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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Impact and outcomes of the Emerging Leaders Programme: a mixed-methods evaluation of a leadership development programme for healthcare professionals.
BACKGROUND: The significance of effective medical leadership in enhancing healthcare outcomes has been widely acknowledged. This study evaluates the Emerging Leaders Programme, a multidisciplinary leadership development initiative for healthcare professionals at a UK Hospital Trust. METHODS: The evaluation spanned three cohorts (2017-2019) and a total of 54 participants, employing mixed methods to assess participant reactions, learning, behaviour changes and organisational impact. Quantitative pre-/post-measures included the Primary Colours Questionnaire (PCQ), Medical Leadership Competency Framework Questionnaire (MLCFQ) and Brief Resilience Scale (BRS), while qualitative data were gathered via free-text comments and long-term follow-up interviews. RESULTS: The programme had high satisfaction ratings, with particularly positive feedback relating to the multidisciplinary cohort and experiential learning via Quality Improvement projects. Findings indicated improvements in participants' leadership skills, knowledge, confidence and job satisfaction. Organisational outcomes included increased organisational interest in quality improvement and individual career progression. CONCLUSION: The results highlight the value of a structured leadership programme in developing healthcare leaders and driving organisational improvements, with long-term effects. Recommendations for future programmes include multidisciplinary involvement, experiential learning, inspiring speakers and embedded mixed-methods evaluation.
Patients' priorities in kidney stone disease.
INTRODUCTION: Engaging with patients and the public is essential to design and deliver impactful research. Enhancing the relevance of research and tailoring treatments to align with patients' preferences can facilitate improved clinical care. METHODS: We aimed to identify the research, support and treatment priorities of individuals with kidney stone disease (KSD) using a 25-question survey in inpatient and outpatient urology departments. RESULTS: Forty-four individuals with KSD responded to our survey; 28 (64%) had experienced multiple KSD episodes and 11 reported 5 or more episodes. Median self-rated quality-of-life (QoL) impact (0 = negligible; 10 = severe) was 7.00 out of 10.00 (interquartile range [IQR]: 5.00-9.00), equivalent in individuals with single and recurrent stone episodes. Pain (n = 34), haematuria (n = 28) and anxiety (n = 22) were the primary factors contributing to QoL impact. Participants prioritised research into preventing recurrence, alleviating pain and slowing stone growth. More than one-third desired more information about KSD. Most (n = 36) felt 'likely' or 'very likely' to take medication to reduce their risk of KSD and 25 would commit to life-long therapy. Daily dosing was acceptable to 13 participants if risk of KSD recurrence was reduced by 50%, rising to 34 respondents if risk of recurrence was reduced by 75%. Most respondents (n = 44) expressed willingness to have genetic testing to facilitate personalised medicine research. CONCLUSIONS: Our findings emphasise symptoms contributing to reduced physical and psychological wellbeing in patients with KSD. We highlight the need for research into developing therapies to prevent stone recurrence, alleviate pain and slow stone growth, and for educational materials. Responses indicate an appetite for personalised medicine and oral medications in KSD.
