Search

Background: Maintenance of physical function, mobility, and independent living are important goals for older adults. However, concerns about falling (CaF) play a central role in the vicious cycle of CaF, inflammation, loss of muscle mass, and decreasing physical function ultimately resulting in negative health outcomes. CaF, like other states of chronic stress and anxiety, can be considered as enduring adverse stimuli affecting the stress systems and the inflammatory system. Therefore, the aim of this study is to investigate whether a reduction of CaF leads to a reduction of stress and therefore possibly reduces chronic low-grade inflammation. Understanding the role and directionality of the effects of inflammation on CaF increases our understanding of age-related loss of mobility and physical function. Methods: In this study, community-dwelling older adults, aged 70 years and older, will be randomly assigned to either a 4-month, multi-component intervention with exercise training and cognitive-behavioral components or to a sham control group with light stretching exercises, cognitive training, and educational health lectures. For the operationalization of specific CaF, the Falls Efficacy Scale—International will be used. Stress and related psychological symptoms will be monitored using established self-reports and by measuring salivary cortisol. Concentrations of C-reactive protein, interleukin 6, interleukin 10, and tumor-necrosis-factor-alpha, as well as gene expression of selected inflammatory transcripts, will be used as surrogate parameters of the inflammatory status at baseline, after the 4-month intervention and 8-month follow-up. Discussion: This study will be the first to test whether CaF are related with stress system activity or reactivity or with markers of inflammation in the context of a multi-component intervention with exercise training and cognitive-behavioral components addressing CaF. The reduction of specific CaF or general psychological symptoms should reverse alterations in stress systems, and / or slow down low-grade inflammation. Changes in activity, as well as psychological and biological pathways leading from CaF to muscle loss will be measured, to disentangle the individual contribution to sarcopenia, and to provide an additional pathway to break or slow-down the vicious cycle of CaF and sarcopenia. Trial registration: German Clinical Trials Register (DRKS): DRKS00029171. Registered 22 July 2022. [ABSTRACT FROM AUTHOR]

Background: The rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive. Our group's phase II multicenter dose evaluation pilot study established the efficacy and safety of an enteral weight-based cholecalciferol loading dose to rapidly restore vitamin D levels in critically ill children. Methods: Our aim is to evaluate the impact of this dosing regimen on clinical outcomes. VITdALIZE-KIDS is a pragmatic, phase III, multicenter, double-blind RCT aiming to randomize 766 critically ill children from Canadian PICUs. Participants are randomized using a 1:1 scheme to receive a single dose at enrollment of enteral cholecalciferol (10,000 IU/kg, max 400,000 IU) or placebo. Eligibility criteria include critically ill children aged newborn (> 37 weeks corrected gestational age) to < 18 years who have blood total 25-hydroxyvitamin D < 50 nmol/L. The primary objective is to determine if rapid normalization of vitamin D status improves HRQL at 28 days following enrollment. The secondary objective is to evaluate the impact of rapid normalization of vitamin D status on multiple organ dysfunction. The study includes additional tertiary outcomes including functional status, HRQL and mortality at hospital discharge and 90 days, PICU and hospital length of stay, and adverse events related to vitamin D toxicity. Additionally, we are performing comprehensive vitamin D speciation and non-targeted metabolite profiling as part of a sub-study for the first 100 participants from whom an enrollment and at least one post-intervention blood and urine sample were obtained. Discussion: The VITdALIZE-KIDS trial is the first phase III, multicenter trial to evaluate whether rapid normalization of vitamin D status could represent a simple, inexpensive, and safe means of improving outcomes following pediatric critical illness. Recruitment was initiated in June 2019 and is expected to continue to March 2026. Trial registration: Clinicaltrials.gov, NCT03742505. Study first submitted on November 12, 2018 https://clinicaltrials.gov/study/NCT03742505 [ABSTRACT FROM AUTHOR]

Background: Rotator cuff calcific tendinitis (RCCT) is a common shoulder disease whose main symptoms include shoulder pain, limited mobility, and calcification deposits in the shoulder. Traditional treatment methods have certain limitations, so finding new treatment methods has become the focus of research. Extracorporeal shock wave (ESW) and platelet-rich plasma (PRP) treatments have attracted much attention due to their non-invasive and tissue repair-promoting properties; however, the efficacy of their combined treatment in RCCT remains unclear. Methods: This study is designed as a single-center, assessment-blind, randomized controlled clinical trial with three parallel groups. Sixty subjects will be recruited and randomly divided into the ESW group, PRP group, and ESW combined with PRP group, in a 1:1:1 ratio. The entire intervention period is 4 weeks, and the follow-up period is 4 weeks. Outcomes will be measured at baseline (T0), after 1 week of intervention (T1), after 2 weeks of intervention (T2), after 4 weeks of intervention (T3), and after an additional 4 weeks of follow-up period (T4). The primary endpoint is the VAS score. Secondary endpoints are ASES, CMS, UCLA, and the location and size of calcified areas. Discussion: This study aims to evaluate the efficacy of ESW therapy combined with PRP in treating RCCT. We compare the effects of single and combined treatments to explore their impact on disease symptoms, functional improvement, and calcification regression. This provides a scientific basis for identifying more effective treatment options. Trial registration: ClinicalTrials.gov NCT06372600. Registered on April 17, 2024; version 1. [ABSTRACT FROM AUTHOR]

Background: Tai Chi (TC) holds a unique and valued place in promoting the physical and mental health of college students. Its significance is underscored by its incorporation as a compulsory physical education course in every university in China. TC, with its rich tradition, places a strong emphasis on posture control as a core sports ability. However, the students in Tai Chi Elective Course (TCEC) have very poor posture control ability. This study protocol investigates the potential of Tan Tui (TT) to address these issues, as TT is a fundamental skill for beginners of traditional Chinese martial arts and has a track record of enhancing lower limb strength and balance, making it a promising choice for improving posture control in TCEC. Methods/design: To investigate the impact of different intensities of TT exercises on posture control in TCEC students, we have designed a randomized, double-blind, parallel-controlled trial. Seventy-six students in the TCEC will be randomly divided into low-intensity Tan Tui (LTT), medium-intensity Tan Tui (MTT), and high-intensity Tan Tui exercises group (HTT) and control group (CON), each with 19 people. The LTT group, MTT group, and HTT group will be given different intensity of TT exercises, and the CON group will be given regular TCEC. The intervention period will be 6 weeks (2 times a week, 20 min each time). At baseline (before), 4 weeks of intervention (middle), and 6 weeks of intervention (after), the Unipedal Stance Test (UST), the Star Excursion Balance Test (SEBT), 60°/s angular velocity knee joint flexion and extension relative peak torque (RPT), and knee joint position perception (KJPP) will be evaluated. Discussion: This is the first randomized controlled trial protocol from the perspective of training intensity to evaluate the effect of different intensity of TT exercises on posture control of students in TCEC. Should our research reveal a significant intervention effect, the results will offer preliminary, higher-quality evidence supporting the positive impact of varying intensities of Tan Tui exercises on posture control in TCEC students. Trial registration: Chinese Clinical Trial Registry ChiCTR2000039109. Registered on October 17, 2020. [ABSTRACT FROM AUTHOR]

