Sleep disturbances are highly prevalent in the perioperative period and are associated with poor recovery outcomes. This is particularly relevant for cardiac surgery patients, among whom sleep architecture disorders are common postoperative complications. Dexmedetomidine, a selective α2-adrenergic receptor agonist, has shown promise in improving sleep quality by promoting non-rapid eye movement (NREM) sleep. However, the efficacy of its non-invasive, intranasal administration for postoperative sleep management remains underexplored. In this prospective randomized study, adult patients undergoing cardiac surgery will be enrolled. Participants will be randomly assigned to receive either intranasal dexmedetomidine or an identical placebo on postoperative days 1–4. The primary outcome was the subjective sleep quality assessed using the Richards-Campbell Sleep Questionnaire (RCSQ) on the second postoperative morning. Secondary outcomes included objective sleep parameters measured by sleep monitors, incidence of delirium, pain scores, patient satisfaction, postoperative ICU length of stay, postoperative in-hospital all-cause mortality, sleep quality, and cognitive function after discharge. Our study will aim to assess the impact of intranasal administration of dexmedetomidine on the effect of sleep disturbance in patients undergoing on-pump elective cardiac surgery. If intranasal dexmedetomidine proves to be effective, it will be a promising strategy for enhancing recovery and may reduce associated neurological complications. ChiCTR2500109422. Registered on September 18, 2025.
People with multiple sclerosis experience physical, cognitive, and medication-related challenges that can compromise oral self-care and increase their risk of oral disease. However, tailored, theory-based oral health interventions for this population remain limited. This trial aims to evaluate two social cognitive theory–based oral health education interventions, delivered via WhatsApp and face-to-face motivational interviewing, to improve oral health knowledge, attitudes, practices, and clinical outcomes among people with multiple sclerosis. This single-centre, three-arm, parallel-group superiority randomised controlled trial will enrol 201 adults with multiple sclerosis aged 18–60 years at the Omid MS Rehabilitation Center in Zanjan, Iran. Participants will be allocated in a 1:1:1 ratio using stratified randomisation with concealed allocation to a 6-week WhatsApp-based oral health education programme, six weekly face-to-face motivational interviewing sessions, or usual care. The primary outcome family will comprise changes from baseline in oral health knowledge, attitude, and practice domain scores, assessed using a 26-item questionnaire that was content-validated and pilot-tested prior to baseline assessment and randomisation. The domains will be tested at the 3-month follow-up in the prespecified hierarchical order of practice, attitude, and knowledge; the immediate post-intervention assessment will provide supportive evidence. Secondary outcomes will comprise changes from baseline in mean Plaque Index and Gingival Index scores. Outcomes will be measured at baseline, immediately after the interventions and at the 3-month follow-up. Clinical examinations will be performed by an assessor blinded to group allocation. Recruitment will begin in November 2025 and continue until January 2026. Following baseline assessment and randomisation, the 6-week interventions will be delivered between February and March 2026, with the immediate post-intervention and final 3-month follow-up assessments completed by June 2026. This trial will compare two theory-informed oral health education approaches with usual care among people with multiple sclerosis. If effective, these interventions may inform accessible, scalable, and technology-assisted oral health promotion for people with multiple sclerosis and provide a basis for future studies of long-term effectiveness, cost-effectiveness, and broader application in chronic disease management. Iranian Registry of Clinical Trials, IRCT20250414065316N1. Registered on 23 Sep 2025.
