Despite growing interest in the therapeutic potential of 3,4-methylenedioxymethamphetamine (MDMA), no targeted measure to systematically assess side effects of MDMA-assisted psychotherapy (MDMA-AP) exists.

Our aim was to develop an MDMA-Assisted Psychotherapy Side Effects Tool (M-SET) to capture side effects over the course of MDMA-AP.

Informed by a systematic review and a review of other relevant questionnaires, we drafted a list of potential side effects. Face and content validation were obtained via a modified two-round online Delphi process involving experts in MDMA-AP and the neuropsychopharmacology of MDMA.

Twelve experts consented to participate over two rounds of Delphi panel deliberations (response rate: Round 1 = 83–92%, Round 2 = 75%). The Delphi panellists were asked to keep, discard, modify or suggest additional items. The final version of the M-SET consists of 165 items across four questionnaires that collect information at screening, baseline, the day of medication sessions and longer term follow-up.

The use of a modified Delphi technique proved a successful method to generate content for the first structured tool designed to evaluate side effects specifically associated with MDMA-AP.

The M-SET is recommended for use in both research and clinical settings. Its implementation has the potential to improve the safety of delivering MDMA-AP as well as support the development of a more systematic and robust evidence base on its safety and tolerability.

To explore the feasibility of a novel multimodal executive function intervention in school-aged children with complex congenital heart disease (cCHD).

Single-centre, single-blinded, randomised-controlled 8-week multimodal personalised executive function intervention (E-Fit) study. Outcomes were measured throughout the intervention, post-intervention (T1) and at 4-month follow-up (T2).

Tertiary care centre between May 2022 and May 2024.

Children 10 to 12 years (M=11.0, SD=0.9) with cCHD without a genetic diagnosis with infant open-heart surgery and reported difficulties (T-scores ≥60) on any of the summary scales of the parent- or teacher-reported Behavior Rating Inventory for Executive Function (BRIEF).

Children with cCHD were randomly assigned to one of two groups: the intervention or the control group. The 8-week intervention was multimodal including three modalities: (1) computerised executive function (EF) training 3x20 min/week with CogniFit; (2) a weekly, remote standardised 1:1 individual EF strategy coaching; (3) analogue games played at convenience. The control group completed activity logs.

Acceptability: Acceptance and Feasibility Scale (AFS) and coach-rated engagement during coaching sessions. Demand: Number of completed computerised training, strategy coaching and analogue game sessions. Implementation: E-Fit Fidelity Measurement System, assessing adherence to core components. Practicality: Retention rate. Integration: AFS integration items. Exploratory efficacy: BRIEF, neuropsychological EF testing and psychosocial variables at baseline, post-intervention (8 weeks) and at 4-month follow-up.

We recruited 42 participants (N_female=20). Acceptability: The intervention was acceptable, with moderate observed engagement. Demand: median number of computerised training sessions completed was 16 of 24 sessions (67%, (IQR; 6 to 19)), all children attended all scheduled coaching sessions, analogue games were played in total a median of 9 times (IQR 4 to 14). Implementation: Coaching sessions could be implemented by the coaches as intended. Practicality: Overall retention rate was 90%. Integration: E-Fit was well integrable into the home setting. Exploratory efficacy favoured the intervention group with improvements in the parent-rated Behavioral Regulation Index of the BRIEF (adjusted Hedge’s (g_A1) = –0.408 to –0.903) and in social responsiveness (g_A1 = –0.427 to –0.521) at T1 and at T2.

E-Fit is a feasible intervention suggesting EF and social responsiveness improvements in children with cCHD. Motivational strategies to improve adherence to computerised training should be refined before a full-scale efficacy trial.

NCT05198583.

Irritability represents one of the most common causes of referral to child and adolescent mental health services. Conceptually, tonic irritability (i.e., persistent grumpy mood) can be distinguished from phasic irritability (i.e., temper outbursts). The objective of this research project is to develop a fine-grained, ecologically valid and multimodal characterisation of tonic and phasic irritability to better understand the differential role of the two components in developmental psychopathology.

The study has a longitudinal observational and experimental design and involves two sites: (a) the Division of Child and Adolescent Psychiatry at the University Hospital of Lausanne and (b) the Division of Youth Mental Health at the Faculty of Psychology at the University of Basel. 220 help-seeking and healthy youths aged 8–14 years and their families will participate in the study consisting of a baseline assessment (i.e., self-report, interviews, cognitive assessments, autonomic measures, as well as in-situ experiments), an ecological momentary assessment (EMA) phase (over 2 weeks, including experience sampling method, cognitive assessment and passive monitoring) and a 1-year follow-up. Statistical analyses will include multilevel regression (e.g., linear mixed modelling).

