Trials

IntroductionIt is well established that young people with moderate-severe (Gross Motor Function Classification System [GMFCS] levels II-V) cerebral palsy (CP) participate in less physical activity compared to typically developed peers, and children with CP who can walk without limitations (GMFCS level I). Frame Running (formerly RaceRunning) is a World Para Athletics sanctioned sport that allows people with moderate-severe CP to access, experience and compete in running using a specialised three-wheeled frame with low rolling resistance. The Run4Health pilot randomised controlled trial (protocol published elsewhere) was designed to investigate the cardiorespiratory benefits of a 12-week frame running training program in young people with CP (aged 8-21 years, GMFCS II-V). Following enrolment of 12 participants in the pilot study, additional funding was secured to expand the Run4Health study to include additional training/study sites, new research questions and outcome measures, based on feedback from consumers. Such changes necessitate an expanded and updated study protocol. This expanded Run4Health study will investigate the effects of a 12- week Frame Running training program on cardiorespiratory health, bone mineral density, gross motor function and capacity, physical activity participation, sleep, pain and quality of life in children and youth (aged 8-21 years) with moderate-severe CP (GMFCS levels II-V). Methods and AnalysisOne hundred and two children and youth with CP (age 8-21 years) classified in GMFCS levels II-V will be recruited across three sites (six training locations) and randomised to receive either 12 weeks of Frame Running training twice weekly for 60 minutes, or 12 weeks of usual care (waitlist control group). Outcomes will be measured at baseline, immediately post-intervention, and 12 weeks post-intervention. The control group will receive the intervention following T3, and have an additional assessment session following 12 weeks of training (T4). Outcomes include cardiorespiratory fitness, bone mineral density, blood pressure, habitual physical activity, body mass index, waist circumference, percentage body fat, gross motor function and capacity, community participation, sleep, pain, quality of life and mood, health utility, feasibility, tolerability, and safety. Adverse events will be monitored, and participants, caregivers and coaches will be interviewed to explore barriers and facilitators to ongoing, sustainable participation in Frame Running. Ethics and DisseminationEthical approval for this study was granted by The Childrens Health Queensland Hospital and Health Service (HREC/21/QCHQ/69281) and the University of Queensland Human Research Ethics Committees (2021/HE000725). Research outcomes will be disseminated via scientific conferences and publications in peer reviewed journals; to therapists and coaches through professional and athletic organisations; and to people with CP and their families. RegistrationAustralian New Zealand Clinical Trials Registry number: ACTRN12621000317897

IntroductionAs a result of improving survival rates, the adverse consequences of rectal cancer surgery are becoming increasingly recognised. Low Anterior Resection Syndrome (LARS) is one such consequence and describes a constellation of bowel symptoms after rectal cancer surgery which includes urgency, faecal incontinence, stool clustering and incomplete evacuation. LARS has a significant adverse impact on Quality-of-Life (QoL) and symptoms are present in up to 75% of patients in the first year after surgery. Despite this, little is known about the natural history and there is poor evidence to support current treatment options. Methods and AnalysisThe objectives of POLARiS are to explore the natural history of LARS and to evaluate the clinical and cost-effectiveness of trans-anal irrigation (TAI) or sacral neural modulation (SNM) compared to optimised conservative management (OCM) for people with major LARS. POLARiS is a prospective, international, open-label, multi-arm, phase 3 randomised superiority trial within a cohort (TWiCs design), with internal pilot phase, qualitative sub-study, process evaluation, and economic evaluation. Approximately 1500 adult participants from UK hospitals and 500 from Australian hospitals who have undergone a high or low anterior resection for colorectal cancer in the last 10 years will be recruited into the cohort. 600 participants from the UK and 200 participants from Australia, with major LARS symptoms, defined as a LARS score of [≥]30, will be recruited to the randomised controlled trial (RCT) element. Participants entering the RCT will be randomised between OCM, TAI or SNM, all with equal allocation ratios. Cohort and RCT participants will be followed up for a 24-month period, completing a series of questionnaires measuring LARS symptoms and QoL, as well as clinical review for those in the RCT. A process evaluation, qualitative sub-study and economic evaluation will also be conducted. The primary outcome measure of the POLARiS cohort and RCT is the LARS score up to 24 months post registration/randomisation. Analyses of the RCT will be conducted on an intention-to-treat basis. Comparative effectiveness analyses for each endpoint will consist of two pairwise treatment comparisons: TAI vs OCM and SNM vs OCM. Secondary outcomes include health-related QoL, adverse events, treatment compliance and cost effectiveness (up to 24 months post registration/randomisation) Ethics and DisseminationEthical approval has been granted by Wales REC 4 (reference: 23/WA/0171) in the UK and Sydney Local Health District HREC (reference: 2023/ETH00749) in Australia. The results of this trial will be disseminated to participants upon request and published on completion of the trial in a peer-reviewed journal and at international conferences Trial Registration NumberISRCTN12834598 Registered 04/08/2023 ACTRN12623001166662 Registered 10/11/2023 Strengths and LimitationsO_LIThe trial is pragmatically designed to optimise and assess recruitment and retainment. C_LIO_LIThis trial includes an economic evaluation of treatment options specific to both the UK and Australia. C_LIO_LILay representatives with personal experience of bowel cancer and LARS have contributed throughout the trial design and ongoing Trial Management Group meetings. C_LIO_LIThere are recognised potential limitations to the LARS score, including limited sensitivity to detect real time change in response to treatment. Additional outcome measures of Quality of Life and a new LARS Patient Reported Outcome Measure (PROM) are being collected to give a more nuanced picture of treatment response. C_LI

