Cisplatin is a widely used chemotherapeutic anti-cancer drug. However, high-dose cisplatin is also known for its dose-limiting toxicities, including irreversible cisplatin-induced hearing loss (CIHL). Sodium thiosulphate (STS) can bind to cisplatin to form an inactive and harmless complex. A topical application is desired, allowing cisplatin to retain its systemic anti-cancer effect.

The SOUND trial is an investigator-initiated randomised controlled multicentre phase III trial to study the efficacy of transtympanic administration of STS against CIHL in a cohort of 100 patients with head and neck cancer treated with cisplatin at a dose of ≥200 mg/m². Each subject will receive transtympanic STS injections in one ear, chosen by randomisation, before each cisplatin infusion. The contralateral ear serves as an internal control. The primary objective is efficacy (ie, clinically relevant benefit) of transtympanic STS injections against CIHL, defined as a difference in threshold shift of ≥10 decibels between baseline and 3 months after treatment in favour of the STS-treated ear. Secondary objectives include the difference in mean threshold shifts on frequencies essential for speech and extended high frequencies, as well as the difference between both ears in the gradation of hearing loss as defined by ototoxicity grading scales.

The medical ethics committee in the Netherlands approved the trial (Clinical Trials Information System (CTIS) 2023-503313-30-00). The results will be disseminated through the CTIS and peer-reviewed scientific journals.

CTIS 2023-503313-30-00 approved by Medical Research Ethics Committee NedMec.

Couples diagnosed with unexplained subfertility are advised to start mild ovarian hyperstimulation and intrauterine insemination (MOH-IUI) as a primary treatment. Natural feedback mechanisms and hormone release are affected by artificially stimulated cycles and induced ovulation. Additional luteal support could positively affect progesterone patterns in the luteal phase. The LUMO study evaluates whether the addition of exogenous progesterone in the luteal phase following MOH-IUI treatment cycle will improve pregnancy and live birth rates.

A multicentre randomised, double-blind, controlled trial will be conducted in Dutch fertility clinics, academic and non-academic hospitals. There are two treatment arms: group A progesterone luteal phase support; group B placebo, without crossover. All initiated MOH-IUI cycles within 6 months after randomisation are included (study period). Participants will start study medication, applying a daily dosage of 2dd 300 mg progesterone (Utrogestan) or 2dd 300 mg placebo in vaginal capsules on the second day after the IUI procedure. Treatment is continued until the onset of menstruation, a negative pregnancy test (IUI+14 days), a miscarriage or until 7 weeks of gestation in case of a viable pregnancy. Follow-up ends at 12 months after the end of study period (18 months after study randomisation). The primary outcome is cumulative pregnancy rate, achieved within 6 months after randomisation, leading to live birth. A total of 1008 patients (504 patients in each group) will be included.

The study was approved by the Central Committee on Research Involving Human Subjects on 30 January 2023. All participating sites have the approval of the local Board of Directors to participate in the LUMO study. An informed consent form will be signed by all participants. Study results will be presented at (inter)national conferences and published in peer-reviewed journals. It is expected that the results of this trial will be used to draft national guidelines on this issue.

The study is registered in the EU CTIS trial register (2022-501534-33-00), the Dutch trial registry (registration number: LTR 24508), ClinicalTrials.gov (NCT05080569) and the WHO registry (universal trial number: U1111-1280-9461).

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.

A thoracic aortic aneurysm (TAA) is often considered a precursor to an acute type A aortic dissection (ATAAD), a life-threatening condition requiring immediate surgical intervention. While both conditions share histopathological similarities, less is known about their overlap in clinical cardiovascular risk factors. This study aimed to map the cardiovascular disease burden in patients with ATAAD and compare it with patients with TAA.

A multicentre retrospective study.

The data were collected from electronic health records of two academic hospitals located in the Netherlands.

Patients who were treated surgically for ATAAD or TAA between 2000 and 2022 were eligible. This study included 731 patients with ATAAD and 480 patients with TAA.

Hypertension was equally prevalent in both groups (50.9% vs 50.6%, p=0.921). Diabetes was uncommon (3.3% vs 6.7%, p=0.638). Hyperlipidaemia (9.6% vs 20.0%, p=0.001) and peripheral arterial disease (8.8% vs 22.7%, p

This study suggests distinct cardiovascular risk profiles in patients with ATAAD and patients with TAA, highlighting the importance of tailored treatment strategies for aortic disease. Further research is needed to investigate the pathophysiological mechanisms underlying these differences and their impact on thoracic aortopathy.

