Stroke affects over 1 million people in Europe and 25,000 in Sweden annually, with high mortality and disability rates. Dysphagia, a common post-stroke issue, occurs in over 50% of patients in the acute phase. Evidence-based studies are lacking on rehabilitative interventions to improve post-stroke dysphagia. Current management focuses on compensatory strategies, but oral neuromuscular training shows promising results. Challenges to rehabilitation programs include poor adherence and the need for effective monitoring technologies. The primary objective of the current trial is to investigate the impact of oral neuromuscular training with a sensor-equipped oral device on post-stroke dysphagia. This national, multicenter, investigator-initiated, randomized, parallel-group trial compares the effect of oral neuromuscular training versus standard care in patients with post-stroke dysphagia. We will enroll 336 consecutive participants who have no prior history of dysphagia and exhibit persistent dysphagia 3 months following the onset of ischemic stroke or intracerebral hemorrhage. Participants will be randomly assigned in a 1:1 ratio to receive either a 12-week intervention consisting of standard routine care combined with oral neuromuscular training (using an oral device with sensors for adherence feedback) or current routine care alone. Standard routine care includes compensatory strategies such as bolus modification, adapted swallowing postures, and maneuvers. The primary outcome is the degree of dysphagia at end of intervention, assessed with Flexible Endoscopy Evaluation of Swallowing (FEES) by blinded evaluators, and analyzed with ordinal regression models. Secondary outcomes are changes in nutritional status, pneumonia, mortality, and quality of life after a 12-week intervention and at 6-month follow-up. This first randomized clinical trial in stroke rehabilitation on neuromuscular oropharyngeal training with sensors to facilitate adherence and comprehensive outcome measures will enable evaluation of this treatment with the potential for significant clinical impact for patients with dysphagia after stroke. ClinicalTrials.gov, identifier: NCT02960737. First registered on 11 November 2016 and later modified to the present multicenter study design on 22 August 2023.

Fidelity is defined as the extent to which an intervention is delivered as intended. Without a clear understanding of fidelity to an intervention, variability in implementation may be confounded with observed outcomes, making valid conclusions about the intervention's efficacy challenging. The MIRROR-TCM (Multisite Replication of a Randomized Controlled Trial - Transitional Care Model) implementation evaluation, discussed here, sought to examine the delivery of the transitional care model (TCM) intervention and factors that influenced fidelity to the implementation of the intervention protocol over time. The TCM includes 10 core components, which aim to support older adults transitioning from the hospital back to the community. The objective of this paper is to describe the operationalization of a fidelity measure for the TCM intervention. Fidelity was operationalized at the element, component, and overall intervention levels. The TCM fidelity score examines 38 elements, which are broken into 8 components. Rules to evaluate an element-level, binary (0/1) fidelity scores were established by the study team, which consisted of clinicians and statisticians, and updated through feedback from the advanced practice registered nurses delivering the intervention. Component-level fidelity was assessed as the proportion of total elements completed from each component. Finally, overall fidelity is calculated as the proportion of required elements completed multiplied by 38 or the total possible elements to complete. Proper evaluation of fidelity to the delivery of an intervention is key in evaluating its implementation. This paper provides new methods to calculate fidelity for a complex intervention, which required the incorporation of 38 elements and nuances that did not require all patients to receive all elements, requiring the creation of clear rules for the exclusion of elements for a participant. The fidelity measure was employed throughout implementation and used to give feedback to the study team and improve fidelity. This paper outlines a novel methodology for flexible fidelity scoring in multicomponent interventions, incorporating rule-based exemptions to accommodate variability in real-world implementation. Future work needs to include validation of the metric through evaluation of fidelity at the participant level to examine its association with clinical outcomes in the parent MIRROR-TCM study, overall and by site.

