Cardiovascular disease (CVD) is the leading cause of mortality in patients undergoing chronic haemodialysis (HD). However, relatively few data exist regarding the influence of dialysis treatment on cardiac biomarkers such as high-sensitivity cardiac troponin I and T (hs-cTnI and hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), complicating their interpretation in the diagnosis of acute coronary syndrome and heart failure. This study aims to investigate the intradialytic kinetics of hs-cTnT, hs-cTnI and NT-proBNP, during HD and haemodiafiltration (HDF), in patients treated with chronic HD.

Single-centre, randomised, open-label, crossover study, comparing high-flux HD (FX 100 dialyser) and postdilution HDF (FX 1000 dialyser), regarding their potential clearance of hs-cTnI, hs-cTnT and NT-proBNP, in 24 stable patients treated with in-centre HD without acute CVD. The study will investigate changes in concentrations during and after high-flux HD and postdilution HDF and calculate reduction ratios, dialyser clearance and clearance by adsorption to the membrane of the selected cardiac biomarkers. Blood samples will be collected at baseline, after 10, 30, 60, 120, 180 and 240 min of dialysis and 30 min postdialysis. After 120 min of dialysis, dialysate will also be collected from the dialyser outlet line. The primary outcome is change from baseline in concentrations of hs-cTnI, hs-cTnT and NT-proBNP during high-flux HD and postdilution HDF.

The study has been approved by the North Denmark Region Committee on Health Research Ethics (N-20240016). Results will be published in an international peer-reviewed journal and disseminated at national and international research meetings.

NCT06526702.

Minimally invasive endoscopic procedures constitute the cornerstone of first-line treatment for bulbar urethral strictures, although their long-term effectiveness is limited by high recurrence rates. The Optilume drug-coated balloon (DCB) is a novel intervention combining mechanical dilation with localised delivery of paclitaxel to reduce recurrence by inhibiting scar tissue formation. While its efficacy has been demonstrated in patients with recurrent strictures, its potential as a first-line option in treatment-naïve patients remains unexplored. The FIRST-CARE trial aims to assess the efficacy and safety of Optilume DCB compared with standard endoscopic treatment in treatment-naïve patients with bulbar urethral strictures.

Design: Two-arm, randomised, single-blind (participant), investigator-initiated, parallel-group, multicentre clinical trial. Patients: The study will enrol 140 adult male patients with treatment-naïve, single bulbar urethral strictures ≤3 cm in length. Interventions: All patients will undergo the assigned procedure under general anaesthesia with 1.5 g intravenous cefuroxime. Optilume group patients will receive ≥5 min balloon dilation with localised paclitaxel delivery. The control group will receive standard endoscopic treatment (eg, direct visual internal urethrotomy, laser or dilatation). In both groups, a 12–14 French Foley catheter will be left in place for 3–5 days. Primary outcome: Freedom from repeat intervention within 12 months of follow-up. Primary analysis: Time-to-event will be defined from the date of intervention to the date a repeat intervention is decided (indicated and planned) due to confirmed recurrence, with censoring at 12 months. Groups will be compared using Kaplan-Meier survival analysis and the log-rank test. Cox regression and modified Poisson regression will be used to estimate HRs and relative risks.

The trial is approved by the Danish National Committee on Health Research Ethics (2401370) and will be conducted in accordance with the Declaration of Helsinki and principles of Good Clinical Practice. In line with national guidelines, all eligible patients are counselled regarding available treatment options prior to enrolment. Results will be disseminated via peer-reviewed publications and scientific presentations.

NCT06827210.

To develop and validate the Internalised Stigma Scale for Gestational Diabetes Mellitus (ISS-GDM), a questionnaire measuring self-reported internalised stigma among women with prior gestational diabetes mellitus (GDM). We hypothesised that internalised GDM stigma could be reliably and validly assessed through a short psychometric instrument.

Cross-sectional validation study.

Follow-up data from the Danish, multicentre Face-it trial for women with prior GDM and their families.

In total, 248 women completed the ISS-GDM approximately 1 year after their GDM affected pregnancy.

