Convolutional Neural Networks for Diabetic Retinopathy

The diagnosis of diabetic retinopathy (DR) through colour fundus images requires experienced clinicians to identify the presence and significance of many small features which, along with a complex grading system, makes this a difficult and time consuming task. In this paper, we propose a CNN approach to diagnosing DR from digital fundus images and accurately classifying its severity. We develop a network with CNN architecture and data augmentation which can identify the intricate features involved in the classification task such as micro-aneurysms, exudate and haemorrhages on the retina and consequently provide a diagnosis automatically and without user input. We train this network using a high-end graphics processor unit (GPU) on the publicly available Kaggle dataset and demonstrate impressive results, particularly for a high-level classification task. On the dat

Safety and cost-effectiveness of individualised screening for diabetic retinopathy: the ISDR open-label, equivalence RCT

Aims/hypothesis Using variable diabetic retinopathy screening intervals, informed by personal risk levels, offers improved engagement of people with diabetes and reallocation of resources to high-risk groups, while addressing the increasing prevalence of diabetes. However, safety data on extending screening intervals are minimal. The aim of this study was to evaluate the safety and cost-effectiveness of individualised, variable-interval, risk-based population screening compared with usual care, with wide ranging input from individuals with diabetes. Methods This was a two-arm, parallel-assignment, equivalence RCT (minimum 2 year follow-up) in individuals with diabetes aged 12 years or older registered with a single English screening programme. Participants were randomly allocated 1:1 at baseline to individualised screening at 6, 12 or 24 months for those at high, medium and low risk, respectively, as determined at each screening episode by a risk-calculation engine using local demographic, screening and clinical data, or to annual screening (control group). Screening staff and investigators were observer-masked to allocation and interval. Data were collected within the screening programme. The primary outcome was attendance (safety). A secondary safety outcome was the development of sight-threatening diabetic retinopathy. Cost-effectiveness was evaluated within a 2 year time horizon from National Health Service and societal perspectives. Results A total of 4534 participants were randomised. After withdrawals, there were 2097 participants in the individualised screening arm and 2224 in the control arm. Attendance rates at first follow-up were equivalent between the two arms (individualised screening 83.6%; control arm 84.7%; difference −1.0 [95% CI −3.2, 1.2]), while sight-threatening diabetic retinopathy detection rates were non inferior in the individualised screening arm (individualised screening 1.4%, control arm 1.7%; difference −0.3 [95% CI −1.1, 0.5]). Sensitivity analyses confirmed these findings. No important adverse events were observed. Mean differences in complete case quality adjusted life-years (EuroQol Five-Dimension Questionnaire, Health Utilities Index Mark 3) did not significantly differ from zero

Safety, Efficacy and Cost Effectiveness of Individualised Screening for Diabetic Retinopathy: The ISDR Randomised Controlled Trial

Background: varying diabetic retinopathy (DR) screening intervals, informed by personal risk-levels, empowers people with diabetes (PWD), and offers reallocation of resources to high risk groups, while addressing the increasing prevalence of diabetes. Safety data on extending intervals is minimal. We evaluated the safety, efficacy and cost effectiveness of individualised risk-based variable-interval population screening compared to usual care, with design input from PWD.Methods: two-arm, parallel assignment, equivalence randomised controlled trial (minimum 2 year follow-up) in PWD aged ≥12 years registered with one English screening programme. Randomisation was 1:1 to individualised screening (6, 12 or 24 months for high, medium and low risk) determined by a risk calculation engine, using local demographic, screening and clinical data, or to annual screening (control). Primary outcome was attendance (safety). A secondary safety outcome was the development of sight threatening DR (STDR). Cost effectiveness was evaluated within a 2 year time horizon from NHS and societal perspectives.Findings: 4534 participants were randomised, 2265 to the individualised and 2269 to the control arm. Attendance rates at first follow-up were equivalent between individualised (1754/2097, 83·6%) and control (1883/2224, 84·7%) arms (difference -1·0, 95% CI -3·2 to 1·2). STDR detection rates were non-inferior: individualised 1·4%, control 1·7% (- 0·3, -1·1 to 0·5). Sensitivity analyses confirmed findings. Incremental QALYs/person were non-significant: EQ-5D-5L 0·035 (CI -0·04, 0·13), HUI3 0·009 (CI -0·09, 0·10). Incremental cost savings were £21·31 (CI 15·24, 26·79)/person for the NHS and £28·87 (CI 21·08, 35·78) including societal costs. 43·2% fewer screening appointments were required in the individualised arm.Interpretation: stakeholders involved in diabetes care can be reassured by this largest ophthalmic RCT in DR screening to date that extended and individualised risk-based intervals can be safely and cost effectively introduced in established screening programmes

Incidence of sight-threatening diabetic retinopathy in an established urban screening programme: An 11-year cohort study