BackgroundThe Vision Impact Project (VIP) is a major community-based eye screening programme running in Kenya with the aim of promoting eye health for all. Previous studies embedded within the programme in Meru County have found that a third of people who are screened require care for an eye problem, however only half of these people manage to access outreach treatment clinics. Access varies between sociodemographic groups, and only 30% of young adults (18-44 years old) were able to access care. In previous mixed-methods work our team conducted interviews and surveys with non-attenders from this left-behind group to explore what could be done to improve access. MethodsYounger adults told us that better counselling at the point of referral would be likely to improve attendance rates. Based on their feedback, we have developed a script that will be read to participants in the intervention arm at the point of referral, and then sent as a reminder SMS the following day. We will assess whether attendance rates are higher among those randomised to receive this enhanced counselling compared to those who receive standard care. The primary outcome will be the proportion of people from the left-behind group who attend triage clinic. Our secondary analysis will examine overall mean attendance across all groups. We will calculate Bayesian posterior probabilities of attendance in each arm every seven days and continually recruit participants until one of two stopping rules have been met: there is a >95% probability that one arm is best or there is a >95% probability that the difference between the arms is <1%. DiscussionThis Bayesian RCT will be embedded into the clinical workflow software that is used to manage referrals and clinic attendance. It will test whether a simple, low-cost, service user-derived intervention is able to improve access to services among a population group that is currently being left behind. Trial RegistrationISRCTN 11329596, Registered on 02 February 2024 Administrative Information O_TBL View this table: org.highwire.dtl.DTLVardef@1d5f90forg.highwire.dtl.DTLVardef@d26da7org.highwire.dtl.DTLVardef@11d2ffdorg.highwire.dtl.DTLVardef@139a021org.highwire.dtl.DTLVardef@3ff4e7_HPS_FORMAT_FIGEXP M_TBL C_TBL

IntroductionAnterior cruciate ligament (ACL) reconstruction is one of the most commonly performed sports medicine procedures. A variety of grafts are currently used for reconstruction, including both allograft and autograft. Despite numerous meta-analyses, there exists no high-quality quantitative synthesis of all randomized controlled trial (RCT) data on graft choice. ObjectiveTo identify the optimal graft choice for ACL reconstruction by performing the first systematic review and network meta-analysis (NMA) to include both functional outcomes and complications. MethodsMultiple digital databases including MEDLINE, Embase, and CENTRAL will be searched independently and in duplicate for RCTs randomizing graft choice in ACL reconstruction in skeletally mature patients. A Bayesian framework with a random-effects model will be used for NMA. Surface under the cumulative ranking curve (SUCRA) values will be used to generate a rank list for each outcome. Results will be reported as mean differences (MD) (or standardized mean difference, if necessary) or relative risk (RR) with 95% credible intervals (CI). Comparisons will be inferred to be statistically significant if the 95% CI of MD does not cross zero or if the 95% CI of relative risk does not cross one. Studies will be assessed for quality using the Cochrane risk of bias assessment tool. Quality of evidence for each network comparison will be determined as per the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach for network meta-analyses. This NMA will be reported according to the PRISMA extension statement for network meta-analyses Outcomes of interestFunctional outcomes of interest including range of motion, return to activity/sport, and IKDC, Lysholm, Tegner, ACL-QOL, and KOOS scores. Persistent laxity as measured by Lachman, Pivot-shift, side-to-side, and measured laxity (e.g. KT-1000) will also be analyzed. Complications (e.g. infection, graft failure, donor site pain), tunnel osteolysis, and failure (including but not limited to graft rupture and/or persistent laxity) will be compared between grafts. Relevance/ImpactThis NMA will be the first high-quality syntheses of all randomized evidence regarding graft choice in ACL reconstruction. As the first analysis to compare all major graft choices independently, it will be used to inform surgeon-patient decision making. It has the reasonable possibility of changing clinical practice.

IntroductionDespite the ubiquity of diverticular disease, the options for reducing the risk of recurrent diverticulitis remain limited and the pathogenesis remains incompletely understood. While high intraluminal pressures within the distal colon and rectum have been proposed as a possible association with diverticular disease, studies on this relationship have been few, inconsistent and not generalisable. The investigators of this pilot study propose that the repeated transient high intraluminal pressures generated within the distal colon and rectum due to ineffective defecatory technique may predispose some patients to an increased risk of diverticulosis and diverticulitis. Therefore, by correcting defecatory technique through the implementation of pelvic floor physiotherapy (PFPT), the investigators hypothesise that there would be a reduction in the risk of recurrent diverticulitis. Methods and analysisThis pilot multi-centre open-label randomised controlled trial will be conducted at Queen Elizabeth II Jubilee Hospital (QEII) and Logan Hospital (LGH) in Brisbane, Queensland, Australia. Eligible adult patients admitted with acute diverticulitis will be considered for enrolment and randomised into two groups in a 1:1 allocation ratio. The aim is to recruit 40 patients with 20 patients per group. The control group will receive standard of care dietary advice. The intervention group will receive PFPT as an outpatient within 4 weeks of discharge. The primary endpoint will be the risk of readmission with recurrent diverticulitis within a 12-month follow-up period. Secondary endpoints will be the risk of surgical intervention and/or interventional radiology (IR) procedure in the subgroup of patients readmitted with recurrent diverticulitis. Feasibility outcomes will review patient compliance and completeness of data collection. Results of this trial will inform study design and sample size required in a larger prospective study. Ethics and disseminationApproval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal. Trial registration numberACTRN126250009274426. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis pilot RCT is the first prospective study to assess the correction of defecatory dysfunction as a method for reducing the risk of recurrent diverticulitis C_LIO_LIA practical design with ease of reproducibility that will inform a larger study adequately powered for hypothesis testing C_LIO_LIOpen-label design poses risk of performance bias C_LIO_LILack of standardisation for pelvic floor physiotherapy interventions may impact generalisability outside of facilities with dedicated pelvic floor units C_LI

IntroductionThe present uptake of predictive genetic counselling among at-risk relatives (ARRs) for cardiogenetic diseases is suboptimal with 40-50% of ARRs being tested after one to three years post- disclosure. Digital technologies are increasingly proposed to improve accessibility, efficiency, and uptake of predictive genetic counselling and, if desired, predictive genetic testing. Therefore, DNA- poli was developed: a digital platform providing family communication support and pre- and post-test genetic counselling for ARRs. The online DNA-poli aims to decrease the threshold for ARRs to seek genetic counselling without compromising the quality of care while increasing the efficiency of genetic care. Here, we describe the study protocol for a randomised controlled trial evaluating DNA- poli in clinical practice. Methods and analysisA non-inferiority multicentre randomised controlled trial with parallel-group design will be conducted. The intervention group using the DNA-poli platform will be compared to a control group receiving regular counselling. Probands with hypertrophic or dilated cardiomyopathy in whom a (likely) pathogenic variant in specific genes with definitive gene-disease validity is identified, will be included like their ARRs and physicians. The primary outcome is the uptake of cardiogenetic counselling six months post-disclosure with an extended follow-up of one year and stakeholders experiences. Secondary outcomes are informed decision-making in ARRs, empowerment, and the satisfaction of all stakeholder groups. In addition, the efficiency of consultations and the genetic care process will be analysed. Descriptive and inferential statistics will be performed to analyse data. Ethics and disseminationThis study protocol was exempted from approval by the Medical Ethical Committee NedMec because the Act of Medical Research Involving Human Subject (WMO) was not applicable (no. 23-066/C). Study findings will be shared with stakeholders, published in journals, and will be presented at both international and national conferences. Registration details NCT06431425 ClinicalTrials.gov

The TEXT4myBACK trial aims to examine the effect of lifestyle-focused program delivered by text message on function in people with non-persistent low back pain. The lifestyle-focused intervention is delivered as a mobile phone text message over a period of 12 weeks. The statistical analysis plan pre-specifies the method of analysis for every outcome and key variables collected in the trial. The primary outcome is a composite endpoint incorporating measures of pain, functional status, patient reported impression of change, generic quality of life, levels of activity, hospital as well as medication use at 3-months follow-up that will be categorised into a hierarchy with number one ranked as most important according to clinical importance. The primary composite endpoint will be analysed using a hierarchical win ratio approach. Win-ratio approach maintains sequential assessment of outcomes while simultaneously assessing the effect of intervention for multiple outcomes as a single measure. Secondary, exploratory and subgroup group analysis have been pre-specified as well.

