a multicentre, double-blind, placebo-controlled randomised trial in 16 university and general hospitals in the Netherlands, in which patients are randomised to acetylsalicylic acid or matching placebo for 90 days. Eligible patients are adults hospitalised for moderate-to-severe CAP or influenza. Patients with antithrombotic or anticoagulant drugs, or those with contraindications for aspirin, are excluded. The primary outcome is the incidence of ACS up to day 180. Secondary outcomes include the incidence of 4-point major adverse cardiovascular events up to day 180, as well as the incidence of major bleeding and clinically relevant non-major bleeding events up to day 90, all-cause mortality up to day 180 and quality of life and societal costs up to day 180. Survival time will be analysed by the log-rank test, stratified for CAP and influenza, with a two-sided alpha of 0.05. Assuming an average baseline ACS risk of 7.5% over 180 days with up to 30% variation across strata, and a 60% hazard reduction due to aspirin, the required sample size to achieve 80% power is 760 patients. Currently, 114 patients are enrolled in the study.

This study is approved by the Medical Ethics Committee Amsterdam UMC (Amsterdam, The Netherlands) under reference number 2023.0741 and registered under EU trial number 2023-504553-12-01 in the EU portal CTIS (Clinical Trials Information System). Results of the study will be published in a peer-reviewed journal.

EU CTIS: 2023-504553-12-01.

To conduct a synthesis of existing empirical and grey literature to identify the contexts and mechanisms that enable the adoption, offer, uptake and return of faecal immunochemical testing (FIT) in the primary care pathway in England, UK, for patients with signs or symptoms of suspected colorectal cancer (CRC). From this, develop a theory about how specific programme activities lead to certain outcomes.

A realist synthesis.

Medline (OVID), EMBASE (OVID), CINAHL (EBSCO), Scopus (Elsevier) and grey literature sources until end of July 2023.

The purpose of the work was to determine how different factors interact within a health system to optimise the approach to implementing and using symptomatic FIT (sFIT) in clinical practice for patient benefit. The criteria used to bound the scope of the synthesis included date (published between 2017 and July 2023), exposure of interest (sFIT in the primary care pathway for patients with signs or symptoms of suspected CRC), geographic location of study (countries that make up the UK), language (English) and participants (adults). Any study design and type of publication was considered.

Given the recognised lack of literature on the implementation of sFIT, it was crucial to include insights from grey literature. To do this, key national groups and organisations—involved or related to this subject—were methodically identified and appropriate papers and reports identified.

A thematic approach was used to identify relevant data in included records and allow realist insights to be obtained. Inductive and deductive coding enabled detection of key data. Arguments were generated and developed into context–mechanism–outcome configurations (CMOCs). Iteratively, an initial list of 38 CMOCs was refined to 14 themes and 19 CMOCs. These were then structured to create a multifaceted, multilevel realist synthesis programme theory.

Systematic searching led to the full appraisal of 99 records to determine suitability of each to confirm, refute or help develop theory. Studies were assessed for rigour and relevance to inform selection. The process resulted in 45 records being chosen for inclusion, of which 28 were from database searches and 17 from grey literature sources.

The key contexts and mechanisms that help optimise adoption, offer, uptake and return of sFIT have been elucidated (although partially). These can be broadly summarised into the 10 ‘Cs’: creating a compelling Case and Conditions for change, reaching Consensus through Collaborative working, fostering a Culture that values Clinical judgement, building Confidence by developing Capabilities and, finally, ensuring Clarity and Coherence of both practical processes and safety netting procedures.

Fundamentally, optimising the adoption, offer, uptake and return of sFIT in primary care for patients with signs or symptoms of suspected CRC is predicated on developing the acceptability of this initiative to every stakeholder at every level within a health system.

Despite the growing volume of research in surgical education (SurgED), the integration of evidence into teaching practice remains fragmented and inconsistent. A structured and continuously updated synthesis is needed to support data-informed curriculum development and promote best practices across training programmes.

This protocol describes the development of a living systematic review and evidence map of SurgED research. Studies will be identified through comprehensive searches of CENTRAL, PubMed and Web of Science, and screened independently by two reviewers, supported by an Artificial Intelligence (AI)-assisted screening tool to improve efficiency. Eligible studies will include both quantitative and qualitative designs involving medical students, surgical residents and faculty. Studies will be categorised across key educational domains such as simulation-based training, competency-based assessment, feedback, mentoring and technology-enhanced learning. The evidence map will be updated at least quarterly, with new studies screened and added in near real-time to ensure that the map remains current and actionable.

As this study does not involve human participants, ethical approval is not required. Findings will be disseminated through peer-reviewed publications, presentations at national and international conferences and open access integration into the Evidence at a glance (EVIglance) evidence platform.

In the Netherlands, approximately 2200 major amputations of the lower extremities are performed each year, the majority in vascular patients. Around 61% of these patients will develop postamputation pain (PAP). PAP is a severe, lifelong, disabling condition profoundly affecting quality of life. During amputations, the common practice is to cut the nerves without employing nerve-surgical techniques to prevent chronic pain due to neuroma formation. In recent years, targeted muscle reinnervation (TMR) has been the most frequently studied technique for treating PAP, inhibiting neuroma formation by rerouting the cut mixed nerve to a functional motor nerve. We hypothesise that a primary TMR procedure during major lower limb amputations will result in a lower prevalence of PAP.

We propose a national, multicentre, randomised, sham-controlled trial comparing TMR with traction neurectomy in major amputations of the lower extremities in patients with vascular disease. 203 patients will be recruited with an indication for a transfemoral to transtibial amputation as a primary or secondary sequela of vascular disease. The subjects are randomly assigned to the TMR group or the traction neurectomy group. PAP will be evaluated 1 year postoperatively as the primary endpoint. Secondary outcomes include quality of life, mobility, neuropathic pain, hospital anxiety and depression, cost-effectiveness and complications.

