Trials最新文献

The ProRIDE randomized clinical trial (RCT) started participant recruitment in February 2022, successfully enrolling 2,000 infants within an 11-month period and achieving a follow-up rate of 97% at six months of age. This narrative article describes critical components of the research protocol, the composition of the research team, community sensitization efforts, and the local performance of the study. The research initiative was conceptualized by a collaborative group of scientists from both high- and low-income countries, and its successful implementation was contingent upon the active involvement and participation of a rural, low-income community. Based on previous study findings in Tanzania, which consistently indicated a high prevalence of severe infections related to multidrug-resistant bacteria, the research team recognized the urgent need for preventive strategies aimed at reducing the incidence of sepsis and severe bacterial infections. Given the scarcity of data from rural areas and the imperative for inclusivity, the rationale for conducting this RCT in a rural context was compelling. We believe that a key factor in the successful completion of this trial was the intentional design of a simple, straightforward, and practical intervention, and study framework. Caregivers administered the study medication at home, thereby mirroring real-world therapeutic practices and enhancing the generalizability of the findings. To ensure adherence to the one-month intervention regimen, the research team conducted a day-seven home visit to confirm proper administration of the investigational product and address any associated early challenges. During this interaction, the field workers reiterated the instructions for the proper application of the product, thereby serving as a reminder to the caretaker regarding its correct usage. Additionally, a thorough planning phase was undertaken prior to the study's commencement, involving extensive collaboration between the researchers from Norway, Muhimbili University of Health and Allied Sciences, Tanzania, and the leadership at Haydom Lutheran Hospital. Through a series of meetings and discussions, the research team in Norway and Tanzania identified specific areas requiring enhancement, particularly in laboratory infrastructure and the training of personnel in blood culture techniques and antimicrobial susceptibility testing. Despite facing numerous challenges both prior to and during the trial, this RCT successfully recruited 2,000 participants within 11 months. This accomplishment can be attributed to the strong collaboration and teamwork exhibited throughout the process. The insights gained from this study may be of particular interest to researchers and scientists aiming to conduct investigations involving infants and children in low-income settings. Trial registrations This trial is registered with ClinicalTrials.gov, NCT04172012. November 21, 2019.

Introduction: Maternal obesity is increasingly linked to adverse health effects across generations, with childhood obesity becoming one of the most critical public health challenges of the twenty-first century. Both a high maternal body mass index (BMI) and excessive gestational weight gain (GWG) are significant and independent predictors of future obesity in both children and adults. This study aims to evaluate the long-term impact of lifestyle interventions during pregnancy on the body composition of mothers and their 15-year-old offspring. Furthermore, we will investigate the influence of these interventions on dysmetabolic traits, and metabolic and inflammatory markers observed in mothers and their offspring 15 years post-pregnancy. The study also aims to examine the relationship between maternal mental health during pregnancy and postpartum, and long-term obesity risk. Finally, we will assess the mental health and health literacy of both mothers and offspring and evaluate its association with obesity risk.

Methods: This study is a follow-up of a randomized controlled trial. In the original trial, 360 pregnant women with a BMI ≥ 30 kg/m² from Odense and Aarhus University Hospitals were randomized to receive either lifestyle intervention, including diet counseling and physical activity from 12 weeks gestation until delivery, or standard care. A total of 301 mother-child pairs are eligible for follow-up. The mothers and their offspring will be invited to a 2-h clinical examination, which includes fasting venous blood samples, DXA scans, anthropometric measurements, and questionnaires addressing diet, physical activity, mental health, and health literacy. Examinations will include continuous glucose monitoring and activity tracking for 7-10 days. Our primary endpoint is the effect of lifestyle intervention during pregnancy on offspring body composition measured by DXA scanning.

Discussion: Our data address critical knowledge gaps in understanding childhood obesity. If pregnancy interventions reduce the risk of offspring's obesity, they could serve as a foundation for implementing changes in clinical practice.

Trial registration: The study was approved by the local ethics committee of the Region of Southern Denmark (S-20220076) and registered on ClinicalTrials.gov (NCT05774652) on March 21, 2023. The findings will be published in international scientific journals and shared with hospitals and policymakers.

Background: People experiencing socioeconomic disadvantage are persistently underrepresented in clinical trials, yet they experience a significantly greater burden of disease than those not experiencing socioeconomic disadvantage. Trials need to be inclusive to ensure that treatments are safe and effective for those who need them most. Resources are needed to support researchers in designing and implementing trials that are inclusive of people experiencing socioeconomic disadvantage. Building on the National Institute for Health and Care Research (NIHR) INCLUDE initiative, we developed the INCLUDE Socioeconomic Disadvantage Framework to support researchers in making trials more inclusive.