IntroductionEngaging individuals with lived experience enhances the rigor and real-world relevance of clinical research. In adolescent idiopathic scoliosis (AIS), where non-surgical evidence remains limited, involving patients and caregivers informs design, recruitment, and retention for future trials. MethodsUsing the Community Engagement (CE) Studio model, we conducted a 1.5-hour virtual session with children aged 10-16 years with AIS and their caregivers residing in North America. Participants (no spinal surgery; with/without brace) were recruited through engagement databases, advocacy organizations, and social media. A trained facilitator led structured discussions. Responses were thematically synthesized, including summaries related to recruitment, retention, study protocol, meaningful outcomes and treatment success. Participants received compensation and a follow-up Qualtrics survey. The CE Studio, based on the Vanderbilt model is advisory, and IRB- exempt. ResultsOf 81 respondents, 31 were eligible and 18 participated (nine girls, nine caregivers) representing seven ethnicities across nine U.S. states. All participants valued the proposed multicenter RCT on scoliosis exercise rehabilitation and expressed willingness to enroll; 78% would accept randomization to either the active or 6-month waitlist control arm. Reported barriers included limited access to physiotherapy (43%), physician skepticism (57%), and bracing preference (43%). The most bothersome symptoms were pain (50%) and brace discomfort (17%). Prioritized outcomes included preventing curve progression, avoiding surgery, pain reduction, and improved appearance. ConclusionsParticipants expressed strong willingness to enroll, emphasizing pain, progression, and access to care as key barriers. Improved communication with providers about non-surgical options was viewed as essential to support shared decision-making.

Introduction9663 major lower limb amputations were performed in UK NHS hospitals, between 2018-2020. Despite this high number, there is no universally accepted peri-operative analgesia regime. The Vascular Society and Vascular Anaesthesia Society of Great Britain and Ireland, in partnership with patients (supported by the James-Lind Alliance), have identified improving outcomes (including preventing/treating pain) for patients who undergo amputations as a key research priority. Methods and methodsA prospective, single-blind, RCT (1:1), comparing pre-incision ultrasound sited PNC (7-day duration) or pre-incision single-shot nerve block and PCA, for those undergoing MLLA. The sample size is 34 patients, powered to detect a primary outcome of 2.5cm(2cmSD) difference on a visual analogue scale (VAS) at day 3. Secondary outcomes include daily pain scores, analgesia use, post-operative nausea and vomiting, Pasero opioid-induced sedation scale and physiotherapy progress. Patient-reported neuropathic pain and quality of life tools (SF36 and EQ5D) are recorded at baseline, day-7, 6-weeks and one-year. Ethics and disseminationThis study was approved by South East Scotland Research Ethics Committee on 03/02/2021. REC reference:21/SS/0013). It is hoped this NIHR-portfolio adopted, RCS(Ed) funded RCT, will provide level-1 evidence for a shared patient and clinician research priority. Trial registration: ISRCTN.com, ISRCTN64207537. Registered on 21/07/2021

Background Randomized controlled trials (RCTs) often have incomplete methods reporting despite widespread adoption of the CONSORT guideline. The editorial process is supposed to detect these shortcomings and request clarifications from authors, which is time-consuming. We developed an LLM-based CONSORT Rohe Nordberg Report that highlights which CONSORT items appear fully or partially reported and checks page references claimed by authors, and then creates follow up questions for authors to more easily correct missing information. Methods This parallel-arm, superiority RCT will randomize eligible RCT submissions (after desk screening) 1:1 into intervention (editorial team and authors receive the Rohe Nordberg Report) or control (standard editorial review only). The primary outcome is whether manuscripts improve their reporting of CONSORT items in the Methods and Results sections between the original submission and first revision. This will be assessed by blinded human reviewers who evaluate the textual changes for improvements between the original and revised manuscripts for each relevant CONSORT item. Secondary outcomes include time to editorial decisions, rejection and non-resubmission rates, if authors can correctly identify where CONSORT items are reported, and extent of revisions. Human evaluators will be blinded to whether the manuscript was in the intervention or control group. Discussion By providing authors and the editorial team with specific follow up questions for each underreported CONSORT item, we hypothesize that basic underreporting will be more efficiently detected and corrected. Using blinded human reviewers as the primary outcome assessors ensures a rigorous, unbiased evaluation. If successful, this approach may help align manuscripts more closely with CONSORT standards, ultimately benefiting evidence synthesis.