We obtained ethical approval from the local ethics committees (Cantonal Research Ethics Commission on Human Beings, CER-VD, #2023-01846) and data collection began in January 2025. The results of the present study will be published in peer-reviewed scientific journals and will be presented at key conferences in the field of child and adolescent mental health, as well as at conferences focusing on EMA. Additionally, findings will be disseminated to practitioners, the educational sector and associations working with youths. We further intend to make the findings accessible to the general public through social media, for instance.

Long-term cancer survivors may suffer from significant bio-psycho-social burden even years after treatment. Yet, a structured approach to detect and address bio-psycho-social burden of long-term cancer survivors in primary care is missing in Germany, although family physicians are the primary medical contact for most patients. In this paper, we describe the DELPHIN study aiming to develop and test a structured care model for long-term cancer survivors. The DELPHIN study and intervention will facilitate networking of regional medical and non-medical services. This protocol describes the intervention as well as the pilot study.

The DELPHIN study comprises a developmental and a feasibility phase. In the developmental phase, we will assess (1) the current care needs of long-term cancer survivors (n=1000) using a cross-sectional questionnaire survey; (2) in an additional cross-sectional questionnaire survey, we will address medical and non-medical care providers to assess current care practice for this patient group (n≥250); (3) a qualitative interview study with both long-term cancer survivors (n=12) and family physicians (n=10) will assess patients’ needs and barriers for effective care. Results will then be triangulated to inform development of the DELPHIN intervention. The intervention shall include the following elements: the DELPHIN mobile app for patients with a digital screening tool, a digital treatment plan, a survivorship passport and information on regional medical and non-medical providers. Additionally, a DELPHIN website and a DELPHIN eLearning tool for family physicians will be developed. The subsequent feasibility study will follow 100 long-term cancer survivors using the DELPHIN app for 4 months, with two assessments (t⁰=baseline; t¹=4 months follow-up) regarding the usability of the app and their health-related quality of life. The eLearning tool will be tested by 50 family physicians using three measurement points to evaluate learning success (t^a=before; t^b=directly after eLearning; t^c=after 4 weeks).

The DELPHIN study seeks to address cancer survivors’ unmet bio-psycho-social needs through implementing a digital mobile application. Positive results in the feasibility study will provide the basis for a future effectiveness study and integration into routine care.

The study was reviewed by the Ethics Committee of the University of Bonn, Germany (No: 2024-409 BO) which did not object to the study.

DRKS00035726.

Patients with haematological malignancies undergoing intensive chemotherapy with or without haematopoietic cell transplantation (HCT) are at high risk of complications that may require intensive care. While some studies advocate for early admission of these patients to the intensive care unit (ICU), it has not been formally demonstrated that admission to the ICU as soon as patients have organ injury may improve their outcomes. To demonstrate the efficacy of implementing the National Early Warning System (NEWS) with immediate ICU admission for patients with NEWS ≥7 to decrease hospital mortality and organ failure.

ALHERT is a randomised cluster, controlled trial carried out in 10 French centres. With their informed consent, adult patients undergoing induction therapy for acute lymphoblastic or myeloblastic leukaemia, autologous or allogeneic HCT in one of the participating centres will be included. Five centres will follow local guidelines for ICU admission (control group) while five centres will assess the NEWS at least three times per day with immediate ICU admission for patients with NEWS ≥7 (interventional group). The primary outcome is hospital mortality without organ sustaining therapy. Secondary objectives will be to study the relative weight of each parameter used to calculate the NEWS for predicting the risk of organ failure requiring life-sustaining organ support, to evaluate the feasibility of implementing early warning scores in routine practice by analysing the proportion of patients with NEWS ≥7 effectively admitted to the ICU in the investigational arm, to assess quality of life with EQ-5D-5L (five level European Quality of Life five Dimensions) and assess the cost-effectiveness of this strategy.

The protocol has been approved by the Comité de Protection des Personnes Ile de France I (Ethics Review ID-RCB: 2024-A00969-38). It is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this study will be presented in peer-reviewed journals and at scientific conferences.

NCT06409767.

