The number of people living with obesity is increasing rapidly worldwide, and the WHO estimates approximately 5 million deaths yearly from non-communicable diseases related to elevated body mass index (BMI). The most effective treatment for weight loss is bariatric surgery, but due to the associated risks and the need for lifelong care, this is not a viable treatment for every patient. With the advent of gut-hormone-based medications to treat obesity, the effectiveness of non-surgical treatment is approaching that of surgical interventions. We therefore aim to investigate the beneficial and harmful effects of laparoscopic bariatric surgery versus any non-surgical treatment.

We will conduct a systematic review with meta-analysis applying our eight-step procedure to assess thresholds for clinical significance and trial sequential analysis to mitigate the risk of random errors. To identify relevant trials, we will search for both published and unpublished trials, without any language restriction, in major medical databases (CENTRAL, MEDLINE, EMBASE, LILACS, SCI-EXPANDED and CPCI-S) and trial registries. The date range covered by the search is from database inception until final search date—within 3 months prior to submission of final results manuscript. Two review authors will independently screen references, extract data and perform risk-of-bias assessment using the Cochrane Risk of Bias Tool 2 and the Grading of Recommendations, Assessment, Development and Evaluations. We will include randomised clinical trials comparing laparoscopic surgery currently in use with any non-surgical comparator in adults or adolescents with BMI >30 kg/m². Quasi-randomised studies or non-randomised studies will not be included. Our critical outcomes are all-cause mortality, serious adverse events and quality of life, and our important outcomes are major cardiovascular events, weight at follow-up, physical function and glycaemic control. In addition, we have two explorative outcomes: metabolic syndrome or Z-score and reported incident of alcohol abuse or other addictive disorder or self-inflicted harm.

This review will collect and perform secondary analysis of data from publicly available sources and ethical approval is therefore not required. The findings will be published in peer-reviewed journals and presented at relevant scientific conferences. We will strive to publish with open access. Awareness will be made through social media platforms. This review aims to help clinicians in identifying best practices in the wide-spanning field of obesity treatment.

CRD420251135341.

To explore maternity care providers’ attitudes toward regional centralisation of vaginal breech birth (VBB) care and gather their recommendations for maintaining clinical proficiency.

Exploratory qualitative study using semi-structured interviews and thematic analysis.

10 hospital-based maternity care professionals (nine obstetricians and one clinical midwife), purposively sampled to represent experience and institutional diversity.

10 hospital maternity units in a metropolitan region of the Netherlands.

Key themes describing provider attitudes towards two proposed models of centralised care (mobile breech team, designated referral centre) and alternative strategies.

Three core themes emerged: (1) proficiency—providers valued regular exposure, formal training and peer support, expressing concern that centralisation would reduce overall workforce readiness; (2) organisation—concerns included unequal access, staffing burden, legal risks and inefficiencies in mobile teams and (3) alternatives—participants preferred a regional breech network with shared training, joint video review and expert on-call support.

Maternity care providers opposed full centralisation of VBB, favouring a networked model that distributes expertise and preserves local access. These insights highlight the importance of involving frontline providers in service redesign.

Not applicable.

To identify early-occurring healthcare and sociodemographic risk factors associated with lower extremity amputation (LEA) by analysing health trajectories up to 10 years before amputation.

A national, observational, registry-based matched case–control study.

The Danish universal healthcare system, using national health registers.

We included 2551 individuals who underwent first-time LEA in 2017–2018 and matched each to two control groups: (1) The Community Controls Group representing the average population who were matched on age, sex and municipality (n=12 748) and (2) a Diabetes Mellitus/Peripheral Arterial Disease (DM/PAD) Control Group matched on age, sex and DM or PAD duration (n=12 478) representing a high-risk population.

Presence of healthcare, sociodemographic and medication-related risk factors associated with LEA was evaluated across three time periods leading up to amputation: the Immediate (0–2 years prior), Early (2–5 years prior) and Long-term (5–10 years prior) risk period.