Decentralized trial approaches involving community pharmacies have gained increasing attention. However, recruitment in community pharmacies faces complex conditions and tailored strategies are necessary. Applying implementation science principles is a promising but underrepresented approach to facilitate recruitment processes. On the example of adherence-enhancing services, we aimed to investigate influencing factors to trial recruitment in the community pharmacy setting and to identify implementation strategies that can optimize trial recruitment. We conducted a qualitative Study Within A Trial (SWAT) embedded within two ongoing trials evaluating adherence services provided in pharmacies. Pharmacists and patients invited to one of the host trials were asked to explain reasons for participation or non-participation in written form, at the pharmacy counter, in short telephone interviews, or in semi-structured interviews. In an inductive/deductive hybrid analysis, we coded all responses deductively based on the constructs of the updated Consolidated Framework for Implementation Research. By using the CFIR-ERIC Matching Tool, barriers were matched to strategies from the Expert Recommendations for Implementing Change. Additionally, we analyzed all data inductively. Thirty-one community pharmacists and 127 patients stated reasons for accepting or declining to participate in one of the studies. Nine pharmacists participated in semi-structured interviews. We identified 18 barriers and 9 facilitators related to trials in community pharmacies. Most barriers were associated with the Individuals domain of the CFIR. Factors influencing innovations’ acceptance were mainly linked to innovations’ adaptability and complexity. Policies and Laws created an additional strong barrier to recruitment. With the CFIR-ERIC Matching Tool, we identified 13 implementation strategies such as local champions, new funding, and ongoing discussions, consultations, and training of study sites. The inductive analysis revealed 8 additional strategies not identified by the CFIR-ERIC Matching Tool, concerning general study design, study materials, and the recruitment process. Trial recruitment in community pharmacies requires targeted implementation strategies addressing local barriers and including known facilitators. Most promising strategies include implementation plans, information materials, and local pharmacy champions, which may help overcome limited resources. Although our results were obtained in adherence-enhancing services, strategies targeting barriers in the Inner Setting and Outer Setting may be particularly transferable to other pharmacy services. ClinicalTrials.gov NCT06094062 (PIPPI-Study). Registered on 23 October 2023; and NCT06126900 (SMAPP-Study). Registered on 13 November 2023.
Postoperative agitation (EA) has a high incidence in pediatric strabismus surgery and risk factors including inhaled anesthetics, surgery itself and pain. Hydromorphone, a semi-synthetic opioid, has been widely used in pediatric patients. However, the effect of hydromorphone on postoperative emergence agitation (EA) in pediatric strabismus surgery is not fully clear. Therefore, the investigation of this study is to evaluate the impact of Hydromorphone on the incidence of EA in pediatric strabismus surgery with sevoflurane anesthesia. Eighty-two patients scheduled for strabismus surgery participated in this study were randomly assigned to the hydromorphone group (n = 41) and the fentanyl group (n = 41). The sedation score of each patient was evaluated at 15 min, 30 min, and 2 h after extubation. The primary outcome was the incidence of EA according to postoperative sedation score in pediatric patients. And the secondary outcomes were postoperative pain score, family satisfaction, and the incidence of postoperative nausea, dizziness, and vomiting. The present study demonstrated that hydromorphone exhibit superior sedative effects compared to fentanyl at 15 min, 30 min, and 2 h after extubation (P < 0.01). And hydromorphone significantly reduced the incidence of EA in the post-anesthesia care unit (PACU) (P < 0.01). In addition, the hydromorphone group showed better analgesic efficacy at 15 and 30 min post-extubation (P < 0.01), but no statistically significant difference in analgesic effect was observed between the two groups at 2 h after extubation (P = 0.17). According to questionnaires, parents in hydromorphone group had higher satisfaction with medical care (P < 0.01), although hydromorphone was associated with dizziness and vomiting. In conclusion, hydromorphone is plausible to reduce the incidence of postoperative agitation and enhances parental satisfaction in pediatric strabismus surgery. The trial was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR). Trial ID: ChiCTR2500113063. Registered on November 24, 2025.
