This study aimed to determine the associations between adherence to the 24-hour movement guidelines and symptoms of anxiety and depression among Colombian university students.

Cross-sectional study.

1125 individuals (mean age 20.2±2.5 years; 56.7% female).

Students sampled from a single public university.

Participants completed validated self-report instruments: the International Physical Activity Questionnaire-Short Form to assess physical activity (PA), sedentary behaviour (SB) and the Pittsburgh Sleep Quality Index to assess sleep duration. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale, with a score of ≥11 used to classify elevated symptoms. Binary logistic regression models were used to estimate associations between adherence to the 24-hour movement guidelines (meeting all three, two, one or none) and mental health outcomes, adjusting for potential confounders.

Only 15.5% of students met all three components of the 24-hour movement guidelines. Meeting a greater number of components was significantly associated with lower odds of depressive and anxiety symptoms. In fully adjusted analyses, students who met all three guidelines were less likely to report anxiety symptoms (OR=0.26; 95%CI 0.13 to 0.54) and depressive symptoms (OR=0.42; 95%CI 0.22 to 0.79) compared with those who met none. Among individual behaviours, sufficient PA and adequate sleep were independently associated with lower odds of both outcomes, whereas high SB was associated with higher odds of elevated symptoms.

In this cross-sectional study, adherence to a greater number of 24-hour movement guideline components was associated with lower levels of anxiety and depressive symptoms in a graded manner. However, the cross-sectional design precludes inference regarding directionality or causality, and bidirectional associations or residual confounding remain possible. Longitudinal and interventional studies are needed to determine whether integrated daily movement behaviours influence mental health outcomes in young adults, particularly in Latin American populations.

Genitourinary syndrome of menopause (GSM) is a chronic, oestrogen-deficient condition that is frequently underdiagnosed and undertreated. Although low-dose vaginal estriol improves epithelial trophism and microbial balance, a substantial proportion of women report persistent symptoms. High-quality randomised evidence evaluating combined therapeutic strategies remains scarce. Energy-based modalities, including the erbium:YAG (Er:YAG) laser (=2940 nm), have been proposed as adjunctive treatments. This trial aims to assess the efficacy of Er:YAG laser therapy combined with vaginal estriol compared with estriol alone in postmenopausal women with GSM.

This is a single-centre, randomised, double-blind, controlled clinical trial. Postmenopausal women aged 45–70 years with vaginal pH ≥5.0 and at least one moderate GSM symptom (Visual Analogue Scale ≥4) will be eligible. Exclusion criteria include current systemic or local hormone therapy, previous vaginal energy-based treatment, abnormal cervical cytology and body mass index ≥35 kg/m². All participants will receive vaginal estriol cream (0.5 mg per dose) daily for 14 days, followed by twice-weekly administration for 16 weeks. Participants will be randomised (1:1) to receive either estriol plus sham Er:YAG laser or estriol plus active Er:YAG laser. Three laser sessions will be delivered at approximately 4-week intervals. Assessments will occur at baseline, monthly during treatment and 4 months after the final session. The primary outcome is the Vulvovaginal Health Index, with the primary endpoint defined as the change from baseline to 4 months post-treatment, reflecting sustained effect. Secondary outcomes include GSM symptom severity, vaginal microbiome composition (16S rRNA sequencing), quality of life (Menopause Rating Scale) and sexual function (Female Sexual Function Index). Data will be analysed using repeated-measures analysis of variance or appropriate non-parametric tests, with significance set at p

Ethical approval has been obtained from the Human Research Ethics Committee of UNINOVE. Written informed consent will be obtained. Findings will be disseminated via peer-reviewed journals and scientific meetings.

NCT06873971.

Developmental regression is when children lose one or more skills they have established. Families caring for these children need timely recognition to assist diagnosis and tailored interventions. Families also need support to develop practical skills for caregiving and strategies to promote family well-being and community participation. Given the high caring demands, flexibly delivered approaches are needed to accommodate family routines. Online delivery of health-related interventions that provide coaching, information, or both has been found to be a feasible and effective option for families. Family Focus is a new family-centred online programme, co-designed with parents and family advocates, clinicians, and researchers to support and empower primary carers.