Background: Approximately onethird of cancer survivors encounter challenges reintegrating into the workforce, often experiencing involuntary unemployment and/or partial or full work disability following diagnosis and treatment. Returning to paid employment presents evident challenges due to uncertainties regarding work ability, perceived employer discrimination, and a lack of support, thereby risking social exclusion. However, interventions addressing return to paid employment among unemployed and/or work-disabled cancer survivors are scarce. Here, we describe the protocol of a randomized controlled trial (RCT), including a process and economic evaluation, evaluating the effectiveness and cost-effectiveness of the PLACES (unemPLoyed cAnCEr survivors Support) intervention aimed at supporting unemployed and/or work-disabled cancer survivors returning to paid employment. Methods: A two-armed RCT with a 12-month follow-up period will be conducted. Eligible participants: (1) are of working age (18–65 years), (2) are diagnosed with cancer between 6 months and 10 years ago, (3) are unemployed and/or partially or fully work-disabled, (4) have completed cancer treatment, and (5) are seeking paid employment and are motivated to initiate work immediately. Participants will primarily be identified through the Dutch Social Security Agency and the Netherlands Cancer Registry and recruited via healthcare professionals. Participants randomly allocated to the intervention group (n = 82) will receive the PLACES intervention: a tailored supported employment intervention based on the principles of Individual Placement and Support (IPS). This includes support in seeking, returning to, and maintaining paid employment. Participants allocated to the control group (n = 82) will receive care as usual. All participants will be asked to complete questionnaires, at baseline (T0), and after 3 (T1), 6 (T2), and 12 (T3) months of follow-up. The primary outcome is paid employment [yes/no]. Secondary outcomes are time until paid employment, change in working hours, work ability, quality of (working) life, and self-efficacy regarding return to work. Additionally, process and economic evaluations will be conducted. Discussion: We hypothesize that the PLACES intervention will be effective in obtaining paid employment, enhancing work ability, and improving quality of life. In addition, we expect the intervention to be cost-effective. If proven effective and cost-effective, actions should be taken to implement the intervention in usual care. Trial registration: NCT06028048. [ABSTRACT FROM AUTHOR]

Background: A recent meta-analysis concluded that outpatient appendectomy appears feasible and safe, but there is a lack of high-quality evidence and a randomized trial is needed. The aim of this trial is to demonstrate that outpatient appendectomy is non-inferior to conventional inpatient appendectomy in terms of overall morbi-mortality on the 30th postoperative day (D30). Methods: SAMBA is a prospective, randomized, controlled, multicenter non-inferiority trial. We will include 1400 patients admitted to 15 French hospitals between January 2023 and June 2025. Inclusion criteria are patients aged between 15 and 74 years presenting acute uncomplicated appendicitis suitable to be operated by laparoscopy. Patients will be randomized to receive outpatient care (day-surgery) or conventional inpatient care with overnight hospitalization in the surgery department. The primary outcome is postoperative morbi-mortality at D30. Secondary outcomes include time from diagnosis to appendectomy, length of total hospital stay, re-hospitalization, interventional radiology, re-interventions until D30, conversion from outpatient to inpatient, and quality of life and patient satisfaction using validated questionnaires. Discussion: The SAMBA trial tests the hypothesis that outpatient surgery (i.e., without an overnight hospital stay) of uncomplicated acute appendicitis is a feasible and reliable procedure in establishments with a technical platform able to support this management strategy. Trial registration: ClinicalTrials.gov NCT05691348. Registered on 20 January 2023. [ABSTRACT FROM AUTHOR]

Background: Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. Methods: In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator's overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. Discussion: The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. Trial registration: ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538 [ABSTRACT FROM AUTHOR]

Background: Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. Methods: The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. Discussion: Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. Trial registration: ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341 [ABSTRACT FROM AUTHOR]

Background: The progressive aging of the population has meant the increase in elderly patients requiring an urgent surgery. Older adults, especially those with frailty, have a higher risk for complications, functional and cognitive decline after urgent surgery. These patients have their functional and physiological reserve reduced which makes them more vulnerable to the effects of being bedridden. The consequences are at multiple levels emphasizing the functional loss or cognitive impairment, longer stays, mortality and institutionalization, delirium, poor quality of life and increased use of resources related to health. We aim to determine whether postoperative physical rehabilitation can prevent functional and cognitive decline and modify the posterior trajectory. Methods/design: This study is a randomized clinical trial, simple blinded, conducted in the Department of Surgery of a tertiary public hospital in Navarra (Hospital Universitario de Navarra), Spain. Patients > = 70 years old undergoing urgent abdominal surgery who meet inclusion criteria will be randomly assigned to the intervention or control group. The intervention will consist of a multicomponent physical training programme, which will include progressive and supervised endurance, resistance and balance training for 4 weeks, twice weekly sessions with a total of 8 sessions, and the group control will receive the usual care. The primary outcome measure is the change in functional (SPPB) and cognitive status (Mini-Mental State Examination) and the change of quality of life (EuroQol-5D-VAS) during the study period. The secondary outcomes are postoperative complications, length of stay, delirium, mortality, use of health resources, functional status (Barthel Index and handgrip strength tests), cost per quality-adjusted life year and mininutritional assessment. The data for both the intervention group and the control group will be obtained at four different times: the initial visit during hospital admission and at months 1, 3 and 6 months after hospital discharge. Discussion: If our hypothesis is correct, this project could show that individualized and progressive exercise programme provides effective therapy for improving the functional capacity and achieve a better functional, cognitive and quality of life recovery. This measure, without entailing a significant expense for the administration, probably has an important repercussion both in the short- and long-term recovery, improving care and functional parameters and could determine a lower subsequent need for health resources. To verify this, we will carry out a cost-effectiveness study. The clinical impact of this trial can be significant if we help to modify the traditional management of the elderly patients from an illness model to a more person-centred and functionally oriented perspective. Moreover, the prescription of individualized exercise can be routinely included in the clinical practice of these patients. Trial registration: ClinicalTrials.gov Identifier: NCT05290532. Version 1. Registered on March 13, 2022. [ABSTRACT FROM AUTHOR]

