Cannabis-based medicine may alleviate breathlessness. This study will investigate whether dronabinol, a synthetic form of ⁹-tetrahydrocannabinol (⁹-THC), reduces breathlessness in patients with severe and very severe chronic obstructive pulmonary disease (sCOPD) compared to placebo.

This single-centre, randomised, double-blinded, placebo-controlled, crossover trial will enrol 30 patients with sCOPD and persistent breathlessness despite optimal treatment. Patients will be recruited from a pulmonary outpatient clinic in Denmark over 24 months. Eligible patients (aged ≥18 years) will receive either dronabinol or placebo for 4 weeks, followed by a 2-week washout, before crossing over to the other treatment for 4 weeks. Exclusion criteria include ongoing infection, substance abuse and significant comorbidities. Primary outcome is breathing discomfort or unpleasantness measured using the 0–10 Numerical Rating Scale. Secondary outcomes include lung function (forced expiratory volume in one second), hair cortisol concentrations, functional tests, plasma THC blood concentrations and questionnaires assessing breathlessness, activity, quality of life, anxiety and depression. Continuous monitoring of vital signs, activity and sleep will be performed using a Garmin Venu 3 smartwatch. Data will be entered into electronic case report forms and monitored by the Good Clinical Practice (GCP) unit in Odense.

This will be the largest randomised, double-blinded, crossover trial to investigate dronabinol in patients with COPD and will provide new knowledge on the efficacy and safety.

Written informed consents will be obtained from study patients. The study has been approved by the Danish Medicines Agency (case number: 2023010659) and the medical research ethics committees (case number: 2301456). It is registered in the European Union Clinical Trials Registry (2024-513593-22-00) and ClinicalTrials.gov (NCT06473701). The trial follows the Declaration of Helsinki II and International Council for Harmonisation-GCP guidelines. Findings will be disseminated in peer-reviewed publications.

The European Union Clinical Trials Registry (2024-513593-22-00) and ClinicalTrials.gov (NCT06473701).

To examine how the population composition, practice organisation and geographical context of general practice clinics are associated with unwarranted variation in prescribing patterns (variation not explained by patient characteristics), using potentially inappropriate medication (PIM) as an indicator of treatment quality.

A nationwide register-based cohort study.

Data on eligible general practice clinics (1703 clinics) in Denmark and their listed patient populations (4 369 915 individuals) were collected from 1 January to 31 December 2021.

Unwarranted variation in PIM was estimated using the clinics’ PIM propensity. PIM propensity in clinics was defined as the ratio between observed and expected PIM incidence among listed patients and was stratified into indicators of underprescribing and overprescribing.

The results demonstrate a 13% difference in PIM propensity between clinics with the highest propensity (90th percentile) and the lowest propensity (10th percentile). When stratifying by underprescribing and overprescribing, we found a relative difference of 12% for underprescribing and 50% for overprescribing between the two groups. Clinics serving male-dominated populations (>55% men 1.11, 95% CI 1.08 to 1.14) and more socially deprived patient populations (deprivation index >40 10.11, 95% CI 1.08 to 1.14) had a higher propensity for overprescribing. Organisational factors associated with overprescribing included single-handed practices (1.08, 95% CI 1.06 to 1.10), smaller patient lists (100 000 citizens: 1.04, 95% CI 1.02 to 1.07). In contrast, disease burden and age distribution in listed patients appeared to have no clinically relevant association with PIM propensity.

This study indicates unwarranted variation in the medical treatment quality, primarily related to overprescribing. Inferior treatment quality was associated with patient composition, practice organisation and geographical context. This emphasises a need for new strategies to address the inverse care law and enhance patient safety.

Cardiovascular disease (CVD) risk remains high but unevenly distributed in patients with type 2 diabetes mellitus (T2DM). Current risk stratification strategies are far from optimal, leading to both undertreatment and overtreatment of patients. The STENO INTEN-CT trial aims to evaluate a strategy of improved CVD risk management by using cardiac CT (coronary artery calcification (CAC)) for stratification and tailoring of multifactorial cardiovascular treatment based on CAC score. We hypothesise that (1) intensified medical treatment will lower CVD event rates in high-risk patients (CAC≥100), and (2) less intensive multifactorial treatment is safe in very low-risk patients (CAC=0).

