An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.

No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.

CRD42025644244.

A large bowel cancer chemoprevention potential has been demonstrated by the consumption of carrots, which represent the major dietary source of polyacetylenes. Their interaction with cancer cells and enzyme systems of animals and humans has been systematically investigated over the last 15 years and has now been characterised as anti-inflammatory compounds with antineoplastic effect. Our objective is to investigate whether selected carrot species with a high content of the polyacetylenes falcarinol (FaOH) and falcarindiol (FaDOH) prevent neoplastic transformation and growth in humans, without side effects.

We will conduct a multicentre prospective binational (Denmark and Sweden) randomised controlled trial, with the aim to test the clinical effects of adjuvant treatment with carrot juice in patients who had an excision of high-risk colon adenomas. Patients from six centres will be randomised to receive either anti-inflammatory juice made of carrots high in FaOH and FaDOH or placebo. We will compare the proportion of participants with recurrent adenoma and mean size of them, found in the 1-year follow-up colonoscopy between the two randomised groups.

Informed written consent will be obtained from all participants before randomisation. The study was approved by the regional ethics committee in Denmark (ref. S-20230072) and Sweden (ref. 2024-04732-01). After completion of the trial, we plan to publish two articles in high-impact journals: one article on primary and secondary outcomes, respectively.

NCT06335420.

This study aimed to explore the psychosocial adaptation processes and coping methods among patients with diabetic retinopathy (DR), emphasising the importance of understanding their lived experiences.

A qualitative study using semi-structured interviews.

A tertiary eye hospital in northeastern Iran.

The participants comprised patients with DR, their families and healthcare professionals.

Qualitative data were analysed based on transactional stress theory using deductive thematic analysis to identify psychosocial adaptation concepts.

65% of participating patients had DR for more than 5 years. Analysis of 49 patient and 14 healthcare professional interviews revealed 6 key themes encompassing 15 categories and 33 subcategories: primary appraisal (threat perception, motivational assessment, self-blame), secondary appraisal (perceived control over disease outcomes, perceived control over emotions, self-efficacy), coping efforts (problem management, emotional regulation), meaning-based coping (positive reassessment, reinforcement of religious beliefs, constructive approach), moderators (seeking information, all-encompassing assistance) and adaptation (emotional health, individual-social functioning).

The analysis revealed that deficits in disease awareness, financial and systemic barriers and emotional distress significantly impeded adaptive coping. Conversely, self-efficacy, social and organisational support, and meaning-based coping strategies were key facilitators. Our findings suggest that facilitating positive psychosocial adjustment in patients with DR may require interventions that address these specific barriers and leverage these facilitators, such as providing comprehensive disease knowledge and constructing robust support systems. This study highlights the potential value of a holistic care approach that integrates medical treatment, targeted patient education and psychological support to improve the overall quality of life for these patients.

In the last 60 years, newborn bloodspot screening (NBS) has expanded as a public health intervention from a single severe childhood genetic disease (SCGD) to up to as many as 80 SCGD and testing of ~40 million newborns/year worldwide. However, the gap between current NBS and its potential to increase the efficiency, effectiveness and global equity of healthcare delivery for SCGD is large and rapidly growing. There are now effective therapeutic interventions—drugs, diets, devices and surgeries—for up to 2000 SCGD. Since almost all SCGD can be identified by bloodspot genome sequencing, it has been a longstanding goal to supplement current NBS with genome sequencing-based NBS (gNBS) for all eligible SCGD. We recently described a novel gNBS platform (named Begin Newborn Genome Sequencing (BeginNGS)) with the potential to overcome several major challenges to gNBS (cost, scalability, false positives and an unprepared healthcare workforce). A pilot clinical trial of BeginNGS for 412 SCGD in a level IV neonatal intensive care unit (NICU) had a true positive rate of 4.2%, sensitivity of 83%, positive predictive value of 100% and clinical utility rate of 4.2%, indicating readiness of the platform for use in a powered, multicentre study.