Background: Potentially curative therapy for locally advanced gastric cancer consists of gastrectomy, usually in combination with perioperative chemotherapy. An oncological resection includes a radical (R0) gastrectomy and modified D2 lymphadenectomy; generally, a total omentectomy is also performed, to ensure the removal of possible microscopic disease. However, the omentum functions as a regulator of regional immune responses to prevent infections and prevents adhesions which could lead to bowel obstructions. Evidence supporting a survival benefit of routine complete omentectomy during gastrectomy is lacking. Methods: OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Eligible patients are operable (ASA < 4) and have resectable (≦ cT4aN3bM0) primary gastric cancer. Patients will be 1:1 randomized between (sub)total gastrectomy with omentum preservation distal of the gastroepiploic vessels versus complete omentectomy. For a power of 80%, the target sample size is 654 patients. The primary objective is to investigate whether omentum preservation in gastrectomy for cancer is non-inferior to complete omentectomy in terms of 3-year overall survival. Secondary endpoints include intra- and postoperative outcomes, such as blood loss, operative time, hospital stay, readmission rate, quality of life, disease-free survival, and cost-effectiveness. Discussion: The OMEGA trial investigates if omentum preservation during gastrectomy for gastric cancer is non-inferior to complete omentectomy in terms of 3-year overall survival, with non-inferiority being determined based on results from both the intention-to-treat and the per-protocol analyses. The OMEGA trial will elucidate whether routine complete omentectomy could be omitted, potentially reducing overtreatment. Trial registration: ClinicalTrials.gov NCT05180864. Registered on 6th January 2022. [ABSTRACT FROM AUTHOR]

Background: Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited. Methodology: This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks. Outcome measures: International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity. Discussion: The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia. Trial registration: Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023. [ABSTRACT FROM AUTHOR]

Background: Otitis media with effusion (OME) is a common disease in ear, nose, and throat clinics characterized by aural fullness and hearing loss and mainly caused by eustachian tube dysfunction (ETD). Tympanostomy tube insertion (TTI) is a conventional surgical treatment option that can alleviate symptoms but does not provide a definitive cure, and it is prone to recurrence. Balloon dilation eustachian tuboplasty (BDET) has become a novel procedure for the treatment of ETD, demonstrating significant potential in addressing the aforementioned limitations. However, it is not widely available in the clinic and few high-quality randomized clinical trials was conducted to investigate its long-term efficacy and security in OME. Therefore, the purpose of this study is to verify the efficacy of BDET combined with TTI for patients with OME and its prospects for providing a definitive cure. Methods and analysis: This is a prospective, parallel-group, single-blind, randomized controlled prospective trial. Totally 124 patients with OME will be randomized into either group A or B. Group A will receive conventional therapy (TTI) while group B will use BDET therapy in addition to TTI. Outcome assessments will take place at baseline and at the 3rd, 6th, 12th, and 24th months after surgery. The primary outcome is eustachian tube function, which will be measured by the eustachian tube dysfunction questionnaire (ETDQ-7) and eustachian tube score (ETS). The secondary outcomes include middle ear function, hearing situation, and quality of life, which will be measured by acoustic impedance measurement, pure-tone audiometry, and Chinese-version Chronic Ear Survey (CCES). The main analysis of change in the outcomes will use mixed-model with repeated measures (MMRM) analyses of variance (ANOVAs). Discussion: This is the first prospective trial in Chinese populations that aims to validate the long-term efficacy and safety of BDET-combined TTI therapy in patients with OME. This parallel-group, single-blind, randomized controlled trial may provide an opportunity to decrease the recurrence rate of OME and explore a definitive cure for patients with OME. This trial's rigorous design enhances the reliability of the findings, ensuring a robust answer to the research question. In the future, the research team will further expand upon the clinical evidence and applications of the BDET combined therapy. Trial registration: Chinese Clinical Trial Registry ChiCTR2400079632. Registered on 8 January 2024, https://www.chictr.org.cn/bin/project/edit?pid=214452. [ABSTRACT FROM AUTHOR]

Background: This randomized clinical trial protocol aimed to investigate the comparative efficacy of an enhanced recovery after surgery (ERAS) protocol versus traditional perioperative care programs in patients with intradural extramedullary spinal tumors. Methods: The study included 180 patients aged 18–80 years, who were randomly assigned to two groups: Group A receiving traditional perioperative care and Group B receiving accelerated rehabilitation perioperative care. The nurse responsible for patient care was informed of the group assignment, but the patients themselves remained blinded to the intervention. The primary outcome measure was the Karnofsky Performance Scale score, which assessed functional status. The secondary outcomes included the Japanese Orthopedic Association Scale, Numeric Pain Rating Scale, length of postoperative hospital stay, duration of urethral catheterization, patient satisfaction questionnaire, and complication rates. Follow-up assessments were conducted telephonically 1 month, 3 months, and 6 months after the surgery. Discussion: This study protocol provided a structured approach to assess the potential benefits of ERAS during the perioperative period for patients with intradural extramedullary tumors, aiming to improve patient outcomes and overall care efficiency. Trial registration: This study has been registered with the China Clinical Trials Registry (Project No: ChiCTR2200063347). Registered on September 5 2022. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) contributes increasingly to disability worldwide. There is ample high-quality research on the treatment of knee and hip OA, whereas research on surgical and non-surgical treatment in hand OA is sparse. Limited evidence suggests that education and exercise may improve pain, function, stiffness, and grip strength in hand OA. The established surgical options in hand OA have disadvantages. Prostheses preserve motion but have a high complication rate, whereas fusions decrease function due to limited movement. There is an unmet need for high-quality research on treatment options for hand OA and a need for the development of effective and safe movement-sparing therapies. This study aims to compare the effects of a motion-preserving surgical treatment (denervation of the proximal interphalangeal (PIP) joint) with a patient education and exercise program on patient-reported outcomes and objective function in painful PIP OA. Methods: In this parallel-group, two-armed, randomized, controlled superiority trial (RCT), 90 participants are assigned to surgical PIP joint denervation or education and exercise. Pain on load 1 year after intervention is the primary outcome measure. Secondary outcome measures include pain at rest, Patient-Rated Wrist and Hand Evaluation (PRWHE), HQ8 score, EQ5D-5L, objective physical function, complications, two-point discrimination, Mini Sollerman, consumption of analgesics, and the need for further surgery. Assessments are performed at baseline, 3 and 6 months, and 1 year after intervention. Discussion: There are no previous RCTs comparing surgical and non-surgical treatment in PIP OA. If patient education plus exercise or PIP denervation improve function, these treatments could be implemented as first-line treatment options in PIP OA. However, if denervation does not achieve better results than non-surgical treatment, it is not justified to use in PIP OA. Trial registration: Prospectively registered in ClinicalTrials.gov (NCT05980793) on 8 August 2023. URL https://classic.clinicaltrials.gov/ct2/show/NCT05980793. [ABSTRACT FROM AUTHOR]

