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Unsupervised machine learning for identifying morphological phenotypes in abdominal aortic aneurysms using fully automated volume-segmented imaging: a multicentre cohort study
Get PDFAims
Thrombo- and microembolic complications following abdominal aortic aneurysm (AAA) repair are hypothesized to be associated with wall thrombus burden. Fully automatic volume segmentation (FAVS) of imaging enables extraction of morphological features from which thrombogenic phenotypes may be identified.
Methods and results
This was a multi-centre retrospective cohort study using FAVS to examine pre-operative imaging for elective AAA repairs (2013–23). Radiological data were matched with National Vascular Registry thromboembolic outcomes data (cerebral, bowel, renal or limb ischaemia). Principal component analysis was used for dimensionality reduction, followed by unsupervised machine learning with k-nearest neighbours clustering, with number of clusters determined using silhouette scores. Clusters were compared using multivariate logistic regression, adjusting for aortic size index, cardiovascular risk parameters, and repair-type. Of 1655 patients, 1455 had sufficient quality imaging for FAVS (145 women and 1310 men). k-nearest neighbours clustering identified two morphological subtypes (n = 878 and n = 577), with sex imbalance (13.8 vs. 4.1% women, P < 0.001). The clusters differed in wall thrombus burden in visceral vessels, infra-renal aorta, aneurysmal neck, and common iliac arteries (P < 0.001). On adjusted multivariate regression, there was no significant differences in thromboembolic events between clusters, although event rate was low (n = 31, 2.1%) (odds ratio 1.56, 95% confidence interval 0.71–3.43, P = 0.23).
Conclusion
Unsupervised machine learning can identify distinct aneurysm morphological phenotypes with significant thrombus burden difference, which exhibit sex imbalance. While thromboembolic events were infrequent and did not differ significantly between clusters, these anatomical phenotypes may provide a framework for future studies investigating embolic risk and sex-specific disease mechanisms
Automated retinal image analysis systems to triage for grading of diabetic retinopathy: a large-scale, open-label, national screening programme in England
Get PDFBACKGROUND: The global prevalence of diabetes is rising, alongside costs and workload associated with screening for diabetic eye disease (diabetic retinopathy). Automated retinal image analysis systems (ARIAS) could replace primary human grading of images for diabetic retinopathy. We evaluated multiple ARIAS in a real-life screening programme. METHODS: Eight of 25 invited and potentially eligible CE-marked systems for diabetic retinopathy detection from retinal images agreed to participate. From 202 886 screening encounters at the North East London Diabetic Eye Screening Programme (between Jan 1, 2021, and Dec 31, 2022) we curated a database of 1·2 million images and sociodemographic and grading data. Images were manually graded by up to three graders according to a standard national protocol. ARIAS performance overall and by subgroups of age, sex, ethnicity, and index of multiple deprivation (IMD) were assessed against the reference standard, defined as the final human grade in the worst eye for referable diabetic retinopathy (primary outcome). Vendor algorithms did not have access to human grading data. FINDINGS: Sensitivity across vendors ranged from 83·7% to 98·7% for referable diabetic retinopathy, from 96·7% to 99·8% for moderate-to-severe non-proliferative diabetic retinopathy, and from 95·8% to 99·5% for proliferative diabetic retinopathy. Sensitivity was largely consistent for moderate-to-severe non-proliferative and proliferative diabetic retinopathy by subgroups of age, sex, ethnicity, and IMD for all ARIAS. For mild-to-moderate non-proliferative diabetic retinopathy with referable maculopathy, sensitivity across vendors ranged from 79·5% to 98·3%, with greater variability across population subgroups. False positive rates for no observable diabetic retinopathy ranged from 4·3% to 61·4% and within vendors varied by 0·5 to 44 percentage points across population subgroups. INTERPRETATION: ARIAS showed high sensitivity for medium-risk and high-risk diabetic retinopathy in a real-world screening service, with equitable performance across population subgroups. ARIAS could provide a cost-effective solution to deal with the rising burden of screening for diabetic retinopathy by safely triaging for human grading, substantially increasing grading capacity and rapid diabetic retinopathy detection. FUNDING: NHS Transformation Directorate, The Health Foundation, and The Wellcome Trust
Barriers to reporting misconduct: exploring support and reporting systems in surgical training
Get PDFWhy do reports of harassment in surgery go unheard? New analysis shows systemic flaws in support and reporting structures that leave trainees vulnerable and silent
Risk of hospital admissions and death in patients with heart failure and chronic kidney disease: findings from a novel multidisciplinary clinic
Get PDFIntroduction:
Patients with heart failure (HF) and chronic kidney disease (CKD) are often sub-optimally treated due to concerns of hyperkalaemia, declining kidney function, and hypotension. They commonly suffer from fluid overload which can lead to frequent hospitalisations and death. This research aims to determine the characteristics associated with hospital admissions and death in patients with CKD and HF.