Malnutrition is a highly prevalent chronic condition that contributes to higher morbidity and mortality in patients with multiple comorbidities. While positive effects of nutritional therapy in the in-hospital setting have recently been demonstrated, the benefits of long-term nutritional therapy after hospital discharge remain uncertain. Herein, we outline the design and rationale of the EFFORTII trial, the largest nutritional trial to date to assess the effects of continued nutritional support after hospital discharge in medical patients, with particular attention to key design decisions regarding nutritional strategy, patient selection criteria and study endpoints.

The Effect of Continued Nutritional Support at Hospital Discharge on Mortality, Frailty, Functional Outcomes and Recovery (EFFORTII) is an investigator-initiated, non-commercial randomised controlled trial designed to evaluate whether ongoing, individualised nutritional therapy after hospital discharge—targeted to meet specific energy and protein requirements—offers a cost-effective approach to lowering mortality, minimising complications and maintaining functional status compared with standard care. Eligible participants are adult, chronically ill medical inpatients at risk of malnutrition. Patients in the intervention group receive individualised nutritional therapy delivered by an experienced dietitian through a combination of telemedicine and in-person consultations. The intervention aims to meet personalised nutritional targets, supported by a trained dietitian. Control group patients receive nutritional counselling at discharge, but no structured nutritional management during follow-up. We designed the trial as an event-driven trial with a target of 247 mortality events (primary endpoint), which will be assessed over approximately 5 years until event-driven endpoint is met. The minimum total sample size is at least 802 participants, based on the assumed treatment HR of 0.70. The main trial is enrolling patients across multiple sites in Switzerland. During the trial, additional sites in Spain joined the study, and their data will be analysed using a patient-level pooled approach.

This study involves human participants and was first granted ethical approval by the Ethics Committee Northwest- and Central Switzerland and then by all participating local ethics committees. Written informed consent will be obtained from all participants. Findings will be disseminated in peer-reviewed journals and academic conferences.

NCT04926597.

Dyspnoea is an existentially burdensome symptom in patients with advanced and progressive diseases such as cancer, chronic obstructive pulmonary disease (COPD) and advanced heart failure. Recent studies have highlighted that symptomatic treatment of dyspnoea is often ineffective and may depend on the underlying disease. Immersive virtual reality (IVR) has emerged as a ‘digital therapeutic’ for conditions such as pain, anxiety, and dyspnoea. Brain functional MRI (fMRI) offers the opportunity to identify distinct patterns of dyspnoea. Current findings are mainly limited to healthy volunteers, but clinical data from patients with life-limiting conditions are needed. The aim of this study is to assess the feasibility of identifying dyspnoea patterns in different life-limiting conditions using fMRI and IVR.

This is an observational monocentric feasibility study, conducted in a tertiary university centre. Healthy volunteers and patients diagnosed with advanced cancer, COPD, or heart failure and suffering from persistent dyspnoea will undergo an fMRI of the brain using IVR. The primary outcome of feasibility will be evaluated using descriptive statistics. Secondary outcomes include analysis of fMRI patterns of dyspnoea across populations, patient-reported burden of participation, and correlation between dyspnoea and psychological symptoms. These preliminary data will help determine the sample size required for a future study evaluating differences in dyspnoea patterns. Exploratory comparison between the characteristics of all four groups will be assessed with Fisher’s test (for proportions) and either independent Student’s t-test or Mann-Whitney test, depending on distribution. Correlations between variables will be tested using the Pearson’s correlation coefficient. Statistical analysis will be performed using STATA.

This study protocol received ethical approval on 23 April 2025 from the Commission cantonale d’éthique de la recherche in the Canton of Geneva, Switzerland. The identification number is 2024-02289. Submission to peer-reviewed journals and presentation in international congresses for the dissemination of the study findings are planned.

Clinical Trials number is NCT07319039; Pre-results.

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.

Despite the high prevalence of chronic low back pain (cLBP), its underlying mechanisms remain poorly understood. Addressing modifiable psychosocial resources and health behaviours such as physical activity offers a promising avenue for reducing the impact of cLBP. Furthermore, although the relationship between physical activity and pain is theorised as a within-person process, previous research has primarily focused on between-person differences. In this article, we present the protocol for the prospective observational study PRIA (Psychologie und Rückengesundheit im Alltag), which is part of a larger interdisciplinary research consortium investigating preventive, diagnostic and therapeutic aspects of cLBP. Drawing on theories from health and pain psychology, the outlined study examines the interplay between different dimensions of cLBP and back health, physical activity and their psychosocial determinants within individuals in their everyday lives.