Arthroscopic rotator cuff repair is the standard of care for rotator cuff tears. However, postoperative pain and recovery remain a significant clinical challenge. While ultrasound-guided interscalene brachial plexus block with liposomal bupivacaine provides sustained analgesia for up to 72h, the addition of esketamine intravenous infusion may offer further benefits through enhanced pain control, mood stabilization, and cognitive support. This study aims to evaluate the synergistic effect of this combination on the quality of postoperative recovery in patients undergoing arthroscopic rotator cuff repair. This single center, randomized controlled trial will enroll 278 patients undergoing arthroscopic rotator cuff repair. Participants will be randomly allocated at a 1:1 ratio to either the intervention or control group. The intervention group will receive a combination of an ultrasound-guided interscalene brachial plexus block with liposomal bupivacaine and a continuous intravenous esketamine infusion, while the control group will receive a saline infusion. The primary outcome is the 15-item Quality of Recovery (QoR-15) score at 24h postoperatively. Secondary outcomes include QoR-15 scores at various time points within 30days, pain scores, total opioid consumption, need for rescue analgesia, incidence of postoperative delirium, hospital anxiety and depression scale scores, sleep quality, length of hospital stay, and adverse events. Guided by Enhanced Recovery After Surgery principles, this randomized controlled trial investigates a novel combination of liposomal bupivacaine block and esketamine infusion to enhance postoperative recovery after arthroscopic rotator cuff repair. It specifically assesses patient-reported recovery through the QoR-15 score, a validated tool encompassing pain, physical comfort, independence, and psychological well-being. As a single-center initiative, this work represents a pivotal step in generating preliminary evidence for this multimodal strategy. This study has been approved by the Ethics Committee at West China Hospital, Sichuan University (approval no. 2025-1908). The trial was prospectively registered with the Chinese Clinical Trial Registry (ChiCTR2500112854) on November 20, 2025.

Acute lateral ankle sprains, especially those affecting the anterior talofibular ligament (ATFL), are one of the most frequent injuries in athletes and active adults. These injuries cause pain, swelling, functional restriction, and high recurrence. The PEACE & LOVE framework discourages the use of cryotherapy, yet ice remains widely used in sports and rehabilitation practice. To date, there is limited high-quality evidence evaluating the effect of cryotherapy within this framework. This trial is designed to investigate whether adding cryotherapy to PEACE & LOVE rehabilitation improves outcomes compared with sham cryotherapy. This single-center, parallel-group, sham-controlled randomized clinical trial will include 60 physically active adults (aged 18-40 years) with grade I-II acute lateral ankle sprains sustained within 48 h. Recruitment has not commenced and is planned from March to May 2026. Follow-up assessments will continue through 12 weeks post-randomization. Participants will be randomly assigned (1:1) to receive either PEACE & LOVE plus cryotherapy (0-4 °C, 20 min, three times daily for 72 h) or PEACE & LOVE plus sham cryotherapy (identical packs at ~20-25 °C with insulation). The primary outcome is pain intensity measured by the Numeric Pain Rating Scale (NPRS) at day 7. Secondary outcomes are functional recovery measured by the Lower Extremity Functional Scale (LEFS) at day 14, week 4, and week 12; ankle swelling assessed by figure-of-eight measurement at baseline and day 7; ankle dorsiflexion via the Weight-Bearing Lunge Test (WBLT) at baseline, week 4, and week 12; short-term analgesic use (paracetamol log, day 0-7); and re-injury rates assessed at week 4 and week 12. Analyses will follow the intention-to-treat principle using ANCOVA adjusted for baseline scores, reporting effect sizes and 95% confidence intervals. This trial will be the first sham-controlled randomized study to evaluate cryotherapy as an adjunct to the PEACE & LOVE framework in acute ankle sprain. Findings will clarify whether cryotherapy provides clinically meaningful benefits in pain relief, function, and recurrence prevention, and may guide evidence-based rehabilitation practice. Clinical Trial Registry India (CTRI): CTRI/2024/09/073357. Registered on April 9, 2024.