The primary outcome was psychometric properties of the ISS-GDM, assessed using Cronbach’s alpha, confirmatory factor analysis (CFA) and Rasch analysis (RA). Secondary outcomes included identification of item anomalies (local response dependence, differential item functioning).

A large proportion of respondents endorsed statements reflecting self-disappointment, self-blame and an altered self-perception. Less endorsed statements included feeling inferior to other mothers or guilt towards family members due to GDM. The ISS-GDM demonstrated satisfactory psychometric properties. CFA indicated that item 2 assessing self-perceived capabilities as a mother did not load onto the main factor, while CFA and RA identified local response dependence and differential item functioning by body mass index. After adjustments, a two-factor solution supported calculating a sum score of items 1 and 3–11, with item 2 retained as a stand-alone indicator of perceived parenting capabilities. The 10-item scale demonstrated acceptable reliability (Cronbach’s alpha=0.78).

The ISS-GDM is a reliable and valid tool for assessing internalised stigma among women with prior GDM. Our findings further suggest that a substantial proportion of women with prior GDM experience self-blame and an altered self-perception due to their diagnosis. The ISS-GDM scale enables research into its prevalence, severity and consequences.

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 how parents of children with de novo retinoblastoma (RB) experience the diagnostic process and acute treatment phase, and to identify factors that may support parental coping and adaptation.

A qualitative interview study using reflexive thematic analysis.

National Retinoblastoma Unit at Aarhus University Hospital, Denmark.

Thirty-one parents (21 mothers, 10 fathers) of 21 children diagnosed with de novo RB were recruited via hospital follow-up clinics and a support group day.

For most parents, the diagnostic process was short. In cases of diagnostic delay, parents described frustration and guilt due to missed symptoms. Receiving the RB diagnosis was described as a surreal experience, accompanied by feelings of shock, grief and loss of control. Parents faced challenges in adapting to rapid medical decisions and the unfamiliar demands of hospital protocols. However, meeting the clinical experts was a relief, as parents felt they were in capable hands, experiencing empathetic communication and a clearly framed treatment plan. Parents emphasised the importance of support systems, including family, healthcare professionals and the child’s resilience, as crucial for coping with and managing the diagnosis.

Parents faced a sudden and disruptive transition from symptom recognition to life-altering diagnosis and treatment. While professional care and communication were experienced as supportive, they did not eliminate the emotional impact. Clinical pathways should prioritise early validation of parental concerns and provide transparent communication, both prior to referral and throughout treatment. Future research should examine longer-term parental adjustment and identify interventions that support emotional resilience beyond the acute phase.

This study compared the effectiveness of first-time use of faster aspart with rapid-acting insulin analogues in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).

This retrospective cohort study used data from 1 January 2017 to 8 May 2021 captured in the Clinical Practice Research Datalink Aurum database in the UK.

Patients with T1D or T2D either initiating faster aspart or another rapid-acting insulin analogue (‘new users’) or switching from a rapid-acting insulin analogue to faster aspart or to another rapid-acting insulin analogue (‘switchers’) were included. The index date was the date of first prescription of faster aspart or a rapid-acting insulin analogue, or of switching to a different rapid-acting analogue or to faster aspart.

A total of 9695 and 2170 patients were included in the new users (T1D, 1737; T2D, 7958) and switchers cohorts (T1D, 1764; T2D, 406), respectively.

Glycated haemoglobin (HbA1c) change at 6 months, occurrence of hypoglycaemia from index to 12 months post-index and treatment persistency from index to discontinuation or censoring.

Numerically greater reductions were observed with faster aspart than rapid-acting insulins in T1D switchers and new users in change in HbA1c at 6 months. Patients with T1D who switched to faster aspart experienced a significant reduction in rate of hypoglycaemia (p=0.0021). Treatment persistency was higher with faster aspart than with rapid-acting insulins among T1D switchers. No distinction in treatment persistency was observed between the treatment groups for T1D new users or T2D switchers.

Reductions in HbA1c were numerically larger with faster aspart in three of four subgroups. There was higher treatment persistency with faster aspart vs rapid-acting insulin analogues among T1D switchers.

