Funnel plots are used to identify intensive care units (ICUs) with a higher than expected risk-adjusted mortality. ICUs with a standardised mortality ratio (SMR) within pre-defined control limits (often the 99.8% CL) are regarded as ‘in control’ and not labelled as a potential outlier for a particular calendar year. However, increased mortality rates not due to random fluctuations within and across the calendar years may be overlooked. We examined whether statistically significant and relevant differences in mortality over time between ICUs regarded as ‘in control’ are present.

A longitudinal register-based study.

88 ICUs in the Netherlands registering the admissions of all critically ill patients in the National Intensive Care Evaluation registry in the Netherlands from 2013 to 2023.

Hospital death analysed in a multivariable logistic regression analysis with a random intercept for ICU. The random intercept variance was translated to the median OR (MOR).

877 ICU-calendar year combinations were included, covering 759 498 unique admissions. The MOR increased from 1.12 (95% CI 1.10 to 1.15) for ICU-calendar year combinations with an SMR within the narrowest 95% CL (N=677) to 1.20 (1.17 to 1.24) for combinations with an SMR within the expanded 99.8% CL (including adjustment for overdispersion) (N=194) and to 1.21 (1.17 to 1.25) when including all ICU-calendar year combinations. Similar results were found for separate calendar years and separate diagnostic groups.

These results show differences in mortality between ICUs that were not labelled as outliers. Assessment of mortality performance should integrate cross-sectional funnel plots, the MOR and longitudinal trends in the SMR to better capture persistent patterns of excess risk.

To describe the normal heart rate (HR) of healthy newborns ≥35+0 weeks’ gestation in the first 10 min after caesarean delivery (CD) with extrauterine placental transfusion, using dry-electrode ECG (NeoBeat).

Single-centre, prospective observational study.

Norwegian County Hospital.

Newborns ≥35+0 weeks’ gestation delivered by CD under regional anaesthesia were eligible for inclusion. Newborns delivered by CD under general anaesthesia, or who needed medical intervention, were excluded.

NeoBeat was attached to the newborn’s chest immediately following delivery. The placenta was delivered without cord clamping after 60–90 s and transferred with the newborn to a resuscitation table. Modified physiology-based cord clamping (PBCC) was performed.

HR was recorded every second for 10 min. HR quartiles were calculated. Events possibly influencing HR were annotated using Liveborn Observation App.

89 newborns with a mean (SD) gestational age of 39+3 weeks (10 days) and birth weight of 3649 (536) g were included. Median (IQR) HR was 164 (117–176) and 169 (145–186) beats per minute at 20 s and 30 s, respectively, peaking at 169 (152–183) beats per minute at 4 min and then slowly decreasing to 157 (146–167) beats per minute at 10 min. HR was not significantly affected by intact-cord blood sampling (mean difference=5.4 (95% CI –1.4 to 12.1)), placental delivery (mean difference=0.7 (95% CI –3.5 to 4.9)) or cord clamping (mean difference =–0.6 (95% CI –2.1 to 0.9)).

This report describes, for the first time, HR quartiles for healthy newborns ≥35⁰ weeks’ gestation from 15 s to 20 s and up to 10 min after CD with extrauterine placental transfusion and PBCC.

To clarify and define the clinical practice concept of early mobilisation after abdominal surgery.

A concept analysis guided by Walker and Avant’s method.

MEDLINE (Ovid), AMED-(Ovid), Embase (Elsevier) and CINAHL (EBSCO) were searched through 5 December 2024.

Relevant studies that included combinations of the terms ‘early mobilisation’, ‘early ambulation’, ‘early acceleration’, ‘abdominal surgery’ and ‘surgical procedures’ were selected. We restricted the search to English full-text publications involving adult patients, limited to the year 2000 and onward. Inclusion criteria were original research articles describing the timing and/or type of mobilisation.

The study derives its defining attributes, antecedents and consequences through data analysis. To enhance understanding of the model, we constructed related and contrary cases of the concept and outlined relevant empirical referents.

In total, 140 studies were included in the analysis. Early mobilisation is characterised by the key defining attributes of initiating active physical movement, including standing, sitting in a chair or walking, within the first 24 hours of surgery. Antecedents include haemodynamic and respiratory stability, adequate pain management, and the patient’s cognitive and physical readiness. Contextual antecedents include competent and adequately staffed healthcare teams. Consequences include improved physiological recovery and enhanced postoperative outcomes.