Methods:
Consecutive patients with CKD stage 3 to 5 and HF (regardless of ejection fraction) attending a large, specialised CKD-HF clinic between 12/Sept/2019 and 11/Nov/2021 were identified and data were collected on demographic factors, renal and heart function, medications, hospitalisations, and death. Multinomial and Cox regressions determined the characteristics of patients requiring hospitalisation and their risk of death, respectively.
Results:
A total of 667 admissions were attributable to 318 patients, 201 admissions were for HF. Men were less likely than women to have been admitted to hospital for HF (RR 0.43, 95% CI 0.20, 0.94) and non-HF causes (RR 0.21, 95% CI 0.10, 0.47). A serum haemoglobin level greater than 100 g/L was associated with fewer HF and non-HF admissions compared to a serum haemoglobin less than 100 g/L (RR 0.26, 95% CI 0.09, 0.74; RR 0.17, 95% CI 0.06, 0.47). Compared to CKD stage 3, CKD stage 4 was associated with an increased risk of HF and non-HF admissions (RR 4.01, 95% CI 1.04, 15.5; RR 4.33, 95% CI 1.13, 16.5). Having a HF admission (HR 2.41, 95% CI 1.27, 4.60), HFrEF (HR 2.18, 95% CI 1.30, 3.63)), CKD stage 4 (HR 1.91, 95% CI 1.16, 3.16), and loop diuretic use (HR 2.24, 95% CI 1.14, 4.40) were associated with a significantly increased risk of death compared to people with no admissions, with HFpEF, CKD stage 3, and no diuretic use, respectively. The use of RAAS inhibitors halved the risk of death compared to non-prescribed patients (HR 0.44, 95% CI 0.27, 0.72).
Conclusion:
Hospital admissions among CKD-HF patients were common, particularly in those with lower serum haemoglobin levels and advanced CKD stage. The risk of death was higher in those with HF admissions, the presence of HFrEF, advanced CKD stage, loop diuretic use, and those not prescribed RAAS inhibitors
Navigating vaccination in pregnancy: Qualitative study in 21 ethnically diverse pregnant women.
Get PDFBackgroundVaccination during pregnancy is crucial for safeguarding maternal and neonatal health, but vaccination rates remain suboptimal, especially in women from Black and Asian ethnic minorities. We explored the perspectives and decision-making processes of pregnant women regarding uptake of the three recommended vaccines in pregnancy: Influenza, Pertussis (whooping cough) and COVID-19. We also explored women's attitudes to taking part in vaccine trials during pregnancy and the use of artificial intelligence (AI) to obtain information on vaccines.MethodsIn 2023, we conducted in-depth telephone interviews with ethnically diverse pregnant women in the Greater London area using convenience and snowball sampling. The interviews focused on participants' views on vaccination during pregnancy, participation in vaccine trials, information-seeking behaviours, and attitudes to emerging technologies for health information. Interviews were transcribed verbatim and thematically analysed. The data collection and analysis were conducted alongside the iterative development of the topic guide and coding framework, with key themes emerging through collaborative team discussions.ResultsTwenty one pregnant women aged 20-39 were interviewed of whom 67% were from ethnic minorities and 29% were from migrant backgrounds. Half the participants (53%) reported hesitancy towards at least one of the vaccines. The analysis revealed several themes: concerns about vaccine safety, particularly regarding newer vaccines due to lack of long-term data; reliance on healthcare professionals for guidance, balanced with personal research; and a strong desire for clear and comprehensive information specifically tailored to pregnant women. Pregnant women reported insufficient information, explanation, or recommendation by midwives. Additionally, there was widespread refusal regarding participation in vaccine trials; and mixed responses to the use of AI (such as chatbots) for obtaining vaccine information.ConclusionsPregnant women's vaccination decisions are complex and require clear, unambiguous communication from healthcare providers, especially midwives, to address their specific concerns. Although information obtained via AI can be useful, responses were mixed
Community Perceptions of Neonatal Infection in Uganda
Get PDFBackground
We investigated awareness of neonatal infections among a population of pregnant women and other community members in Kampala, Uganda. We explored perceived causes of neonatal infections and perceptions of appropriate treatments.