This study is a prospective, pragmatic randomised controlled trial comparing the effectiveness of online parent coaching plus Family Focus (Coaching+FF) to Family Focus alone (FF) for primary carers of children experiencing developmental regression. A sample of 56 families will be randomised in a 1:1 ratio. Outcomes are assessed at baseline, post-intervention and 12-month post-randomisation. The primary outcome is parental stress symptoms at post-intervention. Secondary outcomes include parental depressive and anxiety symptoms, parental engagement in health-promoting activities, family empowerment, family quality of life and child global health outcomes. The study will also examine the uptake and acceptability of specific coaching and FF components and explore the facilitators and barriers to their delivery and implementation.

Ethics approvals were obtained from the participating organisations (Monash Health HREC/107806). Informed consent is obtained from parents/guardians of children prior to study enrolment. Study findings will be disseminated through peer-reviewed publications, conference presentations and lived experience agencies.

ISRCTN25513446.

Pregnancy in women with pre-existing type 1 or type 2 diabetes (T1D, T2D) is associated with increased risk of complications, largely driven by maternal glucose control. Hormonal changes during pregnancy make glucose management more challenging. Physical activity (PA) may improve glucose control and reduce complications; however, little is known about PA patterns in this population and no pregnancy-specific PA guidance exists for women with pre-existing diabetes. Understanding the behaviours and experiences of both pregnant women and the healthcare professionals (HCPs) who support them is needed to inform evidence-based guidance.

This mixed-methods study comprises three sub-studies. The first will recruit 175 pregnant women (75 with T1D and 100 with T2D) who will complete three 7-day monitoring periods, one per trimester. PA will be assessed using wrist-worn accelerometers and exercise diaries, dietary intake via remote food photography, and corresponding continuous glucose monitor and diabetes-related well-being data will be collected.

The second involves a subsample of ~16 women participating in focus groups to explore experiences of being physically active during pregnancy.

The third invites ~100 HCPs involved in diabetes in pregnancy care to complete an online survey, ~10 HCPS will take part in an optional interview about their experiences of providing PA guidance.

The primary outcome is the change in PA across pregnancy. Secondary outcomes include associations between PA, glucose metrics, diet and diabetes-related well-being, and qualitative themes relating to experiences of women and HCP. Quantitative data will be analysed using multilevel modelling and regression analysis, and qualitative data using reflexive thematic analysis.

Ethical approval was granted by the East Midlands Nottingham 1 Research Ethics Committee (25/EM/0190) and University of Exeter Public Health and Sport Sciences ethics committee. Findings will be disseminated through peer-reviewed publications and conference presentations.

Shared decision making (SDM) is advocated as an approach for patient-centred asthma care. However, this approach may not always be feasible or preferred by patients and/or healthcare professionals (HCPs). Knowledge and insights into whether and how the preferred collaboration style in medical decision making is discussed and managed during consultations for severe asthma are limited.

To investigate how HCPs’ and patients’ preferred collaboration styles in treatment decision making are experienced, discussed and managed during consultations.

Qualitative research using semi-structured interviews with HCPs specialised in severe asthma and a focus group with severe asthma patients in The Netherlands. Inductive thematic analysis was used, with results reported according to the COREQ checklist.

Four themes concerning HCPs’ and patients’ experiences were identified: (1) overall preference for SDM, yet (2) ambiguity of SDM’s content, (3) variation in application of SDM and (4) friction between medical focus and patient autonomy in SDM. A fifth theme concerned the discussion and management of collaboration style preferences: limited metacommunication. HCPs and patients seem unable to identify each other’s preferences in collaboration styles. Overall, a lack of communication regarding how to collaborate in making treatment decisions was found. Varying views on meaning and content of collaboration styles, especially SDM, and HCPs’ medical focus seemed to contribute to the lack of communication.

With the lack of communication regarding preferences in collaborating, HCPs and patients are likely to miss out on effective collaboration. Future studies should explore how views and preferences regarding HCP-patient collaboration can be bridged.