This analysis provides a clarified, practice-focused definition of early mobilisation after abdominal surgery. By delineating its key attributes and contextual prerequisites, the study offers a conceptual foundation that can support clinical guidelines, promote consistent implementation and inform future research aimed at optimising postoperative recovery.

Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors.

This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres.

This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis.

NCT07025629.

Co-design of the PREDICT-Kidney online tool by patients, members of the public and healthcare professionals (HCPs), to support the communication of the risk of recurrence following surgical treatment for kidney cancer.

Qualitative co-design study. Using an iterative process, feedback was collected (via workshops), prioritised and implemented.

Online workshops with participants from across the UK were conducted between December 2023 and November 2024.

18 adult participants, including patients surgically treated for kidney cancer, members of the public without a history of kidney cancer and HCPs involved in kidney cancer care.

To produce an online tool to support the communication of risk of kidney cancer recurrence that is easy to use, easy to understand and acceptable to stakeholders. Secondary outcomes are the properties of the feedback collected, including volume and type.

Across nine workshops, 99 discrete feedback items were collected, resulting in 71 actionable changes to the initial prototype tool. Differences in priorities were observed between participant groups, especially around the inclusion of information about competing risks of death. Participants valued the tool for improving consistency of follow-up information, supporting shared decision-making and providing multiple visual formats to communicate risk. Iterative feedback led to refinements in terminology, design, content and delivery, including adjustments to the presentation of recurrence and mortality risk.

A co-design approach was used to improve the PREDICT-Kidney online tool to align with the needs of patients and HCPs. A feasibility study is required to evaluate its use and impact in clinical practice.

Over 50% of patients participating in cardiac rehabilitation (CR) experience poor sleep and/or, closely related, psychological stress. Although stress management interventions are generally available, they are typically underutilised in CR, and sleep remains an underaddressed component within CR. This is concerning, as poor sleep and stress not only reinforce each other but are also associated with poorer cardiovascular health and lower quality of life. Therefore, the primary aim of the OPtimising CArdiac REhabilitation by REfining Sleep and STress (RESST) study is to investigate the (cost-)effectiveness of adding a behavioural intervention targeted at improving sleep and managing stress during CR (RESST intervention) on sleep and psychological stress. Furthermore, the study aims to explore the (bidirectional) associations between sleep, stress and lifestyle behaviours.

This parallel-arm multicentre randomised controlled trial will include 200 CR patients across 3 major CR centres in the Netherlands who experience poor sleep and/or stress. Patients will be randomised in a 1:1 ratio to standard CR or standard CR with the RESST intervention. Standard CR is a structured programme combining exercise, lifestyle guidance and risk management. On top of standard CR, the RESST intervention consists of 5 in-person group sessions targeting sleep and stress and is based on Acceptance and Commitment Therapy and Cognitive Behavioural Therapy. Primary outcomes are accelerometer-assessed and self-reported sleep and perceived stress. Secondary outcomes include quality of life, psychosocial well-being, chronic stress biomarkers (hair cortisol and cortisone), momentary fatigue, momentary stress and physical activity. Linear mixed models will be used to assess changes in outcomes at 3-month (after intervention and/or CR completed) and 6-month follow-up. The momentary data collected with ecological momentary assessment and accelerometry will be analysed using multilevel linear mixed models to explore the (bidirectional) relationship between sleep, stress and other lifestyle components such as physical activity.

This study was approved by the ethics committee of Erasmus MC, Erasmus University Medical Centre, Rotterdam, the Netherlands (MEC-2024-0238). The findings will be disseminated through publications in peer-reviewed journals, presentations at academic conferences and professional and patient publications.

NCT06505109.

To evaluate the association between metformin use and incident osteoarthritis (OA) in people with diabetes and the impact of dosing.

Nested case-control study within a cohort of >1.4 million individuals from Sweden.