Global burden of vision impairment due to age-related macular degeneration, 1990–2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021
Background: Age-related macular degeneration (AMD) is a growing public health concern worldwide, as one of the leading causes of vision impairment. We aimed to estimate global, national, and region-specific prevalence and disability-adjusted life-years (DALYs) along with tobacco as a modifiable risk factor to aid public policy addressing AMD. Methods: Data on AMD were extracted from the Global Burden of Disease, Injuries, and Risk Factor Study 2021 database in 204 countries and territories, 1990–2021. Vision impairment was defined and categorised by severity as follows: moderate to severe vision loss (visual acuity from <6/18 to 3/60) and blindness (visual acuity <3/60 or a visual field <10 degrees around central fixation). The burden of vision impairment attributable to AMD was subsequently estimated. These estimates were further stratified by geographical region, age, year, sex, Healthcare Access and Quality (HAQ) Index, and Socio-demographic Index (SDI) levels. Additionally, the effect of tobacco use, a modifiable risk factor, on the burden of AMD was analysed, and projections of AMD burden were estimated through to 2050. These projections also included scenario modelling to assess the potential effects of tobacco elimination. Findings: Globally, the number of individuals with vision impairment due to AMD more than doubled, rising from 3·64 million (95% uncertainty inverval [UI] 3·04–4·35) in 1990 to 8·06 million (6·71–9·82) in 2021. Similarly, DALYs increased by 91% over the same period, from 0·30 million (95% UI 0·21–0·42) to 0·58 million (0·40–0·80). By contrast, age-standardised prevalence and DALY rates declined, with prevalence rates decreasing by 5·53% (99·50 per 100 000 of the population [95% UI 83·16–118·04] in 1990 to 94·00 [78·32–114·42] in 2021) and DALY rates dropping by 19·09% (8·38 [5·70–11·53] to 6·78 [4·70–9·32]). These rates showed a consistent decrease in higher SDI quintiles, reflecting the negative correlation between HAQ Index and AMD burden. A general downward trend was observed from 1990 to 2021, with the largest age-standardised reduction occurring in the low-middle SDI quintile. The global contribution of tobacco to age-standardised DALYs decreased by 20%, declining from 12·45% (95% UI 7·73–17·37) in 1990 to 9·96% (6·12–14·06) in 2021. By 2050, the number of individuals affected by AMD is projected to increase from 3·40 million males (95% UI 2·81–4·17) in 2021 to 9·02 million (5·72–14·20) and from 4·66 million females (3·88–5·65) to 12·32 million (8·88–17·08). Eliminating tobacco use could reduce these numbers to 8·17 million males (5·59–11·92) and 11·15 million females (8·58–14·48) in 2050. Interpretation: While the total prevalence and DALYs due to AMD have steadily increased from 1990 to 2021, age-standardised prevalence and DALY rates have declined, probably reflecting the effect of population ageing and growth. The consistent decrease in age-standardised rates with higher SDI levels highlights the crucial role of health-care resources and public policies in mitigating AMD-related vision impairment. The downward trend observed from 1990 to 2021 might also be partially attributed to the reduced effect of tobacco as a modifiable risk factor, with declines in tobacco use seen globally and across all SDI quintiles. The burden of vision impairment due to AMD is projected to increase to about 21·34 million in 2050. However, effective tobacco regulation has the potential to substantially reduce AMD-related vision impairment, particularly in lower SDI quintiles where health-care resources are limited. Funding: Gates Foundation.
Missed opportunities for health promotion and disease prevention: lifestyle interventions in primary care for individuals with hypertension, hyperlipidemia, obesity and type 2 diabetes
Non-communicable diseases (NCDs) like hypertension, type 2 diabetes, hyperlipidemia, and obesity, are a leading cause of mortality and have shown rising prevalence trends over the last few decades. Lifestyle interventions, particularly diet and physical activity, are an effective approach to addressing the underlying risk factors of these preventable NCDs, but their integration into the primary care practice remains underutilized. This review synthesizes evidence from systematic reviews and meta-analyses published between 2019 and 2024 to provide evidence-based recommendations for the integration of lifestyle interventions into primary care pathways. The included articles were noted for their risk of bias because of poor study design. While consideration must be given to the quality of evidence for these interventions because of the risk of bias, there is good evidence to support the use of several types of interventions including: diet modification (e.g. food replacement, calorie restriction, intermittent/periodic fasting); diet education and counselling; individual and group-based exercise interventions; interventions that aim to promote general physical activity in daily life; as well as combined dietary and physical activity interventions delivered individually, in groups, at a community level as well as through smartphone-supported applications. It is important for the health and care community to explore and implement alternative means of generating evidence, integrating lifestyle interventions into care pathways and increasing investment in the lifecycle of these interventions, which can promote health and prevent disease.
Development of a patient-centred tool for use in total hip arthroplasty.