This study has been reviewed and approved by the local ethical review body, ‘The Medical Ethics Committee Leiden The Hague Delft’, under the reference: P24.073 on 28 November 2024. Results will be published in peer-reviewed journals.

NCT06719245. Dutch trial registry: NL87196.058.24

There is an urgent need to better understand how information from circulating tumour DNA (ctDNA) can be integrated into routine care for patients with advanced solid cancer.

The implementation of liquid biopsies in routine care of patients with advanced solid cancer trial (LIQPLAT) is a single-centre, single-arm trial investigating the implementation of ctDNA in the routine care of patients with advanced solid cancer. We present a mixed-methods process evaluation embedded in the LIQPLAT trial, following Medical Research Council guidance and the Reach, Effectiveness, Adoption, Implementation, Maintenance framework. We show a logic model, which details the causal chain and related assumptions from recruiting patients into the trial to the goal of improving quality of life and survival. Data collection is longitudinal and includes: semistructured interviews with healthcare professionals (pathologists, biologists, oncologists; planned n=20) and patients (planned n=15) to identify implementation barriers and facilitators; recordings of molecular tumour board meetings to analyse clinical decision-making; the 23-item Normalisation MeAsure Development survey for healthcare professionals (planned n=20) at four time points. Quantitative data from hospital records will be used to assess implementation outcomes like patient acceptance rates and ctDNA workflow success. Qualitative data will undergo thematic and content analysis, and quantitative data will be analysed using a Bayesian framework.

The LIQPLAT trial was approved by the regional ethics committee of Northwestern and Central Switzerland (BASEC 2024-00358). The qualitative aspects of the process evaluation were exempted from ethics review according to the Swiss Human Research Act. We follow guidelines for data security, confidentiality and information governance. Results will be submitted for publication in peer-reviewed journals and discussed at conferences.

NCT06367751, SNCTP000005844.

Many patients who are extubated after receiving mechanical ventilation for acute respiratory failure experience extubation failure (ie, require reintubation hours to days after extubation). High-quality evidence shows that extubating patients directly to non-invasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC), rather than conventional low-flow oxygen, can prevent extubation failure. These guideline-recommended interventions, however, require care coordination involving multiple intensive care unit (ICU) team members and are infrequently used. Interprofessional education (IPE), which teaches members of multiple professions together, could effectively address this implementation gap in complex, team-based, critical care settings, particularly when paired with a customisable protocol.

This batched, stepped-wedge, cluster-randomised, type 2 hybrid effectiveness–implementation trial will test three hypotheses: (1) when compared with traditional online education (OE), IPE increases implementation of preventive postextubation respiratory support, (2) the benefits of IPE are increased when paired with a clinical protocol and (3) preventive postextubation NIV for high-risk patients and preventive postextubation HFNC for low-risk patients reduce in-hospital mortality when compared with conventional postextubation oxygen therapy. The trial will recruit 24 clusters made up of one or more ICUs that care for at least 100 mechanically ventilated patients per year in a large multihospital health system in the USA. All clusters will receive OE, IPE and a clinical protocol, with timing determined by randomisation. We will also randomise half of the clusters to education promoting postextubation NIV for patients at high risk of extubation failure and preventive, postextubation HFNC for patients at lower risk, whereas the other half will be randomised to education promoting postextubation HFNC for all eligible patients. We will include all patients who are invasively mechanically ventilated for at least 24 hours. The primary implementation endpoint is the rate of use of postextubation NIV or HFNC among eligible participants. The primary clinical endpoint is in-hospital mortality truncated at 60 days from intubation.

This study was approved by the institutional review board of the University of Pittsburgh and an independent data safety monitoring board. We describe the methods herein using the Standard Protocol Items for Randomised Trials framework and discuss key design decisions. We will disseminate results to participating healthcare providers, through publication in a peer-reviewed medical journal and via presentations at international conferences.

NCT05523479.

Patient safety culture plays a crucial role in reducing clinical errors. By improving healthcare professionals’ and patients’ understanding of human fallibility and error attribution, patient care can be enhanced, fostering greater engagement from both groups. A Just Culture approach, which balances accountability and learning from errors, is a key factor in fostering this safety culture. The DECIDE Project aims to: (1) examine the conceptualisation of human fallibility within and beyond healthcare, (2) identify barriers and facilitators to Just Culture adoption, (3) assess the impact of psychoeducational interventions on professionals’ and social leaders’ attitudes toward clinical errors and (4) develop a roadmap for Just Culture implementation in healthcare.

A 36-month mixed-methods study including qualitative research, a survey of 1255 healthcare professionals, an experimental study with 180 participants (60 per arm) testing interventions based on cognitive dissonance and reasoned action theories and a consensus conference to develop a Just Culture roadmap. Participants include professionals from hospitals, primary care, long-term care, nursing homes and social leaders in Spain. The qualitative data collected during stages 1 and 4 will be analysed using MAXQDA software. In identifying factors related to the implementation of Just Culture during stage 2, ANOVA, t-tests and multiple linear regression will be conducted. To examine the effects of the interventions in phase 3, a linear mixed-effects model for repeated measures will be employed.

This study has received ethical approval from three institutional review boards. Findings will be disseminated through peer-reviewed publications, conference presentations and policy recommendations aimed at integrating Just Culture into national and international patient safety strategies. By promoting a constructive approach to errors, the project could enhance incident reporting, strengthen professional engagement in safety policies and foster a culture of learning and accountability. Its findings will guide policy recommendations for integrating Just Culture into national and international patient safety strategies, with potential applications beyond Spain.

NCT06835517.