IntroductionEndovenous therapy is the first-choice management for symptomatic varicose veins in NICE guidelines, with 56-70,000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and endothermal heat-induced thrombosis (EHIT), are known complications of endovenous therapy, occurring at a rate of up to 3.4%. In an attempt to reduce VTE, 73% of UK practitioners administer pharmacological thromboprophylaxis. However, no high-quality evidence to support this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE, however, further evidence is needed. The aims of this study are to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective. Methods and analysisA multi-centre, assessor-blind, randomised controlled trial (RCT). We aim to recruit 6660 participants undergoing superficial endovenous interventions under local anaesthesia. Forty sites across the UK, both NHS and private, will be included. Participants will be randomised to either intervention (a single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21-28 days post-procedure to identify asymptomatic DVT. The ultrasound duplex scan will be conducted locally by blinded assessors. Participants will also be contacted remotely for follow-up at 7-days and 90-days post-procedure. The primary outcome is imaging confirmed lower limb DVT with or without symptoms, or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance (ANOVA), adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression. Trial registration numberISRCTN18501431 ARTICLE SUMMARYStrengths and limitations of this study O_LIThe study will serve as a large, randomised controlled trial providing grade A evidence on the most clinically- and cost-effective thromboprophylaxis regimen following superficial endovenous treatment. C_LIO_LIThe primary outcome holds clinical significance. C_LIO_LIUsing VTE prophylaxis may be associated with adverse clinical outcomes, increased risks and may not be cost-effective. C_LIO_LIShould pharmacological thromboprophylaxis be shown to offer no additional benefit to patients undergoing superficial endovenous intervention, stopping this practice has the potential to generate significant cost savings for healthcare providers. C_LI

IntroductionShared decision-making (SDM) is a process whereby patients are supported to reach decisions about their healthcare in collaboration with healthcare professionals. International policy and clinical guidelines highlight the ethical imperative of SDM and recommend SDM for many healthcare decisions and contexts. However, despite decades of SDM research, the impact of implementing SDM interventions within health care remains uncertain. High-quality health technology assessment (HTA) requires an understanding of how interventions to facilitate the adoption and implementation of SDM (e.g., through the use of patient decision aids, decision coaching, question prompt lists, training and feedback, or service changes) impact clinical and health service outcomes. Yet, synthesis of the existing literature is hindered by substantial heterogeneity in the evaluation of interventions to facilitate SDM. A core outcome set (COS) is an agreed standardised set of outcomes that should be measured and reported in all effectiveness studies. There is a COS for SDM in the context of rheumatology (rheuCOS-SDM), designed for use in research studies (e.g., clinical trials or observational studies) evaluating the impact of SDM interventions on clinical outcomes for patients. It is unclear, however, whether the outcome domains identified within a rheumatology context are relevant, comprehensive, or comprehensible when applied to a variety of SDM interventions tailored to and interacting with a range of patient populations, healthcare settings and contexts. The aim of this study is to develop a generic COS for evaluating the impact of SDM interventions on various outcomes. Outcomes for consideration may include assessments of the behaviours and experiences of patients, important others (e.g., carers or relatives) and health professionals, the dynamics within patient-professional interactions, health outcomes for individuals and for the wider population, and the cost-effectiveness of care. The broad scope of the COS will ensure its applicability and utility within diverse healthcare contexts and enable the synthesis of evidence to draw clear conclusions about the impact of SDM interventions, to influence healthcare policy. We define this new, comprehensive COS as the COS-SDM. Methods and AnalysisThrough engagement with key interest holders (including patients and members of the public, clinicians and academics), we agreed on the scope of the COS and to adhere to the Core Outcome Measures in Effectiveness Trials (COMET) handbook and Core Outcome Set-STAndards for Development (COS-STAD) guidelines. This will involve production of a long (comprehensive) list of candidate outcome domains (using evidence synthesis, a COS developed in the context of Rheumatology, and qualitative interviews with interest holders internationally), prioritisation of a short (refined) list of core outcome domains (utilising a sequential two-round international online Delphi), and reaching consensus on the final outcome set (through international meetings, applying modified nominal group techniques and predefined criteria for agreement). Ethics and DisseminationResearch ethics approval has been granted in the UK (University of Bristol Faculty Ethics Committee, ref: 7741; University of Exeter Faculty Ethics Committee, ref: 8207624). The final COS will be disseminated by presentation at international conferences and publication in a peer-reviewed journal. Further dissemination is planned through our patient/public advisory group, professional networks, and executive group channels, to publicise the COS to patient groups, funders, journal editors, international regulatory bodies and HTA boards. RegistrationThis project has been registered in the COMET database (www.comet-initiative.org/Studies/Details/3586).