Aims: systematic annual screening to detect sight-threatening diabetic retinopathy (STDR) is established in the United Kingdom. We designed an observational cohort study to provide up-to-date data for policy makers and clinical researchers on incidence of key screening endpoints in people with diabetes attending one screening programme running for over 30 years.Methods: all people with diabetes aged ≥12 years registered with general practices in the Liverpool health district were offered inclusion. Data sources comprised: primary care (demographics, systemic risk factors), Liverpool Diabetes Eye Screening Programme (retinopathy grading), Hospital Eye Services (slit lamp biomicroscopy assessment of screen positives).Results: 133,366 screening episodes occurred in 28,384 people over 11 years. Overall incidences were: screen positive 6.7% (95% CI 6.5–6.8), screen positive for retinopathy 3.1% (3.0–3.1), unassessable images 2.6% (2.5–2.7), other significant eye diseases 1.0% (1.0–1.1). 1.6% (1.6–1.7) had sight-threatening retinopathy confirmed by slit lamp biomicroscopy. The annual incidence of screen positive and screen positive for retinopathy showed consistent declines from 8.8%–10.6% and 4.4%–4.6% in 2007/09 to 4.4%–6.8% and 2.3%–2.9% in 2013/17, respectively. Rates of STDR (true positive) were consistently below 2% after 2008/09. Screen positive rates were higher in first time attenders (9.9% [9.4–10.2] vs. 6.1% [6.0–6.2]) in part due to ungradeable images (4.1% vs. 2.3%) and other eye disease (2.4% vs. 0.8%). 4.5% (3.9–5.2) of previous non-attenders had sight-threatening retinopathy. Compared with people with type 2 diabetes, those with type 1 disease demonstrated higher rates of screen positive (11.9% vs. 6.0%) and STDR (6.4% vs. 1.2%). Overall prevalence of any retinopathy was 27.2% (27.0–27.4).Conclusions: in an established screening programme with a stable population screen, positive rates show a consistent fall over time to a low level. Of those who are screen positive, fewer than 50% are screen positive for diabetic retinopathy. Most are due to sight threatening maculopathy. The annual incidence of STDR is under 2% suggesting future work on redefining screen positive and supporting extended intervals for people at low risk. Higher rates of screen positive and STDR are seen in first time attenders. Those who have never attended for screening should be specifically targeted.</p

Individualised screening for diabetic retinopathy: the ISDR study—rationale, design and methodology for a randomised controlled trial comparing annual and individualised risk-based variable-interval screening

Introduction Currently, all people with diabetes (PWD) aged 12 years and over in the UK are invited for screening for diabetic retinopathy (DR) annually. Resources are not increasing despite a 5% increase in the numbers of PWD nationwide each year. We describe the rationale, design and methodology for a randomised controlled trial (RCT) evaluating the safety, acceptability and cost-effectiveness of personalised variable-interval risk-based screening for DR. This is the first randomised trial of personalised screening for DR and the largest ophthalmic RCT in the UK. Methods and analysis PWD attending seven screening clinics in the Liverpool Diabetic Eye Screening Programme were recruited into a single site RCT with a 1:1 allocation to individualised risk-based variable-interval or annual screening intervals. A risk calculation engine developed for the trial estimates the probability that an individual will develop referable disease (screen positive DR) within the next 6, 12 or 24 months using demographic, retinopathy and systemic risk factor data from primary care and screening programme records. Dynamic, secure, real-time data connections have been developed. The primary outcome is attendance for follow-up screening. We will test for equivalence in attendance rates between the two arms. Secondary outcomes are rates and severity of DR, visual outcomes, cost-effectiveness and health-related quality of life. The required sample size was 4460 PWD. Recruitment is complete, and the trial is in follow-up. Ethics and dissemination Ethical approval was obtained from National Research Ethics Service Committee North West – Preston, reference 14/NW/0034. Results will be presented at international meetings and published in peer-reviewed journals. This pragmatic RCT will inform screening policy in the UK and elsewhere. Trial registration number ISRCTN87561257; Pre-results

Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

© 2018 The Author(s). Background: To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. Methods: We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged =45 years and have experienced knee pain =4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. Discussion: This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001595303, date of registration 1/12/2017

Individualised variable-interval risk-based screening for sight-threatening diabetic retinopathy: the Liverpool Risk Calculation Engine

Aims/hypothesis Individualised variable-interval risk-based screening offers better targeting and improved cost-effectiveness in screening for diabetic retinopathy. We developed a generalisable risk calculation engine (RCE) to assign personalised intervals linked to local population characteristics, and explored differences in assignment compared with current practice. Methods Data from 5 years of photographic screening and primary care for people with diabetes, screen negative at the first of > 1 episode, were combined in a purpose-built near-real-time warehouse. Covariates were selected from a dataset created using mixed qualitative/quantitative methods. Markov modelling predicted progression to screen-positive (referable diabetic retinopathy) against the local cohort history. Retinopathy grade informed baseline risk and multiple imputation dealt with missing data. Acceptable intervals (6, 12, 24 months) and risk threshold (2.5%) were established with patients and professional end users. Results Data were from 11,806 people with diabetes (46,525 episodes, 388 screen-positive). Covariates with sufficient predictive value were: duration of known disease, HbA1c, age, systolic BP and total cholesterol. Corrected AUC (95% CIs) were: 6 months 0.88 (0.83, 0.93), 12 months 0.90 (0.87, 0.93) and 24 months 0.91 (0.87, 0.94). Sensitivities/specificities for a 2.5% risk were: 6 months 0.61, 0.93, 12 months 0.67, 0.90 and 24 months 0.82, 0.81. Implementing individualised RCE-based intervals would reduce the proportion of people becoming screen-positive before the allocated screening date by > 50% and the number of episodes by 30%. Conclusions/interpretation The Liverpool RCE shows sufficient performance for a local introduction into practice before wider implementation, subject to external validation. This approach offers potential enhancements of screening in improved local applicability, targeting and cost-effectiveness

The number of tree species on Earth

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global groundsourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are 73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness

Native diversity buffers against severity of non-native tree invasions

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species$^{1,2}$. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies$^{3,4}$. Here, leveraging global tree databases$^{5,6,7}$, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions