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Cardiac allograft vasculopathy (CAV) is a critical predictor of the long-term success of heart transplantation and once it is established, progression to graft dysfunction and loss is inevitable, despite adherence to immunosuppression and medications that ameliorate cardiac risk factors. Regulatory T cells (Tregs) are key for maintaining immune balance in the periphery. Studies investigating adoptive transfer of ex vivo expanded Tregs isolated from blood have been shown to be feasible and safe with good evidence for Tregs reducing CAV lesions in animal models of transplantation. Here, we describe the protocol for the ATT-Heart Study which is a phase I clinical trial investigating autologous thymus-derived Treg cell therapy in nine paediatric heart transplant recipients.
Patients will be recruited from the heart transplant waiting list at Great Ormond Street Hospital. Individualised autologous thymus-derived and expanded Tregs (TR006) will be injected into patients 3–6 months after transplant and follow-up will be conducted as per the post-transplant standard of care protocol with no wean of standard of care immunosuppression. Primary endpoint includes occurrence of Dose-limiting Toxicities in patients receiving TR006. Further data from blood tests, endomyocardial biopsy tissue, coronary imaging and clinical follow-up will be collected.
This article is based on the ATT-Heart study Protocol (V.1.1; dated 19 December 2024). The ATT-Heart trial has received a favourable ethical opinion from the Health Research Authority and South-Central Oxford A Research Ethics Committee (IRAS Number: 1008875/REC reference: 24/SC/0333). Clinical trials authorisation approval from UK Medicines and Healthcare products Regulatory Agency has also been received. The clinical trial will be conducted in accordance with the principles of Good Clinical Practice and following the guidelines set as part of the Research Governance Framework for Health and Social Care and all applicable necessary local policies. It is intended that the findings of the clinical trial will be presented at national/international conferences and using social media and through patient groups for dissemination among their members. The results will also be published in international peer-reviewed journals.
Countries face challenges in maternal and newborn care (MNC) regarding costs, workforce and sustainability. Organising integrated care is increasingly seen as a way to address these challenges. The evidence on the optimal organisation of integrated MNC in order to improve outcomes is limited.
(1) To study associations between organisational elements of integrated care and maternal and neonatal health outcomes, experiences of women and professionals, healthcare costs and care processes and (2) to examine how the different dimensions of integrated care, as defined by the Rainbow Model of Integrated Care, are reflected in the literature addressing these organisational elements.
We included 288 papers and identified 23 organisational elements, grouped into 6 categories: personal continuity of care; interventions to improve interdisciplinary collaboration and coordination; care by a midwife; alternative payment models (non-fee-for-service); place of birth outside the obstetric unit and woman-centred care. Personal continuity, care by a midwife and births outside obstetric units were most consistently associated with improved maternal and newborn outcomes, positive experiences for women and professionals and potential cost savings, particularly where well-coordinated multidisciplinary care was established. Positive professional experiences of collaboration depended on clear roles, mutual trust and respectful interdisciplinary behaviour. Evidence on collaboration interventions and alternative payment models was inconclusive. Most studies emphasised clinical and professional aspects rather than organisational integration, with implementation barriers linked to prevailing biomedical system orientations.
Although the literature provides substantial evidence of organisational elements that contribute to improved outcomes, a significant gap remains in understanding how to overcome the barriers in sustainable implementation of these elements within healthcare systems. Interpreted through a systems and transition science lens, these findings suggest that strengthening integrated maternity care requires system-level changes aligning with WHO policy directions towards midwifery models of person-centred care.
Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities.
The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness.
Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments.
ACTRN12625001050448.
The Quadrivalent human papillomavirus (HPV) Vaccine Evaluation Study with Addition of the Nonavalent Vaccine Study (QUEST-ADVANCE) aims to provide insight into the long-term immunogenicity and effectiveness of one, two and three HPV vaccine doses. Here, we describe the protocol for QUEST-ADVANCE.
QUEST-ADVANCE is an observational cohort study including males and females who are unvaccinated or vaccinated with the quadrivalent or nonavalent HPV vaccine in British Columbia, Canada. Female participants who are unvaccinated or vaccinated with 1–3 doses of the quadrivalent or nonavalent HPV vaccine at 9–14 years of age will be recruited approximately 5 or 12 years postvaccination eligibility. Male participants who are unvaccinated or vaccinated with 1 or 2 doses of the nonavalent HPV vaccine at 9–14 years of age will be recruited at approximately 5 years postvaccination eligibility. The study involves a maximum of four visits over a period of 4–5 years for female participants, and two visits over a 12-month period for male participants. At each visit, self-collected swabs (cervico-vaginal or penile) and questionnaire data will be collected. In each study group, a subset of participants will be invited to participate in a substudy evaluating the long-term humoral immunogenicity of the HPV vaccine. Additional blood samples will be collected from participants who are part of the immunogenicity substudy. The total required sample size is 7180 individuals. The primary objectives are (1) to examine vaccine effectiveness in males and females against prevalent genital HPV infections for one, two and three doses of the HPV vaccine compared with unvaccinated participants and (2) to evaluate if there is non-inferior immunogenicity as indicated by type-specific antibody response of one dose of the HPV vaccine in 20–27-year-old females vaccinated at 9–14 years of age compared with historical data of three doses of the HPV vaccine females vaccinated at 16–26 years of age up to 12 years postvaccination.