BackgroundYoung adults living with type 1 diabetes (T1D) often experience sub-optimal outcomes due to competing life demands, disruptions in care, reduced clinic attendance, and difficulties in self-management. To improve outcomes among this population, we developed and piloted the D1 Now intervention using a user-centred and theory-informed approach. This protocol describes a cluster randomised controlled trial (RCT) to test the effectiveness and cost-effectiveness of the D1 Now intervention. MethodsA cluster RCT seeking to recruit 348 young adults (aged 18-25) with T1D from 12 hospital diabetes centres in Ireland. Centres will be randomised to receive either standard care or the D1 Now intervention, which includes two components: an agenda-setting tool and a support worker. The primary outcome is the change in HbA1c from baseline to 12-month follow-up. Secondary outcomes include patient-reported psychosocial outcomes, clinical outcomes, self-management outcomes and healthcare utilisation. We will collect data through blood samples, online patient surveys, and patient records at baseline and 12 months. Additionally, we will conduct a cost-effectiveness evaluation and a mixed-methods process evaluation. DiscussionWe anticipate that the D1 Now intervention will be both effective and cost-effective in improving clinical and psychosocial outcomes for young adults compared to standard care. The findings from the process evaluation will shed light on how the intervention works (or not) and how implementation into health services (if warranted) can be optimised. If effective, D1 Now will offer a sustainable model of care to support engagement and self-management for young adults living with T1D. Trial registrationISRCTN Identifier: ISRCTN28944606. Date applied 01 May 2025

BackgroundPaediatric trials must contend with many challenges that adult trials face but often bring additional obstacles. Decentralised trials, where some or all trial methods occur away from a centralised location, are a promising strategy to help meet these challenges. This scoping review aims to (a) identify what methods and tools have been used to create and conduct entirely online-decentralised trials with children and (b) determine the gaps in the knowledge in this field. This review will describe the methods used in these trials to identify their facilitators and the gaps in the knowledge. MethodsThe methods were informed by guidance from the Joanna Briggs Institute and the PRISMA extension for scoping reviews. We systematically searched MEDLINE, CENTRAL, CINAHL, and Embase databases, trial registries, pre-print servers, and the internet. We included randomised and quasi-randomised trials conducted entirely online with participants under 18 published in English. A risk of bias assessment was completed for all included studies. ResultsTwenty-one trials met our inclusion criteria. The average age of participants was 14.6 years. Social media was the most common method of online recruitment. Most trials employed an external host website to store and protect their data. Duration of trials ranged from single-session interventions up to ten weeks. Fourteen trials compensated participants. Eight trials involved children in their trial design process; none reported compensation for this. Most trials had a low risk of bias in "random sequence generation", "selective reporting", and "other". Most trials had a high risk of bias in "blinding participants and personnel", "blinding of outcome assessment", and "incomplete outcome data". "Allocation concealment" was unclear in most studies. ConclusionsThere was a lack of transparent reporting of the recruitment, randomisation, and retention methods used in many of the trials included in this review. Patient and public involvement (PPI) was not common, and the compensation of PPI partners was not reported in any study. Consent methods and protection against fraudulent entries to trials were creative and thoroughly discussed by some trials and not addressed by others. More work and thorough reporting of how these trials are conducted is needed to increase their reproducibility and quality. Ethics and DisseminationEthical approval was not necessary since all data sources used are publicly available.

ObjectiveTo determine whether facial growth at five years is different for children with a right versus left sided cleft lip and palate. DesignRetrospective cohort study SettingNine UK cleft centres PatientsPatients born between 2000-2014 with a complete unilateral cleft lip and palate (UCLP) Main outcomes measure5-Year-Olds Index scores Results378 children were included. 122 (32%) had a right sided UCLP and 256 (68%) had a left sided UCLP. 5-Year-Olds index scores ranged from 1 (good) to 5 (poor). There was a higher proportion of patients getting good scores (1 and 2) in left UCLP (43%) compared to right UCLP (37%) but there was weak evidence for a difference (Adjusted summary odds ratio 1.27, 95% CI 0.87 to 1.87; P=0.22). ConclusionsWhilst maxillary growth may be different for left versus right sided UCLP, definitive analysis requires older growth indices and arch forms.

