To characterise the reporting practices of sequential multiple assignment randomised trials (SMARTs) in human health research.

Scoping review of protocol and primary analysis papers describing SMARTs published between January 2009 and February 2024.

SMARTs are innovative trial designs that allow for multiple stages of randomisation to treatment, with randomization potentially based on a patient’s response(s) to previous treatment(s). They are uniquely designed to develop sequential adaptive interventions (dynamic treatment regimes (DTRs)) to support personalized clinical decision-making over time. Previous reviews have identified inconsistencies in how the design, implementation and results of SMARTs have been reported in published studies. A comprehensive assessment of SMART reporting practices is lacking and necessary for developing standardised SMART-specific reporting guidelines.

We systematically searched multiple databases for SMART-related protocol and primary analysis papers published between January 2009 and February 2024. Title, abstract and full-text screenings were performed by pairs of reviewers, with disagreements resolved by consensus. Data extraction included study characteristics, design elements and analytical approaches for embedded or tailored DTRs. Results were synthesised qualitatively and presented descriptively.

From 5486 screened studies, 103 (59 protocol papers, 16 primary analysis papers, 14 protocol papers with corresponding primary analysis papers) met the inclusion criteria. Most studies targeted adults (62.7% protocols, 62.5% primary analyses, 42.9% protocol+primary analyses) and were primarily conducted in the USA. Behavioural and mental health constituted the most frequent therapeutic domain. While intervention descriptions and re-randomisation criteria were consistently reported, operational characteristics such as blinding (protocols: 64.4%, primary analyses: 62.5%, protocols+primary analyses: 71.4%) and randomisation details (protocols: 55.9%, primary analyses: 37.5%, protocols+primary analyses: 50.0%) were inconsistently documented. Only 46.7% of primary analyses evaluated embedded DTRs, and none explored deeply tailored DTRs.

Despite the increased adoption of SMART designs, substantial reporting variability persists. Most primary analyses underuse the capability of SMARTs to generate data for developing DTRs. SMART-specific standardised reporting guidelines can help accelerate the scientific and clinical impact of SMARTs.

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

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

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

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

In the Netherlands, approximately 2200 major amputations of the lower extremities are performed each year, the majority in vascular patients. Around 61% of these patients will develop postamputation pain (PAP). PAP is a severe, lifelong, disabling condition profoundly affecting quality of life. During amputations, the common practice is to cut the nerves without employing nerve-surgical techniques to prevent chronic pain due to neuroma formation. In recent years, targeted muscle reinnervation (TMR) has been the most frequently studied technique for treating PAP, inhibiting neuroma formation by rerouting the cut mixed nerve to a functional motor nerve. We hypothesise that a primary TMR procedure during major lower limb amputations will result in a lower prevalence of PAP.

We propose a national, multicentre, randomised, sham-controlled trial comparing TMR with traction neurectomy in major amputations of the lower extremities in patients with vascular disease. 203 patients will be recruited with an indication for a transfemoral to transtibial amputation as a primary or secondary sequela of vascular disease. The subjects are randomly assigned to the TMR group or the traction neurectomy group. PAP will be evaluated 1 year postoperatively as the primary endpoint. Secondary outcomes include quality of life, mobility, neuropathic pain, hospital anxiety and depression, cost-effectiveness and complications.

This study has been reviewed and approved by the local ethical review body, ‘The Medical Ethics Committee Leiden The Hague Delft’, under the reference: P24.073 on 28 November 2024. Results will be published in peer-reviewed journals.

NCT06719245. Dutch trial registry: NL87196.058.24

In addition to hypertension, the constellation of metabolic abnormalities (diabetes mellitus, dyslipidaemia and/or obesity) independently increases the incidence and severity of cardiovascular diseases, and this is compounded by the modern lifestyle and ageing society. The prevalence of metabolic syndrome is high and non-hypertensive heart failure is common in Asians. Adverse cardiac remodelling is an important substrate for cardiac dysfunction in the onset and progression of heart failure and its amelioration improves outcomes and prognosis. A better understanding of metabolic-driven cardiac remodelling is warranted due to the rising prevalence and complexity of metabolic syndrome and strong interests in targeted therapy.

Response of the myocardium to hypertrophic conditions in the adult population is a prospective observational cohort study with an aim to establish the significance of cardiac remodelling by cardiovascular magnetic resonance (CMR). The current recruitment target is 2000 participants. Expanding from the initial population with hypertension, the study examines adults with cardiometabolic conditions, including diabetes, dyslipidaemia, obesity and fatty liver disease. Eligible patients are identified at National Heart Centre Singapore, primary care clinics and through public outreach. Physical, clinical, imaging and biochemical data are collected. Cardiac remodelling features pertaining to hypertrophy, fibrosis and functional changes are assessed on CMR. Body adiposity is mapped by MRI across the heart, liver and abdomen. Outcome data are adjudicated and follow-up assessment will be available in a subset of participants. Blood biomarkers will be investigated in relation to imaging findings. Cross-sectional analysis will establish the implication of cardiometabolic disease towards cardiac remodelling, while follow-up and outcome analysis will infer on disease progression and prognosis.