Background: Returning to work after long-term sick leave can be challenging, particularly in small- and medium-sized enterprises (SMEs) where support may be limited. Recognizing the responsibilities and challenges of SME employers, a web-based intervention (hereafter the SME tool) has been developed. The SME tool aims to enhance the employer's intention and ability to support the sick-listed employee. Based on the Self-Determination Theory, it is hypothesized that this intention is enhanced by intervening in the employer's autonomy, competences, and relatedness targeted at, e.g., communication with sick-listed employee, involvement of other stakeholders, and practical support. This is achieved by means of providing templates, communication videos, and information on legislation. This article describes the design of an effect and process evaluation of the SME tool. Methods: A randomized controlled trial (RCT) with a 6-month follow-up will be conducted with a parallel-group design with two arms: an intervention group and a control group. Sick-listed employees (≤ 8 weeks) of SMEs (≤ 250 employees) at risk of long-term sick leave and their employers will be recruited and randomly allocated as a dyad (1:1). Employers randomized to the intervention group receive unlimited access to the SME tool, while those in the control group will receive care as usual. The primary outcome is the satisfaction of the employee with the return to work (RTW) support provided by their employer. Secondary outcomes include social support, work performance, and quality of work life at the employee level and self-efficacy in providing RTW support at the employer level. Outcomes will be assessed using questionnaires at baseline and 1, 3, and 6 months of follow-up. Process evaluation measures include, e.g., recruitment and use of and perceived usefulness of the SME tool. Additionally, semi-structured interviews with employers, employees, and occupational physicians will explore the interpretation of the RCT results and strategies for the national implementation of the SME tool. Discussion: The SME tool is hypothesized to be valuable in addition to usual care helping employers to effectively support the RTW of their long-term sick-listed employees, by improving the employers' intention and ability to support. Trial registration: ClinicalTrials.gov, NCT06330415. Registered on February 14, 2024. [ABSTRACT FROM AUTHOR]

Background: Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents' mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children's mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children's developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients. Methods: We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists. Discussion: Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children. Trial registration: ClinicalTrials.gov NCT06125093. Date of registration: first submitted 2023–10-23; first posted 2023–11-09. URL of trial registry record. [ABSTRACT FROM AUTHOR]

Background: Postpartum depression (PPD) affects 30–50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD. Methods: The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum. Discussion: The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children. Trial registration: ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024. [ABSTRACT FROM AUTHOR]

Background: Social jetlag is a chronic disruption of sleep timing that is characterized by different sleep timing during workdays and free days. Social jetlag has been associated with disturbed glucose metabolism, insulin resistance, and increased risk of metabolic syndrome and type 2 diabetes. In this study, we aim to investigate whether a combination of bright light therapy in the morning, bright light reduction in the evening and sleep advance instructions for 3 weeks reduces social jetlag and if this results in improvement of glycemic and metabolic control, sleep, mood and quality of life after 3 and 12 weeks in people with prediabetes and type 2 diabetes and to assess possible mediators, compared to regular sleep habits. Methods: In this randomized controlled trial, 60 people with prediabetes or type 2 diabetes with > 1 h social jetlag will be recruited. The intervention consists of bright light therapy (5000 lx) emitted by Vitamine-L (Lumie, UK) for 30 min each morning, combined with the advice to follow sleep advance instructions and to wear bright light-dimming goggles every evening for a period of 3 weeks. The control group adheres to their regular sleep habits and conditions. The primary outcome is glycated hemoglobin (HbA1c) after 12 weeks comparing the intervention and control in an intention-to-treat analysis. Secondary outcomes at 3 and 12 weeks are (1) social jetlag; (2) insulin sensitivity, fasting blood glucose, glucose-lowering medication use, and frequency of perceived hypoglycemia; (3) metabolic outcomes, including body mass index (BMI), waist circumference, body fat percentage, and blood pressure; (4) mood, including depression, fatigue and anxiety (measured with questionnaires); and (5) quality of life measured using EQ5D questionnaire. To assess other factors that might play a role as possible mediators, we will measure (para)sympathetic nervous system activity assessed with ECGs and electrochemical skin conductance tests, sleep quality and sleep phase distribution assessed with a sleep measuring headband (ZMax), the Dim Light Melatonin Onset in saliva samples (in a subgroup) at 3 and 12 weeks, the feeling of satiety and satiation with a 10-cm visual analog scale (VAS), diet using a food frequency questionnaire, and physical activity using an accelerometer (ActiGraph). Discussion: Social jetlag can contribute to poorer glycemic control and metabolic control in those with type 2 diabetes. With this intervention, we aim to reduce social jetlag and thereby improve glycemic and metabolic control. This could offer a way to improve overall population health and to reduce the disease burden of type 2 diabetes. Trial registration: ISRCTN registry ISRCTN11967109. Registered on 9 May 2024. [ABSTRACT FROM AUTHOR]

Background: Infertility produces infertility-related stress in both members of infertile couples, especially for infertile women. Some studies verified the negative relationship between infertility-related stress and outcomes of infertility treatments. Effective mental health care during fertility treatment is urgently needed, but there has been a lack of efficient support services. To reduce the infertility-related stress of infertile women, expressive art therapeutic schemes will be organized and implemented by certified international expressive art therapists. Methods: This study is a randomized controlled trial. Participants in the intervention group will receive expressive art therapies after the baseline investigation. Expressive art therapies will be led by the certified international expressive art therapist. The interventions include progressive muscle relaxation training, music meditation and drawing therapy. Participants in the control group will receive routine care. The Hospital Anxiety and Depression Scale (HADS) and Fertility Problem Inventory (FPI) will be used to investigate the anxiety, depression, and infertility-related stress of all participants at admission and at discharge. Discussion: This study will verify the effectiveness and efficiency of expressive art therapies for infertile women. The results will provide new knowledge on mental health care strategies for infertile women. Trial registration: ChiCTR, ChiCTR2300070618. Registered 14 April 2023. [ABSTRACT FROM AUTHOR]

