Kings Health Partners

Gallium-68 complexes with siderophores, typically isostructural with their iron(III) analogues and recognized by microbial Fe(III)-siderophore complex receptors, are candidates for PET imaging of microbial infection. Here we evaluate [68Ga]Ga-desferrioxamine-B complex ([68Ga]Ga-DFO) for imaging in patients with infected aortic grafts. The trial was registered on clinical trials.gov, NCT05285072 registered 16 March 2022. [68Ga]Ga-DFO was produced from 68Ga-generator eluate in acetate buffer and characterized by radioHPLC, iTLC and LCMS. Its stability in human serum was evaluated in vitro by protein precipitation and size exclusion chromatography, and its biodistribution, pharmacokinetics and dosimetry determined by PET imaging in healthy mice. PET imaging in two patients with aortic graft infections was performed over 90 min, with blood and urine sampling in one patient. Analysis of [68Ga]Ga-DFO identified it as a 1:1 complex of 68Ga with DFO, with > 95% radiochemical purity, stable in human serum in the absence of bicarbonate at high DFO: protein ratio, but not in the presence of bicarbonate with low DFO: protein ratio. It was rapidly cleared renally from healthy mice but in humans, clearance was much slower consistent with significant protein binding. There was no specific uptake at infection sites identified by [18F]FDG scanning. We conclude that future clinical evaluation of the [68Ga]Ga-siderophore approach to infection imaging requires a deeper understanding of the kinetics and thermodynamics of transchelation of 68Ga between the siderophores and transferrin.

The objective of this study was to assess the household costs, catastrophic out-of-pocket (OOP) health expenditure, impoverishment and coping mechanisms used to pay for surgical care in a predominantly rural area of Ethiopia. We conducted a community-based, cross-sectional household survey of 182 people who had undergone a surgical procedure. Participants were interviewed in their homes at six weeks post-operation. Using a contextually adapted version of the Study of global AGEing and adult health (SAGE) questionnaire, we estimated direct and indirect costs of surgical care from a household perspective. Catastrophic out-of-pocket (OOP) health expenditure was estimated using thresholds of 10% and 25% of annual household consumption expenditure. Impacts of surgical care payments on poverty levels was estimated by comparing pre- and post-operative OOP payments. Analysis of variance, t-test and a logit model were used to assess factors associated with catastrophic OOP health expenditure. Most surgical patients were women (87.9%), with 65.0% receiving obstetric surgical care. Direct costs dominated expenditure: direct average medical costs Birr 1649.5 (44.6%), direct average non-medical costs Birr 1226.5 (33.2%), indirect average costs Birr 821.9 (22.2%). Catastrophic OOP surgical care expenditure was experienced by 69.2% households at the 10% threshold and 45.6% at the 25% threshold. The increase in average normalized poverty gap due to OOP surgical care expenditure was higher in non-obstetric (14.1%) compared to obstetric (5.8%) procedures, and for non-emergency (13.3%) compared to emergency care (6.3%). To pay for surgical care, 38.0% of households had sold assets and 5.0% had borrowed money. Due to surgical care, households faced severe financial burdens leading to impoverishment. To mitigate the resulting financial constraints, households implemented hardship coping strategies. Provision of free obstetric surgical care reduced, but did not eliminate, these burdens. There is a pressing need to tailor financial risk protection mechanisms to achieve universal coverage for surgical care.

Automated insulin delivery (AID) systems have significantly advanced diabetes management, progressively reducing user interactions required for optimal glucose management. This review evaluates the current landscape and future potential of AID systems without meal announcement, particularly focusing on real-world insights from open-source AID (OS-AID) technologies. Although commercial AID systems operating in hybrid closed-loop (HCL) mode have improved glycaemic outcomes, they remain dependent on manual meal announcement and user-driven actions, limiting their real-world utility. Current versions of OS-AID systems, developed by the diabetes community, can allow operation without meal announcements, presenting an opportunity to move closer to truly automated diabetes management. Recent clinical trials suggest that OS-AID systems can effectively manage glucose levels without meal announcements, achieving glucose levels comparable with those obtained by AID systems in HCL mode, with the potential of reduced management burden for users. However, practical challenges persist, including the need for expert configuration and handling of rapid changes in insulin sensitivity, such as during exercise or rapid glucose fluctuations following predicted low-glucose. This review synthesises insights from user and healthcare professional experiences, and emerging clinical evidence. It highlights the fact that successful implementation of AID without meal announcement requires advanced algorithmic responsiveness, user personalisation and ongoing clinician engagement. Looking forward, integrating adjunctive therapies, artificial intelligence and enhanced physiological modelling will likely enhance system performance to drive the next generation of diabetes care towards wider adoption and true 'set-and-forget' functionality.