BACKGROUND: The aim of this project was to develop a tool using the experience of previous patients to inform patient-centred clinical decision-making in the context of total hip arthroplasty (THA). We sought out the patients' views on what is important for them, leveraging registry data, and providing outcome information that is perceived as relevant, understandable, adapted to a specific patient's profile, and readily available. METHODS: We created the information tool "Patients like me" in four steps. (1) The knowledge basis was the systematically collected detailed exposure and outcome information from the Geneva Arthroplasty Registry established 1996. (2) From the registry we randomly selected 275 patients about to undergo or having already undergone THA and asked them via interviews and a survey which benefits and harms associated with the operation and daily life with the prosthesis they perceived as most important. (3) The identified relevant data (39 predictor candidates, 15 outcomes) were evaluated using Conditional Inference Trees analysis to construct a classification algorithm for each of the 15 outcomes at three different time points/periods. Internal validity of the results was tested using bootstrapping. (4) The tool was designed by and pre-tested with patients over several iterations. RESULTS: Data from 6836 primary elective THAs operated between 1996 and 2019 were included. The trajectories for the 15 outcomes from the domains pain relief, activity improvement, complication (infection, dislocation, peri-prosthetic fracture) and what to expect in the future (revision surgery, need for contralateral hip replacement) over up to 20 years after surgery were presented for all patients and for specific patient profiles. The tool was adapted to various purposes including individual use, group sessions, patient-clinician interaction and surgeon information to complement the preoperative planning. The pre-test patients' feedback to the tool was unanimously positive. They considered it interesting, clear, complete, and complementary to other information received. CONCLUSION: The tool based on a survey of patients' perceived concerns and interests and the corresponding long-term data from a large institutional registry makes past patients' experience accessible, understandable, and visible for today's patients and their clinicians. It is a comprehensive illustration of trajectories of relevant outcomes from previous "Patients like me". This principle and methodology can be applied in other medical fields.
Tremor Asymmetry and the Development of Bilateral Phase-Specific Deep Brain Stimulation for Postural Tremor.
BACKGROUND: Tremor phase-locked deep brain stimulation (DBS) has been shown to modulate symptom severity in postural tremor, including essential and dystonic tremor, with less energy than existing systems. Previous studies focused on unilateral stimulation; it remains unknown how tremor asymmetry interacts with stimulation in the context of bilateral phase-locked DBS. METHODS: Archival limb acceleration from nine essential tremor patients was analyzed for asymmetries in tremor amplitude, frequency, and instability, and their relationship with continuous high-frequency DBS (cDBS). Bilateral phase-locked DBS was tested in one essential tremor and one dystonic tremor patient. RESULTS: Postural tremor is asymmetric, with larger tremor power linked to smaller amplitude and frequency stability in one hand. These asymmetries were significantly reduced during cDBS, with greater effects on larger amplitude tremors. Bilateral phasic DBS effects were also asymmetric. CONCLUSIONS: This study enhances understanding of tremor asymmetry and its relationship with DBS, offering insights for patient-specific tremor treatments. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Clinical Factors Influencing the Compliance With National Head and Neck Cancer Targets in the United Kingdom: Results From a National Cohort Study
Introduction: In the United Kingdom, it is the standard of care that treatment decisions in all new cases of head and neck cancer (HNC) are discussed at a multidisciplinary team meeting (MDT). The aim of this project was to gain a national perspective on the scope of current HNC treatment, compliance with national cancer pathway targets, and their influence on survival outcomes. Methods: A multicentre, retrospective, national observational study of primary HNC patients was discussed at a specialist MDT between September and November 2021. Results: Data on 1488 patients were included from 50 UK departments. The most common subsite was oropharynx (35.4%, 522), of which 61.7% (263) were HPV positive. Median time of referral to diagnosis, MDT decision to treatment, and referral to first definitive treatment in primary HNCs managed curatively were 37 (interquartile range [IQR] 22–57), 42 (IQR 29–65), and 74 (IQR 54–101) days, respectively. Compliance with the 28-day, 31-day, and 62-day targets were met in 32.8% (488), 33.3% (495), and 34.6% (515), respectively. On multivariate analysis, patients with urgent cancer referrals, T1–T2 stage disease, and not undergoing a general anaesthetic biopsy were associated with greater compliance with national pathway targets. Conclusion: This study highlights the majority of UK HNC patients are not meeting national pathway targets and delays are seen at all points in the HNC journey. Improving adherence with national best practice standards will contribute to reducing time to treatment for HNC.