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-accepted treatment for advanced Parkinson’s disease (PD). Currently, programming of the DBS is done in a trial-and-error manner and it can take up to 12 months to reach optimal stimulation parameters. Technological advances in electrode design and implantable pulse generator capabilities lead to an almost infinite number of stimulation options. To explore the potential benefit of all these technological advances, a conventional trial-and-error approach is no longer sufficient. Consequently, there is a clear need for a more computational approach to programming DBS systems. This pilot study is a prospective trial to prove the feasibility of programming bilateral STN-DBS for PD in a computational fashion based on patient anatomy, electrode position and brain connectivity. In this study, we aim to assess the safety, practical feasibility and technical feasibility of a computational approach for programming newly implanted STN-DBS patients with PD. This computational approach will be based on a patient-specific DBS setting regarding sweet spots and structural connectivity of the STN. The results of this pilot study will be used to develop a computational approach for DBS programming to use in a future randomised clinical trial.

The iDBS trial will be a prospective randomised feasibility study carried out at the Radboud university medical center. A total of 24 patients with PD eligible for bilateral STN-DBS surgery implanted with Boston Scientific Cartesia leads will be included. Patients will be randomised to receive either (1) computational DBS programming (n=12) or (2) conventional DBS programming based on monopolar review (n=12). The primary endpoints are safety (occurrence of stimulation-induced side effects, duration of induced side effects (temporary or permanent), severity of the stimulation-induced side effects) and technical feasibility (time from surgery to DBS initiation, time from surgery to reaching optimal DBS stimulation settings) of the computational workflow.

Ethical approval for this study has been granted by the Medical Ethical Committee region Arnhem-Nijmegen, the Netherlands (2024–17453). This study will be conducted in accordance with the Declaration of Helsinki and all applicable European and Dutch law. All participants will have to provide written informed consent. Results of the study will be submitted for publication in peer-reviewed journals and conferences.

The study is registered in the OMON-registry (NL87334.091.24, NL-OMON57446).

To determine the prevalence of presbyopia and associated risk factors among Bangladeshi recipients of elderly social safety net payments who were not currently using mobile financial services (MFS) and demonstrated numeracy, dexterity and cognitive prerequisites for smartphone use during eligibility screening for the Transforming Households with Refraction and Innovative Financial Technology (THRIFT) trial. Accessing these payments requires use of online banking, as with a smartphone.

Cross-sectional analysis of trial eligibility screening data.

Community-based screening conducted in two rural subdistricts in Kurigram District, Bangladesh.

Among 13 944 Old Age Allowance and Widows’ Allowance (WA) beneficiaries screened, 953 met trial eligibility criteria, including passing a smartphone readiness assessment and completing near vision examinations.

Presbyopia, defined as binocular presenting near visual acuity of N6.3 or worse, correctable to at least N5 with near vision glasses and with distance vision of ≥6/12 in both eyes.

Among 953 participants (mean age 61.4±7.2 years, 62.6% women), presbyopia prevalence was 62.6% (95% CI 59.5 to 65.7). Presbyopia was significantly positively associated with female gender (adjusted prevalence ratio (APR)=1.19, 95% CI 1.02 to 1.41) and receiving WA (APR=1.20, 95% CI 1.04 to 1.38) in multivariable analyses.

This study highlights a substantial burden of uncorrected presbyopia among a prescreened, randomised control trial-eligible subgroup of social safety net beneficiaries in rural Bangladesh, who were not currently using MFS but demonstrated cognitive and functional capacity to use mobile phones, potentially hampering their ability to carry out online banking. Delivery of reading glasses may improve digital financial access and facilitate broader financial inclusion, a hypothesis currently being tested in the parent THRIFT trial.

NCT05510687.

Management of heart failure (HF) is a challenge, with less than one-third of patients meeting physical activity recommendations.1 Existing cardiac rehabilitation programmes are designed to meet class 1A American Heart Association recommendations for physical activity.1 Benefits, facilitators and barriers to these programmes are described...

To identify and prioritise research uncertainties regarding the assessment, management and rehabilitation of patients with problematic hip replacements through a national Priority Setting Partnership (PSP).

A national PSP using the James Lind Alliance (JLA) methodology.

UK.

Patients, carers and healthcare professionals (HCPs) involved in the care of patients with problematic hip replacements.

A steering group was established. The James Lind Alliance methodology was followed throughout. A nationwide survey was conducted to collect unanswered questions. These were refined, prioritised through an interim survey and ranked at a final consensus workshop.