The Steno INTEN-CT trial is an investigator-initiated, pragmatic, open-label, event-driven randomised controlled trial including patients with T2DM without known CVD. All participants (expected n=7300) will be invited for a non-contrast coronary CT scan. After the scan, participants will be randomised to either standard treatment (blinded for CAC results) or CAC-based treatment. Participants in CAC-based treatment and their general practitioner (GP) will receive information on CAC and a recommendation of multifactorial treatment. High-risk participants in the interventional arm will be invited for one or more initial study visits to intensify treatment with a combination of sodium glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, high-dose lipid-lowering, antihypertensive and antithrombotic treatment. Very low-risk patients in the interventional arm will be recommended less intensive treatment targets. After initial study-related activities, all participants will continue to be taken care of by their GP guided by specific treatment recommendations. The primary outcome in the primary hierarchical analysis (the rate of the combined CVD endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for heart failure) will be monitored through national health registries. The trial is event-driven, but a median follow-up of 5 years is expected. Key secondary outcomes include patient-reported outcomes, quality-adjusted life years and healthcare costs.

The protocol V.1.9 is approved by the Research Ethics Committee and the Danish Medicines Agency and the Danish Data Protection Agency. The results of the study—positive, negative or neutral—will be published in peer-reviewed journals and through www.clinicaltrials.org.

NCT05700877.

To evaluate the impact of video use in out-of-hours primary care (OOH-PC) telephone triage by examining how triage outcomes (ie, ended by telephone, clinic consultation or home visit) changed during a period with video service failure.

Observational register-based study, using periods of video service failure as a randomisation mechanism for a controlled study.

OOH-PC in four of the five Danish regions.

All telephone triage contacts to the OOH-PC call centres between April 2020 and December 2021.

Video service failures resulted in a subset of telephone triage contacts without the option of using video as a triage tool. Video service failures were identified algorithmically based on observed periods without video use.

Proportion of telephone triage contacts with clinic consultations or home visits as triage outcome during a period of video service failure compared with matched reference telephone triage contacts taking place during normal service (1:10), presented as risk ratios (RR) with 95% CI).

The algorithm identified 6605 telephone triage contacts during video service failure. Compared with matched contacts during normal service, these had a 15% higher risk of resulting in a clinic consultation (RR: 1.15, 95% CI 1.09 to 1.20). This effect was primarily isolated to the year 2021 (RR: 1.23, 95% CI 1.16 to 1.31) compared with 2020 (RR: 1.05%, 95% CI 0.97 to 1.13). Video service failure did not significantly affect the risk of a home visit.

Results strongly suggest that the unavailability of the video service is likely to significantly increase the number of clinic consultations in OOH-PC as a triage outcome. Whether this effect is likely to persist in the long term remains unclear.

Early-life exposures, such as nutritional deficiencies, stress, smoking, toxins, medications, diseases, infections and inflammation may affect multiple physiological and metabolic systems in the offspring, including hormonal regulation, bone metabolism and mineralisation, and body composition. Moreover, the effect of these early-life exposures on later health may potentially be mediated through adverse neonatal epigenetic reprogramming of bone-related genes affecting health later in life, especially skeletal development and bone density. Thus, to advance this research further, the overall aim of the project is to investigate if (a) neonatal epigenetic and genetic signature; (b) maternal risk factors during preconception and pregnancy, such as medicine use, diseases, socioeconomic status, major life events, weight, growth and lifestyle; (c) risk factors at birth, such as instrumental delivery, mode of delivery, medicine use, injuries, diseases, weight, size for gestational age, ponderal index, gestational age; and (d) childhood risk factors, such as diseases, medicine use, major life events, weight, growth and lifestyle are associated with hormonal status, lipids, bone turnover markers, bone mineral density, fat mass and lean body mass at age 18–19 years.