QUEST-ADVANCE was approved by the Research Ethics Board of the University of British Columbia/Children’s and Women’s Health Centre of British Columbia (H20-02111). Individual electronic informed consent or assent will be obtained from each participant before any study-specific procedures are undertaken. Results will be published in an international peer-reviewed journal and on the study website.
International consensus guidelines support the initial administration of 30 mL/kg of intravenous fluids for haemodynamic resuscitation of newly diagnosed septic shock. Practice variation exists between the volume of fluids administered and timing of vasopressor commencement. The optimal approach in patients with septic shock is uncertain.
Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis is a 1000-participant multicentre, randomised, open-label, parallel group clinical trial conducted in patients with septic shock presenting to the emergency department in participating sites in Australia, New Zealand and Ireland. Participants are randomised (1:1) to either restricted fluids and early vasopressors or a larger initial intravenous fluid volume and later vasopressors. The primary outcome is days alive and out of hospital at day 90 postrandomisation. Secondary outcomes are all-cause mortality at day 90, time from randomisation until death (to day 90), days alive and at home at day 90 and ventilator-free, vasopressor-free and renal replacement-free days to day 28 postrandomisation and death or disability at 6-month and 12-month postrandomisation. Health-related quality of life will be assessed at day 180 and 12 months following randomisation.
The study was approved by Northern Sydney Local Health District Human Research Ethics Committee (HREC2020/ETH02874) on 21 January 2021. Patients will be enrolled under a waiver of prior consent. The patient or next-of-kin (or equivalent according to local jurisdiction) is approached at the first available opportunity and given a trial information sheet. According to local approvals, the patient or next-of-kin chooses to either continue in the trial or opt-out/decline continued participation. Results will be disseminated in peer-reviewed journals and presented at academic conferences.
Cognitive behavioural therapy (CBT) serves as a first-line treatment for internalising disorders (ID), encompassing depressive, anxiety or obsessive-compulsive disorders. Nonetheless, a substantial proportion of patients do not experience sufficient symptom relief. Recent advances in wearable technology and smartphone integration enable new, ecologically valid approaches to capture dynamic processes in real time. By combining ecological momentary assessment (EMA) with passive sensing of behavioural and physiological information, this project seeks to track daily fluctuations in symptom-associated constructs like affect, emotion regulation (ER) and physical activity. Our central goal is to determine whether dynamic, multimodal markers derived from EMA and passive sensing can predict treatment non-response and illuminate key factors that drive or hinder therapeutic change.
PREACT-digital is a subproject of the Research Unit FOR 5187 (PREACT), a large multicentre observational study in four outpatient clinics. PREACT channels state-of-the-art machine learning techniques identify predictors of non-response to CBT in ID. The study is currently running and will end in June 2026. Patients seeking CBT at one of four participating outpatient clinics are invited to join PREACT-digital. They can take part in (1) a short version with a 14-day EMA and passive sensing phase prior to therapy, or (2) a long version in which the short version’s assessments are extended throughout the therapy. It is estimated that 468 patients take part in PREACT-digital, of which 350 opt for the long version of the study. Participants are provided with a smartwatch and a customised study app. We collect passive data on heart rate, physical activity, sleep and location patterns. EMA assessments cover affect, ER strategies, context and therapeutic agency. Primary outcomes on (non)-response are assessed after 20 therapy sessions and therapy end. We employ predictive and exploratory analyses. Predictive analyses focus on classification of non-response using basic algorithms (ie, logistic regression and gradient boosting) for straightforward interpretability and advanced methods (LSTM, DSEM) to capture complex temporal and hierarchical patterns. Exploratory analyses investigate mechanistic links, examine the interplay of variables over time and analyse change trajectories. Study findings will inform more personalised and ecologically valid approaches to CBT for ID.
The study has received ethical approval from the Institutional Ethics Committee of the Department of Psychology at Humboldt Universität zu Berlin (Approval No. 2021–01) and the Ethics Committee of Charité-Universitätsmedizin Berlin (Approval No. EA1/186/22). Written informed consent will be obtained from all participants prior to enrolment. Results will be disseminated through peer-reviewed journals and presentations at national and international conferences.
DRKS00030915; OSF PREACT: http://osf.io/bcgax; OSF PREACT-digital:
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