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.

Osteoarthritis (OA) is a degenerative and progressive joint condition causing pain and disability. Physical exercise is recognised as the most effective intervention since individuals with this condition often experience muscle weakness, balance deficits and chronic pain. Additionally, knee osteoarthritis (KOA) is associated with central sensitisation, contributing to chronic pain conditions. Transcranial Direct Current Stimulation (tDCS), a non-invasive neuromodulation technique, has been employed to induce changes in pain perception by altering cortical excitability, potentially reducing chronic pain.

This is a protocol for a randomised controlled trial. Participants will be allocated to two groups: G1 (active tDCS combined with exercise) and G2 (sham tDCS combined with exercise). The intervention protocol will last for 5 weeks, with two sessions per week on non-consecutive days. Pain intensity will be assessed as the primary outcome using the Numeric Rating Scale (NRS). The sample size was calculated based on a minimum clinically important difference of 3 points on the NRS between groups, with a statistical power of 80% and a significance level of 5%. Secondary outcomes will include physical function and global perceived change.

This protocol was approved by the Research Ethics Committee of the Trairi School of Health Sciences, Federal University of Rio Grande do Norte (Approval Number: 6.801.827), and it is in accordance with the Declaration of Helsinki for human research. Results will be published in peer-reviewed journals and presented at scientific events. This trial is registered in the Brazilian Clinical Trials Registry.

Brazilian Clinical Trials Registry (RBR-5pb2g33).

Acknowledging equality, diversity and inclusion (EDI) in research is not only a moral imperative but also an important step in avoiding bias and ensuring generalisability of results. This protocol describes the development of STAndards for ReporTing EDI (START-EDI) in research, which will provide a set of minimum standards to help researchers improve their consistency, completeness and transparency in EDI reporting. We anticipate that these guidelines will benefit authors, reviewers, editors, funding organisations, healthcare providers, patients and the public.

To create START-EDI reporting guidelines, the following five stages are proposed: (i) establish a diverse, multidisciplinary Steering Committee that will lead and coordinate guideline development; (ii) a systematic review to identify the essential principles and methodological approaches for EDI to generate preliminary checklist items; (iii) conduct an international Delphi process to reach a consensus on the checklist items; (iv) finalise the reporting guidelines and create a separate explanation and elaboration document; and (v) broad dissemination and implementation of START-EDI guidelines. We will work with patient and public involvement representatives and under-served groups in research throughout the project stages.

The study has received ethical approval from the Imperial College London Research Ethics Committee (study ID: 7592283). The reporting guidelines will be published in open access peer-reviewed publications and presented in international conferences, and disseminated through community networks and forums.

The project is pre-registered within the Open Science Framework (https://osf.io/8udbq/) and the Enhancing the Quality and Transparency of Health Research Network.

Adolescents living with HIV (ALHIV) are a priority population for achieving global HIV prevention and treatment targets but experience poorer outcomes than adults. Long-term follow-up is essential to understand their transition into adulthood. By linking self-reported survey data with routine laboratory records, we established a social science clinical cohort of ALHIV South Africa’s Eastern Cape to explore factors shaping their long-term health and well-being.

Eligible participants were adolescents who were part of a three-wave quantitative cohort of ALHIV and not living with HIV (2014–2018) and had consented (adolescent and caregiver) to having their self-reported interviews linked with routine health records (n=1563). Adolescents were recruited into the existing three-wave cohort through clinic and community-based methods (97% enrolment, >90% retention over three waves). Between 2019 and 2022, we abstracted laboratory test records from the National Health Laboratory Services database for all eligible participants, with matching based on demographic variables. Individuals with at least one HIV-related record form our ‘lifelong social science cohort’, a total of 956 ALHIV (852 of 1107 ALHIV and 104 of 456 HIV-uninfected).

A total of 32 886 laboratory test records from 2004 to 2023 were matched through three rounds of data extraction, using iteratively refined record-linking searches. Most records were viral load (8864) and CD4 count (6801) results, with a median of 10 (IQR: 7–14) and 8 (IQR: 5–11) tests per matched adolescent, respectively. Overall, 956 of 1563 adolescents (61%) were successfully linked to laboratory data, including 852 of 1107 (77%) ALHIV. Analysis of the matched cohort survey-laboratory data provided several insights. Self-reported antiretroviral therapy adherence was strongly associated with viral suppression, even after adjusting for covariates. The strongest predictors of suppression were not reporting missed doses in the past 3 days, past week and not missing clinic appointments in the past year. Among adolescent girls and young women living with HIV, access to safe and affordable facilities, and kind and respectful staff were associated with a higher likelihood of multiple improved HIV-related outcomes, including viral suppression. Exposure to sexual and intimate partner violence predicted worse viral load outcomes among adolescents.

This integrated prospective cohort provides an opportunity to characterise long-term HIV treatment outcomes among ALHIV in Africa. We will investigate how individual, familial, community and healthcare experiences in childhood, and adolescence shape these outcomes. Since the COVID-19 pandemic happened during the period of matched data, we will also investigate the potential effect of the COVID-19 pandemic on adolescent HIV treatment outcomes, with potential subgroup analyses for individuals with available COVID-19-related results.

Fathers are intricately bound to the experience of adolescent mothers and their children. Yet, fathers of children born to adolescent mothers, particularly within the context of HIV, remain neglected in the literature. These exploratory analyses provide insight into the characteristics of fathers of children born to adolescent mothers affected by HIV in South Africa.

Eastern Cape Province, South Africa.

Cross-sectional data from a prospective cohort study.