IsletSwipe, a mobile platform for expert opinion exchange on islet graft images.
We previously developed a deep learning-based web service (IsletNet) for an automated counting of isolated pancreatic islets. The neural network training is limited by the absent consensus on the ground truth annotations. Here, we present a platform (IsletSwipe) for an exchange of graphical opinions among experts to facilitate the consensus formation. The platform consists of a web interface and a mobile application. In a small pilot study, we demonstrate the functionalities and the use case scenarios of the platform. Nine experts from three centers validated the drawing tools, tested precision and consistency of the expert contour drawing, and evaluated user experience. Eight experts from two centers proceeded to evaluate additional images to demonstrate the following two use case scenarios. The Validation scenario involves an automated selection of images and islets for the expert scrutiny. It is scalable (more experts, images, and islets may readily be added) and can be applied to independent validation of islet contours from various sources. The Inquiry scenario serves the ground truth generating expert in seeking assistance from peers to achieve consensus on challenging cases during the preparation for IsletNet training. This scenario is limited to a small number of manually selected images and islets. The experts gained an opportunity to influence IsletNet training and to compare other experts' opinions with their own. The ground truth-generating expert obtained feedback for future IsletNet training. IsletSwipe is a suitable tool for the consensus finding. Experts from additional centers are welcome to participate.
The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation
The rising incidence of colorectal cancer and ulcerative colitis underscores an urgent need for regenerative solutions to address functional deficits after colectomy. However, the creation of clinically applicable large intestine scaffolds remains underdeveloped. Here, we report the successful generation and thorough characterisation of transplantable-sized porcine large intestinal scaffolds via perfusion decellularisation. This method effectively preserved extracellular matrix (ECM) structural and biochemical integrity while minimising immunogenicity through cellular component removal. Crucially, native vasculature remained intact, confirmed by histology, DNA quantification, and high-resolution CT angiography. Despite efficient decellularisation, challenges including residual nucleic acids, ECM heterogeneity, and partial microvascular occlusion were noted, echoing ongoing limitations in engineered, perfusable, full-thickness scaffolds. In vivo implantation demonstrated favourable biocompatibility and host integration; however, thrombosis occurred due to the lack of pre-seeded cells, emphasising the necessity of recellularisation for functional perfusion prior to implantation. This study addresses significant field limitations, presenting the first reproducible approach for structurally intact, perfusable, full-thickness large intestinal scaffolds of transplantable dimensions. Our innovations offer a strong foundation for future integration of patient-derived cells, stem cells, and organoids, progressing toward clinically viable, scalable, tissue-engineered large intestine constructs, from xenogeneic sources, relevant for regenerative medicine, disease modelling, and pharmacological screening.
Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant.
Immunological processes that underpin human immune responses to therapeutics and vaccine components, such as vaccine adjuvants, remain poorly defined due to a paucity of models that faithfully recapitulate immune activation in lymphoid tissues. We describe precision-cut human lymph node (LN) slices as a functioning, architecturally preserved, full-organ cross-sectional model system. Using single-cell transcriptomics and multiplexed imaging, we explore early inflammatory response to a potent, clinically relevant liposomal vaccine adjuvant containing a TLR4-agonist and QS-21 saponin. Both TLR4 and NLRP3 inflammasome activation are involved in the direct initiation of the inflammatory response to adjuvant by monocytes and macrophages (Mon./Mac.) with secretion of interleukin (IL)-1β, but not IL-18, dependent on TLR4 signaling. Innate lymphoid cells, including natural killer cells, are indirectly activated by Mon./Mac.-produced cytokines, signaling downstream to B cells via interferon-γ secretion. Resident LN stromal populations, primed both directly and indirectly by vaccine adjuvant, are instrumental in mediating inflammatory cell recruitment, particularly neutrophils.
Selective remodelling of the adipose niche in obesity and weight loss.