Polypharmacy and antibiotic use—particularly dicloxacillin targeting Staphylococcus aureus—were strongly associated with LEA across all time periods. Dicloxacillin was prescribed on average 7.8 years prior to major amputation, with long-term ORs of 2.99 (95% CI 2.51 to 3.56) and 2.07 (95% CI 1.75 to 2.46) compared with community and DM/PAD controls. Opioid and paracetamol use also showed strong associations. Individuals with LEA were more likely to live alone and have lower educational attainment. Frequent dental visits were inversely associated with risk.

This study identifies characteristics associated with LEA, including long-term exposure to dicloxacillin and opioid analgesics, alongside polypharmacy and socioeconomic disadvantage. These factors were detectable up to 10 years before amputation and may serve as early indicators for risk identification and guide targeted general practitioner interventions.

To explore patients’ experiences and perspectives on using a direct-to-consumer smartwatch with single-lead electrocardiography (1L-ECG) for ambulatory rhythm diagnostics in primary care.

Qualitative study using semi-structured interviews and thematic analysis.

Primary care patients referred for ambulatory rhythm monitoring in a diagnostic centre.

Eighteen adults with paroxysmal palpitations, of whom nine were female patients (50%), aged 32–85 (median 66) years.

Participants simultaneously wore a smartwatch with 1L-ECG capability (Withings ScanWatch) and a conventional Holter monitor for 7 days.

Patient experiences and perceived barriers and facilitators to smartwatch use for rhythm monitoring, reported after the monitoring period.

Patients found the smartwatch more user-friendly and feasible than the Holter monitor. Difficulties included uncertainty about when to initiate recordings, challenges capturing brief episodes and anxiety triggered by automated algorithm outputs. Participants emphasised the importance of accessible healthcare support for interpretation and reassurance.

This study shows that smartwatch-based 1L-ECG monitoring is feasible and acceptable for ambulatory rhythm diagnostics in primary care. Prior to routine implementation, it is crucial to address the identified challenges: particularly anxiety related to algorithm results, uncertainty about when to record and accessible clinician support.

A cancer diagnosis not only profoundly impacts individuals but also the very core of their families, reshaping their lives in many ways. However, there is a lack of focus on the well-being and health of the entire family across adult cancer research. This is concerning given that one-third of the Danish population will get a cancer diagnosis before the age of 75, suggesting that many Danes will become caregivers during their lifetime. In addition, identifying vulnerable families is challenging, and the determinant factors for their vulnerability are unknown.

The principal aim of this study is to investigate family health during cancer treatment. This will be done by gathering information on various parameters such as perceived support, quality of life and self-efficacy in patients with cancer and families across the cancer trajectory. Additionally, the study seeks to pinpoint particularly vulnerable families and investigate contributing factors to their vulnerability.

This mixed-methods study follows a sequential explanatory design, combining patient-reported outcomes in a longitudinal, prospective multicentre survey with interviews conducted with a nested sampling of the participants from the survey. A total of 240 patients diagnosed with prostate-, breast-, gastrointestinal- and lymphoma cancer, and designated adult family caregivers will be recruited from six different sites for the survey. Variables such as family health, needs and perceived support, quality of life, self-efficacy, depression, stress and resilience will be explored. Survey data will be collected at baseline, 3, 6, 12 and 18 months. The interviews (n=12–15) will be conducted twice with patients and caregivers jointly: once during the treatment phase (3 months) and once after completion of treatment (12 months). For the survey part, we estimated a sample size with 90% power and 5% significance to detect a minimal clinically important change in the Family Health Scale. Assuming an SD of 2x22 = 31, based on a cross-sectional SD of 22, 44 patients per group were required; to allow for dropout, 60 per group (240 total) were included. Patient and caregiver characteristics will be summarised descriptively. Longitudinal patient-reported outcomes will be analysed with linear mixed regression, separately for patients and caregivers. Changes will be reported as mean differences with 95% CIs and compared with published minimal clinically important differences or, if unavailable, 0.3xbaseline SD. For the qualitative part, thematic analysis by Braun and Clarke is chosen to extract data, identify patterns and analyse data and themes from the interviews. NVivo will be used for coding interview data.

