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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.
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;
Primary healthcare (PHC) should be the cornerstone of equitable, efficient and high-quality healthcare in low- and middle-income countries. However, numerous challenges undermine its effectiveness in these settings.
To identify recommendations to improve PHC by integrating user preferences and provider capacity to deliver patient-centred and competent care in the Mendoza Province, Argentina.
Modified RAND Corporation/University of California, Los Angeles (RAND/UCLA) Delphi method.
Health system of the Province of Mendoza, Argentina.
32 public health experts from Mendoza.
Proposals were developed from secondary data, the People’s Voice Survey, an electronic cohort of people with diabetes, qualitative studies of users’ and professionals’ experiences and reviews of interventions in primary care.
Experts had to evaluate proposals according to five criteria selected from the evidence to decision framework (impact, resource requirements, acceptability, feasibility and measurability).
The 19 final recommendations emphasise policy continuity, evidence-based policy-making and standardisation of healthcare processes. Key areas include optimising healthcare processes, managing appointments for non-communicable diseases and ensuring competency-based training in PHC. Implementing performance-based incentives and improving financial sustainability were also highlighted. Other recommendations focus on the Digital Transformation Act, user participation in healthcare design and skills development for active engagement. Collaborative definitions of quality care, incident reporting systems and performance metrics are critical to improving healthcare quality.
This process provided decision-makers with contextualised information for health policy development. These interventions represent a step towards improving PHC, particularly chronic disease management, and provide a foundation for future regional research and health policy.
FreshRSS 