The initial survey yielded 201 questions, refined to 32. The interim survey had 191 respondents, leading to 19 questions at the final workshop. The top 10 research priorities were agreed on.

This PSP identified key research priorities for problematic hip replacements, focusing on diagnosis, pain management, perioperative optimisation and infection. These priorities can inform researchers and funders to improve outcomes for affected patients.

The aim is to explore co-design facilitators’ perspectives and experiences of using co-design to improve intrapartum care in four sub-Saharan African settings. The inquiry focuses particularly on how they fostered engagement, built trust and mitigated unintended consequences during the co-design process.

Qualitative interview study with reflexive thematic analysis.

Sixteen public and private not-for-profit hospital-based maternity units in Benin, Malawi, Tanzania and Uganda (four per country).

A total population sample of 10 co-design facilitators involved in a hospital-based co-design project implemented in maternity units in Benin, Malawi, Tanzania and Uganda were interviewed. Semistructured interviews were conducted between December 2022 and January 2023.

Co-design facilitators viewed co-design as a collaborative process to develop contextually relevant solutions. Our findings elucidate their role in facilitating consensus-building and fostering stakeholder ownership amidst significant power divides. They described approaches co-design facilitators take to maintain ongoing stakeholder engagement and manage misaligned expectations in a trusting and collaborative environment, while being mindful of existing tensions and power imbalances. They also highlighted key challenges faced, including navigating norms, power imbalances and unintended consequences.

This study underscores the importance of power-sharing, fostering ownership and engaging end users equitably and continuously in co-design efforts, while also being aware of how to address its potential unintended consequences. Further research is needed to understand co-design facilitators’ impact on co-design and how to address unintended consequences for stakeholders during and after co-design activities in intrapartum interventions in low-resource settings.

This study aimed to investigate the association between smoking behaviours during early pregnancy and the risk and severity of gestational diabetes mellitus (GDM), with a particular focus on smoking status, smoking intensity and secondhand smoke exposure.

Secondary analysis of prospectively collected cohort data.

Multi-centre study conducted in South Korea (Korean Pregnancy Outcome Study) between March 2013 and January 2017.

From 4537 pregnant women initially enrolled, 3457 singleton pregnancies were included after excluding cases with transfer, loss to follow-up, twin pregnancies, miscarriages and pre-existing diabetes mellitus. All participants were women of Korean ethnicity.

Primary outcome was GDM and its subtypes (A1GDM: diet-controlled; A2GDM: insulin-requiring). Secondary outcomes were associations with active smoking (before pregnancy and during early pregnancy), smoking intensity dose–response relationships (pack-years) and secondhand smoke exposure among never-smokers.

Among 3457 participants, 231 women (6.7%) were diagnosed with GDM (198 A1GDM, 33 A2GDM). Active smoking before pregnancy (adjusted OR (aOR) 3.98, 95% CI 1.58 to 9.30) and during early pregnancy (aOR 9.90, 95% CI 2.97 to 29.45) were significantly associated with A2GDM, while no significant association was observed with A1GDM. A clear dose-response relationship was observed, with smoking intensity >4 pack-years markedly increasing A2GDM risk (aOR 20.68, 95% CI 6.75 to 59.39). Detailed pack-year analysis showed 4–6 pack-years (aOR 20.57, 95% CI 5.80 to 65.46) and >6 pack-years (aOR 25.98, 95% CI 3.21 to 146.45). Among never-smokers, secondhand smoke exposure showed a borderline association with overall GDM risk (aOR 1.33, 95% CI 0.98 to 1.81).

Maternal active smoking before and during early pregnancy, as well as higher smoking intensity, was associated with an increased risk of pharmacologically treated GDM (A2GDM). Although secondhand smoke exposure did not reach statistical significance, the trend suggested a potential association with GDM risk among never-smokers. These findings provide important evidence for public health strategies for prenatal care, as smoking cessation and environmental smoke avoidance during prenatal and early antenatal care in women reduce the risk of gestational diabetes.

To assess the prevalence and associated factors of dietary practices among antenatal women in Colombo district, Sri Lanka.