The World Health Organization (WHO) recommends that adolescents engage in at least 60min of moderate-to-vigorous physical activity (MVPA) daily across the week to support healthy growth and development. Despite this guideline, physical inactivity is prevalent among adolescents in South Africa. This is concerning given the increasing burden of overweight and obesity. While nutrition is a critical driver of these conditions, physical activity represents a complementary and scalable strategy to improve overall adolescent health. This study aims to assess the effect of providing a skipping rope and an informational pamphlet to adolescents aged 10-14years in South Africa on their physical activity intentions and behaviors. This study is a two-arm parallel-group, individual 1:1, unblinded randomized trial, nested within the Design and Evaluation of Adolescent Health Interventions and Policies in Sub-Saharan Africa (DASH) project. The intervention consists of providing adolescents 10-14years old in a community setting in South Africa with a skipping rope and a pamphlet with general instructions for rope skipping and messages emphasizing the importance of regular physical activity. About 700 adolescent boys and girls are enrolled as part of this study. The intervention was administered during the first wave of data collection for the DASH study, or baseline, and outcomes will be assessed at both baseline and endline (12months), during the second wave of data collection for DASH. As a primary outcome, the trial will test whether providing skipping ropes and pamphlets to intervention participants will increase their amount of weekly MVPA over 12months, compared to participants in the control group, who will receive no materials. Secondary outcomes will be intention to do physical activity, assessed toward the end of the baseline interview, and meeting the WHO recommendations for physical activity, assessed at endline. The physical activity questionnaire was developed from the Physical Activity Questionnaires for Adolescents. Improving physical activity behaviors and reducing sedentary time among adolescents are critical for fostering healthy lifestyles into adulthood. Assessing the effectiveness of this intervention to enhance physical activity intention and behaviors in South Africa is particularly important given the increasing burden of overweight and obesity. ClinicalTrials.gov NCT06516549. Registered on July 17th 2024. https://clinicaltrials.gov/study/NCT06516549 .

Ideally, evidence-based decisions about healthcare interventions should be informed by access to up-to-date information from all relevant RCTs, making it essential that the reports are published soon after study completion. However, studies have consistently shown that between 25 and 50% of clinical trials remain unpublished or are only published many years after completion. The WHO has noted a slow but steady increase in the number of RCTs since the mid-2000s, particularly in sub-Saharan Africa (SSA). However, the extent of publication bias of SSA RCTs remains unknown. Therefore, our study objectives were to assess (1) the proportion of completed RCTs from SSA that have been published and (2) the time from completion to publication. This cross-sectional study, consisting of a retrospective analysis of registered SSA RCTs, aims to report the proportion of completed and terminated SSA RCTs registered in ClinicalTrials.gov and the Pan African Clinical Trials Registry (PACTR) and their time to publication. Our search yielded 7896 records, of which 3026 RCTs met our inclusion criteria for analysis. We identified journal publications for 1983 (65.5%) RCTs. The overall median time to publication from the primary completion date was 34.2months (95% CI: 32.4 to 35.5). Overall, we found a substantial proportion (34.5%) of unpublished SSA RCTs. Moreover, the median time to publication from primary completion was 34.2months. The persistence of publication bias threatens the integrity of evidence-based healthcare practice, particularly given that consumers depend on peer-reviewed journal publications as conventional and trusted sources to stay informed. Our findings underscore the importance of continued research to test and implement preventative strategies to mitigate publication bias.

Robust empirical evidence supports the effectiveness of physical and cognitive training in preventing and delaying cognitive decline. Emerging research suggests distinct neurobiological mechanisms underpin the effects of these different training modalities. An unresolved question is whether the mechanisms through which these training modalitiesimpart their effect interact synergistically to improve cognitive outcomes, rather than exerting additive effects, differ. In addition, past research has been inconsistent in adequately controlling for or documenting the dosage of physical and/or cognitive training. Consequently, the aim of this study is to assess the relative effectiveness of physical and cognitive training conducted in isolation or concurrently, whilst rigorously controlling and documenting the treatment parameters. This study is a three-arm randomised controlled trial conducted over a 3-month period, comparing cognitive training, physical activity, and a combination of both interventions. Older cognitively healthy participants (n = 126) aged 60-75years will be recruited from the community. The physical only training will require participants to cycle on a cycle ergometer at above 60% of their age-predicted heart rate maximum for 50min with a 3-min warm-up and cool-down period. The cognitive only training will require participants to complete up to five different cognitive tasks selected from a set of eight on the BrainHQ platform during each 50-min training session. The concurrent cognitive and physical training will require participants to undertake both treatments at the same time. Primary outcomes, assessed pre- and post- intervention, will include speed of processing and episodic memory assessed with the NIH Toolbox, as well as general driving skills assessed on a driving simulator. Findings will inform the design of interventions and population health advice aimed at mitigating cognitive decline. If a substantial synergetic effect is detected, it may lead to the use of more widespread concurrent physical and cognitive training and the potential development of methods to make concurrent training practical. Findings will also provide important clarification as to the relative benefit of the two modes of training. Prospective registration with Australia and New Zealand Clinical Trial Registry (ACTRN12624001088538) on 10th September 2024 and World Health Organisation International Clinical Trials Registry (U1111-1280-3851).