This prospective longitudinal study combines online questionnaires with ecological momentary assessment of health behaviours, cognitions, affect, social support and pain using a smartphone-based app (movisensXS) and continuous measurement of physical activity by accelerometry (movisens Move 4). Parameters will be recorded at baseline (T0), daily for the following 14 days (five times per day at 09:00, 12:00, 15:00, 18:00 and 21:00, resulting in up to 70 measurement occasions), 3 and 6 months later (T1 and T2). A total of 230 participants (115 individuals with cLBP and 115 without cLBP) aged 18–64 years will be enrolled. The associations between cLBP and the measured parameters will be examined using multilevel models.

The university’s ethics committee at the MSB Medical School Berlin approved the study on 8 March 2021 (approval number MSB-2021/59, amendment approved on 10 November 2023, amendment number MSB-2023/145). Ethical approval for the FOR 5177 initial screening was granted by Charité – Universitätsmedizin Berlin (EA1/058/21). All participants provided written informed consent. The results of this research will be published in peer-reviewed international journals, presented at national and international conferences, and reported to the German Research Foundation.

DRKS00032978.

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.

Due to the documented benefits of peripheral resistance training (RT) and inspiratory resistance training, known as inspiratory muscle training (IMT), in patients with cardiovascular disease, both exercise forms are regularly used in cardiac rehabilitation. However, little is known about the haemodynamic responses to different intensities of dynamic RT, isometric RT, and IMT in patients with coronary artery disease (CAD). This study is designed to evaluate and compare the acute haemodynamic responses elicited by different RT and IMT modalities in patients with CAD.

This study design is a prospective, single-centre, randomised crossover trial. A total of 20 participants with CAD will be included. All participants will undergo four different exercise training interventions: IMT, isometric wall squat training (IWS), dynamic leg press training (DLP) and isometric handgrip training (IHG). For each intervention, participants will perform two intensity modalities in randomised order: IMT (low vs high), IWS (low vs moderate), DLP (low vs high) and IHG (low vs moderate). The primary outcomes are the acute exercise-induced haemodynamic responses (esp. systolic blood pressure, pulse rate, stroke volume, cardiac output) across the different exercise training interventions, as well as the changes in haemodynamic responses during the recovery phase for each intervention. Secondary outcomes include changes in tissue oxygen saturation, oxygen saturation, and perceived dyspnoea and exertion. The study period is planned for 2025.

The study has been approved by the Ethics Committee of the German Sport University Cologne (Ethical Approval Code: 209/24). The findings will be disseminated through international peer-reviewed publications. This study is supported by the Alexander von Humboldt Foundation via the partnership with the Coordenacão de Aperfeicoamento de Pessoal de Nível Superior (CAPES)(CAPES-Humboldt Research Fellowship for Experienced Researchers) and by research funding from Edwards Lifesciences LLC (Limited Liability Company).

German Clinical Trials Register DRKS00035668.

The aim of this study is to identify and analyse research priorities across the osteopathic profession internationally, to determine how different interested parties conceptualise research importance and to examine how contextual factors influence research prioritisation.

A mixed methods sequential exploratory design combining an umbrella review, a thematic analysis, an expert consensus agreement and an international cross-sectional survey was used to define, validate and evaluate research priorities.

An international online survey, available in nine languages, was distributed through professional osteopathic organisations and network worldwide, a patient representative organisation and social media.

2229 respondents including patients (7.4%), practitioners (42.1%), students (17.4%), educators (13.5%), researchers (5.0%) and policy makers (4.3%) from across 42 countries.

Primary outcomes were interested party’s conceptualisation of research importance and validation of the priorities in Research for Osteopathic Care (PROCare) framework. Secondary outcomes included current research priorities across interested parties groups and influence of contextual factors on prioritisation.

Three distinct approaches to priority-setting emerged: conservative (42.9%), sceptic (20.2%) and enthusiast (36.9%). Organising research priorities as a construct built from domains and subdomains was shown to be internally valid (Cronbach’s α=0.911). ‘Patient safety’ (nominated by 82% of relevant countries) and ‘physical activities and mobility’ (51.0%) were the most prioritised subdomains. ‘Digital health’ ranked lowest (28th of 28 subdomains). Significant geographic variations were observed mainly for the overall importance to most research domains. Strong consensus emerged around core priorities including patient safety, physical activity promotion and understanding treatment mechanisms.