This descriptive cross-sectional study examined dietary practices among antenatal mothers in four Medical Officer of Health areas in Colombo, Sri Lanka. A total of 422 participants were selected using stratified random sampling. Data were collected via a validated Food Frequency Questionnaire and analysed using SPSS V.26. Dietary diversity, food variety and animal-source food consumption were assessed. Poisson regression identified predictors of dietary practices, adjusting for socio-economic and pregnancy-related factors. The statistical significance was set at p

Of the 380 antenatal mothers (mean age: 30.72±3.96 years), most were married (98.2%) with 73.7% living in urban areas. Regarding dietary practices, 64.7% had high dietary diversity, while 35.3% had low diversity. Of the sample, 52.1% had a high food variety score and 64.7% had a high animal-source food score. More than half (64.7%) had appropriate dietary practices. Fruits, vitamin A-rich vegetables and rice were the most consumed foods. Key factors influencing dietary practices included age, religion, education, employment and geographical location.

This study highlights the prevalence and factors influencing dietary practices among antenatal mothers. Although the predominant mothers had fair dietary diversities, a considerable number were found to have poor dietary practices. Better dietary practices were associated with major educational attainment, formal employment status and selected residential areas, while younger age, low educational qualification and housewife status were associated with poorer nutrition. The findings indicate that there is an urgent need for interventions related to nutrition for specific vulnerable groups so that they can improve their maternal nutrition and produce better pregnancy outcomes through education and support programmes.

Glaucoma is one of the leading causes of irreversible blindness and is characterised by progressive loss of retinal ganglion cells. While therapies to lower intraocular pressure slow the progression of the disease in most patients, a significant subset still shows progression despite treatment. Transcorneal electrical stimulation (TES) may potentially activate neuroprotective pathways and slow the progression of visual field defects. The OkuStim 2 System is a medical device for TES which was originally developed for the treatment of retinitis pigmentosa and similar retinal dystrophies and shall now be tested for the treatment of glaucoma. Stimulation of the diseased retina with weak currents can activate signalling pathways and the release of substances that have a protective effect on the retinal cells. This neuroprotective effect might preserve physiological functions of the retina for longer and slow down its gradual degeneration. Long-term use is required to maintain this effect. The TES-GPS study is investigating the safety and efficacy of TES in open-angle glaucoma.

TES-GPS (short title for glaucoma pilot study) is a prospective, randomised, double-blind, sham-controlled, single-centre pilot study at the University Medical Center Mainz. 50 patients with progressive visual field loss due to open-angle glaucoma will be randomised 1:1 to receive either TES with the OkuStim 2 System or sham stimulation. The primary endpoint is the change in visual field sensitivity (Humphrey mean deviation) after 18 months. Secondary endpoints include changes in visual acuity, intraocular pressure, optical coherence tomography (OCT) parameters and quality of life (National Eye Institute Visual Function Questionnaire 25, NEI-VFQ 25). The intervention consists of weekly 30 min TES sessions, which are conducted in the patient’s home after initial training in the clinic. The study comprises up to 13 scheduled visits over 18 months.

The study is conducted in accordance with ISO14155, Medical Device Regulation (EU) 2017/745, International Council for Harmonisation Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from the Ethics Committee of the Landesaerztekammer Rheinland-Pfalz in Mainz and from Bundesinstitut fuer Arzneimittel und Medizinprodukte. Results will be published in peer-reviewed journals and presented at scientific conferences.

NCT06682962.

Metabolic bariatric surgery (MBS) can lead to substantial fat-free mass loss (FFML) due to malnutrition, decreased protein intake and insufficient physical activity. Disproportional FFML has been associated with an increased risk for adverse health outcomes. Resistance training (RT) combined with protein intake contributes to maintenance and increase of fat-free mass (FFM) in healthy individuals. However, it is unclear whether RT and protein supplementation can prevent FFML after MBS.