Generalised anxiety disorder (GAD) is common and increasingly recognised in primary care. Although antidepressants and psychological therapies are first-line treatments, many patients have residual anxiety and limited access to therapy. Evidence for effective next-step pharmacological options for treatment resistant anxiety remains limited. This paper describes the protocol for the PETRA trial, which will evaluate the clinical and cost-effectiveness of adding pregabalin to antidepressant treatment, compared with placebo, for people with GAD who have not responded or partially responded to antidepressant treatment. PETRA is a multicentre, individually randomised, double-blind, placebo-controlled superiority trial conducted in UK primary care. Participants are recruited by the study team from approximately 150 General Practices and randomised in a 1:1 ratio, using minimisation, to either pregabalin or a matching placebo for 26 weeks (followed by a tapering period where their dosage is reduced over approximately 4 weeks). Sample size is 498. Eligible participants are adults aged 18–74 years, who have been taking antidepressant medication for at least 8 weeks, received treatment with at least one other antidepressant before their current antidepressant and meet ICD-11 criteria for GAD and score ≥ 12 on the revised clinical interview schedule (CIS-R) total score. Follow-up assessments are at 3, 6, 12, 26 and 30 weeks. Our primary outcome measure will be anxiety symptoms measured with GAD-7 at 12 weeks (continuous score). Secondary outcomes are anxiety (GAD-7) at other time points, depressive and panic symptoms, suicidal thoughts, self-rated global improvement, adherence to study medication, serious adverse events, adverse effects, alcohol consumption and benzodiazepine use, quality of life and resources and costs used. The 30-week assessment will investigate symptoms during the withdrawal from pregabalin. Exploratory analyses will include cognitive tasks. A cost-effectiveness analysis and a nested qualitative study will evaluate the implementation and intervention acceptability. The trial findings will inform primary care prescribing practice by providing an accurate and generalisable estimate of the clinical and cost-effectiveness of prescribing pregabalin to individuals with generalised anxiety who have not responded or only partially responded to antidepressant treatment. Controlled Trials ISRCTN Registry, ISRCTN 16993990, registered on 19/09/2023. First participant enrolled in January 2024.
This narrative methodological review aims to critically examine the role of blinding (masking) in minimizing bias in randomized clinical trials (RCTs), with particular attention to the methodological challenges associated with its implementation. Dental research is used as a field of application to illustrate how general principles of blinding operate in complex, non-pharmacological clinical settings. A narrative synthesis was conducted based on methodological and empirical literature addressing blinding in RCTs. Classical and contemporary publications from biomedical and dental research were examined to identify key concepts, recurring challenges, and methodological strategies related to blinding. The evidence was analyzed from a conceptual and methodological perspective, integrating insights from the literature with the authors’ experience in clinical dental research. The reviewed literature indicates that, although blinding is a central strategy for reducing performance and detection bias, its feasibility in dental RCTs is frequently constrained by the procedural and operator-dependent nature of interventions. Ethical considerations, perceptible differences between treatment arms, and the assessment of subjective outcomes were identified as common barriers. When full blinding is not achievable, alternative methodological approaches—such as blinded outcome assessment, standardized protocols, and transparent reporting—emerge as important strategies to mitigate bias. Blinding presents distinct methodological challenges in dental randomized clinical trials, reflecting broader difficulties encountered in non-pharmacological research. While complete masking is often unattainable, careful trial design, explicit acknowledgment of limitations, and appropriate compensatory strategies can substantially strengthen internal validity. This review provides a methodological reflection on blinding that may inform the design and reporting of RCTs in dentistry and other complex clinical fields.
Body dysmorphic disorder (BDD) is a prevalent and impairing mental disorder that typically onsets in adolescence. Cognitive-behavior therapy (CBT) may be effective for adolescent BDD, although the supporting evidence is currently limited. CBT for BDD is a highly specialized treatment, creating a considerable gap in access to care for young people. Therapist-guided Internet-delivered CBT (ICBT) may help bridge this gap. The primary aim of this study is to determine the efficacy of a therapist-guided ICBT program for children and adolescents with BDD versus an active comparator. Secondary aims are to examine the 6-month durability of the treatment effects and to evaluate its relative cost-effectiveness from multiple perspectives. This is a 3-site superiority randomized controlled trial including 154 young people (12–17 years) with BDD recruited throughout Sweden. Participants are randomized 1:1 to 12 weekly modules of either therapist-supported ICBT primarily based on exposure with response prevention or an active comparator consisting of therapist-supported Internet-delivered relaxation training. Data will be collected at baseline, mid-treatment, post-treatment, and 1 month (primary endpoint), 3 months, and 6 months post-treatment. The primary outcome is BDD symptom severity measured with the Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder, Adolescent version. All study personnel who can be blinded to study aims/hypotheses and group allocation will be blinded. Assessors conducting post-treatment and follow-up assessments will be external to the research team and blinded to study aims/hypotheses and group allocation at all assessment points. Analyses will be conducted according to the intention-to-treat principle and will follow a pre-specified statistical and health economic analysis plan. Participant recruitment started on 22 February 2024 and is currently ongoing. Data analysis for the primary aim will commence after the last participant reaches the primary endpoint. ClinicalTrials.gov NCT06262412. Registered on 16 February 2024, https://clinicaltrials.gov/study/NCT06262412 .
