The 2012 Kidney Diseases Improving Global Outcomes clinical practice guideline recommends prescribing continuous renal replacement therapy (CRRT) doses in patients with acute kidney injury (AKI) between 20 and 25 mL/kg/hour, with a need to consider further augmentation to 25–30 mL/kg/hour. Observational data have shown that lower-dose CRRT (

Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library will be searched for studies from inception to present. We will evaluate the risk of bias using the modified Cochrane tool for randomised controlled trials and the Cochrane Risk of Bias In Non-randomised Studies—of Interventions tool for cohort studies. Two reviewers will independently complete study selection, data extraction and bias assessment. Inclusion criteria will be randomised controlled trials and observational studies (cohort) including patients with AKI receiving CRRT. The exposure will be lower dose-intensity CRRT (

Ethics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication.

CRD420251135606.

The substantial case detection gap in the field of child tuberculosis (TB) disease is largely driven by inadequate diagnostic tools and approaches. Chest radiographs (CXRs) remain a key component in the evaluation of children and young adolescents (0–15 years) with presumptive TB, aiding clinicians in making the diagnosis and discriminating children with TB from those with other diseases. Widespread use and optimal interpretation of CXR is hampered by a lack of access to well-trained specialists to interpret images. Artificial intelligence CXR interpretation software, termed computer-aided detection (CAD), is now well developed for adults, yet few products have been evaluated in children. The CXR features of child TB are different from those of adults, and as a result, the performance of these CAD algorithms, largely developed for use in adults, will be suboptimal when used in children. Adapting, or fine-tuning adult CAD algorithms, using CXR images from children with presumptive TB, could allow optimisation of these products for use in children. We, therefore, set out to develop a large image and data repository collected from children evaluated for TB (called Catalysing Artificial Intelligence for Paediatric Tuberculosis Research, CAPTURE) with the purpose of evaluating current CAD products and then working with developers and other partners to optimise CAD algorithms for use in children.

We identified approximately 20 studies, from which potentially up to 11 000 CXRs could be used for the proposed project. CXRs and data were eligible for inclusion in the CAPTURE repository if collected from high-quality child TB diagnostic studies that enrolled children with presumptive TB and if CXRs were obtained as part of the baseline assessment. All lead investigators of these studies are members of the CAPTURE consortium. The images and metadata contributed are centrally collated and the key variable of TB case classification as confirmed, unconfirmed or unlikely TB, using an established consensus case definition, is available. All CXRs included in the CAPTURE repository have a consensus radiological interpretation allocated by a panel of independent expert child TB CXR readers who have classified them as ‘unreadable’, ‘normal’, ‘abnormal typical of TB’ or ‘abnormal not typical of TB’. To determine diagnostic performance of existing CAD products, we will evaluate these against a primary composite clinical reference standard (confirmed TB and unconfirmed TB vs unlikely TB), as well as other secondary microbiological and radiological reference standards. A subset of images will be subsequently allocated to a ‘training set’ and made available to developers, academic groups or other parties to either develop novel paediatric CAD products or fine-tune existing adult ones, which will then be re-evaluated by the CAPTURE team using an image subset (‘validation set’) that is independent of the training set.

The CAPTURE study has been approved by Stellenbosch University Health Research Ethics Committee (N22/09/113), with additional ethics approval or waivers by relevant local authorities obtained by consortium members contributing data if required. The final pooled, harmonised and cleaned dataset, as well as the deidentified, renamed CXR images, is stored on a secure cloud-based server. All analyses of existing CAD products, as well as the paediatric-optimised products, will be published in peer-reviewed publications and shared with other stakeholders like the WHO and donor and procurement organisations to guide policy updates and procurement pathways to ensure widespread uptake.

Shared decision-making is widely advocated in policy and practice, but how it is to be applied in a high-stakes clinical decision such as major lower limb amputation due to chronic limb-threatening ischaemia or diabetic foot is unclear. The aim of this study was to explore the communication, consent, risk prediction and decision-making process in relation to major lower limb amputation.

A qualitative study (done as part of a broader mixed-methods study) using semi-structured interviews. Interview transcriptions were analysed using thematic analysis.

Vascular centres in three large National Health Service hospitals in Wales and England, UK, between 1 October 2020 and 30 September 2022.

A purposive sample of 18 patients for whom major lower limb amputation was considered as a treatment option/carried out, with interviews conducted before or within 4 months of amputation and 4–6 months after amputation. A further purposive sample of 20 healthcare professionals (including eight surgeons) involved in supporting or conducting major lower limb amputation decision-making.

