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☐ ☆ ✇ BMJ Open

Protocol: Faecal microbiota transfer in liver cancer to overcome resistance to atezolizumab/bevacizumab - a multicentre, randomised, placebo-controlled, double-blind phase II trial (the FLORA trial)

Por: Rauber · C. · Roberti · M. P. · Vehreschild · M. J. · Tsakmaklis · A. · Springfeld · C. · Teufel · A. · Ettrich · T. · Jochheim · L. · Kandulski · A. · Missios · P. · Mohr · R. · Reichart · A. · Waldschmidt · D. T. · Sauer · L. D. · Sander · A. · Schirmacher · P. · Jäger · D. · Michl — Septiembre 10th 2025 at 05:45
Introduction

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.

Methods and analysis

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).

Ethics and dissemination

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.

Trial registration number

NCT05690048.

☐ ☆ ✇ BMJ Open

Mis- and disinformation and perceptions of healthcare policy among Latinos in the USA: protocol for a multi-method social media sentiment analysis study

Por: Wilson · F. A. · Stimpson · J. P. · Young · M.-E. D. T. · Bustamante · A. V. · Ponce · N. A. · Ortega · A. N. — Julio 4th 2025 at 04:45
Introduction

It is unclear how mis- and disinformation regarding healthcare policy changes propagate throughout Latino communities via social media. This may lead to chilling effects that dissuade eligible individuals from enrolling in critical safety net programmes such as Medicaid. This study will examine pathways and mechanisms by which sentiment in response to mis- and disinformation regarding healthcare policies on social media differentially impact health disparity populations, thus supporting the design of tailored social media interventions to mitigate this.

Methods and analysis

We will search social media from X/Twitter, Facebook/Instagram and Reddit for keywords relating to health benefit programmes. Demographic, geographical location and other characteristics of users will be used to stratify social media data. Posts will be classified as fake-news-related or fact-related based on curated lists of fake-news-related websites. The number, temporal dissemination and positive or negative sentiment in reacting to posts and threads will be examined using the Python-based Valence Aware Dictionary and sEntiment Reasoner (VADER). Using a crowd-sourcing methodology, a novel Spanish-language VADER (S-VADER) will be created to rate sentiment to social media among Spanish-speaking Latinos. With the proposed approach, we will explore reactions to the dissemination of fake-news- or fact-related social media tweets and posts and their sources. Analyses of social media posts in response to healthcare-related policies will provide insights into fears faced by Latinos and Spanish speakers, as well as positive or negative perceptions relating to the policy over time among social media users.

Ethics and dissemination

Our study protocol was approved by the University of California, Los Angeles IRB (IRB#23–0 01 123). Results from this study will be disseminated in peer-reviewed journals and conference presentations, and S-VADER will be disseminated to public repositories such as GitHub.

☐ ☆ ✇ BMJ Open

Effect of alcohol consumption and tobacco smoking on psychological distress: a quasi-experimental study using the 2022 Kenya demographic health survey data

Por: Kamau · K. · Andeso · P. · Muga · W. · Karisa · A. · Musyoki · D. · Kuria · J. M. · Kadengye · D. T. · Izudi · J. — Junio 17th 2025 at 10:56
Objective

Alcohol consumption and tobacco smoking have the potential to increase psychological distress. We evaluated the effect of alcohol consumption and tobacco smoking on psychological distress among adults in Kenya using a quasi-experimental study.

Design

Quasi-experimental study.

Setting

Kenya.

Participants

Adults aged 15–54 years.

Methods

We analysed the 2022 Kenya Demographic Health Survey data. The primary exposure was alcohol consumption, and tobacco smoking was the secondary exposure. The outcome was psychological distress. We employed propensity score matching to achieve comparability on observed covariates between the exposed and unexposed groups. We then performed conditional logistic regression analysis, adjusting for matched pairs to establish a cause-effect relation between the exposures of interest and the outcome. We reported the OR and 95% CI. We conducted a sensitivity analysis using Mantel–Haenszel bounds to check for the robustness of the cause-effect findings to unmeasured confounders.

Results

Of the 46 609 participants included in the study, 6450 (13.8%) consumed alcohol, while 2353 (5.0%) smoked tobacco. Overall, 1091 (2.3%) participants reported psychological distress. Among alcohol consumers, 352 (32.3%) reported psychological distress, compared with 115 (10.5%) among tobacco smokers. In a 1:1 ratio, we matched 10 070 individuals based on alcohol consumption and 4270 based on tobacco smoking status. In propensity-score-matched analysis, alcohol consumption (OR 2.76, 95% CI 2.06 to 3.70) and tobacco smoking (OR 2.04, 95% CI 1.29 to 3.24) showed an effect on psychological distress.

Conclusion

This study found that alcohol consumption and tobacco smoking increase psychological distress among adults aged 15–54 years in Kenya. There is, therefore, a need to screen for psychological distress among people who drink alcohol or smoke tobacco to provide them with prompt mental health interventions.

☐ ☆ ✇ BMJ Open

Timing of mechanical ventilation and its association with in-hospital outcomes in patients with cardiogenic shock following ST-elevation myocardial infarction: a multicentre observational study

Por: Arabi · A. · Al Suwaidi · J. · Daoulah · A. · AlQahtani · A. A. · Shahid · Z. · Jamjoom · A. · Elmahrouk · A. · AlShehri · M. · Panduranga · P. · Al Rawahi · A. S. M. · Livingston · G. S. · Mousa · A. A.-d. T. · Aloui · H. · Aldossari · M. · Yousif · N. · Noor · H. · Rajan · R. · Al Mahm — Junio 4th 2025 at 20:04
Objective

To evaluate the association between the timing of invasive mechanical ventilation (MV) initiation and clinical outcomes in patients with cardiogenic shock (CS) secondary to ST-elevation myocardial infarction (STEMI).