The BeginNGS study is a single group, international, multicentre, adaptive clinical trial to compare utility, acceptability, feasibility and cost-effectiveness of BeginNGS gNBS (experimental intervention) with standard NBS (control). A minimum of 10 000 neonates (aged 50 000 US children per year.

This study was approved by the WCG Clinical institutional review board on 14 February 2024, and the most recent amendment approved on 7 October 2025 (approval number 20235517). Study findings will be shared through research consortium workshops, national and international conferences, community presentations and peer-reviewed journals.

NCT06306521.

Lynch syndrome (LS) carriers have a 20–46% lifetime risk of colorectal cancer (CRC) due to mismatch repair gene variants. Mesalamine (5-ASA, 5-aminosalicylic acid), used safely in patients with ulcerative colitis, may reduce CRC risk in LS by decreasing microsatellite instability, a key driver of LS-related cancer. This study evaluates 5-ASA’s efficacy as a tolerable chemopreventive drug, aiming to improve long-term CRC prevention in LS.

This multicentre, multinational, randomised, double-blind, two-arm, phase II clinical study will compare the effects of a 2-year daily intake of 5-ASA (2000 mg) to placebo in LS carriers. The primary objective is to assess whether mesalamine reduces colorectal neoplasia, both benign and malignant, compared with placebo in LS carriers, as detected by colonoscopy at the end of the treatment period (24 months±1 month) and on study completion. Secondary objectives include evaluating whether 5-ASA reduces neoplasia/tumour multiplicity and progression compared with placebo at specified time points, examining variations in the effects of 5-ASA versus placebo based on cancer history, sex and age (

The trial is currently open for enrolment, having received ethical approval from the Regional Ethical Review Board in Stockholm and funding from the Swedish Research Council. The study protocol is the finalised V.10.0 (11 April 2024), transitioned to the European Clinical Trials Information System. LS remains underdiagnosed, which may limit recruitment. The results are of global interest and will be published in peer-reviewed journals and presented at scientific conferences.

ClinicalTrials.gov: NCT04920149. EudraCT: 2019-003011-55. EU CT: 2024-514765-19-01.

Stroke volume is a major determinant of tissue perfusion and, therefore, a key parameter to monitor in patients with haemodynamic instability and hypoperfusion. Left ventricular outflow tract (LVOT) velocity-time integral (VTI) measurement using pulsed-wave Doppler is widely used as an estimation of stroke volume and should be a competence required for every intensive care unit (ICU) physician. Artificial intelligence (AI) applied to ultrasound facilitates the acquisition of adequate images. The aim of the present study is to evaluate the interchangeability of LVOT VTI measurements obtained by minimally trained operators and expert physicians, both guided by AI.

This is a prospective multicentre randomised controlled trial. ICU patients in whom fluid administration is considered necessary will be included. A minimally trained operator and an expert will independently measure LVOT VTI, guided by the UltraSight AI software to obtain the best five-chamber view, before and after a 250 mL fluid challenge. The order of acquisition between each operator will be randomised. 100 patients will be included.

The primary endpoint is the relative difference in LVOT VTI between operators. Secondary outcomes include the concordance of the therapeutic decision made by the blinded physician in charge of the patient based on the measures obtained by each operator, and the agreement between absolute values of LVOT VTI obtained by minimally trained and expert operators.

The study has been reviewed and approved by a regional ethics committee (Comité de Protection des Personnes—Ile de France II—n°24.00671.000291). An information note will be given to the participant before he or she participates in the study. The present study will be disseminated through peer-reviewed publications and academic and medical conferences.

NCT06486467.

Type 1 diabetes (T1D) demands self-management skills, knowledge and confidence to prevent medical complications. Adolescents living with T1D have distinct developmental challenges resulting in a worsening in glycaemic stability, irregular care and an increased risk for complications all while transitioning to adult healthcare. Age-specific online platforms could facilitate transition by fostering self-management education and support. The Support online self-guided training platform has been shown to increase the confidence of adults with T1D in managing their glycaemia. We aim to test the effectiveness of Support-t (ie, adapted for youth), compared with usual care, in improving haemoglobin A1c (HbA1c) and to understand the context of its implementation.