Five major categories were identified that highlighted the challenges of ensuring shared decision-making associated with major lower limb amputation: (i) patients’ limited understanding, (ii) variable patient attitudes to decision-making, (iii) healthcare professionals’ perceived challenges to sharing decision-making, (iv) surgeons’ paternalism and (v) patients’ and healthcare professionals’ decisional regret/possible consequences of challenges.

Amputation is a life-changing decision for both patients and healthcare professionals, with huge consequences. Despite being considered the gold standard, our findings highlight several challenges to effective shared decision-making for major lower limb amputation. Shared decision-making training for healthcare professionals is paramount if these limitations are to be addressed and patients are to feel confident in being adequately informed about the treatment decisions that they make.

NCT04903756.

The Cohort of Health-Related Outcomes in Chronic Illness Care in General Practice was established using data collected as part of a cluster-randomised trial. This aims to support the trial’s follow-up and enable further examination of the interplay between chronic disease, multimorbidity (MM), polypharmacy (PP) and quality of life (QoL) in a Danish general practice setting.

The cohort comprises 35 977 adult patients from 250 general practices participating in a cluster-randomised trial and had a response rate of 22.4%. Participants were either registered as chronic care patients or had attended an annual chronic disease consultation. They completed a comprehensive questionnaire on self-reported chronic conditions, medication use, QoL, treatment burden and patient-centred care. Additionally, 431 general practitioners (GPs) from the participating practices completed a questionnaire about managing patients with complex MM.

Among participants, 51.9% were female, the mean age was 65.6 (SD 12.9) years, 93.1% had education beyond basic schooling, and half were retired. Conditions from more than one organ system-based disease group were reported by 82.2%, and 94.6% used one or more prescription medications. The main challenges reported by the participating GPs in managing patients with complex MM were keeping time and obtaining an overview of the patient’s health status.

Cohort data will be linked with Danish registries to improve the detection and treatment of chronic conditions and PP in general practice.

The cluster randomised trial (MM600) is registered with ClinicalTrials.gov ID: NCT05676541.

Adolescent pregnancy is a global issue. Early childbearing is strongly linked to poverty and negative health outcomes, including increased neonatal death risk. This study explores spatial patterns of adolescent pregnancies and neonatal deaths and their association with socioeconomic characteristics.

This population-based study used spatial analysis techniques to investigate the geographical distribution of adolescent pregnancies, socioeconomic characteristics and neonatal mortality rate (NMR).

The 645 municipalities of State of Sao Paulo, Brazil.

All live births to mothers residing in the State of Sao Paulo, Brazil, between 2004 and 2020.

The socioeconomic indicators used were: municipal human development index and per capita income (PCI). Spatial patterns were assessed for spatial autocorrelation (Moran’s I, LISA), and smoothed using local Bayesian estimation. Spearman’s correlation was used to ascertain the relationship between the percentage of live births to adolescent mothers and socioeconomic indexes. This calculation was also undertaken between different maternal age groups of NMR.

The study analysed over 10 million live births, with 14.3% attributed to adolescent mothers. Spatial analysis revealed significant clustering of adolescent pregnancies, strongly associated with lower socioeconomic indicators. NMR also exhibited spatial clustering, particularly after smoothing. Statistically significant differences were observed in PCI medians between high–high and low–low clusters for adolescent births. High and low incidence areas of NMR, both in all maternal ages and stratified by adolescent and non-adolescent mothers, demonstrated considerable overlap.

The results indicated the existence of clustering areas of adolescent pregnancy and neonatal deaths and suggested that the prevalence of births to adolescent mothers is not distributed equally and is higher in lower socioeconomic developed areas.

Patients receiving haemodialysis are at very high risk of fragility fracture, yet there are no proven treatments for fracture prevention. We will advance a pilot study on the feasibility of a large, pragmatic, randomised controlled trial (RCT) of denosumab for fragility fracture prevention in haemodialysis.

PRevEnting FracturEs in REnal Disease-1 is a pragmatic, open-label, pilot study of an RCT of a denosumab care pathway embedded in routine care haemodialysis centres.

