Despite the continued burden of opioid overdose in communities in the USA, effective treatments for opioid use disorder (OUD), such as medication for opioid use disorder (MOUD), remain underused. Motivational interviewing techniques and linkage to MOUD via digital health are innovative practices developed to overcome persistent barriers to accessing MOUD treatment. These practices are merged in a comprehensive digital health platform, RecoveryPad (developed by the Center for Progressive Recovery). Our study, ‘Using System Dynamics Modeling to Foster Real-time Connections to Care’ (NIH Award #: 1R61DA057675-01), is a pilot to assess the feasibility and behaviour change potential of RecoveryPad for our target audience of people experiencing OUD.

This study will recruit 40 participants in Connecticut and New York through online platforms, such as social media and digital advertising, and direct access via quick-response (QR) codes distributed by local community partners. Eligibility assessment and enrolment will be conducted virtually. Individuals reporting symptoms indicating moderate to severe OUD who are at least 18 years of age are eligible for the study, excluding those who are currently receiving MOUD, pregnant or incarcerated. Enrolled participants will interact with an automated chatbot, live recovery coaches and, if desired, be referred to a telehealth MOUD provider via the RecoveryPad platform. Participants will have access to the platform for 30 days and will be asked to complete brief surveys to assess MOUD engagement and secondary outcomes at 30 and 90 days. Additionally, system dynamics (SD) models will be developed at the individual level to simulate participant interactions with RecoveryPad, and at the community level to improve understanding of the systems affecting OUD and MOUD access.

This project received approval from the Yale University Human Investigation Committee in 2024 (HIC # 2000034414). All participants will complete an electronic consent form with detailed study information and release of information to obtain data related to MOUD appointment attendance. Findings and conclusions from this pilot will be disseminated via peer-reviewed publication, advisory board meetings and meetings with community partners.

NCT05832879.

To explore participants’ experiences of potential adverse effects of the Informed Health Choices secondary school intervention across three trial sites and to revise a framework of potential adverse effects of interventions to improve critical thinking about health choices.

This was a qualitative study. We extracted and analysed relevant data from separate process evaluations in each country. Data came from surveying teachers, observing lessons and group and individual interviews with students, teachers and other stakeholders. We modified and applied framework analysis, including five stages: (1) development of an initial framework of potential adverse effects, (2) familiarisation with the data, (3) indexing, (4) abstraction and synthesis and (5) revising the framework. We applied reflexive strategies individually and as a team.

Lower secondary school in five randomly sampled subcounties of Kisumu County in Kenya, districts representing all five provinces in Rwanda, and six districts in the central region of Uganda, between 2022 and 2024.

Students and teachers in the intervention arms of the trials, parents of students in the intervention arms and administrators at intervention schools, as well as curriculum developers and policy-makers.

The intervention involved providing teachers with a 2–3-day training workshop, and digital classroom resources, including lesson plans for 10 lessons to be delivered over the course of one semester.

We generated findings about potential increases in adverse misunderstandings, anxiety related to transfer of learning, adversely experienced cognitive dissonance, work or schoolwork-related stress, inequity, conflicts and waste. The revised framework includes the same categories of potential adverse effects as our initial framework: decision-making harms, psychological harms, equity harms, group and social harms, waste and other harms. We revised other elements of the framework, including definitions of the categories and its structure.

This study provides insight into the potential adverse effects of interventions to improve critical thinking about health choices. The findings complement those of the trials and country-level process evaluations.

Mental disorders are among the leading causes of the global burden of disease and are often associated with severe functional impairment and high societal costs. Psychotherapeutic, psychopharmacological and internet-based mental health interventions have proven to be helpful, but challenges remain, including only moderate response rates, high relapse rates and barriers to accessing mental healthcare. Much of the existing evidence stems from studies conducted in controlled, often standardised settings that only partially reflect real-world conditions, contributing to a ‘scientist-practitioner gap’. Moreover, the mechanisms of change, such as the interaction between treatment intensity, common factors (eg, the therapeutic relationship) and specific intervention techniques, have not been sufficiently investigated. In particular, the relationship of changes in personality functioning (PF) with mental and physical health has not yet been extensively researched.