BackgroundThe efficacy of excimer laser ablation (ELA) in de novo atherosclerotic lesions of lower extremity artery disease (LEAD) is unknown. ObjectivesThis real-world study aimed to evaluate the safety and efficacy of ELA combined with drug-coated balloon (DCB) versus DCB alone in LEAD patients. MethodsIn this prospective, multicenter, real-world trial (ChiCTR2100051263), patients with de novo atherosclerotic lesions of LEAD were enrolled and allocated to either ELA + DCB or DCB-alone group in a 1:1 ratio. The primary endpoint was 12-month primary patency, with secondary endpoints including technical success, clinically driven target lesion reintervention (CD-TLR), and changes in ankle-brachial index (ABI). ResultsA total of 136 patients were enrolled in the study. At baseline, patients in the ELA + DCB group presented significantly higher Rutherford classification (3.7 {+/-} 0.9 vs. 4.2 {+/-} 1.0, p = 0.007) and longer mean lesion lengths (7.4 {+/-} 2.5 cm vs. 8.4 {+/-} 1.9 cm, p = 0.012). The ELA + DCB group demonstrated significantly superior 12-month primary patency (87.5% vs. 71.2%, p = 0.03) and technical success rates (92.7% vs. 79.4%, p = 0.046) compared to the DCB-alone group. Kaplan-Meier analysis further confirmed sustained patency benefit with ELA + DCB (p = 0.015). ConclusionIn this real-world trial, ELA appears to be a promising therapy for LEAD in terms of safety and efficacy. However, these findings need to be corroborated by larger, randomized studies. Clinical Trial RegistrationURL: https://www.chictr.org.cn/. Unique identifier: ChiCTR2100051263

BackgroundMounting evidence from randomized controlled trials have shown that antibiotics can be a safe and effective treatment for appendicitis. Patients and surgeons must work together to choose the optimal treatment approach for each patient based on their own preferences and values. We developed a novel decision support tool (DST) to facilitate shared decision making for appendicitis. The effect of this DST on decisional outcomes remains unknown. MethodsWe conducted an online randomized field test in at-risk individuals comparing the DST to a standard infographic as a control. Individuals were randomized 3:1 to the DST (intervention) or infographic (control). The primary outcome was the total decisional conflict scale (DCS) score measured before and after exposure to the DST. Secondary outcomes included between-group DCS scores, and between group comparisons of the acceptability of DST or infographic. Results180 individuals were included in the study after quality control checks. Total DCS scores decreased significantly after viewing the DST (59.0 to 14.6, p<0.001) representing movement from a state of high to low decisional conflict. Individuals exposed to the DST reported higher acceptability ratings (3.7 vs. 3.3, p<0.001) and had more individuals who would completely agreed that they would be willing to try antibiotics (45% vs. 21%, p=0.008). ConclusionsThe novel appendicitis DST significantly decreased decisional conflict in this online randomized field test. Users rated the tool as highly acceptable and expressed increased willingness to consider antibiotics as a treatment approach after viewing it. Study FundingThis work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [grant number T32DK070555]; and a generous gift from Marty and Linda Ellison. The development of aspects of the decision support tool was funded by the Patient Centered Outcomes Research Institute. The funding sources had no role in the study design, collection, analysis, or interpretation of data, in the writing of the manuscript or in the decision to submit for publication.

ObjectiveEvaluate the effect of risk communication tools on the understanding of statistical risk of complications occurring in patients undergoing a surgical or interventional procedure. Summary Background DataInformed consent is an essential process in clinical decision-making, through which healthcare providers educate patients about the benefits, risks and alternatives of a procedure. Numerical risk information is by nature probabilistic and difficult to communicate. Aids which support statistical risk communication and studies assessing their effectiveness are needed. MethodsA systematic search was performed across Medline, Embase, PsycINFO, Scopus and Web of Science until July 2021 with a repeated search in September 2022. Studies examining risk communication tools (e.g. informative leaflets, audio-video) in adults (age>16) patients undergoing a surgical or interventional procedure were included. Studies only assessing understanding of non-statistical aspects of the procedure were excluded. Both randomised control trials (RCTs) and observational studies were included. Cochrane risk-of-bias and the Newcastle-Ottawa Scale were used to assess the quality of studies. Due to heterogeneity of the studies, a narrative synthesis was performed (PROSPERO ID: CRD42022285789). ResultsA total of 4348 articles were identified and following abstract and full-text screening a total of 11 articles were included. 8 studies were RCTs and 3 were cross-sectional. The total number of adult patients was 1030. The most common risk communication tool used was additional written information (n=7). Of the 8 RCTs, 5 showed statistically significant improvements in the intervention group in outcomes relating to recall of statistical risk. Quality assessment of RCTs found some concerns with all studies. ConclusionsRisk communication tools appear to improve recall of statistical risk. Additional prospective trials are warranted which can compare various aids and determine the most effective method of improving patient understanding.