Methods: The Framework was developed over five phases: (1) outlining an initial draft of the Framework, (2) refining the initial draft Framework with public contributors, (3) refining the draft Framework with wider contributors, (4) finalising the Framework with all contributors, and (5) launch and application of the Framework.

Results: The Framework entails four key questions: (1) Who should my trial results apply to? (2) Are people from different socioeconomic backgrounds likely to respond to the intervention in different ways? (3) Will my trial intervention and/or comparator make it harder for people from different socioeconomic backgrounds to take part in the trial? (4) Will the way I have planned and designed my trial make it harder for people from different socioeconomic backgrounds to take part? The Framework includes worksheets to support trial teams in considering strategies to address barriers to inclusion. In 2023, the Framework was launched at a webinar with ~300 registrants and is currently available to download from the Trial Forge website: https://www.trialforge.org/trial-diversity/socioeconomic-disadvantage-framework/. Public contributor considerations, collated through project meetings, to make trials more inclusive for people experiencing socioeconomic disadvantage are also appendaged to this article to support trial teams further.

Conclusion: The Framework and public contributor considerations can be used to support researchers to design and conduct more inclusive trials. Future work should include evaluation of such Frameworks, further engagement with funders to increase uptake, and development and evaluation of strategies to improve inclusion.

Background: Military-connected mothers (MCM; mothers who are either service members or veterans or spouses of a service member or veteran) experience significant trauma exposure associated with post-traumatic stress symptoms and ultimately deficits in parental functioning. Maternal trauma and its mental health and functional sequelae can have significant consequences for children, including adverse mental health outcomes. Existing evidence-based treatments (EBT) available to MCM to address trauma have not been adapted for military culture and do not fully resolve symptoms or address the bidirectional relationship between symptoms and parental functioning. In this project, preliminary data will be collected on a newly adapted version of an innovative intervention: Parenting-STAIR Modular (PSTAIR-M), which addresses trauma symptoms and parenting among MCM. PSTAIR is a novel intervention, combining two existing EBTs: Skills Training in Affective and Interpersonal Regulation Narrative Therapy (STAIR), targeting maternal emotion dysregulation and mental health symptoms, and dyadic Parent-Child Care (PC-CARE), targeting parental functioning.

Methods: This study is a two-arm randomized controlled trial in which we will randomly assign N = 120 trauma-exposed MCM who exhibit elevated symptoms of PSTD or depression and/or low parenting self-efficacy, and one identified child (ages 2-10) to PSTAIR-M or treatment as usual. This trial will be conducted at three community mental health clinics operated by the Cohen Veterans Network. Assessments will occur at three timepoints: (1) Pretreatment, (2) mid-treatment (following session 11 in the treatment condition), and (3) posttreatment (following session 16 in the treatment condition). Assessments will include data on mental health and parenting outcomes as well as mechanisms which may account for observed effects of PSTAIR-M. Each assessment will also include a dyadic observation of mother and child, independently coded to capture parenting skills.

Discussion: Data collection will establish initial efficacy and will set the stage for further study of this intervention. Successful treatment with an efficient, personalized intervention has the potential to prevent adverse outcomes for MCM and their children and to interrupt the intergenerational cycle of trauma in military family systems.

Trial registration: ClinicalTrials.gov NCT06262178. Registered on February 15, 2024.

Background: Intravenous anesthesia during endoscopic retrograde cholangiopancreatography (ERCP) is associated with a high incidence of respiratory depression. High-flow nasal cannula (HFNC) therapy uses a mild positive pressure load to enhance carbon dioxide washout and reduce rebreathing, thereby improving respiratory function. Therefore, it is widely used to prevent hypoxemia and hypercapnia. We aim to investigate the efficacy of a new HFNC device (AIRVO 3™) in improving respiratory status during sedated ERCP.

Methods: In a multicenter randomized controlled study involving two groups-the HFNC and low-flow nasal cannula (LFNC) groups, adult patients undergo ERCP under sedation. For sedation, either the dexmedetomidine or midazolam protocol is used according to the guidelines. Pethidine hydrochloride and pentazocine are administered intravenously as analgesics. The primary endpoint is the incidence of hypoxemia, defined as peripheral oxygen saturation (SpO₂) ≤ 90% during intravenous anesthesia. As a secondary outcome, percutaneous CO₂ concentration is measured to assess the device's effectiveness in preventing hypercapnia. Furthermore, sedative and analgesic doses are evaluated to determine whether device use helps prevent the occurrence of hypercapnia and hypoxemia.