Participants were aged 35–80 years in 2005, without diabetes or OA. We identified persons with incident diabetes between 2006 and 2016 and excluded those with OA before the diabetes diagnosis and those with an incident OA diagnosis within 3 years of the diabetes diagnosis. Cases were defined as individuals with incident OA before 2020 and were matched with up to four controls without OA in the same period, by sex, diabetes duration, birth year (±1 year) and date of diabetes diagnosis (±180 days) using incidence density sampling. Metformin use before the index date (OA diagnosis) was the main exposure. Secondary exposures were quartiles of total metformin use (defined daily doses (DDD)) and duration-adjusted use (DDD/day), reflecting average daily use. We estimated risk ratios with 95% CIs using conditional logistic regressions, adjusted for age at diabetes diagnosis, education, immigration status and comorbidities.

Incident OA diagnosis in primary or specialist care (International Classification of Diseases codes M15–M19).

We identified 4007 cases and 14 111 controls. Any metformin use was not associated with OA risk (risk ratio (RR) 1.02, 95% CI 0.93 to 1.12). Results for higher total use (0.98 (95% CI 0.86 to 1.11)) and duration-adjusted use (0.92 (95% CI 0.79 to 1.07)) showed no or inconclusive associations.

In individuals with incident diabetes and no prior OA, metformin was not linked to a lower risk of developing OA.

Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence.

This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years.

The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences.

2023–5 08 316-27-00.

NCT06398028.

V.12, 18 March 2025

To evaluate the feasibility and relevance of the LIFE-UP Day audit, a simple, 1-day benchmarking tool based on the multidisciplinary LIFE-UP bundle (Limit sedation, optimise nutritional Intakes, engage Families, promote Exercise and follow-UP the patients after discharge) and assessing the implementation of postintensive care syndrome (PICS) prevention strategies in daily practice.

Exploratory multicentre cross-sectional audit study.

Eight Belgian adult intensive care units (ICUs), between April and July 2024.

All patients present at 08:00 on the audit day and hospitalised for ≥24 hours.

An independent nurse collected data on sedation, analgesia, nutrition, family empowerment, physical exercise and post-ICU follow-up. A multidimensional LIFE-UP composite score (raw 0–10 points), normalised to a 5-point scale, was created to quantify adherence to PICS prevention practices based on current recommendations. Feasibility was evaluated through data accessibility, resource needs, cooperation of ICU teams and the ability to complete the audit within 1 day. Relevance was evaluated through adherence to the bundle, assessed by comparing LIFE-UP scores between ICUs. Quantitative results were expressed as median and IQR.

The audit was tested in 87 patients aged 68 (59–74) years, 9 (5–15.5) days after their admission. The audit was feasible across all ICUs: necessary data were available, resources required were minimal and cooperation was excellent. The LIFE-UP score highlighted significant variability between ICUs (2.5 (1.75–2.75), p

The LIFE-UP Day audit proved feasible and provides a first structured framework for benchmarking. Broader implementation will be essential to validate the LIFE-UP score, refine the model and ultimately determine whether it can translate into improved patient and family outcomes.

To examine trends and demographic characteristics of syphilis incidence in Japan using a large nationwide claims database with family linkage, with particular focus on differences by sex, age, HIV status and family relationships.

Retrospective cohort study.

JMDC claims database (JMDC Inc, Tokyo, Japan), a nationwide administrative claims database in Japan, using data from 2016 to 2023.

Individuals aged 16–59 years enrolled in the JMDC database, including employees of medium-to-large companies and their dependents (n=12.5 million).

Syphilis cases were defined by International Classification of Diseases, 10th Revision (ICD-10) codes (A50–A53) with concurrent treatment with relevant antibiotics. We determined syphilis incidence rates per 100 000 person-years, stratified by sex, age, HIV status and family relationships. We also investigated within-couple concordance patterns and reinfection rates.

Among 16.4 million individuals, 9357 syphilis infections were identified among 8881 individuals. Incidence increased markedly during the pandemic, reaching 48.2 (men) and 12.9 (women) per 100 000 person-years in 2023. Men showed consistently high incidence in their 20s–50s, whereas female incidence peaked in the 10s–20s. Among 2 294 184 married couples, dependent women (ie, housewives) showed comparably high incidence to age-matched men (10–20 per 100 000 person-years). In 1286 couples with at least one syphilis case, 12.4% of wives in their 20s were also diagnosed, compared with 2%–3% in older groups. In 20s couples, the proportion of syphilis among wives only and husbands only was similar. Subgroup analysis revealed notably high incidence among unmarried female dependent youths (2022: 66.7 per 100 000 person-years). Individuals living with HIV had substantially elevated incidence (3000–15 000 per 100 000 person-years) and reinfection rates.