Abstract Aim/background Ethnic inequalities in stroke incidence are well-established, but long-term trends and the impact of socioeconomic status (SES) remain understudied. We estimated incidence rates by ethnicity over 30-years, and differences by SES, using the South London Stroke Register (1995–2024). Methods We conducted a population-based study including all residents of a geographically defined area of South London, calculating standardised incidence rates using census-derived denominators and the 2013 European Standard Population. The area-level Index of Multiple Deprivation was the indicator of SES. Poisson regression estimated incidence rate ratios comparing ethnic-minority vs White groups, adjusting for age, sex, and SES, with ethnicity-SES interaction testing and marginal rates derived by subgroup. Results Among 7,726 people with first-ever stroke, overall standardised incidence decreased 34% between 1995–1999 and 2010–2014 (198;[187.8–208] to 131;[122.4–138.9] per 100,000), then increased 13% in 2020–2024. Black-African and Black-Caribbean populations had higher baseline incidence persisting across all periods. Ethnic inequalities narrowed initially but subsequently widened, with incidence twice as high in Black-African (IRR=2.31;[2.03–2.62]) and Black-Caribbean (IRR=2.00;[1.73–2.31]) groups compared to White groups in 2020–2024. Patterns were consistent across stroke subtypes, with the largest inequalities in primary intracerebral haemorrhage. Ethnic differences in incidence attenuated on SES adjustment but remained significant. Within ethnic groups, most deprived Black-African and Black-Caribbean populations showed highest incidence. Conclusion Stroke incidence has risen sharply in the past five years, driven by rising incidence rates in Black-African and Black-Caribbean populations, with reduction in the White population. Achieving equity requires ensuring uptake of cardiovascular risk programmes across all socioeconomic and ethnic groups, with earlier risk management for groups who develop stroke 10-12 years younger than the general population.

Cholangiocarcinoma (CCA) is a rare type of cancer which arises from the bile duct epithelium and carries a poor prognosis. One of the main risk factors in the Western world is primary sclerosing cholangitis. Surgical resection has traditionally been the only curative treatment but can only be offered to patients with early disease, excluding those with locally advanced disease. Despite initial poor outcomes, liver transplantation (LT) has evolved as a viable treatment for a select group of patients with CCAs that are deemed unresectable. This review aims to explore the evolution of the role of LT in patients with CCA.

Co-production is increasingly being used to develop sustainable improvements in health service delivery that are shaped by the experiences and needs of a diverse range of stakeholders including patients and healthcare providers. The process also offers a compelling means of fundamentally addressing the key issues of acceptability and applicability of digital health tools that contribute to ongoing inequity in the use of digital health technologies. However, creating and moderating hybrid digital health co-production teams is hindered by heightened obstacles to inclusivity and equitability of the cost and complexity of digital healthcare, and the diverse digital experience amongst the relevant stakeholders. With previous examples of co-production that involve direct interaction between developers and diverse groups of patients and staff rare, this integrative review has collated the latest evidence on engaging these diverse stakeholders in healthcare innovation, with best practice in co-production, and presents it within a framework representing the five core steps of co-production: Set-up, Discovery, Definition, Development, and Delivery. This guidance includes structured and tailored training in co-production and the concepts of digital health, surfacing and challenging existing assumptions around data security and confidentiality, defining funding models, introducing and refining protypes of increasing sophistication, and structured implementation and evaluation of both the co-production process and its outputs.

Background: Enterococcus faecalis (E. faecalis) is a prototypical resistant bacterium in root canal infections and a leading cause of endodontic treatment failure. German chamomile (Matricaria chamomilla) flower extract has been used as a traditional medicine to treat infections. The aim of this study was to investigate the antimicrobial efficacy of chamomile extract on the removal of E. faecalis root canal biofilm. Materials and Methods: Chamomile flower extract was prepared and subjected to detailed chemical analysis. For the in vitro biofilm model, human mandibular premolars (n=48) with 18-20mm working length were used. Root canal preparation was performed using the ProTaper® Next system. Each sample was split longitudinally and reassembled within a pre-prepared silicone matrix, and a mature E. faecalis biofilm was grown for seven days. Samples were randomised into four groups (n=12 for each arm) based on the type of irrigant protocol comprising normal saline, 3% sodium hypochlorite (NaOCl), dual irrigation with 17% ethylenediaminetetraacetic acid (EDTA) and 3% NaOCl, and chamomile extract. After irrigation, residual biofilms were measured in (n=9/group) using densiometric measurements. Observational analysis of residual biofilm was performed in (n=3/group) using Scanning Electron Microscopy (SEM). Results: Phytochemical investigations showed that chamomile extract is rich in antimicrobial components such as flavonoids, polyphenolic compounds, tannins, and others. Spectrophotometry analysis showed a statistically significant difference between the normal saline group with mean optical density (OD)= 0.63044; ±0.106 and each of EDTA and NaOCl group (mean OD=0.35922; ±0.091), chamomile group (mean OD=0.37611; ±0.106) at p<0.001, and the NaOCl group (mean OD=0.46344; ±0.096) at p<0.01. No statistically significant difference between chamomile group and NaOCl and the dual EDTA and NaOCl irrigation protocol. SEM images showed removal of E. faecalis biofilm and smear layer was in the order: dual EDTA and NaOCl irrigation>chamomile extract>NaOCl. Conclusions: Chamomile flower extract has an apparent removal efficacy of E. faecalis biofilm from root canals. It may be a promising antimicrobial material to be used as a natural endodontic irrigation solution.