Weight loss significantly improves metabolic and cardiovascular health in people with obesity1-3. The remodelling of adipose tissue (AT) is central to these varied and important clinical effects4. However, surprisingly little is known about the underlying mechanisms, presenting a barrier to treatment advances. Here we report a spatially resolved single-nucleus atlas (comprising 171,247 cells from 70 people) investigating the cell types, molecular events and regulatory factors that reshape human AT, and thus metabolic health, in obesity and therapeutic weight loss. We discover selective vulnerability to senescence in metabolic, precursor and vascular cells and reveal that senescence is potently reversed by weight loss. We define gene regulatory mechanisms and tissue signals that may drive a degenerative cycle of senescence, tissue injury and metabolic dysfunction. We find that weight loss reduces adipocyte hypertrophy and biomechanical constraint pathways, activating global metabolic flux and bioenergetic substrate cycles that may mediate systemic improvements in metabolic health. In the immune compartment, we demonstrate that weight loss represses obesity-induced macrophage infiltration but does not completely reverse activation, leaving these cells primed to trigger potential weight regain and worsen metabolic dysfunction. Throughout, we map cells to tissue niches to understand the collective determinants of tissue injury and recovery. Overall, our complementary single-nucleus and spatial datasets offer unprecedented insights into the basis of obese AT dysfunction and its reversal by weight loss and are a key resource for mechanistic and therapeutic exploration.
What spatial omics is teaching us about field cancerisation in prostate and bladder cancer.
BACKGROUND AND OBJECTIVES: Field cancerisation is the process that results in a group of cells acquiring some of the phenotypic changes of cancer prior to transformation into cancer. Clinically, an important challenge remains the ability to distinguish clonal lineages and microenvironments within cancerised fields that will remain indolent from those that will progress to malignant transformation. Spatial 'omics' can help us investigate genetic, epigenetic, transcriptomic, proteomic, and cellular microenvironments that transform normal cells into a cancerised field, and subsequently into cancer. In this review, we will discuss how spatial omics techniques have expanded our understanding of field cancerisation in prostate and bladder cancer, and the challenges associated with this research. METHODS: We identified key articles relating to field cancerisation in bladder and prostate cancer. Special emphasis was placed on studies that used modern spatial profiling technologies and studies that were designed to investigate changes within normal tissue rather than simply using it as a control for tumour tissue. RESULTS: Spatial omics research into field cancerisation has identified interesting early findings that have informed our understanding of: transformation of the benign epithelium and mechanisms of intra-prostatic clonal expansion for prostate cancer; clonal expansion within the normal urothelium; mutations that are unique to cancerised fields within the bladder; and how field cancerisation may prime the urothelium for cancer transformation. CONCLUSIONS: Spatial omics profiling of field cancerisation can inform risk stratification and personalised treatment options. However, there are a number of challenges associated with the technologies that must be overcome before the potential of spatial omics can be fully realised in clinical practice.
Leadership training in healthcare: a systematic umbrella review.
The importance of effective clinical leadership has been reflected in an increase in leadership development programmes. However, there remains a lack of consensus regarding the optimal structure, content and evaluation of such programmes. This review synthesised evidence from reviews of leadership development interventions for healthcare professionals published prior to October 2024, including content, methods, evaluation strategies and impact. Title, abstract and full-text screening were conducted in duplicate by two reviewers. Data extraction was piloted by two reviewers and conducted by a single reviewer. Quality appraisal was conducted using the Risk of Bias in Systematic Reviews tool by a single reviewer, with generative artificial intelligence serving as the second reviewer. 86 systematic and non-systematic reviews met inclusion criteria. Regarding educational methods, leadership training effectiveness was associated with experiential learning, mixed-methods approaches, coaching or mentoring, longitudinal designs, goal-setting, and 360-degree feedback. Group learning and interprofessional education were noted for fostering teamwork. Programmes tailored to participants' needs and organisational contexts showed better outcomes. Content reported to be effective included interpersonal skills, self-awareness, emotional intelligence, leadership theory, communication and teamwork. Evaluations primarily relied on self-reported measures. Training outcomes were largely positive at the individual level, with participants reporting increased confidence and competence. Organisational and clinical outcomes were less frequently assessed. The long-term impact on patient outcomes and return on investment remains uncertain. Leadership development programmes were found to enhance individual competencies. However, evidence supporting long-term, system-wide impact remains limited due to reliance on self-reported evaluations and a lack of standardised evaluation approaches.