Background: Particulate contamination due to infusion therapy (administration of parenteral nutrition and medications) carries a potential health risk for infants in neonatal intensive care units (NICUs). This particulate consists of metals, drug crystals, glass fragments, or cotton fibers and can be generated by drug packaging, incomplete reconstitution, and chemical incompatibilities. In-line filters have been shown to remove micro-organisms, endotoxin, air, and particles in critically ill adults and older infants, but its benefits in newborn remain to be demonstrated. Moreover, 50% of inflammatory episodes in the setting of NICUs are blood culture-negative. These episodes could be partly related to the presence of particles in the infusion lines. Methods: A multicenter randomized single-blind controlled trial was designed. All infants admitted to NICUs for which prolonged infusion therapy is expected will be enrolled in the study and randomized to the Filter or Control arm. All patients will be monitored until discharge, and data will be analyzed according to a "full analysis set." The primary outcome is the frequency of patients with at least one sepsis-like event, defined by any association of suspected sepsis symptoms with a level of c-reactive protein (CRP) > 5 mg/L in a negative-culture contest. The frequency of sepsis, phlebitis, luminal obstruction, and the duration of mechanical ventilation and of catheter days will be evaluated as secondary outcomes. The sample size was calculated at 368 patients per arm. Discussion: This is the first multicenter randomized control trial that compares in-line filtration of parenteral nutrition and other intravenous drugs to infusion without filters. Sepsis-like events are commonly diagnosed in clinical practice and are more frequent than sepsis in a positive culture contest. The risk of these episodes in the target population is estimated at 30–35%, but this data is not confirmed in the literature. If the use of in-line filters results in a significant decrease in sepsis-like events and/or in any other complications, the use of in-line filters in all intravenous administration systems may be recommended in NICUs. Trial registration: ClinicalTrials.gov, NCT05537389, registered on 12 September 2022 (https://classic.clinicaltrials.gov/ct2/show/results/NCT05537389?view=results). [ABSTRACT FROM AUTHOR]

Background: The preoperative body surface and nasal decolonization may reduce the risk of surgical site infections (SSI) but yields conflicting results in the current orthopedic literature. Methods: We perform a single-center, randomized-controlled, superiority trial in favor of the preoperative decolonization using a commercial product (octenidine® set). We will randomize a total number of 1000 adult elective orthopedic patients with a high risk for SSI and/or wound complications (age ≥ 80 years, chronic immune-suppression, American Society of Anesthesiologists score 3–4 points) between a decolonization (octenisan® wash lotion 1 × per day and octenisan® md nasal gel 2–3 × per day; during 5 days) and no decolonization. Decolonized patients will additionally fill a questionnaire regarding the practical difficulties, the completeness, and the adverse events of decolonization. The primary outcomes are SSI and revision surgeries for postoperative wound problems until 6 weeks postoperatively (or 1 year for surgeries with implants or bone). Secondary outcomes are unplanned revision surgeries for non-infectious problems and all adverse events. With 95% event-free surgeries in the decolonization arm versus 90% in the control arm, we formally need 2 × 474 elective orthopedic surgeries included during 2 years. Discussion: In selected adult orthopedic patients with a high risk for SSI, the presurgical decolonization may reduce postoperative wound problems, including SSI. Trial registration: ClinicalTrial.gov NCT05647252. Registered on 9 December 2022. Protocol version: 2 (5 December 2022). [ABSTRACT FROM AUTHOR]

Background: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25–80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). Methods and analysis: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). Discussion: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. Trial registration: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023. [ABSTRACT FROM AUTHOR]

Background: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. Methods: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. Discussion: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). Trial registration: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. Methods: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. Discussion: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. Trial registration: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021. [ABSTRACT FROM AUTHOR]

Abstract Background A recent meta-analysis concluded that outpatient appendectomy appears feasible and safe, but there is a lack of high-quality evidence and a randomized trial is needed. The aim of this trial is to demonstrate that outpatient appendectomy is non-inferior to conventional inpatient appendectomy in terms of overall morbi-mortality on the 30th postoperative day (D30). Methods SAMBA is a prospective, randomized, controlled, multicenter non-inferiority trial. We will include 1400 patients admitted to 15 French hospitals between January 2023 and June 2025. Inclusion criteria are patients aged between 15 and 74 years presenting acute uncomplicated appendicitis suitable to be operated by laparoscopy. Patients will be randomized to receive outpatient care (day-surgery) or conventional inpatient care with overnight hospitalization in the surgery department. The primary outcome is postoperative morbi-mortality at D30. Secondary outcomes include time from diagnosis to appendectomy, length of total hospital stay, re-hospitalization, interventional radiology, re-interventions until D30, conversion from outpatient to inpatient, and quality of life and patient satisfaction using validated questionnaires. Discussion The SAMBA trial tests the hypothesis that outpatient surgery (i.e., without an overnight hospital stay) of uncomplicated acute appendicitis is a feasible and reliable procedure in establishments with a technical platform able to support this management strategy. Trial registration ClinicalTrials.gov NCT05691348. Registered on 20 January 2023.

Abstract Background Tai Chi (TC) holds a unique and valued place in promoting the physical and mental health of college students. Its significance is underscored by its incorporation as a compulsory physical education course in every university in China. TC, with its rich tradition, places a strong emphasis on posture control as a core sports ability. However, the students in Tai Chi Elective Course (TCEC) have very poor posture control ability. This study protocol investigates the potential of Tan Tui (TT) to address these issues, as TT is a fundamental skill for beginners of traditional Chinese martial arts and has a track record of enhancing lower limb strength and balance, making it a promising choice for improving posture control in TCEC. Methods/design To investigate the impact of different intensities of TT exercises on posture control in TCEC students, we have designed a randomized, double-blind, parallel-controlled trial. Seventy-six students in the TCEC will be randomly divided into low-intensity Tan Tui (LTT), medium-intensity Tan Tui (MTT), and high-intensity Tan Tui exercises group (HTT) and control group (CON), each with 19 people. The LTT group, MTT group, and HTT group will be given different intensity of TT exercises, and the CON group will be given regular TCEC. The intervention period will be 6 weeks (2 times a week, 20 min each time). At baseline (before), 4 weeks of intervention (middle), and 6 weeks of intervention (after), the Unipedal Stance Test (UST), the Star Excursion Balance Test (SEBT), 60°/s angular velocity knee joint flexion and extension relative peak torque (RPT), and knee joint position perception (KJPP) will be evaluated. Discussion This is the first randomized controlled trial protocol from the perspective of training intensity to evaluate the effect of different intensity of TT exercises on posture control of students in TCEC. Should our research reveal a significant intervention effect, the results will offer preliminary, higher-quality evidence supporting the positive impact of varying intensities of Tan Tui exercises on posture control in TCEC students. Trial registration Chinese Clinical Trial Registry ChiCTR2000039109. Registered on October 17, 2020.