The PSYMPACT (Psychological Impact Factors of Mental Health Treatments) study will use a longitudinal study design with a naturalistic sample (N 3000) to examine changes in psychopathology, PF and allostatic load in psychotherapeutic, psychopharmacological and internet-based treatments. The aim is to identify factors contributing to improvements and deteriorations in mental and physical health across different settings, including common and specific factors. Additionally, to provide patient perspectives, qualitative interviews will be conducted with individuals with varying levels of severity of mental health problems. Allostatic load will be assessed using repeated hair cortisol measurements. Furthermore, ecological momentary assessment will be used to examine the diurnal variability of PF as well as its more momentary correlates and longer-term outcomes. The central research questions and aims include (1) the assessment of common factors across different treatment settings, (2) associations of specific and common factors with improvements in mental health, including PF, (3 and 4) the importance of treatment intensity and interaction effects with common and specific factors, (5) the association of changes in psychopathology with changes in allostatic load, (6) the trait and state variability of PF, (7) the identification of patients who deteriorate under specific treatments and (8) patients’ perspectives on the effectiveness of different treatment modalities.

Approval was obtained from the Ethics Committee of the Department of Education and Psychology at the Freie Universität Berlin, Germany. Results will be submitted to peer-reviewed specialised journals and presented at national and international conferences.

Before data collection started in November 2024, the study was registered in the German Clinical Trials Register (https://www.drks.de/search/de/trial/DRKS00035560).

Engaging patients in surgical safety is challenging and has not been thoroughly investigated. Although surgical checklists and other safety protocols have been introduced across various surgical fields, preventable adverse events still occur, highlighting the need for additional research. A Patient’s Safety Checklist (PASC) has been developed and validated for use by surgical patients. Its effect on patient safety and patient outcomes is currently being investigated in a Stepped Wedge Cluster Randomised Controlled Trial (NCT03105713). In connection with this trial, we have examined elective patients’ experiences with using the PASC.

An exploratory qualitative study was conducted based on individual in-depth telephone interviews with 31 elective surgical patients. The interviews were carried out across three Norwegian hospitals including seven surgical specialties. The patients interviewed were part of the trial’s intervention arm and had used PASC. The interviews were transcribed verbatim, and reflective thematic analysis was applied.

Three themes were identified in the data: patient awareness, patient actions and utility value. Patients perceived PASC to increase awareness around surgical information, preparations, what to speak up about and which information to seek and repeat. This awareness led to a series of actions, such as ensuring medication control, optimising their own health, contacting healthcare professionals, asking questions, and for some no actions were needed. Patients perceived PASC to have high utility value for their surgical preparation.

The PASC enhanced patients’ involvement in surgical care and safety by ensuring they received systematic, accurate, clear, and understandable information and instructions throughout the surgical pathway. It is one of the few existing interventions that specifically focuses on assisting patients in preparing for surgery and managing their recovery. Further research is needed on the implementation of PASC and its adaptation to other clinical settings.

NCT03105713.

This study aimed to examine how older adults form beliefs about their memory and how these beliefs are influenced by their level of concern about dementia. Inaccurate beliefs and excessive worrying, indicative of erroneous metacognition, are associated with negative health outcomes. This research can help identify mitigation for these harmful effects.

Qualitative focus groups; thematic analysis.

Focus group discussion with healthy older adults hosted at a university in central London.

35 healthy older individuals (women=29) without any psychiatric or neurological diagnoses, over the age of 65 years (mean 75.31, SD: 6.15). 13 participants were identified as having a high level of worry about dementia and 22 as having low worry. Groups were matched for cognitive performance on the Telephone Mini Addenbrooke’s cognitive assessment (Tele-MACE).

Participants were assigned to a focus group depending on their level of worry about dementia. During focus groups, a vignette prompted discussion around lifespan changes in memory and how this affected concerns around memory. This allowed investigation of the differences in beliefs about memory.

Thematic analysis revealed two key themes. First, older adults appear to base their definition of ‘normality’ of their own memory on comparisons. These comparisons were between themselves and others and between themselves now and their own past self. Despite similar strategies to define ‘normality’, those with high dementia worry had stricter definitions of what they determined as normal. The second theme described narratives around the ‘self’ and the ‘other’. There was a difference between those with high versus low worry; those with high worry had a strong focus on the ‘self’, while those with low dementia worry focused on ‘others’.

Comparison is a common metacognitive strategy used in forming beliefs about memory. Targeting the use of comparison is potentially valuable in interventions aiming to alleviate older adults’ memory concerns. Addressing self-focused thinking, for example, with cognitive behavioural therapy, could improve harmful levels of high worry.

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.

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.

To assess atrial fibrillation (AF) burden, symptoms and quality of life (QoL) in endurance athletes with paroxysmal AF.

Prospective cohort study.

Otherwise healthy endurance athletes with paroxysmal AF in Norway, Australia and Belgium. The current study presents baseline measurements collected before the intervention of a randomised controlled trial on effects of individually tailored training adaptation.