The PROCare framework provides a validated structure for evaluating osteopathic research priorities across diverse interested parties. While geographic variations exist in priority emphasis, fundamental agreement on key research domains suggests potential for internationally coordinated research strategies. Future work should focus on developing mechanisms to ensure balanced representation of conservative, sceptic and enthusiast perspectives in research planning.

Given that low retention rates are a prevalent challenge in clinical trials, which ultimately affects trial validity, it is recommended that interventions be developed and evaluated to increase trial retention. In the context of trial retention, incorporating behavioural science is endorsed, as it provides a theoretical foundation for considering human behaviour. We hypothesised that an intervention informed by self-determination theory could increase retention in a randomised allergy trial on intralymphatic immunotherapy, as the support of basic psychological needs for autonomy, competence and relatedness is anticipated to lead to more sustained engagement and better outcomes.

To assess the acceptability and feasibility of the intervention and evaluation design, following the complex intervention framework by the Medical Research Council, before proceeding to a randomised evaluation.

A parallel two-arm randomised feasibility study was conducted within the randomised allergy trial.

All participants at one Danish site were eligible for recruitment.

The intervention was a web app informed by self-determination theory to support the basic psychological needs through its thoughtfully designed features. Participants were allocated unblinded across treatment groups to complete daily online questionnaires over a 100-day period from May to August 2022. All participants received a daily text message with a link for the questionnaires. On completion, participants in the control group received a confirmation message, while participants in the intervention group had a browser with the menu of the web app opened for them. The features within the menu were voluntary to use.

The prespecified assessments included evaluating the recruitment rate, retention rate (which reflected both sustained participation and the proportion of completed daily questionnaire entries), the suitability of outcome measures and the acceptability of the intervention and evaluation design to both participants and staff. Qualitative data were collected through a collaborative learning process with participants from the intervention group in November 2022.

A total of 30 participants were invited, randomly assigned 1:1 and analysed, resulting in a recruitment rate of 100%. None were lost to follow-up as all remained in the study for the entire duration. The response rate was 84.5% in the intervention group and 79.1% in the control group, indicating satisfactory retention. Outcome measures were deemed appropriate. No unintended adverse events were identified. The collaborative learning meetings involved three participants in the first meeting and two in the second, comprising a total of five different individuals. Participants found the intervention acceptable. They used it differently but agreed that its components were useful. Technical issues needed fixing, and voluntary free text boxes and registration of medication dosage should be added.

The intervention and evaluation design were assessed as acceptable and feasible. Technical issues were fixed, and additional response options were added before a randomised evaluation.

ILIT.NU: EudraCT 2020-001060-28. ClinicalTrials.gov NCT05191186.

Multimorbidity contributes significantly to poor population health outcomes while straining healthcare systems. Although some multimorbid patients experience an accelerated health decline (a decline in well-being or functional status that cannot be attributed to the natural ageing-related health deterioration), others can remain stable for years. Identifying risk factors for accelerated health decline in persons with multimorbidity could help prevent complications and reduce unnecessary interventions. Our review, therefore, aims to map the evidence on the clinical, biographical and healthcare-related factors associated with an accelerated health decline in multimorbid individuals.

We will use the evidence-mapping review methodology. We will perform a systematic comprehensive literature search in Medline via Pubmed, Cochrane Library, EMBASE, Web of Science and Google Scholar using two broad concepts: ‘multimorbidity’ and ‘longitudinal studies’. We will search with MeSH terms (eg, ‘Multimorbidity’ (Majr), ‘Longitudinal Studies’ (Majr)) and free text words (eg, multimorbidity, multiple chronic condition*, longitudinal), from inception to date of the final search. All original quantitative studies involving participants in primary care and related healthcare settings will be included. Abstract/titles and full-text screening and data extraction will be performed independently by two or more researchers to minimise selection and reporting bias, with conflicts resolved by consensus. The data will be analysed qualitatively, and topics will be extracted to create evidence clusters. Risk factors will be classified in groups and cross-referenced against the outcomes from respective studies into combinations of exposure-outcome clusters. The resulting evidence clusters will be described narratively and presented as bubble plots. The search, initiated in January 2023, will be updated following this protocol review to reflect the most current evidence; exact dates will be reported in the results manuscript.

Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated through publications in peer-reviewed journals and presentations at local, national and international conferences.

https://osf.io/q72xa/