The study will be conducted in accordance with the Helsinki Declaration. Measures will be taken to ensure confidentiality, data protection and participant safety throughout the study. The results will be published in peer-reviewed journals and conference presentations.

ClinicalTrials.gov: NCT06433349. Protocol version 2.0, June 2024.

Total diet replacements (TDRs) and weight loss medications (WLMs) have proven effective in producing substantial weight loss for individuals with obesity. Evidence is lacking on whether combining these treatments is effective and cost-effective in primary care for adults with obesity class I (body mass index (BMI) 30–34.9) or uncomplicated obesity class II or higher (BMI≥35 without obesity-related disease).

LightCARE is a 2-year 1:1 randomised, parallel-group, clinical superiority trial with blinded outcome assessment evaluating the benefits and harms of an intensive weight loss (IWL) intervention compared with usual care for adults with obesity in Denmark and the UK. The trial will include 400 participants aged 18–60 years with obesity class I or uncomplicated obesity class II or higher. The IWL programme aims to achieve and maintain a weight loss of ≥20% through a flexible and individualised combination of TDR, behavioural support, including physical activity and sleep guidance, and WLM if needed and will continue for 2 years. The control group will receive usual care offered in each country, typically consisting of brief behavioural support for weight loss. The primary outcome is body weight 2 years after randomisation. Secondary outcomes will include the proportion of participants achieving ≥20% weight loss, Short-Form-36 Mental Component Score, 4-m gait speed and Metabolic Syndrome Severity-Z score. Serious adverse events, the incidence of eating disorders and bone mineral density will be evaluated as safety outcomes. We will also examine the cost-effectiveness of the intervention, within the trial and in the longer term through modelling. We will conduct a process evaluation to inform any future implementation.

Ethical approval was granted in Denmark (December 2023, H-23051332) and the UK (August 2024, 24/SC/0210). Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.

NCT06321432.

Fluid overload (FO) is a common complication following cardiac surgery with cardiopulmonary bypass (CPB) and is associated with increased morbidity and mortality. Loop diuretics, particularly furosemide, are widely used to promote sodium and water excretion, but their postoperative use remains largely empirical. International guidelines recommend early assessment of diuretic response using spot urinary sodium concentration, traditionally measured by automated laboratory analysers. Recent advances now enable bedside measurement of natriuresis using point-of-care (POC) urinary sodium sensors. This trial aims to determine whether real-time bedside natriuresis monitoring using a POC device can guide safer and more effective diuretic strategies in the postoperative management of FO.

The EASY-CS trial is a prospective, single-centre, open-label, randomised controlled trial designed to evaluate whether a natriuresis-guided furosemide titration protocol improves diuresis within 48 hours following cardiac surgery with CPB. A total of 102 adult patients undergoing elective cardiac surgery with CPB and requiring postoperative intravenous (IV) furosemide for FO will be randomised in a 1:1 ratio to either standard care (n=51; furosemide titration based on clinical judgement) or a natriuresis-guided arm (n=51), in which furosemide dosing is adjusted according to urinary sodium concentration. All patients will receive an initial 20 mg dose of IV furosemide. In the intervention group, urinary sodium will be measured every 6 hours using a POC sodium sensor (LAQUAtwin Na⁺ metre, Horiba, Japan). If the spot urinary sodium is

Secondary outcomes include urinary sodium concentration and urine output at 24 hours, natriuresis at 48 hours, and the venous excess ultrasound score at 48 hours, as determined by transthoracic echocardiography. The study will also assess total loop diuretic dose administered, cumulative fluid balance over 48 hours and the incidence of postoperative complications at day 30, including cardiovascular, renal, respiratory and gastrointestinal events. Safety endpoints include the presence of hypotension, hypokalaemia or acute kidney injury before each diuretic administration. Randomisation will be stratified by EuroSCORE II (

Ethical approval has been obtained from the Institutional Review Board (IRB) of Amiens University hospital (IRB-ID: 2025-A00925-44). The study’s results will be disseminated through peer-reviewed publications and presentations at national and international conferences.