The long-term success of metabolic and bariatric surgery (MBS) depends largely on adherence to health-promoting behaviour following MBS. Especially, adherence to healthy dietary behaviour in line with guidelines appears to be of the utmost importance. The primary objective of the present study is to evaluate the effect of adherence to dietary behaviour recommendations and the percentage of total weight loss (%TWL) after MBS. Adherence is hypothesised to have a positive influence on the %TWL, 24 months after MBS. Furthermore, we investigate the association of various sociodemographic, organisational, psychological and behavioural factors prior to and after MBS and their effect on %TWL.

The present study is a single-centre observational, prospective, longitudinal cohort study conducted in Germany. Data are collected at nine measurement points (T0: 4 weeks prior to MBS; T1: 2 weeks after MBS, T2: 5 weeks after MBS; T3: 3 months after MBS; T4: 6 months after MBS; T5: 12 months after MBS; T6: 18 months after MBS; T7: 24 months after MBS; and T8: 36 months after MBS). Adherence to dietary behaviour recommendations is assessed using the Dietary Behavior Inventory-Surgery (DBI-S). N=325 patients applying for MBS will be included in the study. A regression analysis approach is chosen to answer the primary research question. The primary outcome %TWL is regressed at T7 (24 months after MBS) in a causal analysis on dietary adherence (DBI-S score) at T3–T7, with the covariates age, gender, marital status, educational attainment, employment status, Patient Health Questionnaire-4 score and body mass index at T0 and MBS method at T1. Stepwise hierarchical regression analyses are performed and analysed for significant model differences using ² difference tests. Effect sizes are estimated by R². Group differences are analysed using t-tests and Analyses of variance (ANOVAs). Bivariate correlations of continuous variables are examined using regression/correlation analyses.

The Ethics Committee of the Medical Faculty of the University of Essen-Duisburg has approved the conduct of the study (24-11969-BO). Results will be disseminated through manuscripts in clinical/academic peer-reviewed journals, presentations at academic conferences and communications with partners, participants and other stakeholders. Key findings will also be published in lay language on a publicly accessible website and disseminated via various (social) media channels.

The study has been prospectively registered on 8 October 2024 in the German Clinical Trials Register (DRKS00034888).

Care pathways (CPs) are widely used to standardise and improve healthcare delivery. However, CP development is often shaped by value (or normative) complexity. This study empirically explores how value complexity unfolds in a CP development programme.

A qualitative single-case study was conducted as part of a 2-year action research programme. The study followed a ‘research-follow-action’ strategy, in which action and learning occurred during the programme phase, followed by retrospective analysis using Greenhalgh et al’s ‘rules of thumb’ as a reflective lens.

A Dutch specialised rehabilitation hospital (13 sites, 800 employees approximately, ~16 000 patients annually). In three CP development cycles, 11 multidisciplinary teams were guided in CP development in a quality collaborative approach.

26 respondents participated in 44 reflective conversations; 19 respondents completed reflective questionnaires and 169 participatory observation reports were included. Participants were purposively sampled and included representatives from the leadership triad (rehabilitation physicians, managers and healthcare professionals) and members of senior management involved in CP development.

Two overarching themes were identified: goal (mis)alignment and prolonged decision-making processes negatively impacted motivation and impeded CP development. Goal alignment between stakeholders was hindered by shifting organisational priorities, creating tensions between improving care quality and ensuring financial viability. Decision-making was challenged by role uncertainty and the complexities of multidisciplinary collaboration in CP development teams. Reflective dialogues, small-scale experimentation and financial modelling supported teams in navigating these tensions to varying degrees.

This study illustrates how value complexity unfolds in CP development and underscores the importance of ongoing stakeholder management, reflectivity, formative evaluation and dialogue. Greenhalgh et al’s rules of thumb provided interpretive value in exploring these complexities but require a solid theoretical understanding and an awareness of the rules’ interrelationships. A complexity-informed approach integrating ongoing reflection and adaptability can enrich CP development methodologies, enabling healthcare professionals and action researchers to engage constructively with value complexity in complex change processes. Further research is needed to develop and implement practical strategies for enhancing stakeholder engagement and decision-making in diverse healthcare settings.