We will conduct a multisite, assessor-blinded, randomised controlled, parallel group, two-arm, superiority trial, evaluating effectiveness and implementation of Support-t versus usual care in 200 adolescents (14–16 years old) living with T1D. The active arm will have an 18-month access to Support-t, and their healthcare team will be trained on the platform’s content. The control arm will receive usual care. The primary outcome is HbA1c at 18 months. Secondary outcomes include self-efficacy for diabetes self-management, transition readiness, diabetes-specific quality of life, diabetes distress, continuous glucose monitoring metrics, number of severe hypoglycaemic events, diabetic ketoacidosis, T1D-related emergency department visits and hospitalisations as well as engagement and satisfaction. A subgroup of participants in the active arm and of healthcare providers will be interviewed assessing barriers, facilitators, engagement and fidelity of the intervention. Primary analysis will be by intention-to-treat. The difference in mean HbA1c at 18 months (with a 95% CI) will be calculated between both arms. A cost-effectiveness analysis is also planned.

December 8, 2024 version of the protocol was approved by the McGill University Health Centre Research Ethics Board (MP-37-2024-9734). Results will be disseminated through peer-reviewed publications and patient-partners’ network.

ClinicalTrials.gov (NCT05910840).

The aim of this study was to analyse associations between crowded housing and children’s indoor living environment, respiratory and allergic disorders and general health.

A cross-sectional study.

Sweden, using data from the Swedish National Environmental Health Survey 2019.

The study sample included 48 512 children (aged 6–10 months, 4 years and 12 years). We also investigated associations in vulnerable subgroups, such as children with asthma and those living under unfavourable socioeconomic conditions.

Primary outcomes in the living environment were at least one sign of mould, poor indoor air quality, unpleasant odours, too warm indoors in summer and too cold indoors in winter. Primary outcomes for children’s health were asthma, airway problems, breathing difficulties, rhinitis symptoms, mould and mites allergy, pollen allergy, furred pet allergy and good general health.

About one in five children lived in an overcrowded home. Factors from the indoor living environment such as perceived poor indoor air quality and mould were significantly associated with crowded housing. Moreover, children who lived in overcrowded conditions were less likely to report good general health than children in non-crowded households (OR 0.64, 95% CI 0.54 to 0.76). This association was even stronger in children with asthma (OR 0.51, 95% CI 0.34 to 0.77). Few significant associations were, however, observed with the respiratory and allergic health outcomes.

Crowded housing is associated both with a poor indoor environment and with poorer general health in children. Children with asthma may experience even poorer general health.

Autism and neurodevelopmental disorders (NDDs) are complex conditions that manifest as significant impairments in social communication and behaviour. Early detection and intervention play a pivotal role in improving outcomes, largely due to the high brain plasticity in infants. The PRECO-TSA study aims to validate the effectiveness of systematic use of the Prévention de l’Autisme (PREAUT) grid for early screening and referral strategies for autism and NDDs in infants, focusing on a coordinated approach that integrates maternal and child protection centre with medical-psychological centres. The goal is to evaluate a streamlined referral system to improve early detection and facilitate effective interventions for children at higher risk of autism.

The PRECO-TSA study is a prospective, pragmatic, multicentre, cluster-randomised controlled trial using an incomplete stepped-wedge design, which maximises external validity. The study includes a 6-month baseline phase, a 3-month semiobservation phase and a 6-month follow-up phase. The 36-month patient inclusion period is followed by a 48-month passive follow-up through the National Health Data System, data collection includes demographic and clinical information, with hierarchical mixed models used to analyse the impact of early screening and referral for autism and NDDs.