Methods
We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with 97 participants: 25 community leaders who took part in 3 FGDs, 12 pregnant women who took part in IDIs, and 60 pregnant women who took part in 8 FGDs, between November 2019 and October 2020. Data were analyzed thematically. This work formed part of the PROGRESS study, an observational cohort study undertaken in Kampala, Uganda, between November 2018 and April 2021.
Results
Beliefs about causes, signs, symptoms, and treatment of infants with suspected infections impacted health-seeking behavior. Some illnesses were perceived to be caused by environmental factors while others were believed to have social or behavioral causes, such as the promiscuity of the male partner causing infections or the mother being bewitched. Local herbs and traditional remedies were the most preferred method of treatment and were commonly relied on to address various health issues rather than conventional medicines. Notably, no participant mentioned vaccines as a way of preventing infections.
Conclusions
Pregnant women and community members’ understanding of the causes and treatment of neonatal illnesses were diverse, including environmental, social–behavioral, and supernatural causes, while both conventional and traditional remedies were perceived as appropriate treatments and sought accordingly. Understanding community perceptions and practices around neonatal infections is key to improving neonatal health interventions and outcomes
Bloodstream Infections in Critical Care Units in England, April 2017 to March 2023: Results from the First Six Years of a National Surveillance Programme
Get PDFBackground: Patients in critical care units (CCUs) are at an increased risk of bloodstream infections (BSIs), which can be associated with central vascular catheters (CVCs). This study describes BSIs, CVC-BSIs, organism distribution, percentage of antimicrobial resistant (AMR) organisms, and case fatality rates (CFRs) over the first six years of a voluntary national CCU surveillance programme in England. Methods: Surveillance data on BSIs, CVCs, and bed-days between 04/2017 and 03/2023 for adult CCUs were linked to mortality and AMR data, and crude rates were calculated. Results: The rates of CCU-BSIs and CCU-CVC-BSIs were stable for the first three years (3.6 and 1.7 per 1000 bed-days in 2019/20), before increasing by 75% and 94% in 2020/21, respectively, and returning to near pre-pandemic levels by 2022/23. Gram-negative bacteria accounted for 50.3% of all CCU-BSIs, followed by Gram-positive bacteria (39.6%) and Candida spp. (8.6%). Klebsiella spp. saw increases in percentage AMR, whereas other organisms saw declines or similar levels. The overall CFR was 30.2%. Conclusions: BSI incidence in CCUs remained stable across the study period, except for an increase in 2020/21 which reverted by 2022/23. These data provide a benchmark for CCUs and give insight into long-term AMR patterns where comparable national data are limited
Developing a role for patients and the public in the implementation of health and social care research evidence into practice: the PIPER study (Pathways to Implementation for Public Engagement in Research) realist evaluation protocol
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While patients and the public are routinely involved as active collaborators in health and social care research, they are rarely involved in the implementation of research. The PIPER (Pathways to Implementation for Public Engagement in Research) research questions are:
1. How can patients, carers, service users and the public be involved in the implementation of health and social care research evidence into practice?
2. What types of roles, contributions and impact can patients, carers, service users and the public make to the implementation of health and social care evidence into practice?
3. How can we support patients, service users, carers and the public to contribute to the implementation of health and social care evidence into practice?
4. How can we co-produce the knowledge that explores a greater role for patients, carers, service users and the public in the implementation of health and social care evidence into practice?
Methods
Our overarching methodological framework is realist evaluation. This study includes four work packages with a cross-cutting co-production theme.
•Work Package 1: A realist review of published literature, grey literature and sources such as blogs.
•Work Package 2: Interviews with 40–60 people using a realist approach.
•Work Package 3: A series of workshops to co-design the PIPER Toolkit.