BackgroundLarge language models (LLMs) are increasingly used in randomized clinical trial (RCT) screening, but their potential for sociodemographic bias remains unclear. ObjectiveTo determine whether LLM-based trial screening judgments vary with patient sociodemographic characteristics when clinical details and eligibility criteria are held constant. Design, Setting, and ParticipantsCross-sectional evaluation of Phase II-III RCT protocols from ClinicalTrials.gov (U.S. adult populations; 2023-2024). For each protocol, we created 15 physician-validated clinical vignettes rendered in 34 versions: one control (no identifiers) and 33 identity variants spanning gender, race/ethnicity, socioeconomic status, homelessness, unemployment, and sexual orientation. ExposuresIdentity labels applied to otherwise identical vignettes, evaluated by nine contemporary LLMs. Main Outcomes and MeasuresPrimary eligibility domain score (1-5 Likert scale) comparing identity variants versus control. Secondary: adherence, resources, risk-benefit, and trust/attitude domains. Mixed-effects models estimated adjusted mean differences with multiplicity-corrected P values; differences <.10 considered trivial. ResultsOf 69 protocols, 58 met inclusion criteria. Analysis of 5,324,400 model evaluations showed eligibility judgments were largely stable: most identity-related differences fell within {+/-}0.05 (transgender woman -.008 [95% CI -.04 to .02]; White male .036 [.01 to .07]). Only homelessness exceeded the trivial threshold (-.121 [-.15 to -.09], P<.001). Secondary domains revealed socioeconomic gradients, particularly for adherence (homeless -.595, P<.001) and resources (homeless -.715, P<.001), with smaller trust/attitude effects and negligible risk-benefit differences. Conclusions and RelevanceBias in LLM-assisted trial screening is conditional. Within fixed criteria, models reason consistently; outside them, they echo the inequities of their data. Responsible deployment in clinical research depends on preserving that boundary so that automation strengthens fairness in trial access rather than inheriting distortion.

BackgroundKnee pain affects one in three adolescents, which makes it one of the most common pain sites. Guideline recommendations about the clinical selection of patients likely to benefit from interventions are unclear, which leads to treatment heterogeneity and the potential of wasted resources among adolescents with a good prognosis. In contrast, adolescents with a poorer prognosis may not receive sufficient care. A newly developed clinical decision-support tool (The MAP-Knee Tool) intends to support clinicians in engaging with patients and adjusting the clinicians evidence-based practices to accommodate patient preferences and treatment needs via a shared decision-making process. The aims of this trial are 1) to investigate the effectiveness of using a clinical decision-support tool (The MAP-Knee Tool) compared with usual care in adolescents with non-traumatic knee pain in reducing pain measured by KOOS-Child Pain after 12 weeks and 2) to investigate how the intervention worked, for whom, why and under which circumstances applying realist evaluation methodology. MethodsThis trial is a cluster-randomised superiority trial with a delayed intervention and a realist evaluation. Six hospital departments start with a usual care period of 4 months before randomly crossing over to using the intervention (The MAP-Knee Tool) after 4, 6, or 8 months, respectively. We will recruit 290 adolescents suffering from non-traumatic knee pain diagnoses who are followed for one year, with the change in KOOS-Child Pain after 12 weeks considered the primary endpoint. Secondary outcomes include 1) Global Rating of Change, 2) EQ-5D-Youth, 3) Anterior Knee Pain Youth, 4) the International Physical Activity Questionnaire short version, and 5) sports participation. The realist evaluation will utilise a prospective, qualitative approach for collecting data needed to develop and test a program theory and identify context-mechanism-outcome configurations essential for understanding how outcomes are achieved within specific contexts. DiscussionThis trial focuses on how the initial clinical encounter can be improved to meet the support and management needs of adolescents with chronic knee pain seeking treatment for knee pain in secondary care and investigates how the intervention worked, for whom, why and under which circumstances. Trial registrationClinicaltrials.gov (NCT05791513). Prospectively registered on March 30th, 2023.