Design

Retrospective analysis of a multicentre registry.

Setting

Data were obtained from the Gulf-Cardiogenic Shock registry, which includes hospitals across six countries in the Middle East.

Participants

1117 patients diagnosed with STEMI and CS. Of these, 672 (60%) required MV and were included in this analysis.

Primary and secondary outcome measures

The primary outcome was in-hospital mortality. Secondary outcomes included comparisons of baseline characteristics, Society of Coronary Angiogram and Intervention (SCAI) shock stage, and clinical parameters among groups based on time to MV.

Results

Participants were categorised by time from shock diagnosis to MV: early (≤15 min), intermediate (30 min) and late (≥60 min). Median times were 15 min (IQR 10–20), 30 min (IQR 25–35) and 60 min (IQR 45–70), respectively. Baseline characteristics were comparable across groups. Increased delay in MV was associated with a higher mortality risk during the first 60 min post-diagnosis, beyond which the risk plateaued. Delayed MV was an independent predictor of in-hospital mortality (OR 2.14, 95% CI 1.36 to 3.38, p

Conclusions

Early initiation of MV in patients with STEMI complicated by CS was associated with lower in-hospital mortality. These findings highlight the importance of timely respiratory support, warranting further investigation in prospective or randomised controlled studies.

☐ ☆ ✇ BMJ Open

Understanding the relationship between adolescents with tuberculosis and health services: an indepth qualitative study from Cape Town

Por: Wademan · D. T. · Hoddinott · G. · Kavalieratos · Z. · Mlomzale · M. · Marthinus · A. J. · Jola · L. N. · Jacobs · S. · Mcimeli · K. · Seddon · J. — Mayo 25th 2025 at 02:10
Introduction

Adolescents’ experiences (10–19 years-old) with tuberculosis (TB) remain poorly understood. Descriptions of adolescent TB experiences, particularly how they interact with the health system, are scarce. We aimed to understand adolescents’ experiences of TB health services in the Western Cape, South Africa. We focused on how TB services were aided or hindered through interactions with healthcare providers and health system processes.

Methods

Teen TB, an observational study in Cape Town, enrolled 50 newly diagnosed adolescents with multidrug-resistant and drug-susceptible TB. A subset of 20 was selected for serial qualitative data collection, with 19 completing all tasks between December 2020 and September 2021. 52 interviews were conducted and thematically analysed using a case descriptive process for experiences across the TB care cascade.

Findings

Adolescents criticised the difficulties and delays they encountered in obtaining an accurate TB diagnosis. Initial misdiagnoses and delayed TB diagnoses were reported, despite seeking help from multiple healthcare providers at different facilities. Adolescents questioned whether the financial, social and emotional costs of TB care outweighed the costs of delaying treatment initiation and adherence. Adolescents reported that the treatment regimen, adherence support processes and interactions with the health system posed significant challenges to maintaining adherence. Encouragingly, however, most adolescents reported being well treated and cared for by health workers.

Conclusion

Our study shows that adolescents experience challenges throughout their TB treatment journeys. More adolescent-focused research is needed to tailor treatment and healthcare processes to their needs.

☐ ☆ ✇ BMJ Open

Recurrence of hypoglycaemia and associated factors among neonates admitted with perinatal asphyxia in Northwest Ethiopia: multicentre, retrospective follow-up study with negative binomial regression

Por: Gedefaw · G. D. · Asmare · T. B. · Abate · A. T. · Wondie · W. T. · Ayenew · M. E. · Bazezew · A. M. · Siyoum · T. M. · Worku · D. T. · Endeshaw · Y. S. — Abril 5th 2025 at 14:42
Objective

To estimate the recurrence of hypoglycaemia and the associated factors in neonates with birth asphyxia admitted to the neonatal intensive care unit in Northwest Amhara region’s comprehensive specialised hospitals, Northwest Ethiopia, in 2024.

Design

A multicentre, institution-based, retrospective follow-up study.

Setting

Tertiary hospitals in Northwest Amhara Regional State, Northwest Ethiopia, from 1 July 2020 to 30 July 2024.

Participants

A total of 761 neonates with perinatal asphyxia were admitted to the neonatal intensive care unit of selected public hospitals in Northwest Amhara from July 2020 to July 2024.

Outcome measure

The primary outcome measure of this study was recurrence of hypoglycaemia. Furthermore, the factors associated with recurrence of hypoglycaemia in newborns with perinatal asphyxia were noted.

Results

The average number of hypoglycaemia cases among neonates with birth asphyxia was 2.05 (95% CI 1.939, 2.163) over the 28-day follow-up period. Meningitis (adjusted incidence rate ratio (AIRR)=1.16; 95% CI 1.04, 1.30), feeding in less than 72 hours (AIRR=1.17; 95% CI 1.05, 1.31), stage 3 hypoxic-ischaemic injury (AIRR=1.20; 95% CI 1.04, 1.39), length of hospital stay (AIRR=1.01; 95% CI 1.01, 1.03) and macrosomia (AIRR=1.39; 95% CI 1.19, 1.63) were significant factors associated with recurrence of hypoglycaemia.

Conclusions and recommendations

The current study indicated that the mean recurrence of hypoglycaemia in newborns experiencing perinatal asphyxia was considerably higher. Presence of neonatal meningitis, delayed initiation of feeding 72 hours after birth, stage 3 hypoxic-ischaemic injury, length of hospital stay and macrosomia were the key factors associated with recurrence of hypoglycaemia.

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