This study was funded by the French Ministry of Health (PREPS-20-0186) and was approved by Ile de France I Ethics Committee CPP (number CPPIDF1-2023-DI29-Cat2). The results will be submitted for publication in peer-reviewed journals.

NCT05815095.

To describe the prevalence of cardiovascular disease (CVD) at the time of diagnosis of adult-onset type 1 (T1D) and type 2 (T2D) diabetes, in a recent cohort and compare to a previous cohort from the same region. Further, to explore factors influencing the prevalence of pre-existing CVD, including age, sex, body mass index (BMI) and C-peptide; in the later cohort also heart failure, hyperlipidaemia, tobacco use and physical activity.

Two prospective cross-sectional cohort studies compared.

All primary health care centres and hospitals in Kalmar and Kronoberg counties in Southeastern Sweden.

Adults with newly diagnosed T1D or T2D (classified by combination of islet antibodies and C-peptide) in 1998–2001 and 2016–2017.

Prevalence of hypertension and CVD at diagnosis of diabetes, and associations with beta-cell function, in two cohorts collected 15 years apart. Further, to explore factors influencing the prevalence of hypertension and CVD, and level of C-peptide.

In patients with newly diagnosed T2D, mean age-at-onset had decreased (66±14.1 years vs 63±12.6, p≤0.001) and mean BMI had increased (29.0±5.4 vs 31.4±5.8 kg/m², p≤0.001). Prevalence of pre-existing myocardial infarction had decreased in both T1D (18% vs 7%, p=0.03) and T2D (25% vs 11%, p≤0.001). Pre-existing hypertension had increased in both T1D (23% vs 40%, p=0.01) and T2D (44% vs 61%, p≤0.001). C-peptide level was lower and was associated with several cardiovascular conditions in newly diagnosed T2D in 2016–2017 (p=0.048 p≤0.001).

Patients with newly diagnosed T2D were younger, with higher BMI, compared with 15 years earlier, a challenge for diabetes care. Prevalence of pre-existing myocardial infarction had decreased notably, in line with, but still less than in the general population; while pre-existing hypertension had increased, in both diabetes types. C-peptide was associated with several cardiovascular conditions in newly diagnosed T2D in the recent cohort, which warrants further investigation.

Distal radius fractures account for one-fifth of all fractures in the active elderly population and may cause chronic pain, loss of hand function and reduced work productivity, imposing a significant socioeconomic burden. Most are initially treated with closed reduction and casting, but 30% subsequently require surgery due to insufficient realignment. The current approaches for analgesia for closed reduction are suboptimal. A brachial plexus nerve block provides complete pain relief and muscle relaxation distal to the elbow, potentially creating better conditions for realignment of the fractured bone ends. This may ultimately translate into reduced need for surgery and result in better functional outcomes and fewer complications compared to a haematoma block, which is the current standard care in Denmark.

The BLOCK Trial is an investigator-initiated, parallel-group, allocation-concealed, outcome assessor and analyst-blinded, superiority, randomised, controlled, clinical multicentre trial performed at 11 Danish emergency departments. Eligible adult patients with a distal radius fracture who need closed reduction will be included and allocated 1:1 to either an ultrasound-guided brachial plexus nerve block or a haematoma block. The primary outcome is the proportion of patients with distal radius fracture surgery 90 days after closed reduction. We will include 1716 participants to detect or discard a relative risk reduction of surgery of 20%. Secondary outcomes include treatment-related complications, patient-reported wrist function, pain during closed reduction and proportion of patients with unacceptable radiographic fracture position immediately after closed reduction.

The trial is approved by the Danish Medicines Agency and the Danish Research Ethics Committees (EU CT number: 2024-512191-35-00). All results will be summarised on www.theblocktrial.com, clinicaltrials.gov and euclinicaltrials.eu after publication. Primary and secondary outcome results from 0 to 90 days will be presented in the main article and submitted to a peer-reviewed journal. Results from outcomes on the 12-month follow-up will be presented separately.

NCT06678438.