Chronic kidney disease presents a formidable challenge to global healthcare systems. With ongoing advancements in surgical techniques, kidney transplantation has emerged as a principal therapeutic modality for individuals afflicted with end-stage renal disease, markedly enhancing their long-term prognosis and overall quality of life postoperatively. Nevertheless, the occurrence of delayed graft function represents a prevalent early complication following kidney transplantations, mainly stemming from the ischemia-reperfusion injury incurred by the transplanted kidneys and the utilization of extended criteria donor organs. The manifestation of delayed graft function can precipitate primary allograft nonfunction, acute rejection episodes, and potentially fatal outcomes. Vigilant attention to perioperative fluid management emerges as a cornerstone in mitigating the risk of delayed graft function. Recent strides in Goal-directed fluid therapy have garnered substantial attention within critical care contexts, with empirical evidence underscoring its favorable impact on postoperative outcomes in critically ill cohorts. However, the efficacy of Goal-directed fluid therapy specifically in the context of kidney transplantation remains a subject of ongoing debate and scrutiny. Hence, the imperative arises to investigate potential strategies aimed at attenuating the incidence of delayed graft function in this patient demographic. A multicenter, randomized, single-blind, two-arm parallel-group, controlled trial will be undertaken to assess the efficacy of norepinephrine in conjunction with Goal-directed fluid therapy on graft function recovery among individuals slated for kidney transplantations. Patients will be allocated randomly to either a control or intervention arm, wherein conventional fluid management or the administration of norepinephrine infusion combined with Goal-directed fluid therapy will be administered, respectively. The primary objective of this study is to investigate the potential efficacy of norepinephrine infusion in conjunction with goal-directed fluid therapy in mitigating the occurrence of delayed graft function among individuals undergoing kidney transplantations. The findings of this investigation have the potential to advance the field of perioperative care in kidney transplantations by providing insights into optimized management strategies. ClinicalTrials.gov NCT06367205. Registered on April 16, 2024.
Patients with neck pain often experience proprioceptive dysfunction and other impairments. Although strengthening exercises and cervical joint mobilization effectively improve proprioception, their comparative effects remain unclear. This study compared cervical joint mobilization and strengthening exercises in patients with neck pain to assess their effects on proprioception and other outcomes, namely pain, muscle strength, ROM, and disability, and to explore correlations among these outcomes. This assessor-blinded randomized clinical trial (IRB-14-2024-06-07-95/IRB-PGS-2024-03-574) registered at ClinicalTrials.gov (NCT06960525). This study included 26 patients with chronic neck pain divided into two groups: (1) joint mobilization plus standardized care and (2) strengthening exercise plus standardized care. Both groups underwent 12 sessions over 4 weeks. Outcome measures included active cervical movement sense, joint position error, visual analog scale, hand-held dynamometer, inclinometer, and neck disability index. Outcomes were measured immediately after the 1st and 12th sessions. Patients in both groups showed significant improvements in all outcome measures, particularly at the 12th session. However, no significant differences were found between the groups for any outcome. Both cervical joint mobilization and strengthening exercises, delivered alongside standardized care, were associated with improvements in proprioception and other outcomes in patients with chronic neck pain in the short term, with no statistically significant between-group difference detected.