NN1218-4967.

To develop, evaluate and validate the musculoskeletal health climate questionnaire (MHCQ), a multidimensional questionnaire for measuring musculoskeletal health climate.

Cross-sectional test–retest study including systematic scale development and psychometric validation.

The questionnaire was developed following the best practice recommendations for scale development outlined by Boateng et al (2017), including item development, scale development and scale evaluation with input from experts, stakeholders and the target population. Validation was conducted among employees in three physically demanding occupations in Denmark (care workers, slaughterhouse workers and residential painters), where a total of 1420 participants were recruited through labour unions. Of these, 796 completed the retest survey 30 days later. Exploratory and confirmatory factor analyses (EFA and CFA, respectively), internal consistency (Cronbach’s α), test–retest reliability (intraclass correlation coefficients (ICC)) and SEM were used to assess the psychometric properties. Criterion validity was examined via associations with pain points, pain medication use and sickness absence. Construct validity was assessed using correlations with the prevent for work questionnaire (P4Wq).

EFA and CFA supported a four-factor model (supervisor’s practices, workplace practices, worker involvement practices and workers’ pain practices) with good to excellent fit (comparative fit index, 0.96–0.99; root mean square error of approximation, 0.04–0.06). All scales showed high internal consistency (α=0.80–0.88) and excellent test–retest reliability (ICC=0.86–0.92). Associations with musculoskeletal outcomes supported criterion validity. Weak to moderate correlations with the P4Wq subscales (rho

The MHCQ provides a validated, multidimensional tool to assess workplace climate related to musculoskeletal health. It can support workplace assessments and prevention efforts by capturing shared perceptions of leadership, support, involvement and pain-related norms. Further longitudinal research and the use of objective outcome data are needed to assess predictive validity and strengthen the instrument’s applicability across settings.

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.

Transvaginal and transabdominal cerclage procedures have become established interventions to prevent mid-trimester pregnancy loss and preterm birth. Transabdominal cerclage seems to be superior to transvaginal cerclage in women with a history of a failed transvaginal cerclage. However, with the availability of a less invasive laparoscopic procedure, there is limited evidence concerning which type of cerclage to recommend to many other risk groups. The objective of this trial is to compare laparoscopic abdominal cerclage and transvaginal cerclage in women at moderate to high risk of spontaneous preterm birth.

The trial is an open, multicentre, superiority, parallel arm randomised controlled investigator-initiated trial with an embedded internal pilot. Women in whom the clinician has clinical equipoise between laparoscopic and transvaginal cerclage are randomised to either laparoscopic abdominal or transvaginal cerclage in a ratio of 1:1. The trial extends from sites in Denmark, Finland and Norway. The primary outcome is birth

The Central Denmark Region Committee on Biomedical Research Ethics, Denmark, Helsinki University Hospital Ethics committee, Finland and the Regional Committees for Medical and Health Research Ethics, Norway approved the trial. This protocol is published prior to complete data collection and analysis. Important protocol changes will be made publicly available on ClinicalTrials.org, on the trial website and distributed electronically to all active sites. Positive, inconclusive as well as negative results from the trial will be published in peer-reviewed international scientific journals.

NCT06122506.

To evaluate the effects of diabetes mellitus (DM) and body mass index (BMI) on long-term all-cause mortality in chronic total occlusion (CTO) patients.

Retrospective, nationwide cohort study.

Swedish Coronary Angiography and Angioplasty Registry, between June 2015 and December 2021.

24 284 patients with angiographically confirmed CTO. Prior coronary artery bypass graft surgery excluded. Subgroups were defined by DM status and BMI categories (underweight, healthy weight, overweight, obesity).

Long-term all-cause mortality, assessed by Kaplan-Meier analysis and multivariable Cox proportional hazards regression.

DM was present in 30.3% of patients and conferred a 31% higher risk of mortality (HR: 1.31, 95% CI: 1.20 to 1.42; p2, lowest risk (nadir) at 32 kg/m² and modest rise above 35 kg/m².