Population-based, nationwide, cross-sectional clinical study with potential for longitudinal reassessment. Danish women and men aged 18–19 years old will be selected at random from the Danish National Population Registry and invited if they have available neonatal dried blood spot cards. A total of 2000 individuals will be enrolled. The study combines register data, and neonatal epigenetic and genetic analyses from stored blood with clinical and survey data. Body composition will be measured using dual-energy X-ray absorptiometry. Adult blood and hair samples will be obtained to assess hormonal status, lipids and bone turnover markers. Height, weight, waist and hip circumference, and blood pressure will be measured. Questionnaires on well-being, sleep patterns, dietary and exercise habits, onset of puberty, use of cannabis, nicotine, alcohol and pain medication will be included. Information on medicine use, diseases, socioeconomic status, major life events, weight, growth and lifestyle will be obtained from the national administrative and health registers at the time of conception and during pregnancy for the parents, as well as from the participants throughout their lifetime. Health registries include the Danish Medical Birth Register, the National Patient Register, the Danish National Prescription Register, the National Child Health Register and Statistics Denmark. Multivariate regression analyses will be performed.

This nationwide study has been approved by the Regional Committees on Health Research Ethics for Southern Denmark (S-20230105). The study participants will be enrolled in the study following their informed written consent. Results will be submitted for publication. The Strengthening the Reporting of Observational Studies in Epidemiology Statement guidelines will be used for reporting.

NCT06509776.

Atopic dermatitis (AD) is a chronic, relapsing, heterogeneous skin disease affecting 2%–7% of adults, with roughly 30% having moderate-to-severe disease. AD symptoms, like intense itching and skin pain, carry a substantial disease burden that negatively impacts patients’ quality of life (QoL) and psychosocial well-being. Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to and neutralises interleukin-13 with high potency. Three clinical trials with lebrikizumab (ADvocate 1 and 2; ADhere) demonstrated significant clinical benefit in patients with AD, while the 3-year long-term extension study of lebrikizumab (ADjoin) further demonstrated long-term efficacy and safety in patients with AD. The ADTrust study will evaluate patient well-being, their relationship with their skin, long-term effectiveness, and safety of lebrikizumab, treatment satisfaction, and long-term effect of lebrikizumab treatment on different aspects of patients’ lives, including itch, pain, sleep, fatigue, work impairment and overall QoL among adult patients with moderate-to-severe AD in a real-world setting.

This non-interventional, prospective, observational, real-world evidence study will involve approximately 150 sites across Europe and approximately 1200 adults with moderate-to-severe AD treated with lebrikizumab for 2 years. The primary endpoint is patient well-being assessed by the 5-item WHO Well-Being Index (WHO-5) questionnaire. Key secondary endpoints include clinical effectiveness (Eczema Area and Severity Index and Investigator’s Global Assessment Scale), disease symptomatology and control (Patient-Oriented Eczema Measure, 24-hour peak pruritus, skin pain, fatigue and sleep quality Numerical Rating Scale, and safety and tolerability. Other validated endpoints will evaluate physician-reported and patient-reported QoL and treatment satisfaction (Dermatology Life Quality Index, Treatment Satisfaction Questionnaire-9), patients’ work productivity and impairment (Work Productivity and Activity Impairment (WPAI)-AD) and disease control (AD Control Tool). Novel experimental endpoints will also be evaluated with the aim to assess patients’ relationship with their skin (SkinLove questionnaire), disease control (intensity and frequency of flares) and an Effectiveness Diary^+© (a brief monthly survey on a voluntary basis with the aim to assess the long-term impact of lebrikizumab on three fundamental aspects of the patients’ life: the well-being (WHO-5), the itch intensity (24 hours peak pruritus) and the frequency and intensity of flares). Statistical analyses will be descriptive and explorative and based on observed cases. Missing data imputation may be used to handle missing data for primary endpoints and secondary effectiveness endpoints.

This study will be conducted according to the protocol, which has ethics committee approval (Hamburg Ethic Committee in Germany: 2024-101358-BO-ff), and all applicable laws and regulatory requirements for each participating country. The results will be disseminated through scientific publications and congress presentations.

NCT06815380 (Pre-results).