ClinicalTrials.gov Identifier: NCT07077772.

The Cardiometabolic function in Offspring, Mother and Placenta after Assisted Reproductive Technology (COMPART) study is a prospective cohort study aiming to explore health outcomes in mothers and children following assisted reproductive technology (ART), with a particular focus on frozen embryo transfer (FET) versus fresh embryo transfer (fresh-ET). The increasing prevalence of ART and FET emphasises the need to assess potential health risks associated with the procedures, both in pregnancy, such as pre-eclampsia and large for gestational age offspring, and in the children, such as obesity and cardiometabolic dysfunction.

The cohort will include 600 pregnant women, their potential partner and their offspring in a 1:1:1 ratio of pregnancies achieved after ART with FET, ART with fresh-ET and women who conceived naturally. The study will involve extensive data collection from electronic medical records; parental questionnaires; biochemical, genetic and epigenetic analyses in blood, urine and placental tissue; and medical imaging (fetal ultrasound and PEA POD scan) and clinical examinations. Outcomes are grouped into six work packages (WPs) related to fetal growth (WP1), pregnancy (WP2), placenta (WP3), offspring (WP4), genetics (WP5) and epigenetics (WP6).

The COMPART study aims to provide valuable insights into the impact of ART and FET on maternal and offspring health and the underlying mechanisms responsible. The study seeks to advance reproductive medicine, shape clinical practice and guidelines and ultimately ensure maternal-fetal health following ART. The study has been approved by the Danish Ethics Committee (H-23071266; February 2024).

NCT06334003

Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective biomedical intervention for HIV prevention, but its access and utilisation are challenging, especially in high-burden settings such as Kenya. For potential PrEP users, long delays and repeated consultations with several providers are obstacles to both PrEP uptake and continuation. The One-Stop PrEP Care project aims to promote the use of PrEP among clients in the health system and enhance client satisfaction by reducing the waiting time.

We are conducting a 1:1 cluster-randomised trial to evaluate whether One-Stop PrEP Care achieves equivalent or better PrEP outcomes compared with the standard of care model in 12 high-volume HIV clinics in Kisumu County, Kenya. In the One-Stop model, all core PrEP components, including HIV risk evaluation, HIV testing and PrEP dispensing, are provided by one provider in a single consultation room. Programme data from ≥2400 new PrEP clients will be abstracted for 12 months each to obtain primary endpoints of PrEP initiation and continuation. Adherence will be assessed via blood drug level testing. A nested cohort of up to 300 PrEP clients will be enrolled and followed every 3 months to provide in-depth data on individual HIV prevention behaviour, risk perception and how they align PrEP use with perceived risk. We will also evaluate programme costs.

Ethical approval was obtained from the University of Washington Institutional Review Board (IRB) on 8 July 2022 (IRB ID: STUDY00015873) and the Kenya Medical Research Institute Scientific and Ethics Review Unit (SERU) with a letter dated 4 May 2023 (Ref: 4697). Project findings will be shared with stakeholders, including the Ministry of Health, County health officials and participants. Results will be disseminated through manuscripts, policy briefs and health meetings.

Plans for communicating important protocol modifications include timely notifications to all study team members and training on the changes, and updates to relevant stakeholders, including the two IRBs, through protocol amendment submissions.

V. 2.0 dated 21 May 2024.

NCT03194308.

This scoping review aimed to map studies on behaviour change interventions that address antibiotic treatment-seeking behaviour for respiratory tract infections in primary and community care settings.

This review is based on the Joanna Briggs Institute guidelines for scoping reviews, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.

A literature search in January 2024 and May 2024 was performed across Medline, Embase, CINAHL, PsycINFO, Web of Science Core Collection, Scopus, EThOS and Google Scholar was performed.

Eligible studies described behaviour change interventions in primary and community care settings, published from 2000 onward across all countries.

Descriptive data relating to study details and intervention functions were gathered and organised according to the Capability, Opportunity, Motivation and Behaviour change framework in a predeveloped data extraction sheet. Dual data extraction occurred, and inter-rater reliability results are reported (K=0.83).

