Strong primary healthcare enhances resource efficiency and resilience. Type 2 diabetes poses a growing global health challenge, with Argentina’s healthcare system struggling to detect and manage the disease effectively. Many patients bypass primary healthcare for secondary facilities, undermining continuity of care and increasing costs. Following a diagnostic process in collaboration with policymakers, we propose evaluating a redesigned primary care model consisting of codesigned evidence-based implementation strategies to improve type 2 diabetes management in Mendoza, Argentina.

This is an efficient, parallel-arm cluster randomised controlled Hybrid Type II trial with 12 clusters (administrative areas with 2–3 health facilities) allocated 1:1 to control (usual care) or intervention. In phase I, we will codesign, pilot and refine an implementation strategy package. In phase II, we will conduct the trial: 9-month baseline data collection, 15-month intervention and 6-month sustainability period. We will enrol a cohort of 396 patients with type 2 diabetes at primary healthcare centres and follow them for 12 months during the intervention and 6 months sustainment using routine clinical records and patient surveys. In phase III, we will conduct analysis, report and disseminate findings. The primary outcome will be a composite outcome including glycaemic control (glycated haemoglobin (HbA1c)

All study activities will comply with national and international ethics guidelines, presenting minimal risk to participants. The protocol was submitted and approved by the local independent ethics committee at the Mendoza Ministry of Health (Consejo Provincial de Evaluación ética en investigación en Salud-Provincial Health Research Ethics Review Board, Reference number: 149/2024). Facility-level permission will be obtained for participation and sharing of deidentified data. Written informed consent will be required from study participants, who will receive information on the study’s purpose, procedures, risks and benefits. Dissemination activities and outputs will include writing and submitting manuscripts for publication; writing policy briefs to support strategy implementation in other regions or countries; and tailoring outputs for patients, clinicians and researchers. We anticipate that improvements in disease management and patient experience will have clinical and economic benefits related to reduced usage of secondary-level and tertiary-level facilities, lower cost per visit and a reduced number of clinical events related to diabetes.

ISRCTN63277390.

Patients in intensive care units (ICUs) and their families face existential physical, psychosocial and spiritual distress. Integrating palliative care (PC) into ICU care may benefit patients, relatives and ICU clinicians. Prior PC studies have shown a reduction in ICU length of stay (LOS) and distressing symptoms without altering overall mortality. A shorter ICU LOS may alleviate the burden for patients and relatives and help optimise the use of limited intensive care resources. PC in the ICU, however, remains underused, partly due to limited access and knowledge of ICU clinicians. Also, robust data regarding the effectiveness and cost-effectiveness of PC treatment in the ICU are scarce. We established the ‘enhancing palliative care in ICUs’ (EPIC) study to implement a system-based harmonised practice model across European ICUs. The aim is to investigate if early integration of PC via telemedicine, clinician education and bedside tools is effective and cost-effective, ultimately benefiting patients, relatives and ICU clinicians.

This multicentre, controlled, cluster-randomised, non-blinded stepped-wedge design trial with crossover phase aims to recruit around 2,000 patients from five European countries. All adult patients admitted to participating ICUs—with an ICU LOS exceeding 72 hours, where cancer is not the primary cause of critical illness, and who are not expected to die within the next 24 hours—are screened for the need for specialised PC based on the attending physician’s judgement. This judgement is triggered by the presence of one or more of the following: (1) significant disagreement among ICU team members and/or relatives about the appropriateness of current ICU treatment, (2) considerations of limiting life-sustaining therapy or (3) the anticipation that a specialised PC consultation may benefit the patient, their relatives or the ICU team. Patients identified as needing specialised PC and their relatives are then enrolled after obtaining written informed consent.

The complex intervention consists of (a) a blended-learning programme to foster knowledge and attitude about PC among ICU clinicians, (b) bedside tools, including a checklist to identify patients in need of PC and a factsheet and (c) standardised telemedical consultations from trained EPIC interventionists. Patient and relative follow-up is conducted 3 months post-ICU discharge. Outcomes include clinical measures (including ICU LOS (primary outcome), severity of critical illness, invasive treatments and health-related quality of life), economic endpoints (resource use, costs, cost–consequence situation, cost-effectiveness), ICU clinician burnout and distress, and patient and family perception about the quality of symptom management, care and communication. Endpoint analyses will employ generalised linear mixed models, accounting for the clustered data structure and stepped wedge design.

EPIC complies with the Declaration of Helsinki and has been approved by all local ethics committees. A decision-making structure is established to ensure trial procedures are carried out according to Good Clinical Practice. Study findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public. Sets of anonymised study data will be made available following Findable, Accessible, Interoperable, and Reusable principles.

NCT06605079.

Haemophilia is a rare inherited bleeding disorder with complex support and costly treatment. Comprehensive care for people with haemophilia (PwH) must take place in structured and continuously evaluated treatment centres. The aim of the Public Assistance for People with Haemophilia in Brazil Project (PATCH Project) is to assess the infrastructure, human resources and healthcare delivery processes of Brazilian Blood Centres (BC) involved in the provision of haemophilia care.

This is a nationwide cross-sectional study involving 98 BC across Brazil’s 26 states and the Federal District, focusing on the care provided to PwH. A self-administered structured questionnaire was prepared, based on national and international recommendations for management, treatment and outcomes assessment in PwH. The criteria of the World Federation of Haemophilia and the European Association for Haemophilia and Allied Disorders will be used to define standards of quality.

Ethical approval for this study was granted by the Human Research Ethics Committee of the Federal University of Goiás, the coordinating centre (protocol CAAE 53863221.8.0000.5078), and subsequently by all participating institutions. Written informed consent is obtained from all participants prior to enrolment. Study findings will be disseminated through publication in peer-reviewed journals and presentation at international scientific conferences. Research data will be managed in accordance with ethical and legal standards and will be made available on reasonable request to support future investigations.

Not applicable

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.

To explore patient perspectives on using a digital adherence technology (DAT) for tuberculosis (TB) treatment, specifically, the TB Treatment Support Tools (TB-TST) intervention, which integrates a mobile app designed to enhance patient-centred support, monitoring and communication, alongside a drug metabolite test.

Qualitative study conducted as part of a pragmatic randomised controlled trial.

Four public reference hospitals in Argentina. All patients in the intervention group were invited to participate; 33 patients in the intervention group and five treatment supporters were included.

Data collection and analysis: semistructured interviews were conducted. The normalisation process theory guided analysis to understand factors that enable or hinder the intervention’s integration into routine practice for TB treatment medication adherence.

Patients identified medication reminders, educational messages and direct communication with treatment supporters (TSs) as the most helpful components of the intervention. Many reported using the app to ask TSs questions they felt uncomfortable raising with physicians in person. Initially, many patients did not fully understand the purpose and use of the metabolite test. Over time, their understanding of the app improved, though some continued to misinterpret the test results. Motivation to adhere to TB treatment was primarily driven by a desire to protect family members and resume normal daily activities. Reported barriers to app use included time constraints due to work, technical issues, limited internet connectivity and the burden of medication side effects. While the intervention was generally perceived as supportive and user-friendly, patients suggested improvements such as faster response times from TSs, expanded availability and better technical reliability and internet access.

These findings highlight the importance of tailoring digital adherence interventions to meet the diverse needs of patients and reinforce the pivotal role of the TS as a trusted and accessible source of guidance throughout TB treatment.

NCT04221789; https://clinicaltrials.gov/ct2/show/NCT04221789.