Abstract Background Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. Methods The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. Discussion Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. Trial registration ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341

Abstract Background Potentially curative therapy for locally advanced gastric cancer consists of gastrectomy, usually in combination with perioperative chemotherapy. An oncological resection includes a radical (R0) gastrectomy and modified D2 lymphadenectomy; generally, a total omentectomy is also performed, to ensure the removal of possible microscopic disease. However, the omentum functions as a regulator of regional immune responses to prevent infections and prevents adhesions which could lead to bowel obstructions. Evidence supporting a survival benefit of routine complete omentectomy during gastrectomy is lacking. Methods OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Eligible patients are operable (ASA

Abstract Background The progressive aging of the population has meant the increase in elderly patients requiring an urgent surgery. Older adults, especially those with frailty, have a higher risk for complications, functional and cognitive decline after urgent surgery. These patients have their functional and physiological reserve reduced which makes them more vulnerable to the effects of being bedridden. The consequences are at multiple levels emphasizing the functional loss or cognitive impairment, longer stays, mortality and institutionalization, delirium, poor quality of life and increased use of resources related to health. We aim to determine whether postoperative physical rehabilitation can prevent functional and cognitive decline and modify the posterior trajectory. Methods/design This study is a randomized clinical trial, simple blinded, conducted in the Department of Surgery of a tertiary public hospital in Navarra (Hospital Universitario de Navarra), Spain. Patients > = 70 years old undergoing urgent abdominal surgery who meet inclusion criteria will be randomly assigned to the intervention or control group. The intervention will consist of a multicomponent physical training programme, which will include progressive and supervised endurance, resistance and balance training for 4 weeks, twice weekly sessions with a total of 8 sessions, and the group control will receive the usual care. The primary outcome measure is the change in functional (SPPB) and cognitive status (Mini-Mental State Examination) and the change of quality of life (EuroQol-5D-VAS) during the study period. The secondary outcomes are postoperative complications, length of stay, delirium, mortality, use of health resources, functional status (Barthel Index and handgrip strength tests), cost per quality-adjusted life year and mininutritional assessment. The data for both the intervention group and the control group will be obtained at four different times: the initial visit during hospital admission and at months 1, 3 and 6 months after hospital discharge. Discussion If our hypothesis is correct, this project could show that individualized and progressive exercise programme provides effective therapy for improving the functional capacity and achieve a better functional, cognitive and quality of life recovery. This measure, without entailing a significant expense for the administration, probably has an important repercussion both in the short- and long-term recovery, improving care and functional parameters and could determine a lower subsequent need for health resources. To verify this, we will carry out a cost-effectiveness study. The clinical impact of this trial can be significant if we help to modify the traditional management of the elderly patients from an illness model to a more person-centred and functionally oriented perspective. Moreover, the prescription of individualized exercise can be routinely included in the clinical practice of these patients. Trial registration ClinicalTrials.gov Identifier: NCT05290532. Version 1. Registered on March 13, 2022.

Abstract Background Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited. Methodology This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks. Outcome measures International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity. Discussion The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia. Trial registration Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.

Abstract Background Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. Methods In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator’s overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. Discussion The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. Trial registration ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538

Abstract Background Osteoarthritis (OA) contributes increasingly to disability worldwide. There is ample high-quality research on the treatment of knee and hip OA, whereas research on surgical and non-surgical treatment in hand OA is sparse. Limited evidence suggests that education and exercise may improve pain, function, stiffness, and grip strength in hand OA. The established surgical options in hand OA have disadvantages. Prostheses preserve motion but have a high complication rate, whereas fusions decrease function due to limited movement. There is an unmet need for high-quality research on treatment options for hand OA and a need for the development of effective and safe movement-sparing therapies. This study aims to compare the effects of a motion-preserving surgical treatment (denervation of the proximal interphalangeal (PIP) joint) with a patient education and exercise program on patient-reported outcomes and objective function in painful PIP OA. Methods In this parallel-group, two-armed, randomized, controlled superiority trial (RCT), 90 participants are assigned to surgical PIP joint denervation or education and exercise. Pain on load 1 year after intervention is the primary outcome measure. Secondary outcome measures include pain at rest, Patient-Rated Wrist and Hand Evaluation (PRWHE), HQ8 score, EQ5D-5L, objective physical function, complications, two-point discrimination, Mini Sollerman, consumption of analgesics, and the need for further surgery. Assessments are performed at baseline, 3 and 6 months, and 1 year after intervention. Discussion There are no previous RCTs comparing surgical and non-surgical treatment in PIP OA. If patient education plus exercise or PIP denervation improve function, these treatments could be implemented as first-line treatment options in PIP OA. However, if denervation does not achieve better results than non-surgical treatment, it is not justified to use in PIP OA. Trial registration Prospectively registered in ClinicalTrials.gov (NCT05980793) on 8 August 2023. URL https://classic.clinicaltrials.gov/ct2/show/NCT05980793 .

Abstract Background This randomized clinical trial protocol aimed to investigate the comparative efficacy of an enhanced recovery after surgery (ERAS) protocol versus traditional perioperative care programs in patients with intradural extramedullary spinal tumors. Methods The study included 180 patients aged 18–80 years, who were randomly assigned to two groups: Group A receiving traditional perioperative care and Group B receiving accelerated rehabilitation perioperative care. The nurse responsible for patient care was informed of the group assignment, but the patients themselves remained blinded to the intervention. The primary outcome measure was the Karnofsky Performance Scale score, which assessed functional status. The secondary outcomes included the Japanese Orthopedic Association Scale, Numeric Pain Rating Scale, length of postoperative hospital stay, duration of urethral catheterization, patient satisfaction questionnaire, and complication rates. Follow-up assessments were conducted telephonically 1 month, 3 months, and 6 months after the surgery. Discussion This study protocol provided a structured approach to assess the potential benefits of ERAS during the perioperative period for patients with intradural extramedullary tumors, aiming to improve patient outcomes and overall care efficiency. Trial registration This study has been registered with the China Clinical Trials Registry (Project No: ChiCTR2200063347). Registered on September 5 2022.