The study was approved by the SingHealth Centralised Institutional Review Board (2015/2603). Written informed consent is obtained from all participants. Study findings will be reported in peer-reviewed journals and at scientific conferences.

ClinicalTrials.gov, NCT02670031.

Childhood obesity has surged globally, leading to various metabolic comorbidities and increased cardiovascular risks. Early intervention in lifestyle and feeding practices during infancy is crucial to mitigate these risks. This study evaluates the efficacy of a mobile web app-based intervention tool, named the Feeding, Lifestyle, Activity Goals (FLAGs) to promote healthier eating behaviours and lifestyle habits in infants from birth to 12 months.

This two-arm randomised controlled trial will enrol 220 caregiver-infant pairs per arm at KK Women’s and Children’s Hospital, Singapore, with recruitment expected from January to December 2025. Eligible participants include women at ≥34 weeks’ gestation or up to 3 days post delivery with pre-pregnancy overweight/obesity (body mass index (BMI) >23 kg/m²) and/or a diagnosis of diabetes. Caregiver-infant pairs will be randomised to the FLAGs intervention or control group. Over 12 months, both groups will receive standard infant care. The intervention group will undergo regular assessments via the FLAGs web app built-in assessment tool, assessing infant feeding practices, sedentary behaviour and physical activity. The intervention group will also receive FLAGs personalised guidance and weekly digital nudges. Maternal and infant data will be collected at baseline and at 12 months. Primary outcomes are infant BMI, weight-for-length and body composition at 12 months. Secondary outcomes include lifestyle behaviours and eating habits assessed through validated questionnaires when the infants are 1 year old. We will perform both intention-to-treat and per protocol analysis.

Ethical approval has been obtained from the SingHealth Centralised Institutional Review Board (Ref: 2024/3224). Written informed consent will be obtained from all participants. Study findings will be disseminated via peer-reviewed publications and academic conferences, with de-identified data available on reasonable request. This trial is registered on ClinicalTrials.gov (ID: NCT06457750).

NCT06457750.

Radiological imaging is a central facet of the multidisciplinary evaluation of suspected child physical abuse. Current guidelines for the imaging of suspected child physical abuse are often unclear, incomplete and highly variable regarding recommendations on critical questions, thereby risking clinical heterogeneity, unstructured decision-making and missed diagnoses. We, therefore, aim to develop and report an evidence-based and consensus-derived international guideline for the radiological investigation of index and contact children in the context of suspected physical abuse and to ascertain areas of scientific uncertainty to inform future research priorities.

The international guidelines for the imaging investigation of suspected child physical abuse (IGISPA) consensus group includes formal representation from 127 recognised experts across 14 subspecialties, six continents and 32 national and/or international organisations. Participants will be divided into five longitudinal subgroups (indications for imaging, skeletal imaging, visceral imaging, neuroimaging and postmortem imaging) with three cross-cutting themes (radiography, genetics and adaptations for low- and lower-middle-income countries). Each subgroup will develop preliminary consensus statements via integration of current evidence-based guidelines, systematic literature review and the clinical expertise of a multinational group of experts. Statements will then undergo anonymised voting in a modified e-Delphi process and iterative revision until consensus (≥80% agreement) is achieved. Final statements will undergo both internal and external peer review prior to endorsement.

As an anonymous survey of consenting healthcare professionals, this study did not require ethical approval. Experts provided written informed consent to participate prior to commencement of the modified Delphi process. The IGISPA consensus statement and any subsequent guidance will be published open access in peer-reviewed medical journals.

Recent legislation in the UK regarding requirements for new developments to increase biodiversity may have significant implications for the environment and population health. Despite this, relatively little is known regarding the health and social benefits of increasing biodiversity in densely populated urban areas.

This protocol outlines plans for a mixed-method, longitudinal, natural experiment study which will evaluate the planned, biodiversity-focused redevelopment of six small urban parks in Edinburgh, Scotland (UK). Using systematic observation (at baseline, 1 month post-intervention and 1 year post-baseline) and a longitudinal household survey (at baseline and 1 year post-baseline), the primary outcomes of personal well-being, and secondary outcomes of nature connectedness and park usage behaviours, will be assessed, respectively. Consent for data linkage of respondent’s health records will also be sought. Process evaluation will employ semi-structured, qualitative interviews with stakeholders and walk-along interviews with local residents in order to understand implementation processes. Space-related well-being will also be assessed using citizen science approaches.

This study was approved by the University of Edinburgh’s School of Health in Social Sciences ethics committee. This study will provide further evidence for policymakers, the public and researchers of the health and social well-being effects of urban biodiversity interventions. Study findings will be disseminated via public forums such as community workshops and through publication in peer-reviewed journals and presentation at scientific conferences.