Abstract Background Effective care of people with cognitive impairment and their families depends, among other things, on the cooperation of the professionals involved in their care. An effective dementia care management support model for people with dementia and their families for the outpatient sector has been further developed for ambulatory and hospital settings. The intersec-CM randomized controlled trial (RCT) implemented this intersectoral care management (iCM) model into routine care in three hospitals in Bielefeld and Greifswald (Germany). Care managers (CMs) trained in advance for the study used a computer-based information management system (IMS) to assess patients’ health and care needs and to develop individualized care plans. The iCM aimed to improve hospital-to-primary-care transitions and ensure cross-sectoral care. This was accompanied by a process evaluation to complement the data collected in the RCT. The aim was to understand how the complex intervention works in the selected real-world setting. This paper presents the results of this process evaluation. Methods For the process evaluation, a mixed-method design was chosen and applied. The evaluation was based on the guidelines of the British Medical Research Council for the implementation and process evaluation of complex interventions (MRC framework). A method triangulation was conducted consisting of several successive phases (t1: qualitative, t2: quantitative, t3: qualitative). Results The sample (t1: individual interviews n = 30, t2: survey n = 177, t3: individual interviews n = 33) consisted of patients and their relatives, clinical physicians, social workers, carers, general practitioners, care managers (CMs), and project management. The process evaluation showed that intersectoral iCM could be implemented in the hospitals. The CMs were partially successful in assessing needs, developing individual treatment plans, and coordinating and monitoring the needs of people with cognitive impairment and their families. They found it difficult to work with the different actors in the healthcare system because of the rigid daily routines and lack of time in the clinics. Overall, the results show that (1) people with cognitive impairment and their families can benefit from the intervention and (2) iCM can help with the flow of information between health professionals. Conclusions The present process evaluation underlines the necessity and meaningfulness of process evaluations to understand the functionality and procedural feasibility of an RCT. Through the study, significant insights into the “black box” of the implementation of the iCM intervention could be gained. Trial registration ClinicalTrials.gov NCT03359408. The trial was registered on December 2, 2017.
Suicidal behaviours represent significant public health concerns. People who present with suicidal ideation and/or self-harm are at an increased risk of suicide. The presence of co-existing or comorbid mental and physical health conditions, coupled with neurobiological factors, exacerbates mental health conditions and increases the risk of suicidal behaviours. Psychotherapeutic interventions, including Cognitive Behavioural Therapy, have been considered first line of treatment for several standalone and comorbid populations. However, research into CBT tailored for people at risk of suicide and self-harm while living with mental and physical health comorbidities is lacking. Therefore, this pragmatic trial aims to examine the effectiveness of an enhanced CBT in addition to standard care in reducing suicidal ideation, compared to standard care only. The study will follow a pragmatic randomised controlled trial design. The primary outcome is post-intervention severity of suicidal ideation and secondary outcomes include self-harm behaviours, depression and anxiety, coping, hopelessness, impact of comorbid conditions, and mental well-being. Additionally, blood and salivary samples will be collected to measure biomarkers of inflammation, hypothalamic–pituitary–adrenal (HPA)- axis, neural plasticity, and the tryptophan-kynurenine pathway. Participants will be randomised following stratification and blocking into the intervention and control arm, and the data will be collected at baseline, post-intervention, and a 3-month follow-up. A participant safety plan specific to the project has been developed and will be implemented throughout the study duration. This protocol has been developed following the SPIRIT guidelines. People who live with long-term physical health conditions and co-existing depression, anxiety and distress are at increased risk of suicidal ideation and self-harm. Using a pragmatic randomised controlled trial methodology, the results of this study will contribute to improving our knowledge of implementing an evidence-based CBT intervention on suicidal ideation including self-harm behaviours, psychological state and biological factors. Prospectively registered on ISRCTN, ISRCTN17751649. Registered on 21 August 2024, https://doi.org/10.1186/ISRCTN17751649.