Abstract Background Returning to work after long-term sick leave can be challenging, particularly in small- and medium-sized enterprises (SMEs) where support may be limited. Recognizing the responsibilities and challenges of SME employers, a web-based intervention (hereafter the SME tool) has been developed. The SME tool aims to enhance the employer’s intention and ability to support the sick-listed employee. Based on the Self-Determination Theory, it is hypothesized that this intention is enhanced by intervening in the employer’s autonomy, competences, and relatedness targeted at, e.g., communication with sick-listed employee, involvement of other stakeholders, and practical support. This is achieved by means of providing templates, communication videos, and information on legislation. This article describes the design of an effect and process evaluation of the SME tool. Methods A randomized controlled trial (RCT) with a 6-month follow-up will be conducted with a parallel-group design with two arms: an intervention group and a control group. Sick-listed employees (≤ 8 weeks) of SMEs (≤ 250 employees) at risk of long-term sick leave and their employers will be recruited and randomly allocated as a dyad (1:1). Employers randomized to the intervention group receive unlimited access to the SME tool, while those in the control group will receive care as usual. The primary outcome is the satisfaction of the employee with the return to work (RTW) support provided by their employer. Secondary outcomes include social support, work performance, and quality of work life at the employee level and self-efficacy in providing RTW support at the employer level. Outcomes will be assessed using questionnaires at baseline and 1, 3, and 6 months of follow-up. Process evaluation measures include, e.g., recruitment and use of and perceived usefulness of the SME tool. Additionally, semi-structured interviews with employers, employees, and occupational physicians will explore the interpretation of the RCT results and strategies for the national implementation of the SME tool. Discussion The SME tool is hypothesized to be valuable in addition to usual care helping employers to effectively support the RTW of their long-term sick-listed employees, by improving the employers’ intention and ability to support. Trial registration ClinicalTrials.gov, NCT06330415. Registered on February 14, 2024.

Abstract Background Pulmonary rehabilitation (PR) is accepted as standard care for individuals with COPD. We conducted an international, multi-centred randomized controlled trial (RCT) to determine if adding balance training to PR would reduce the incidence of falls in people with COPD. While there have been many trials investigating the effectiveness of PR, few have involved international collaboration. Successful execution of rehabilitation trials requires a significant investment of time, staffing, and resources. With the recent completion of the Balance Training for Fall Reduction in COPD RCT, we report on the design, implementation, and execution of our trial using project management phases. We also highlight our lessons learned for consideration in future multi-centre rehabilitation trials. Methods This was a retrospective review of the planning, preparation, timelines, and personnel training involved in the execution of this study using four of the five project management phases described by Farrell et al. in 2010: (1) initiation, (2) planning, (3) execution, and (4) monitoring and controlling. We report descriptive statistics as percentages and counts and summarize our lessons learned. Results Ten outpatient PR programs in three continents participated. Thirty-one personnel worked on the trial across all sites. Enrolment began in January 2017 and was suspended in March 2020 due to the COVID-19 pandemic. Approximately 1275 patients were screened, 455 (36%) were eligible, 258 (57%) consented, 243 (53%) participated, and 130 (61%) completed the 12-month follow-up assessment. Lessons learned through our experience included (1) ensuring awareness of funder policies and considering the impact on collaborating sites; (2) preparing for the possibility of human resource and program disruptions; (3) anticipating site dropout and having a contingency plan in place; (4) planning and monitoring process measure data before, during, and after trial initiation; (5) ensuring frequent and consistent communication with and between collaborating sites; (6) maximizing features of database platform to ensure data set completeness and controlled data access; and (7) identifying strategies for increasing patient engagement in a high-demand study. Conclusions We identify seven lessons learned through our experience conducting an international, multicentre rehabilitation-based RCT. These lessons can provide guidance to other trialists conducting studies with similar logistics and may assist with future trial planning and implementation.

Abstract Background Postpartum depression (PPD) affects 30–50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD. Methods The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum. Discussion The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children. Trial registration ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024.

Abstract Background Social jetlag is a chronic disruption of sleep timing that is characterized by different sleep timing during workdays and free days. Social jetlag has been associated with disturbed glucose metabolism, insulin resistance, and increased risk of metabolic syndrome and type 2 diabetes. In this study, we aim to investigate whether a combination of bright light therapy in the morning, bright light reduction in the evening and sleep advance instructions for 3 weeks reduces social jetlag and if this results in improvement of glycemic and metabolic control, sleep, mood and quality of life after 3 and 12 weeks in people with prediabetes and type 2 diabetes and to assess possible mediators, compared to regular sleep habits. Methods In this randomized controlled trial, 60 people with prediabetes or type 2 diabetes with > 1 h social jetlag will be recruited. The intervention consists of bright light therapy (5000 lx) emitted by Vitamine-L (Lumie, UK) for 30 min each morning, combined with the advice to follow sleep advance instructions and to wear bright light-dimming goggles every evening for a period of 3 weeks. The control group adheres to their regular sleep habits and conditions. The primary outcome is glycated hemoglobin (HbA1c) after 12 weeks comparing the intervention and control in an intention-to-treat analysis. Secondary outcomes at 3 and 12 weeks are (1) social jetlag; (2) insulin sensitivity, fasting blood glucose, glucose-lowering medication use, and frequency of perceived hypoglycemia; (3) metabolic outcomes, including body mass index (BMI), waist circumference, body fat percentage, and blood pressure; (4) mood, including depression, fatigue and anxiety (measured with questionnaires); and (5) quality of life measured using EQ5D questionnaire. To assess other factors that might play a role as possible mediators, we will measure (para)sympathetic nervous system activity assessed with ECGs and electrochemical skin conductance tests, sleep quality and sleep phase distribution assessed with a sleep measuring headband (ZMax), the Dim Light Melatonin Onset in saliva samples (in a subgroup) at 3 and 12 weeks, the feeling of satiety and satiation with a 10-cm visual analog scale (VAS), diet using a food frequency questionnaire, and physical activity using an accelerometer (ActiGraph). Discussion Social jetlag can contribute to poorer glycemic control and metabolic control in those with type 2 diabetes. With this intervention, we aim to reduce social jetlag and thereby improve glycemic and metabolic control. This could offer a way to improve overall population health and to reduce the disease burden of type 2 diabetes. Trial registration ISRCTN registry ISRCTN11967109 . Registered on 9 May 2024.

Abstract Background Infertility produces infertility-related stress in both members of infertile couples, especially for infertile women. Some studies verified the negative relationship between infertility-related stress and outcomes of infertility treatments. Effective mental health care during fertility treatment is urgently needed, but there has been a lack of efficient support services. To reduce the infertility-related stress of infertile women, expressive art therapeutic schemes will be organized and implemented by certified international expressive art therapists. Methods This study is a randomized controlled trial. Participants in the intervention group will receive expressive art therapies after the baseline investigation. Expressive art therapies will be led by the certified international expressive art therapist. The interventions include progressive muscle relaxation training, music meditation and drawing therapy. Participants in the control group will receive routine care. The Hospital Anxiety and Depression Scale (HADS) and Fertility Problem Inventory (FPI) will be used to investigate the anxiety, depression, and infertility-related stress of all participants at admission and at discharge. Discussion This study will verify the effectiveness and efficiency of expressive art therapies for infertile women. The results will provide new knowledge on mental health care strategies for infertile women. Trial registration ChiCTR, ChiCTR2300070618. Registered 14 April 2023.