•Work Package 4: Pilot evaluation of the PIPER Toolkit.
Results
The scoping of the literature will be informed by the development of an initial programme theory that identifies the potential breadth of the field of public involvement in implementation. Data from the WP2 interviews will be used to iteratively refine the development of the context, mechanism and outcomes (CMOs). This will inform the PIPER Toolkit, which will consist of a set of ‘Guiding Principles’ supported by ‘Practical Resources.’ The PIPER Toolkit will enable an individual or a group to plan and undertake implementation activities. More specifically, the Guiding Principles will enable the Practical Resources to be tailored to specific implementation strategies for an individual or group.
Discussion
Patient and public involvement in implementation is an emerging area of practice and is likely to significantly strengthen over the next decade. The PIPER Toolkit will recognise this early stage of development, identifying the key system enablers that organisations need to have in place to support this activity. The Toolkit will support patients and the public and implementation teams to navigate the field of implementation practice. The PIPER study will challenge the field of implementation and knowledge mobilisation research to develop clearer forms of partnership with patients and the public in both research and practice
Novel start codon variant in the 5’UTR of LDLR associated with familial hypercholesterolaemia
Get PDFFamilial hypercholesterolaemia (FH) is a genetic disorder due to pathogenic variants in LDLR, APOB, and PCSK9 genes, characterised by elevated low-density lipoprotein cholesterol (LDL-C) concentration and a significantly increased risk of premature coronary heart disease. Annotating whole genome sequencing data of 536 FH patients using the VEP plugin UTRannotator, we identified a novel variant c.−35C > G in the 5’ untranslated region (5’UTR) of LDLR, predicted to introduce an upstream translation initiation codon and upstream open reading frame (uORF) that is out of frame with the LDLR coding sequence. Using promoter and epitope reporter assays, we demonstrate that the c.−35C > G variant leads to the preferential utilisation of the upstream AUG codon over the wild-type LDLR translation start site. We additionally conducted reporter assays for a previously reported variant that introduces a novel AUG codon through a deletion at position −22 of the 5’UTR (c.−22del) and obtained similar results. These findings confirm a novel type of FH-causing LDLR variants, leading to a premature start of translation and a truncation, underscoring the need for expanded genetic screening beyond coding regions. Future studies should focus on further characterising 5’UTR variants to better understand their role in FH
The budget impact analysis of nicotine replacement therapy among patients who smoke tobacco and have mental illness in South Africa and the implications.
Get PDFBackground
Tobacco use is the world's leading preventable cause of death, with the highest burden in low and middle-income countries (LMICs). Those who have mental illness are particularly vulnerable, with a smoking rate two to five times higher than that of the general population. Quitting smoking has demonstrated benefits for mental health, including reducing stress and improving the quality of life. However, the economic feasibility of introducing Nicotine Replacement Therapy (NRT) in the psychiatric medical environment in South Africa has not yet been explored. This study aims to address this gap by assessing the impact on the budget of implementing an NRT-based smoking cessation program in a psychiatric hospital.
Methods
This retrospective and cross-sectional study followed a budget impact analysis framework. Data were retrieved between May 19 and Aug 18, 2023, from 214 patients' medical records. Using primary and secondary data, an ingredients costing approach was used to estimate direct treatment costs of NRT smoking cessation. All costs were expressed in ZAR (South African currency). The economic evaluation was conducted from the payer's perspective, and the results were reported at a 5% discount rate. A two-way 10% sensitivity analysis was conducted.
Results
The study showed that study participants were primarily black, male, unemployed, diagnosed with schizophrenia and smoked lightly (69.16% ±3.46). Implementing the 3-month treatment period of NRT smoking cessation program would result in an expenditure of R1 478 915.42 for 214 patients. The hospital will require an additional 0.15% (±0.0095) of the total hospital budget and 6.09% (±0.31) of the hospital pharmacy budget.
Conclusion
Our findings indicate that while implementing a NRT is crucial for improving the overall health outcomes among patients with mental illnesses, substantial investment would be required. The budgetary allocation for NRT smoking cessation interventions would vary by treatment settings and program duration. Consequently, careful consideration of budget allocation and resource distribution is necessary to ensure the program's sustainability within the broader healthcare framework in South Africa
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