Abstract Background Negative symptoms are experienced by up to 60% of the individuals with schizophrenia and represent a stronger indicator of current and future functioning than positive symptoms. These symptoms respond poorly to pharmacological and existing psychosocial interventions, highlighting the need for targeted treatments. Previous research suggests that defeatist performance beliefs, combined with metacognitive deficits, may contribute to negative symptoms. A recent pilot study, adapting the cognitive intervention metacognitive training (MCT) to address negative symptoms, found symptom reduction, primarily due to improved reflective functioning and reduced perceived stigma. The current study aims to further assess the efficacy of this intervention and to explore potential mechanisms of change in negative symptoms. Methods Ninety participants aged 18 and older with a psychotic disorder will be recruited from psychiatric care settings in Sweden. Participants will be randomly assigned to either the intervention group (MCT-Minus) or a control group receiving supportive counselling (SC). Data will be collected at baseline, post-intervention, and at 12-week and 12-month follow-ups. Magnetic resonance imaging (MRI) will be performed at baseline and post-intervention. Exit interviews will be held after completing the intervention. The primary outcome is change in negative symptom, measured by the Clinical Assessment Interview for Negative Symptoms (CAINS), across all time points. Repeated measures ANCOVA will be used to evaluate primary outcomes. Additional analyses will address changes in positive symptoms and potential mechanisms of change, including metacognition and internalized stigma. Qualitative data from exit interviews will be analyzed using reflexive thematic analysis. Discussion This study is designed to evaluate the efficacy of MCT-Minus compared to supportive counselling. Given the limited treatment options for negative symptoms in schizophrenia, the findings may have important clinical implications. Trial registration This study was registered on the 6th of November 2023 on Clinical Trials with the trial registration number NCT06127004. Statistical analyses will be preregistered on the Open Science Framework.
Abdominal aortic aneurysm (AAA) is a potentially lethal condition if left untreated. AAA growth is a predictor of rupture as well as decreased survival. Minimally invasive infrarenal endovascular aortic repair (EVAR) is the primary option for AAA treatment. One of the most common complications after EVAR is the presence of type 2 endoleaks (T2ELs), i.e., continued retrograde perfusion of the aneurysm sac by aortic side branches, typically the lumbar arteries. In many cases, a T2EL prevents optimal aneurysm exclusion and is associated with continued aneurysm growth. Thus, a low but persistent risk of rupture and a high rate of reinterventions remain an issue/concern in the presence of T2ELs. In addition, failure of aneurysm sac shrinkage even without concomitant endoleak is associated with decreased long-term survival. Pre-emptive as well as postoperative selective side branch occlusion to prevent or treat T2ELs is time-consuming and technically demanding with a low technical and clinical success rate. Therefore, perioperative, nonselective embolization of the aneurysm sac during EVAR has been proposed to prevent T2EL and promote sac shrinkage (PREVAR—Clinical Trial NCT05575570). Patients scheduled for EVAR at the Department of Vascular Surgery, Rigshospitalet Copenhagen University Hospital, The Heart Center, Denmark, are offered inclusion in this study. Patients are randomized to infrarenal EVAR (control) or infrarenal EVAR plus sac embolization with Shape Memory plugs (SMP) (intervention). The plugs are based on a resorbable scaffolding and a small radiopaque marker causing minimal imaging artifacts on computed tomography angiography (CTA). The number of plugs is individually calculated based on aneurysm sac flow volume. Postoperative follow-up (FU) is performed after 3 months, 1 year, and 5 years with both contrast-enhanced ultrasound (CEUS) and 3-phase CTA (without contrast, arterial phase, and venous phase). AAA sac volume change is the primary endpoint. Incidence of T2EL, reintervention rate, and long-term survival are the secondary endpoints. The study is terminated after the final patient has completed the 5-year FU. EVAR has revolutionized AAA treatment since its introduction. In the short term, outcomes are superior to open aortic repair in anatomically suitable candidates. However, the high incidence of T2ELs and failure of AAA sac shrinkages associated with reinterventions and decreased survival in many patients. Preliminary data on intraoperative AAA sac embolization during EVAR seems to promote sac shrinkage. SMP plugs are tested and CE marked (Conformité Européenne) for embolization treatment but the effect of aneurysm sac embolization during EVAR is poorly known. This randomized study investigates the effect of aneurysm sac embolization with SMP plug material in a single-center setting. Clinical Trial, PREVAR—Clinical Trial NCT05575570, registered October 12, 2022, https://clinicaltrials.gov/study/NCT05575570.