Young mothers (10–24 years of age) and their children (0–68 months). All mothers completed detailed study questionnaires, including standardised and study-specific measures, relating to their self, their children and the fathers of their children. Summary statistics are presented based on maternal self-report of father characteristics. ² tests and t-tests (Fisher’s exact/Kruskal-Wallis tests, where appropriate) were additionally used to explore sample characteristics (including father characteristics, maternal experience and child characteristics) according to paternal age and father involvement in childcare (defined by responses to four maternal self-report questions). Father characteristics were also explored according to maternal HIV status and maternal mental health status.

40% of fathers were adolescents (10–19 years) at the birth of their children. Overall, father involvement was low (19.5%). Compared with noninvolved fathers, involved fathers were more likely to be older when their child was born (21 years vs 20 years, t=4.30, p=0.04), to be in a relationship with the mothers of their children (74.8% vs 47.2%, ²=40.8, p≤0.0001), to reside with their children and their mothers (14.7% vs 3.7%, ²=49.3, p≤0.0001) and to attend the first antenatal appointment (4.3% vs 1.5%, ²=5.21, p=0.02). A quarter (25.4%; 227/894) of the adolescent mothers in the sample were living with HIV. The prevalence of maternal HIV was found to be higher among adolescent mothers of children born to older fathers compared with adolescent fathers (31.7% vs 15.9%, ²=28.3, p≤0.001). Likewise, depressive symptoms were more prevalent among adolescent mothers of children born to older fathers compared with adolescent fathers (9.9% vs 5.3%, ²=6.08, p=0.01). Adolescent mothers reporting poor mental health were less likely to be in a relationship with the fathers of their children (41.8% vs 54.1%, ²=7.32, p=0.03) and more likely to experience domestic violence perpetrated by the fathers of their children (8.2% vs 3.3%, ²=6.07, p=0.01) and to engage in arguments about finances with the fathers of their children (30.0% vs 17.0%, ²=10.8, p=0.001). While some differences in individual subscales were identified, overall composite scores of child cognitive development did not differ according to father age or father involvement.

Analyses provide the first preliminary description of the fathers of children born to adolescent mothers affected by HIV in South Africa. Fathers are inherently tied to the experiences of adolescent mothers and their children. Father involvement with their children was low. Further research is required to explore the potential barriers to father involvement and pathways to overcome these. Efforts to bolster father engagement, such as the inclusion of fathers within maternal and child service provision, may have benefits for fathers, adolescent mothers and their children. There was a high prevalence of adolescent fatherhood in the study. Adolescent fathers may have specific needs requiring tailored intervention for adolescent parent families. The need for the inclusion of fathers within policy, programming and research remains.

People living alone with neurodegenerative conditions face unique difficulties in maintaining independence and accessing appropriate health and social care support. Consolidating current understanding regarding these unique difficulties would better inform health and social care services and enable more tailored and appropriate service delivery. The proposed scoping review will summarise evidence from studies that provide evidence about people with dementia, Parkinson’s disease, Huntington’s disease or motor neurone disease who live alone. This protocol sets out the processes that will be followed in the subsequent scoping review to ensure that a transparent, rigorous and reproducible approach is used to identify, select and synthesise relevant evidence.

This scoping review protocol uses well-established methodology outlined by the Preferred Reporting Items for Systematic review and Meta-Analysis and the Joanna Briggs Institute. Relevant publications will be searched using PubMed, Web of Science Core Collection, CINAHL and AgeLine via EBSCOhost and EMBASE, PsycInfo and Social Policy and Practice via Ovid. Grey literature will be searched via Google looking specifically for pdf documents. As there was no previous review on the topic, no date restrictions will be applied to the searches. Piloting of the search strategy provided an estimate of the number of titles likely to require title and abstract screening, which, along with prior experience from a similar review approach, informed the feasibility of the proposed strategy. For research publications, a two-stage screening approach will be undertaken. The first stage will involve screening titles and abstracts for relevant literature on people with neurodegenerative conditions living alone in the community. The second stage will involve full text screening of selected articles. For grey literature, the first 20 PDFs per website identified in Google will be downloaded and screened. Summary data will be extracted from publications selected for inclusion. Data synthesis will involve tabulating study characteristics and findings and preparing narrative summaries to identify commonalities, gaps and areas for future research.

Ethical approval is not required for this review, as the information included is in the public domain and people with lived experience are consultees rather than research participants. Consultation with people with lived experience, stakeholders and experts linked with the National Institute for Health and Care Research Policy Research Unit in Dementia and Neurodegeneration University of Exeter will help to ensure the relevance and applicability of findings. Dissemination will include a policy report and peer-reviewed publications aimed at informing policy, practice and improving support services for people living alone with neurodegenerative conditions.

In Brazil, previous research has highlighted that clinical teachers have little interest in teaching palliative care to undergraduate medical students and there is a need to obtain greater understanding of the reasons for this disinterest.

Our objective was to explore the challenges experienced by Brazilian clinical teachers responsible for palliative care in undergraduate medical education.

A qualitative exploratory study using semistructured interviews and analysed by thematic analysis. A total of six teachers responsible for teaching palliative care to medical students in the state of São Paulo, Brazil, were recruited. Interviews were conducted via video conferencing.

Four themes were identified from the data: (1) conflicting ideals on clinical care, (2) teaching in palliative care: from the possible to the ideal, (3) missed teaching opportunities in palliative care and (4) challenges of palliative care in the health system. The main challenge of teaching palliative care was the lack of understanding of the concept and importance of palliative care within the healthcare system.

Challenges in teaching palliative care in Brazil include limited understanding of its importance, conflicting clinical care perspectives and emotional discomfort. Targeted strategies are recommended to prepare clinical teachers, integrate palliative care into curricula and address systemic barriers in similar low and middle income contexts.