Perioperative adverse events increase morbidity and mortality. The rate and severity of complications and the risk for subsequent mortality are increased after high-risk procedures and in elevated-risk patients. Over the past decades, a multitude of prognostic studies identified perioperative risk factors at the population level. However, to allow for the advancement of precision surgery strategies, improved risk prediction on the individual patient level is warranted. Comprehensive, consecutive, multisource, structured, high-quality patient-related and procedure-related data sets, together with thorough follow-up and combined with state-of-the-art machine-learning analyses, are needed to facilitate precise prediction of perioperative complications. Therefore, we designed and currently conduct the Heidelberg Perioperative Deep Data study (HeiPoDD). Here, we report the rationale and design of the HeiPoDD study.

HeiPoDD is a prospective, single-centre, exploratory cohort study aiming to build up a large-scale deep-data base and corresponding biomaterial collection. 1040 adult patients planned for elective high-risk, non-cardiac surgery for any indication at Heidelberg University Hospital, Germany will be included. The obtained study-specific data set includes clinical data, lab values, genome- and proteome analysis as well as plasma, serum and peripheral blood mononuclear cells (PBMC) collected before and at days 1, 3 and 7 postsurgery. Urine samples are collected before and at day 1 postsurgery. Structured follow-up for perioperative complications such as redo-surgery, length of intensive care stay or length of hospital stay is conducted at days 30, 90 and 1 year postsurgery and for disease progression and survival after 3 and 5 years postsurgery. All study data will be transferred to the HeiPoDD registry to allow merging with all available routine clinical data from the hospital information system including imaging studies as well as haemodynamic and respiratory biosignals. Biomaterials will be stored in the HeiPoDD biomaterial bank to allow further analyses.

The trial protocol and amendments were approved by the ethics committee of the University of Heidelberg (S-758/2021). The protocol is registered with the German Clinical Trial Register (DRKS00024625). Participating patients’ data will be recorded only in pseudonymised form. After completion of the study, data collected during the study will be kept on file for up to 30 years. Biomedical samples collected during the study and entered into the biobank will be held for the same amount of time. The findings will be disseminated in peer-reviewed academic journals.

This study aimed to examine the reproductive concerns and their influencing factors among adolescents and young adults with acute leukaemia and to explore the relationship between reproductive concerns and patients’ quality of life.

A cross-sectional study.

The haematology departments of four tertiary-level hospitals in Hunan province, China.

Convenience sampling method was used to recruit 233 adolescents and young adults with acute leukaemia, from June 2024 to December 2024.

The primary outcome was assessed using the Chinese version of the Reproductive Concerns After Cancer and the secondary outcome was measured by the 12-item Short Form Health Survey.

Adolescents and young adults with acute leukaemia had a mean reproductive concerns score of 55.57±7.57, a quality of life physical component summary (PCS) score of 38.54±8.58 and a mental component summary (MCS) score of 39.84±8.78. Univariate analysis showed significant differences in reproductive concerns based on fertility status, place of residence, education level, fertility counselling and family history of acute leukaemia (p

Adolescents and young adults with acute leukaemia exhibited moderately high levels of reproductive concerns, particularly those who had no children, had a low education level, resided in rural areas, had a family history of acute leukaemia or had received fertility counselling. Therefore, we suggest that healthcare providers prioritise addressing reproductive concerns in high-risk patients by offering tailored, high-quality and continuous fertility counselling and psychological support. Strengthening these strategies can help alleviate reproductive concerns and improve both mental health and overall quality of life in this population.

Guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF) reduces morbidity and mortality and remains widely underused. An HFrEF polypill containing all four pillars of GDMT has been proposed as an implementation strategy to improve GDMT treatment rates and subsequent patient outcomes. We present the design and protocol for a proof-of-concept, pilot type I hybrid randomised clinical trial evaluating an HFrEF polypill compared with usual care among patients with HFrEF in Sri Lanka to evaluate short-term feasibility.

This multi-centre, open-label, pilot type I hybrid randomised clinical trial will recruit 40 adults with HFrEF from two public hospital sites in Colombo, Sri Lanka. Participants will be randomised to an HFrEF polypill (containing bisoprolol, losartan, eplerenone, and dapagliflozin in three available strengths) or usual care and followed for 4 weeks. The primary outcome is feasibility of recruitment measured by recruitment rate and adherence to study protocols measured by completion rate of study-related procedures. Other key outcomes include adherence to GDMT and assessment of serious adverse events among other exploratory outcomes.

The study has been approved by the ethics review committee at the Faculty of Medicine, University of Kelaniya (Sri Lanka), the institutional review board at Washington University in St. Louis (United States), and the National Medicines Regulatory Authority (Sri Lanka). The findings of this pilot trial will inform the design and implementation of a future large-scale type I hybrid trial to assess the efficacy and safety of an HFrEF polypill in improving clinical outcomes.

Sri Lanka Clinical Trials Registry (SLCTR/2024/003); ClinicalTrials Registry (NCT06831864).