The SuDDICU trial evaluated the effectiveness of selective digestive decontamination (SDD), a prophylactic antibiotic regimen comprising oral, gastric and intravenous (IV) components in ventilated adults admitted to intensive care. The trial recruited 9289 participants in 26 clusters across Australia and Canada. There was no difference in the primary outcome of in-hospital mortality, but a reduction in new positive blood cultures and antibiotic organisms. We conducted a concomitant process evaluation in Canadian sites. Our objectives were to quantify participant reach, intervention fidelity and understand drivers of implementation. Multiple methods process evaluation comprising quantitative data on participant reach and intervention fidelity, and qualitative data using key informant interviews and non-participant observation. Analyses were informed by the Consolidated Framework for Implementation Research (CFIR). Of 6317 patients screened in Canadian clusters, 577/3020 (19.1
Abstract Background Pathological fatigue is one of the most prevalent and disabling symptoms across chronic neurological, post-infectious, and inflammatory diseases, yet effective treatments remain limited. Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe, non-invasive neuromodulatory intervention that targets neuroimmune and autonomic pathways implicated in the development and persistence of fatigue. This randomized controlled trial investigates whether home-based taVNS can reduce fatigue severity in a transdiagnostic population. Methods This study is a randomized, double-blind, sham-controlled, parallel-group clinical trial conducted at the University Hospital Magdeburg. Eligible adult participants (≥ 18 years) with clinically significant chronic fatigue from two diagnostic clusters (neurological disorders and post-infectious syndromes) will be enrolled and randomized (1:1) to receive either active taVNS or sham stimulation for 4 weeks. Stimulation is self-administered at home twice daily for 30 min. The primary outcome is change in fatigue severity from baseline to the end of the intervention, assessed using the Modified Fatigue Impact Scale (MFIS). Secondary outcomes include quality of life (WHOQOL-BREF), depressive symptoms (BDI-II), daytime sleepiness (ESS), cognitive performance (SDMT and TAP subtest alertness), neurophysiological markers (resting-state EEG and P50 sensory gating) and HRV indices (Garmin Vivosmart 5). Blinding integrity will be assessed at study end. Data will be analyzed according to an intention-to-treat framework. No interim analyses are planned. Adverse events will be monitored continuously. Discussion This is to be the first transdiagnostic study to evaluate home-based taVNS as a potential therapeutic approach for pathological fatigue across multiple chronic disease groups. The combination of rigorous blinding, digital monitoring, and parallel assessment of clinical and physiological parameters allows for an in-depth evaluation of both treatment effectiveness and mechanistic correlates. If successful, taVNS could offer a scalable and accessible intervention for a large and underserved patient population. Trial registration The trial was registered in the German Clinical Trials Register (DRKS) under the identification number DRKS00038292. Registered on December 01, 2025. URL: https://drks.de/search/de/trial/DRKS00038292 .
Child sex trafficking (CST) has significant, long-term health consequences for children and their families. Given higher risk of CST for middle school-aged children, the significant time spent by students in schools under staff supervision, and the opportunity to provide CST prevention programming to school staff, our team developed and launched the cluster randomized controlled trial (cRCT), CSTOP Now!. The purpose of this investigation is to examine the effectiveness of recruitment strategies to enroll middle school staff into the cRCT. Both training conditions were delivered through an asynchronous online learning management system to school staff. A two-stage recruitment began with 50 counties randomly assigned to intervention or attention control conditions. Administrators in middle schools within these counties were contacted and invited into the cRCT; 37 middle schools joined the cRCT. Six school-level staff recruitment strategies were used and evaluated for effectiveness in enrolling participants. The most effective strategy was champion recruitment (69