Normothermic Machine Perfusion (NMP) of the Liver as a Platform for Therapeutic Interventions during Ex-Vivo Liver Preservation: A Review.
Liver transplantation is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. This has necessitated the adoption of innovative technologies and strategies to protect these higher-risk grafts from the deleterious effects of traditional preservation and ischaemia reperfusion injury (IRI). The advent of normothermic machine perfusion (NMP) and rapid growth in the clinical adoption of this technology has accelerated efforts to utilise NMP as a platform for therapeutic intervention to optimise donor livers. In this review we will explore the emerging preclinical data related to ameliorating the effects of IRI, protecting the microcirculation and reducing the immunogenicity of donor organs during NMP. Exploiting the window of opportunity afforded by NMP, whereby the liver can be continuously supported and functionally assessed while therapies are directly delivered during the preservation period, has clear logistical and theoretical advantages over current preservation methods. The clinical translation of many of the therapeutic agents and strategies we will describe is becoming more feasible with widespread adaptation of NMP devices and rapid advances in molecular biology and gene therapy, which have substantially improved the performance of these agents. The delivery of novel therapeutics during NMP represents one of the new frontiers in transplantation research and offers real potential for successfully tackling fundamental challenges in transplantation such as IRI.
Developing Trustworthy Artificial Intelligence Models to Predict Vascular Disease Progression: the VASCUL-AID-RETRO Study Protocol.
INTRODUCTION: Abdominal aortic aneurysms (AAAs) and peripheral artery disease (PAD) are two vascular diseases with a significant risk of major adverse cardiovascular events and mortality. A challenge in current disease management is the unpredictable disease progression in individual patients. The VASCUL-AID-RETRO study aims to develop trustworthy multimodal predictive artificial intelligence (AI) models for multiple tasks including risk stratification of disease progression and cardiovascular events in patients with AAA and PAD. METHODS: The VASCUL-AID-RETRO study will collect data from 5000 AAA and 6000 PAD patients across multiple European centers of the VASCUL-AID consortium using electronic health records from 2015 to 2024. This retrospectively-collected data will be enriched with additional data from existing biobanks and registries. Multimodal data, including clinical records, radiological imaging, proteomics, and genomics, will be collected to develop AI models predicting disease progression and cardiovascular risks. This will be done while integrating the international ethics guidelines and legal standards for trustworthy AI, to ensure a socially-responsible data integration and analysis. PROPOSED ANALYSES: A consensus-based variable list of clinical parameters and core outcome set for both diseases will be developed through meetings with key opinion leaders. Blood, plasma, and tissue samples from existing biobanks will be analyzed for proteomic and genomic variations. AI models will be trained on segmented AAA and PAD artery geometries for estimation of hemodynamic parameters to quantify disease progression. Initially, risk prediction models will be developed for each modality separately, and subsequently, all data will be combined to be used as input to multimodal prediction models. During all processes, data security, data quality, and ethical guidelines and legal standards will be carefully considered. As a next step, the developed models will be further adjusted with prospective data and internally validated in a prospective cohort (VASCUL-AID-PRO study). CONCLUSION: The VASCUL-AID-RETRO study will utilize advanced AI techniques and integrate clinical, imaging, and multi-omics data to predict AAA and PAD progression and cardiovascular events. CLINICAL TRIAL REGISTRATION: The VASCUL-AID-RETRO study is registered at www.clinicaltrials.gov under the identification number NCT06206369. CLINICAL IMPACT: The VASCUL-AID-RETRO study aims to improve clinical practice of vascular surgery by developing artificial intelligence-driven multimodal predictive models for patients with abdominal aortic aneurysms or peripheral artery disease, enhancing personalized medicine. By integrating comprehensive data sets including clinical, imaging, and multi-omics data, these models have the potential to provide accurate risk stratification for disease progression and cardiovascular events. An innovation lies in the extensive European data set in combination with multimodal analyses approaches, which enables the development of advanced models to facilitate better understanding of disease mechanisms and progression. For clinicians, this means that more precise, individualized treatment plans can be established, ultimately aiming to improve patient outcomes.