We will recruit at least 60 participants at high risk of fracture from at least 6 haemodialysis centres in Ontario, Canada. They must be aged 40 years or older, have access to provincial drug coverage, have appropriate baseline calcium and parathyroid hormone levels and be deemed suitable for denosumab by their kidney care provider. Participants will be randomised 1:1 to denosumab (with supports to mitigate hypocalcaemia) versus usual care using block randomisation by a central statistician (computer-generated sequence). Primary outcomes include recruitment feasibility and adherence. Secondary outcomes include safety (hypocalcaemia) and participant satisfaction with our protocol and processes. Study investigators and data analysts will be blind to treatment allocation.

We will present results descriptively. The trial was approved by Clinical Trials Ontario and local research ethics boards across study sites.

Primary and secondary outcomes will be published on trial completion.

This pilot will inform the feasibility of conducting a large-scale, efficiently run, pragmatic RCT to test whether a denosumab care pathway safely reduces the risk of fragility fracture in patients receiving haemodialysis. Results have the potential to transform fracture care in real-world patients with kidney and metabolic bone disease.

NCT05096195.

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.

Intrusive nightmares are a hallmark symptom of post-traumatic stress disorder (PTSD), contributing significantly to psychiatric comorbidities, impaired physical health and diminished social functioning. Currently, no pharmacological treatments are specifically approved for managing PTSD-related nightmares. However, emerging evidence suggests that adrenoceptor-targeting agents may offer therapeutic potential. Notably, clonidine and doxazosin have demonstrated efficacy in reducing PTSD-associated nightmares, as indicated by findings from open-label studies and small randomised controlled trials.

This study is a multicentre, double-blind, randomised (1:1:1), placebo-controlled, parallel-group interventional trial. A total of 189 eligible patients will be randomly assigned to receive clonidine, doxazosin or placebo, with a once-daily oral dose administered at bedtime for 10 weeks. The primary efficacy endpoint is the Clinician-Administered PTSD Scale B2 score at week 10, which measures the frequency and intensity of nightmares. Secondary efficacy endpoints include other PTSD-specific symptoms. Additionally, the safety of clonidine and doxazosin will be assessed.

The study was approved by the Ethics Committee of the State of Berlin (Ethik-Kommission des Landes Berlin) (Reference: 21-683-Haupt-IV E 13), on 14 March 2022 and by the relevant federal authority, the Bundesinstitut für Arzneimittel und Medizinprodukte, reference 4044931. The study was conducted in accordance with the relevant guidelines and regulations. The study results will be published in peer-reviewed journals and presented at both national and international conferences.

NCT05360953, EudraCT 2021-000319-21.

There is evidence for significant inequalities in morbidity and mortality due to cancer and other major non-communicable diseases (NCDs) both within and between European countries. Up-to-date evidence highlighting best practices for future policies is needed to reduce these inequalities.

The objective is to map and summarise published evidence on the impact of national and/or supranational policies on social inequalities in cancer and other NCDs, and their risk factors in Europe, and explore the nature and characteristics of these policies. The criteria for studies to be included are Population: any population group(s), whole population(s) or supranational population in Europe. Concept: any national or supranational policy directly targeting social inequalities in NCDs and/or their risk factors, or NCDs or their risk factors in general, while reporting effects on inequalities or targeting root causes of social inequality. Context: policies implemented by one or more governments or authorities in the WHO European region, in one or more sectors, and applied in a primordial, primary, secondary or tertiary prevention context. The policies may be universal, targeted or proportionate universal. The review will follow the Johanna Briggs Institute guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. We will search 13 databases from 2008 up to present for eligible experimental or quasi-experimental studies in any language, and reference lists of relevant reviews and included studies. The databases for the main search will include MEDLINE, Embase, Cochrane CENTRAL, Global Health, American Psychological Association (APA) PsycInfo, Cumulated Index in Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC), Web of Science Core Collection, Sociological Abstracts, Scopus, EconLit, The Social Interventions Research and Evaluation Network and FRANCIS. Study quality will be assessed using the Effective Practice and Organisation of Care (EPOC) risk of bias tool or the Risk of Bias in Non-Randomised studies of Interventions (ROBINS-I) tool depending on study design. Results will be synthesised narratively using descriptive statistics and visuals.

Ethical approval will not be sought as scoping reviews do not involve primary data collection or direct interaction with human participants. The results of this review, which is part of the JA-PreventNCD project, funded by the European Commission, and involving 25 European countries, will feed into one of the project’s deliverables, which comprises recommendations for policymakers based on the best available knowledge. We will also aim to present the results of the review at international conferences and publish the full review in an international peer-reviewed journal.

This protocol is registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/H7MUW).