The scoping review identified 38 eligible studies, which consisted of randomised controlled trials (7/38), cluster randomised controlled trials (6/38), randomised experiments (5/38), cross-sectional studies (5/38), qualitative investigations (5/38) and quasi-experimental designs (4/38). Most interventions focused on educational resources (15/38), digital tools (7/38) and community campaigns (6/38), with fewer targeting decision-making processes (4/38) or psychological drivers of antibiotic-seeking behaviour (3/38). Only one study was conducted in low-income and middle-income countries, and only one separately assessed behaviour change as a measured outcome.

This scoping review highlights a wide range of research methodologies within the topic area. There was some limited evidence of intervention efficacy for antibiotic prescription rates, particularly interventions focused on enhancing knowledge and access to resources. However, more emphasis is needed on standardising outcome measures and evaluating long-term outcomes.

Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in patient series of severe acute brain injury. The KETA-BID trial aims to examine the efficacy and safety of S-ketamine for SDs in severe acute brain injury, as well as the feasibility of the trial design.

This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acute brain injury (ie, traumatic brain injury, aneurysmal subarachnoid haemorrhage or spontaneous intracerebral haemorrhage). During surgery, an electrocorticography (ECoG) strip is placed adjacent to injured brain tissue. Patients are continuously monitored throughout their stay at the neurointensive care unit and the neurosurgical step-down unit. In the case of an SD, physiological optimisation of intracranial pressure, brain tissue oxygen tension (PbtO₂), core temperature and blood glucose is initiated. Participants developing SD clusters are randomised for continuous infusion with S-ketamine or matching placebo in a 1:1 allocation with full blinding of the treatment allocation. Infusion rates (ie, dose) and duration of trial medication are adjusted following a dosing algorithm according to SD occurrence. Surviving participants are followed until 6 months after the injury with recording of functional outcome. The primary outcome is occurrence of SDs per hour of monitoring after randomisation.

The Scientific Ethics Committee of the Capital Region of Denmark (H-21056972), the Danish Medicines Agency (EudraCT 2021-003716-12), as well as the Clinical Trials Information System (CTIS 2024-515315-22-00) approved this trial. This trial will provide insight into both SD and the clinical effects of ketamine following severe acute brain injury, presenting a potential new treatment for these patients. The findings will be submitted for publication in peer-reviewed publications.

NCT05095857.

European cardiovascular guidelines recommend systematic atrial fibrillation (AF) screening in community-dwelling high-risk patients. However, little is known about the impact of abnormal screening findings, including AF and non-AF incidental findings on the target population. This gap highlights the need to assess both the benefits and potential harms from patients’ perspectives to fully understand the impact of AF screening. Therefore, the aim of this study is to explore patients’ experiences with AF screening among those who received abnormal findings from ambulatory ECG monitoring.

We conducted a qualitative study using semistructured interviews, analysed thematically. Participants in the PATCH-AF trial, based in Amsterdam primary care, were purposively sampled based on their screening results (AF or non-AF incidental findings), sex and socioeconomic status.

We achieved data saturation after conducting 16 interviews (6 with interviewees diagnosed with AF and 10 with non-AF incidental findings). Participants had a median age of 76 (73–79) years, and 56% were male. Their experiences, whether positive or negative, fluctuated throughout the screening process and depended on their initial motivations for participation in AF screening (seeking extra health checks, finding explanations for pre-existing symptoms or contributing to medical research), expectations and perceived benefits from clarification, diagnostic workup or treatment. Influencing factors included the type of finding (AF or non-AF incidental finding), healthcare provider communication and individual characteristics such as age, socioeconomic status and medical history.

This qualitative study highlights both positive and negative AF screening experiences from the patients’ perspective. It underscores how patients’ motivations and expectations for participation, the type of ambulatory ECG finding and communication and follow-up by healthcare providers shape their overall experiences. Healthcare providers should be aware of these factors to optimise screening consultations. Clear guidelines on communicating abnormal ambulatory ECG findings, especially incidental findings, are warranted.

The Netherlands Trial Register (NTR) number NL9656.