AF burden (percentage time in AF) was measured by insertable cardiac monitors (Confirm Rx, Abbott). AF-related symptoms and QoL were assessed using the Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire (AFEQT) with any score

43 athletes (age 57±10 (mean±SD), range 33–75 years, 3 women) were included. The athletes were monitored for 50±18 days. Median AF burden was 0.18% (IQR 0%–2.6%). Out of 29 athletes with at least one AF episode, 21 (72%) had AF episodes >60 min. 13 athletes (30%) had AFEQT overall score 60 min were associated with reduced QoL (mean AFEQT score 78 vs 90, p=0.001 and 78 vs 90, p=0.001, respectively). There were large individual variations between the athletes concerning AF burden, symptoms and QoL.

Although most athletes were still competing, more than half had troublesome symptoms. One-third had reduced QoL, which was associated with higher AF burden and longer duration of AF episodes. Variations between the athletes highlight the need for individually tailored AF management in athletes with paroxysmal AF.

NCT04991337.

To characterise neonatal intensive care unit (NICU) parents’ grieving process across time and to identify their perspectives on the healthcare providers’ actions that acted as facilitators or barriers to the grieving process in the short (3–9 months) and longer term (18–24 months).

Longitudinal mixed-methods study combining standardised grief and care satisfaction scales with qualitative data collected through semistructured interviews. The qualitative component was guided by an interpretive description approach, which is well-suited for generating clinically relevant insights into complex human experiences such as parental grief. Triangulating quantitative and qualitative data enhanced insight into how parental grief and perceptions of care evolved between 3–9 months and 18–24 months post loss.

Tertiary-level NICU hospital in British Columbia, Canada.

13 parents participated in the study, including 10 mothers and three fathers. Among them were two couples who participated as individuals. Their median age was 35 years (IQR: 32–38).

Quantitative data obtained through the application of the Perinatal Grief Scale (PGS) and care satisfaction scale and qualitative data collected through semistructured interviews. Data were collected at two points (3–9 months and 18–24 months post loss) to track parents’ grief over time.

The PGS scores indicated active grieving without complicated grief, while the Care Satisfaction Scale reflected high overall satisfaction with care. Thematic analysis identified two primary grieving stages: the initial traumatic event during NICU hospitalisation and the complex adjustment to life post loss. Key factors influencing parents’ coping mechanisms included respecting the infant’s dignity, enhancing communication and decision-making, preserving the bond between parents and the NICU team, nurturing enduring connections with the infant and aiding in finding meaning from the experience.

The study outlined the stages parents experience during and after infant loss, offering practical steps for NICU professionals to aid families in their healing process.

Asthma is a leading cause of morbidity and healthcare use among children. Risk factors of childhood asthma include atopic predisposition and severe wheezing episodes caused by rhinovirus infection in early life. In children with first-time rhinovirus-induced wheezing, we aim to study the response of a short corticosteroid treatment to prevent recurrent wheezing and asthma.

This is a double-blind, randomised, placebo-controlled, phase IV, international multicentre trial involving eight sites in Norway, Sweden and Finland. Two hundred and eighty 3–23 months old steroid-naïve children are randomised 1:1 to receive oral dexamethasone (0.3 mg/kg/day) versus placebo in 3 days for their first wheezing episode and rhinovirus infection. Rhinovirus is diagnosed with multiplex PCR. The two co-primary outcomes are time to next physician-confirmed wheezing episode, and time to asthma, within 24 months from inclusion. Asthma is defined as fulfilment of the 2007 National Asthma Education and Prevention Program—criteria for initiating asthma controller medication in children aged 0–4 years. Primary interaction analyses are age, gender, atopic predisposition, risk genotypes and viral co-detection. The optimal cut-off on the rhinovirus genome load used to define a true rhinovirus infection will be assessed by exploring interactions between rhinovirus genomic loads and study drug on the co-primary outcomes. Secondary outcomes are number of wheezing episodes, duration and severity of each wheezing episode, bronchial hyperreactivity, quality of life and safety (height/weight development) at 24 months from inclusion.

Rhinovirus positive children with acute wheezing fulfilling inclusion and exclusion criteria are enrolled after informed consent from both caregivers. This trial has received ethical approval from all sites. Results will be submitted to Competent Authorities and disseminated via peer-reviewed publications and conferences within paediatrics and other relevant fields. If proven effective, findings may be implemented directly into paediatric clinical guidelines.

NCT03889743.