The SafeBoosC-III trial compared treatment guided by cerebral oximetry monitoring for the first 72h after birth with usual care in 1601 extremely preterm infants. Incidence of death or severe brain injury at 36weeks of postmenstrual age did not differ between the cerebral oximetry and usual care group (relative risk with cerebral oximetry, 1.03; 95% CI 0.90 to 1.18). To assess the probability of clinically important benefit or harm, we conducted secondary analyses in a Bayesian framework. Primary analyses used a weakly informative prior assuming a wide range of effects, to assess the probability that treatment guided by cerebral oximetry monitoring carried an a priori defined clinically important benefit or harm (a relative risk below 0.90 or above 1.10) or any benefit or harm (a relative risk differing from 1.0) for death or severe brain injury. Secondary analyses used an evidence-based prior derived from relevant prior trials. Posterior probabilities of clinically important benefit or harm were 1.5% and 19.2%, respectively. Posterior probabilities of any benefit or harm were 28.7% and 71.3%, respectively. Probabilities derived from secondary analyses using evidence-based priors were consistent with those from the primary analysis. Treatment guided by cerebral oximetry monitoring during the first 72h after birth in extremely preterm infants resulted in posterior probabilities of 1.5% for a clinically important benefit and 19.2% for a clinically important harm with respect to the incidence of death or severe brain injury at 36weeks of postmenstrual age. ClinicalTrials.gov NCT03770741. Registered on 12 July 2018.

We have previously described a free, public web-based tool, Trials to Publications, https://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/TrialPubLinking/trial_pub_link_start.cgi, which employs a machine-learning model based on title, abstract, and other metadata features to predict which publications are likely to present clinical outcome results from a given registered trial in ClinicalTrials.gov. We have now updated and expanded the scope of the tool, by extracting mentions of ClinicalTrials.gov registry numbers (NCT numbers) from the full-text of 3 online biomedical article collections (open access PubMed Central (PMC), EuroPMC, and OpenAlex), as well as retrieving biomedical publications that are mentioned within the ClinicalTrials.gov registry itself. These mentions greatly increase the number of linked publications identified by the tool and should assist those carrying out evidence syntheses as well as those studying the metascience of clinical trials.

Locally recurrent rectal cancer (LRRC) is an emerging area for research; however, it represents significant challenges as a relatively rare form of advanced pelvic malignancy, from both a recruitment and study setup and delivery perspective. To date, there have been relatively few published trials in this setting. High-quality, multi-centre, prospective studies could offer helpful insights regarding the challenges associated with delivering studies in rare disease settings such as LRRC, and how to effectively address them. The Locally Recurrent Rectal Cancer-Quality of Life (LRRC-QoL) study is an international, multi-centre, mixed-methods study of health-related quality of life (HrQoL) in LRRC. The International Surgical Trials Toolkit was utilised as a guideline in navigating site setup processes and to describe the challenges encountered during this study. A modified Quintet Recruitment Intervention (QRI) was used as a framework to identify recruitment challenges and drive improvements. Overall, 227 patients were recruited to the LRRC-QoL study across 14 countries. Significant challenges were encountered during site setup, including issues related to legal agreements which were further complicated by Brexit, expenses related to translation, and requirements for multiple ethical approvals. Delays during study setup and recruitment challenges occurred due to the COVID-19 pandemic. Several strategies were identified through the modified QRI with a positive impact on recruitment. Recruitment pathways were refined to a more streamlined, centralised approach, facilitated by verbal consent to contact. Recruitment rates also improved with the introduction of multiple options for participation, including traditional paper-based methods, online, and via telephone. Patient information leaflets were refined following patient and public involvement (PPI) work. Several approaches identified during the LRRC-QoL study should be considered in the development of future studies and trials recruiting patients with LRRC. These include undertaking PPI during study development, identifying flexible recruitment strategies which complement sites' existing clinical processes, and partnering with existing collaborative networks. Study registration The LRRC-QoL study registration reference: ISRCTN13692671 (https://doi.org/10.1186/ISRCTN13692671).