In the EffectiveNess of pRotein supplementatIon Combined witH resistance Exercise training to counteract Disproportional fat-free mass loss following metabolic bariatric surgery (ENRICHED) randomised controlled trial, 400 patients scheduled to undergo MBS will be randomised in a 1:1 ratio to the ENRICHED perioperative care programme (intervention group) or the standard perioperative care programme of the Dutch Obesity Clinic (control group). The study is currently recruiting participants at two centres in the Netherlands: Nieuwegein and Amsterdam. The postoperative standard programme consists of 13 group sessions spread over a period of 18 months. As part of the ENRICHED programme, RT and protein supplementation will be added 3 weeks after MBS. Additional whole-body RT consists of home-based training sessions two to three times a week, and supervised RT sessions of 45–60 min once weekly, performed at 60–75% of one-repetition maximum (1-RM). Protein supplementation will start by adding 20 g of whey protein to the daily intake. The supplementation will be gradually increased with 20 g every 4 weeks until a total of 60 g whey protein a day is reached. After 12 weeks of protein supplementation, the focus shifts towards incorporating protein-rich food products into the daily dietary intake. The primary endpoint is the prevalence of disproportional FFM loss, defined as FFML/total weight loss ≥30%, at 3 months post-MBS. Secondary endpoints are differences in body composition, muscle strength and function, cardiorespiratory fitness, (cardio)metabolic health, health-related quality of life, gastrointestinal discomfort, cost-effectiveness of the intervention and treatment satisfaction. Outcomes will be assessed preoperatively and at 3, 6 and 12 months postoperatively.

The study protocol V.2.0 was approved by the Medical Research Ethics Committee Oost-Nederland (NL-OMON57119) on 9 April 2025. All participants will provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and conference presentations. Insights gained in this study will provide evidence for a patient-tailored intervention that could be implemented in clinical practice.

NCT07156552.

Few artificial intelligence (AI) clinical decision support systems (CDSSs) are ever evaluated in practice. Although some signal of clinical effectiveness may be needed to justify AI deployment and testing, such data are typically unavailable in early-stage research. This conundrum is especially relevant in the intensive care unit (ICU), where conditions like sepsis and acute respiratory distress syndrome (ARDS) require high-stakes decisions. Our group developed the AI ventilator assistant (AVA), a novel AI CDSS for patients with sepsis ARDS receiving invasive mechanical ventilation. But the promising results of predictive performance estimates are not sufficient to assess AVA’s clinical safety and appropriateness prior to future evaluation and deployment. Therefore, we propose a Clinician Turing Test as a novel validation approach to determine whether clinicians can distinguish AVA-generated treatment recommendations from those enacted by real human clinicians. If AVA’s recommendations are consistently indistinguishable from those of real clinicians, thereby ‘passing’ this Turing test, this would provide a strong preclinical signal of safety and appropriateness.

This multisite, randomised, electronic, vignette-based Phase 1b study will use a Clinician Turing Test design. We aim to recruit 350 critical care clinicians, including physicians and advanced practice providers from six US hospitals. Participants will review nine clinical vignettes of patients with sepsis and ARDS derived from the Molecular Epidemiology of Severe Sepsis in the ICU cohort and an associated profile of a suggested treatment plan. For each participant–vignette combination, the source of the treatment profile will be randomly assigned (AI-generated by AVA vs the actually enacted treatment from real human clinicians) in a 1:1 allocation. The primary endpoint is the participants’ accuracy in identifying whether a treatment profile was AI-generated or human-generated, assessed using equivalence testing through a mixed-effects logistic regression model with random effects for participants and vignettes. Secondarily, a fitted binary classifier will assess discrimination ability using the C-statistic. Secondary endpoints include clinicians’ perceptions of the safety and appropriateness of the treatment profiles, confidence in distinguishing AI-generated and human-generated recommendations, interest in AI CDSSs for sepsis and ventilator management and the time to complete the survey. This novel Phase 1b design provides preliminary but essential information about an AI CDSS’s clinical appropriateness without the risk or cost of actual deployment, thereby informing decisions about future clinical implementation and evaluation in real clinical environments.

This protocol was approved by the Institutional Review Board of the University of Pennsylvania (Protocol #858201). Results are expected in 2026 and will be submitted for publication in peer-reviewed journals and presented at scientific conferences.

NCT07025096.

Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation technique that has been shown to improve cognition and mood when applied to certain brain structures and regions. Despite research demonstrating that iTBS may have clinical utility in treating cognitive and mood changes, no study has yet been conducted to explore the potential to modulate the neurophysiological changes that can underpin cognitive and mood changes during the menopause transition. Cognitive and psychological symptoms are commonly reported by females experiencing the menopause transition, and it is thought that these symptoms arise due to various neurophysiological, metabolic and endocrinological changes. Despite being common, there is a lack of treatments available for managing these symptoms and a scarcity of data regarding the mechanisms by which they occur.