In this nationwide CTO cohort, DM independently predicted higher long-term mortality, accompanied by more severe comorbidities and greater CTO complexity, and insulin therapy further elevated hazard. Overweight and obese patients had better survival, while underweight individuals had the poorest prognosis. These findings underscore the importance of individualised risk assessment and management strategies in CTO patients, particularly those with DM or low BMI.

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

Ischaemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively affects patient and graft outcomes. Anaesthetic conditioning (AC) refers to the use of anaesthetic agents to mitigate IRI. AC is particularly associated with volatile anaesthetic (VA) agents and to a lesser extent to intravenous agents like propofol. VA like sevoflurane interferes with many of the processes underlying IRI and exerts renal protective properties in various models of injury and inflammation. We hypothesise that a sevoflurane-based anaesthesia is able to induce AC and thereby reduce post-transplant renal injury, reflected in improved graft and patient outcome, compared with a propofol-based anaesthesia in transplant recipients of a deceased donor kidney.

Investigator-initiated, multicentre, randomised, controlled and prospective clinical trial with two parallel groups. The study will include 488 kidney transplant recipients from donation after brain death (DBD) or donation after circulatory death (DCD) donors. Participants are randomised in a 1:1 design to a sevoflurane (intervention) or propofol (control) group. The primary endpoint is the incidence of delayed graft function in recipients of DCD and DBD donor kidneys and/or 1-year biopsy-proven and treated acute rejection. Secondary endpoints include functional delayed graft function defined as failure of serum creatinine levels to decrease by at least 10% per day for three consecutive days; primary non-function is defined as a permanent lack of function of the allograft; length of hospital stay and postoperative complications of all kinds, estimated glomerular filtration rate at 1 week and 3 and 12 months calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; readmissions at 3 and 12 months, graft survival and all-cause mortality at 12 months.

The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2025.

NCT02727296.

CANN2021 is a nationwide cohort of Norwegian high school students created with the aim of addressing emerging issues in epidemiology of cannabis use through the initial surveillance and examination of its correlates, causes and consequences.

Between 25 February 2021 and 10 April 2021, a core baseline sample of 3490 students (48% boys; 11th grade 35.5%, 12th grade 31.2%, 13th grade 33.3%) from 34 high schools in Norway anonymously completed comprehensive e-surveys assessing their cannabis-related involvement and experiences. A total of 1510 (43.3%) participants (45.8% boys; 11th grade 28.9%, 12th grade 31.1%, 13th grade 40.0%) provided identifying information and consented to administrative contact entailing individual-level linkages of their survey responses to their health and census data as recorded in various national registries since 2010, thus establishing the CANN2021 registry-linkages cohort.

The core baseline sample (N=3490) was largely representative of the Norwegian high school youth between the ages of 17 and 19 years, and as such of relevance to national surveillance needs. One in five (20.3%) reported having used cannabis at least once during their lifetime; of these, 40.9% consented to registry linkages.

E-survey data from the registry cohort will be linked at the individual level to health and administrative registries such as the Norwegian Patient Registry, Education, Crime, Income and Population Registry in 2025, 2029 and 2031. The retrospective and prospective linkages of baseline e-surveys with registry data can thus be used to address a range of epidemiological and public health questions, including examination of temporal associations between various types of early cannabis involvement and putative risk and protective factors, and subsequent health and social outcomes.

Major depressive disorder (MDD) is a major global healthcare challenge. This is, in part, due to the lack of treatment response and chronic course of MDD. Such a course of illness is often termed treatment-resistant depression (TRD) and is seen in over one-third of people with MDD. Reasons for treatment resistance are not well established, nor is the definition of TRD. Duration and severity of depression, however, are associated with TRD and are also associated with cognitive deficits. Thus, TRD could be particularly prone to cognitive deficits and at heightened risk for neuroprogression. While the cognitive profile of MDD has been investigated in several systematic reviews, no systematic review of cognition in TRD exists to date. The present study will fill this gap in the literature. It is expected that TRD will show more severe cognitive deficits than generally reported in MDD and deficits in all cognitive functions are expected.