Discussion: This study aims to generate evidence supporting the utility of HFNC as a potential therapeutic device for ERCP under sedation by determining whether the incidence rates of hypercapnia and hypoxemia are lower in the HFNC group than in the LFNC group. TRIAL REGISTRATION {2A,2B}: The study was registered as jRCTs072240096 on January 16, 2025.

Background: People with a learning disability are frequently excluded from clinical trials, with around two thirds of trials either directly or indirectly excluding this group. This contributes to the shocking health inequalities they experience, with people with a learning disability having higher rates of long-term health conditions and dying on average 20 years younger than the general population. Improving inclusion of under-served groups in trials is a priority area for research funders and regulators. A UK-wide collaboration, 'No Research About Us, Without Us', was formed to explore and address the barriers to engaging and involving people with a learning disability in research. The project consisted of a number of intersecting work streams. This paper reports the findings from Working Group 3 which aimed to produce practical examples about how a trial could be redesigned to ensure it is more inclusive of people with a learning disability.

Methods: The redesign process consisted of three steps: (1) identifying an appropriate trial using predefined criteria, (2) selecting a tool to systematically review the trial, and (3) identifying barriers to inclusion of people with a learning disability and proposing alternative design approaches that could have widened access to the trial.

Results: Following review of a funder's portfolio, we selected a platform trial (PANORAMIC) which had sought to include people with a learning disability as a high-risk group for COVID-19 and yet had only made up 0.01% of those recruited. Using the INCLUDE Impaired Capacity to Consent Framework, our co-produced analysis identified practical strategies that could have ensured greater inclusion of people with a learning disability. This included involving people with a learning disability at the earliest design stage, revisiting eligibility criteria, making reasonable adjustments (e.g. high-quality easy read versions of all documents), and simplifying overly complex study processes.

Conclusion: To achieve better health equity and improve the quality of clinical trials, researchers must pay greater attention to accessible study design and ensure appropriate accommodations are in place to enable inclusion of people with a learning disability. We outline some practical strategies that can inform the design and conduct of future trials to improve inclusion.

Background: Children exposed to high levels of couple distress are at increased risk for a range of adjustment problems, including behavioral, emotional, and academic difficulties. These relational burdens can also interfere with adult mental health, the coparenting relationship, and the capacity to provide warm and consistent caregiving. Despite these challenges, many couples delay seeking help until their relationship is seriously deteriorated. This randomized controlled trial investigates the effects of two flexible self-help interventions: the OurRelationship program (OR) and couple-focused bibliotherapy (BT). We hypothesize that the OR will outperform BT which in turn will outperform a waitlist (WL) control in reducing communication conflict-the primary outcome-between baseline and post-intervention. We hypothesize that any couple intervention (OR or BT) will outperform WL in reducing impact on child wellbeing-the secondary outcome-between baseline and post-intervention for children with such impact at baseline.

Methods: Parenting couples (N = 350) with one or more children living at home, who report either high levels of parental conflict or relationship distress, are recruited via municipal family services in 11 or more Danish sites. Participants enroll through an online platform, complete a screener, provide informed consent, and fill out a baseline survey before randomization. Families are randomly assigned in a 1:1:1 ratio to OR, BT, or a WL. Online questionnaires are completed at baseline (T₁, before randomization), post-intervention (T₂, 10 weeks after randomization), and at 3-month and 12-month follow-ups (T₃ and T₄, respectively). Dyadic multilevel models, with repeated measures (Level 1) nested within couples (Level 2), will be used to examine group differences in change trajectories across time for continuous outcomes.

Discussion: Including both a BT condition and a WL control allows us to test whether the OR offers added benefit over an accessible low-tech self-help option. Apart from the previous pilot, this is the first trial to evaluate the OR independently of its developers and the first study conducted outside the USA.

Trial registration: Registered at ClinicalTrials.gov (ID = NCT07125118). Approved by Aarhus University's Research Ethics Committee-Behavioural and Social Sciences (registration number BSS-2024-018-S2, February 26, 2024) and registered with Aarhus University's internal data protection registry (Datatilsyn no. 1732).