The aim of this 5-week randomised, sham-controlled, double-blinded pilot clinical trial (n=72) is to assess the underlying mechanisms of action of iTBS in females in the late menopause transition and the relationship with cognition and mood. Data will be analysed using Stata^TM. Normality checks will guide the choice between parametric and non-parametric tests. Generalised linear models will assess within-subject and between-subject effects across timepoints, with additional regression analyses exploring associations between biomarkers, cognition and mood. Effect sizes, CIs and relevant test statistics will be reported, with significance set at p

The study protocol has been reviewed and ethically approved by the Western Sydney University Human Research Ethics Committee (H16200; 8 November 2024). All participants will provide written informed consent prior to enrolment. Results from this trial will be disseminated via peer-reviewed publications and conference presentations, with findings shared in accordance with open science and data transparency principles.

ACTRN12625000030471, Australian New Zealand Clinical Trials Registry

Rheumatoid arthritis (RA) is a heterogeneous disease, which current treatment guidelines insufficiently accommodate, as they predominantly emphasise the suppression of disease activity. However, a step towards personalised medicine is preferred to further optimise treatment and requires homogeneous subgroups with similarities in pathophysiological mechanisms and treatment responses. Prior research has already demonstrated notable differences in the pathophysiology of patients with autoantibody-positive and autoantibody-negative RA, as well as differences in treatment responses, which may serve as a strong basis for personalised medicine. Additionally, there is evidence suggesting that an early treatment response is indicative of future courses. Based on these findings, we designed a personalised medicine trial in RA that compares the effectiveness and cost-effectiveness of a tailor-made approach with routine care.

The PeRsonalIsed Medicine in RA (PRIMERA) trial is a multicentre, open-label, randomised controlled trial that includes 300 adult patients with newly diagnosed, DMARD-naïve RA, according to 2010 American College of Rheumatology/EULAR criteria. Patients are randomised into either routine care or a tailor-made approach. Both management approaches use a treat-to-target strategy, aiming for low disease activity (LDA, Disease Activity Score using 44 joints (DAS) ≤2.4). In routine care, initial treatment consists of methotrexate along with a single intramuscular dose of glucocorticoids (GCs) and treatment can be intensified after 3, 7 and 10 months if LDA is not reached. Conversely, initial treatment in the tailor-made approach depends on the presence of autoantibodies, with patients with autoantibody-positive and autoantibody-negative RA starting with hydroxychloroquine or methotrexate together with a single intramuscular dose of GCs, respectively. Medication intensifications will be allowed at months 1, 3, 4, 7 and 10. Intensifications at months 1 and 4 depend on whether patients have an early sufficient response to GCs and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively. The tailor-made approach is superior to routine care if no more biological DMARDs (bDMARDs) or tsDMARDs are used after 10 months of treatment, while the mean DAS over time is lower. Our primary outcome is the proportional difference in bDMARD or tsDMARD usage after 10 months of treatment between routine care and the tailor-made approach. Secondary outcomes are DAS over time, time to achieve LDA, cost-effectiveness and patient-reported outcome measurements over time.

Ethical approval has been granted by Erasmus MC Medical Ethics Review Committee (MEC-2020-0825). The results will be disseminated through peer-review journals and medical congresses.

ISRCTN16170070.

Total mesorectal excision (TME) is highly effective for early-stage rectal cancer, but is associated with considerable morbidity, which can substantially impair the quality of life (QoL) of patients. For very early tumours (low-risk cT1), local excision (LE) offers the possibility of organ preservation (OP) with reduced morbidity; however, its application is limited to a selected group. For early tumours where upfront LE is not feasible, primary OP with (chemo)radiotherapy as an alternative to TME surgery has been evaluated in the STARTREC phase II/III studies, which reported promising 1-year OP rates.

The STARTREC-3 trial aims to increase the 2-year OP rate from 60% to 80% in early rectal cancer (cT1–3abN0) and from 30% to 60% in early-intermediate rectal cancer (cT1–3abN1, ≤3 mesorectal nodes measuring ≤8 mm) by intensifying neoadjuvant treatment in different study arms.