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be performed of the databases Embase, Pubmed/MEDLINE, PsychINFO and Cochrane including peer-reviewed studies on humans using standardised cognitive tests. Pilot searching was performed in January 2025 and the full search will be commenced in June 2025, with additional searches following completion. Where sufficient data are reported, a meta-analysis comparing deficits in TRD with MDD and healthy control participants will be performed; alternatively, effects based on norms will be calculated. Meta-regression, subgroup and sensitivity analyses will be conducted to explore moderators that are sufficiently reported in the literature. The quality of studies will be assessed by the Newcastle-Ottawa Scale.

Ethical approval is not necessary to perform the study, and results will be presented at a suitable conference and published in a peer-reviewed journal.

CRD42024538898.

For several decades, mortality has decreased more rapidly among individuals with a higher socioeconomic position than among those with a lower position. This widening social inequality gap has increasingly been recognised as an important aspect of public health research and policies. The objective of this study was to examine trends in educational inequality in healthy life expectancy (HLE) in Denmark between 2010 and 2021 at the age of 30 years.

The study is a population-based study based on register data on longest attained education, standard life tables and self-reported health information from nationwide health surveys.

The study is conducted among the general adult population in Denmark.

Participants include respondents from the Danish National Health Survey and the Danish Health and Morbidity Survey in 2010, 2013, 2017 and 2021 aged ≥30 years.

Expected lifetime in good self-rated health, with no long-standing illness and with no activity limitations was estimated by Sullivan’s method, and educational inequality was expressed by the Slope Index of Inequality.

Between 2010 and 2021, educational inequality in HLE increased among both men and women for long-standing illness (5-year trend: +1.1 and +1.2 years) and activity limitations (+2.4 and +2.6 years) but remained stable among men (+0.1 year) and decreased among women (–0.3 year) for self-rated health. For the latter two indicators, the inequality gap narrowed after 2017.

Trends in educational inequality in HLE in Denmark 2010–2021 vary by health indicator. Steadily widening gaps were demonstrated for long-standing illness, while narrowing gaps were seen after 2017 for activity limitations and self-rated health. Future studies are encouraged to explore potential health risk behaviours that may explain or modify these inequality trends.

To describe self-reported treatment and exercise strategies among patients with long-lasting low back pain (LBP) 1 month after consultation at a specialised hospital-based Medical Spine Clinic and evaluate their associations with changes in pain and disability 1 and 3 months after consultation.

Prospective cohort study using questionnaire data before consultation (baseline) and 1 and 3 months after consultation.

Specialised hospital-based Medical Spine Clinic, Denmark.

1686 patients with long-lasting LBP completed the baseline questionnaire; 908 patients responded at 1 month, of them 623 responded at 3 month.

Patients were categorised by treatment (physiotherapy, chiropractic treatment, physiotherapy+chiropractic treatment and no recommended treatment) and exercise strategy (exercise continued, exercise ceased, exercise initiated and not exercising).

Pain was assessed by the numeric rating scale (NRS: 0–10), and disability was assessed by the Oswestry disability index (ODI: 0–100).

1-month postconsultation, half of the patients received no recommended treatment; most others received physiotherapy (42%). Nearly half of the patients continued exercise, 28% continued to be inactive, and 22% initiated exercise. For the population as a whole, pain changed by –0.74 (95% CI –0.90; –0.58) and –1.02 (95% CI –1.22; –0.83) points on the NRS at 1- and 3-month follow-up, respectively, and disability by –2.65 (95% CI –3.51; –1.78) and –4.48 (95% CI –5.59; –3.38) points on the ODI. Differences between treatment strategies were small. However, the two groups not exercising improved less compared with those who continued exercise when adjusted for age, sex and baseline level (order of magnitude from 0.07 to 1.18 points on the NRS and from 4.01 to 9.08 points on the ODI). For pain, these group differences were statistically significant at 1 month (p

Mean improvement was negligible, with no differences between treatment strategies. However, patients not exercising showed no or less improvement, highlighting the importance of exercise in managing long-lasting LBP.