Abstract Background Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. Methods This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. Discussion There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). Trial registration ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Abstract Background Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals’ quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention (“NeuroNation MED”) in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. Methods This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT (“NeuroNation MED”) for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. Discussion This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. Trial registration German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Abstract Background Hypertensive disorders of pregnancy (HDP) pose significant risks to both maternal and fetal health, contributing to global morbidity and mortality. Management of HDP is complex, particularly because of concerns regarding potential negative effects on utero-placental circulation and limited therapeutic options due to fetal safety. Our study investigates whether blood pressure monitoring through a mobile health (mHealth) application can aid in addressing the challenges of blood pressure management in pregnant individuals with HDP. Additionally, we aim to assess whether this intervention can improve short-term maternal and fetal outcomes and potentially mitigate long-term cardiovascular consequences. Methods This prospective, randomized, single-center trial will include 580 pregnant participants who meet the HDP criteria or who have a heightened risk of pregnancy-related hypertension due to factors such as multiple pregnancies, obesity, diabetes, or a history of HDP in prior pregnancies leading to preterm birth. Participants will be randomized to either the mHealth intervention group or the standard care group. The primary endpoint is the difference in systolic blood pressure from enrollment to 1 month after childbirth. The secondary endpoints include various blood pressure parameters, obstetric outcomes, body mass index trajectory, step counts, mood assessment, and drug adherence. Conclusions This study emphasizes the potential of mHealth interventions, such as the Heart4U application, to improve blood pressure management in pregnant individuals with HDP. By leveraging technology to enhance engagement, communication, and monitoring, this study aims to positively impact maternal, fetal, and postpartum outcomes associated with HDP. This innovative approach demonstrates the potential of personalized technology-driven solutions for managing complex health conditions. Trial registration ClinicalTrials.gov NCT05995106. Registered on 16 August 2023.

Abstract Background Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as “the interest in establishing and guiding the next generation,” can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU? intervention. Methods In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention. Discussion We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U? intervention. We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL. Trial registration ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.

Abstract Background Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients. Methods An unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m2 and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients’ all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients). Discussion Our proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers. Trial registration Clinicaltrials.gov NCT05828823. Registered on 25 April 2023.

Abstract Background Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem. Methods This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score. Discussion Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function. Trial registration Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .

Abstract Background Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction. Methods Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study’s primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle. Discussion The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery. Trial registration ChiCTR2200064041, registered on 24th September, 2022.

Abstract Background Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks’ gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. Methods Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants 90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. Discussion Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. Trial registration ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

Abstract Background Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier phenotypic conversion from iRBD to Parkinson’s disease and Lewy body dementia, cognitive training focusing on executive functions could have disease-modifying effects for individuals with iRBD. Methods The study CogTrAiL-RBD investigates the short- and long-term effectiveness and the feasibility and underlying neural mechanisms of a cognitive training intervention for individuals with iRBD. The intervention consists of a 5-week digital cognitive training accompanied by a module promoting a healthy, active lifestyle. In this monocentric, single-blinded, delayed-start randomized controlled trial, the intervention’s effectiveness will be evaluated compared to an initially passive control group that receives the intervention in the second, open-label phase of the study. Eighty individuals with iRBD confirmed by polysomnography will be consecutively recruited from the continuously expanding iRBD cohort at the University Hospital Cologne. The evaluation will focus on cognition and additional neuropsychological and motor variables. Furthermore, the study will examine the feasibility of the intervention, effects on physical activity assessed by accelerometry, and interrogate the intervention’s neural effects using magnetic resonance imaging and polysomnography. Besides, a healthy, age-matched control group (HC) will be examined at the first assessment time point, enabling a cross-sectional comparison between individuals with iRBD and HC. Discussion This study will provide insights into whether cognitive training and psychoeducation on a healthy, active lifestyle have short- and long-term (neuro-)protective effects for individuals with iRBD. Trial registration The study was prospectively registered in the German Clinical Trial Register (DRKS00024898) on 2022–03-11, https://drks.de/search/de/trial/DRKS00024898 . Protocol version: V5 2023–04-24.

Abstract Introduction Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called “Adappt,” aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences. Method A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with “Adappt.” Discussion Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care. Trial registration This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).

Abstract Background Current management of mesenteric ischemia is primarily endovascular stent treatment. Typical CMI symptoms are postprandial abdominal pain, food fear, weight loss, and diarrhea. Revascularization is often necessary, as mesenteric ischemia may progress to bowel necrosis and death if left untreated. This study aims to compare the outcome using bare metal stent (BMS) or covered stent (CS) in the endovascular treatment of chronic and acute on chronic mesenteric ischemia. Methods This is an investigator-driven, prospective, randomized, single-blinded, and single-center, national cohort study at the Copenhagen University Hospital, Denmark. A total of 98 patients with chronic mesenteric ischemia (CMI) and acute-on-chronic mesenteric ischemia (AoCMI) will be randomized to treatment with either BeSmooth BMS (Bentley Innomed GmbH) or BeGraft CS (Bentley Innomed GmbH). Randomization occurs intraoperatively after lesion crossing. Discussion There is currently no published data from prospective controlled trials regarding the preferred type of stent used for the treatment of chronic and acute-on-chronic mesenteric ischemia. This trial will evaluate the short- and long-term outcome of BMS versus CS when treating CMI and AoCMI, as well as the benefit of a more intense postoperative surveillance program. Trial registration ClinicalTrials.gov NCT05244629. Registered on February 8, 2022.

Abstract Background The inter-reviewer reliability of the risk of bias (RoB) assessment lacked agreement in previous studies. It is important to analyse these disagreements to improve the repeatability of RoB assessment. The objective of the study was to evaluate the frequency and reasons for disagreements in RoB assessments for randomised controlled trials (RCTs) that were included in multiple Cochrane reviews in the field of hypertension. Methods A cross-sectional study was employed. We retrieved any RCTs that had been included in multiple Cochrane reviews in the field of hypertension from ARCHIE. The results of the RoB assessments were extracted, and the distributions of agreements and possible reasons for disagreement were analyzed. Results Twenty-six Cochrane reviews were included in this study. A total of 78 RCTs appeared in more than one Cochrane review. The level of agreement ranged from domain to domain. “Blinding of outcome assessment” showed a reasonably high level of agreement (94.9%), while “incomplete outcome data”, “selective outcome reporting” and “other sources of bias” showed moderate levels of agreement (74.6%, 79.2% and 75.6%, respectively). However, the domains of “allocation concealment”, “random sequence generation” and “blinding of participants and personnel” showed low levels of agreement (24.4%, 23.5%, and 47.4%, respectively). In the domains of “allocation concealment” and “blinding of participants and personnel”, the agreement group had higher proportion of publication year ≤ 1996 than the disagreement group (P = 0.008 and P