STARTREC-3 is embedded in the STARTREC master trial protocol, which uses an adaptive platform study design allowing early termination of inferior treatment arms and the addition of novel arms. The multicentre STARTREC-3 trial investigates three parallel, non-comparative treatment strategies for patients with early and early-intermediate rectal adenocarcinoma who prefer OP over primary TME surgery. All arms start with 5x5 Gy radiotherapy, followed by: an endoluminal boost via contact X-ray brachytherapy (arm 1), an external beam radiotherapy (EBRT) boost by MR-guided EBRT (arm 2) or three cycles of capecitabine oxaliplatin systemic treatment chemotherapy (arm 3). Treatment allocation is predefined and centre-dependent. Response evaluations (MRI and endoscopy) are planned at 14–16 weeks and 26 weeks after onset of radiotherapy. The primary endpoint is the proportion of patients with successful OP at 24 months from onset of therapy. Secondary endpoints include toxicity, QoL, functional and oncological outcomes. Data will be analysed separately for early (cN0) and early-intermediate (cN1) disease. The total planned sample size is 210 patients across the three arms. Interim analyses will be performed for each study arm to determine early failures and discontinue ineffective arms.

The trial was approved by the medical ethics committee NedMec of the Netherlands and is registered in the EU Clinical Trials Information System (CTIS). The results will be published in an international peer-reviewed journal.

CTIS EU 2024-514620-17-00

Post-COVID syndrome manifests with a diverse array of symptoms for which no standard care plan currently exists. Many questions were raised by patients, which underscored the need for a validated patient-reported outcome measure (PROM). Therefore, a post-COVID module was developed to be included in the Assessment of Burden of Chronic Conditions (ABCC-) tool. The ABCC-tool evaluates and visualises the perceived physical, emotional and social burden of one or multiple chronic disease(s) using a balloon diagram and aims to facilitate person-centred care and structured discussions between patients and healthcare professionals. This study explores the patients’ perspective on the content of the ABCC-tool for post-COVID and the tool’s usability in a home-based setting.

All patients who completed the ABCC-tool for post-COVID were invited for an online semi-structured interview. We selected post-COVID patients who had used the tool in the past three months. Interviews were audio recorded and analysed using a thematic approach with Atlas.ti version 23.

Nineteen post-COVID patients (10 males, mean age 56) were interviewed between May and August 2024. The tool was regarded as user-friendly, and patients indicated they would use the tool again in the future. Patients valued the tool’s broad range of topics, some of which are often overlooked in standard healthcare consultations. The tool was comprehensible and relevant according to all patients. The balloon diagram was easy to understand, but a legend explaining the colours of the balloons was preferred. Other suggestions for improvement included adding open-text fields and periodic reminders to increase usability and adding long-term data.

The ABCC-tool is a promising instrument for post-COVID patients, offering a structured way to monitor and communicate experienced burden in addition to standard healthcare consultations. Refinements addressing usability and comprehensiveness are recommended to facilitate its integration into clinical practices.

Cognitive impairment is considered a challenge in medication management for both the affected patient as well as their caregiver. Numerous studies have investigated interventions aiming to improve medication therapy safety in this population; however, there is insufficient knowledge on interventions which support patients and caregivers effectively. The aim of this systematic review is to (1) identify interventions to improve medication therapy safety in older patients with cognitive impairment, and (2) to evaluate their effectiveness.

We will conduct a systematic review of literature with participatory elements of public involvement in every step of the process. Five literature databases (PubMed, CENTRAL, Embase, PsycINFO and CINAHL) will be screened to identify interventions to improve medication therapy safety in older (≥65 years of age) adults with cognitive impairment. To support methodology and evidence synthesis, we will conduct expert panel discussions as well as focus group discussions of caregivers and healthcare professionals. Study selection, data extraction and bias assessment will be conducted independently by two reviewers. For data synthesis, studies will be organised by setting (eg, community setting, hospital setting, nursing home setting).

The responsible Ethics Committee of the Medical Faculty of Heidelberg granted approval for the public involvement strategies in this project (S-562/2024). Results will be presented by publication in an academic journal and at scientific conferences.

CRD42024623352.