Using a large claims database with family linkage, we found that while male syphilis incidence remained dominant, high rates were also observed among dependent women and youths. These findings suggest that syphilis risk may extend beyond traditionally recognised high-risk populations and emphasise the need for targeted screening and preventive strategies in broader demographic groups.

This study aimed to determine the prevalence of fetal malnutrition (FM) among term singleton newborns at birth using clinical assessment of nutritional status (CAN) score. The study also compared the CAN score with selected anthropometric indices to describe their ability to identify FM. Furthermore, it sought to identify maternal and neonatal factors linked with FM among term infants delivered in four public hospitals in South Ethiopia.

Cross-sectional study.

The study was conducted at four public hospitals in South Ethiopia Regional State.

480 live-born full-term babies and their mothers delivered at four public hospitals between 6 June 2021 and 19 April 2022.

FM status at birth was the outcome variable. FM was assessed using both the CAN score and selected anthropometric indices. At birth, measurements of height, weight, head circumference (HC) and mid-arm circumference (MAC) were taken. The MAC/HC ratio, body mass index (BMI) and ponderal index (PI) were computed and contrasted with reference curves. By examining and calculating subcutaneous tissue and muscle loss, the CAN score was used to determine the newborn’s CAN status. A CAN score of

This study of 480 newborns found varying rates of FM depending on the diagnostic criteria used. The prevalence of FM was highest when assessed by CAN score (26.04%), followed by PI (17.29%), BMI (16.25%), MAC/HC ratio (13.54%) and birth size-for-gestational-age (11.25%). Not attending formal education (AOR 3.31 95% CI 1.14 to 9.64), age between 25–29 years (AOR 2.66 95% CI 1.19 to 5.98), primi-parity (AOR 9.63 95% CI 1.42 to 65.46), having

FM was prevalent among term neonates, with the CAN score showing higher prevalence than anthropometric indices. Education level of the mother, primi-parity, fewer ANC visits, maternal age between 25–29 years and PIH were significant risk factors. FM might be most effectively recognised using the CAN score, which can be done without advanced tools.

To document the first application of the WHO New Vaccine Introduction Prioritization and Sequencing Toolkit (NVI-PST) in the WHO Eastern Mediterranean Region and to describe how Iran’s National Immunization Technical Advisory Group (NITAG) adapted and implemented the framework to develop a prioritised roadmap for vaccine introduction during 2025–2030.

Policy implementation case study applying a structured multicriteria decision analysis-informed prioritisation framework through a three-phase process including framework adaptation, evidence synthesis, ordinal ranking of candidate vaccines, weighted aggregation and development of sequencing scenarios.

National immunisation governance process in Iran, coordinated by the Ministry of Health and Medical Education and Iran’s NITAG, with technical support from the WHO Country Office.

Core and non-core members of Iran’s NITAG and key immunisation stakeholders involved in the deliberative prioritisation process.

Human papillomavirus (HPV) vaccine ranked highest in both importance and feasibility, followed by pneumococcal conjugate vaccine (PCV) for high-risk adults and seasonal influenza vaccine for high-risk groups. Two sequencing scenarios were proposed: both placed HPV first, with either PCV or influenza third after the already-approved hexavalent vaccine. Respiratory syncytial virus (RSV) and varicella vaccines were classified as low priority for the 5-year horizon. The toolkit enabled structured multistakeholder deliberation, improved the transparency and reproducibility of prioritisation, and supported systematic integration of epidemiological, economic and programme evidence. The main implementation challenges arose from national evidence constraints, particularly gaps in adult RSV and pneumococcal disease burden, limited locally generated cost-effectiveness analyses and uncertainty in long-term budget impact estimation under macroeconomic instability, rather than from limitations of the toolkit itself.

The NVI-PST proved feasible under national leadership and generated credible, consensus-based recommendations aligned with Iran’s public health priorities and programme constraints. Minor refinements (streamlined evidence compendium, simpler weighting, stronger secretariat support) would make the toolkit lighter and more sustainable, especially for resource-constrained settings. This Iranian experience provides a replicable model for structured multi-vaccine prioritisation in the Eastern Mediterranean Region and beyond.