The DynAIRx Project Protocol: Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity.

Background: Structured Medication Reviews (SMRs) are intended to help deliver the NHS Long Term Plan for medicines optimisation in people living with multiple long-term conditions and polypharmacy. It is challenging to gather the information needed for these reviews due to poor integration of health records across providers and there is little guidance on how to identify those patients most urgently requiring review. Objective: To extract information from scattered clinical records on how health and medications change over time, apply interpretable artificial intelligence (AI) approaches to predict risks of poor outcomes and overlay this information on care records to inform SMRs. We will pilot this approach in primary care prescribing audit and feedback systems, and co-design future medicines optimisation decision support systems. Design: DynAIRx will target potentially problematic polypharmacy in three key multimorbidity groups, namely, people with (a) mental and physical health problems, (b) four or more long-term conditions taking ten or more drugs and (c) older age and frailty. Structured clinical data will be drawn from integrated care records (general practice, hospital, and social care) covering an ∼11m population supplemented with Natural Language Processing (NLP) of unstructured clinical text. AI systems will be trained to identify patterns of conditions, medications, tests, and clinical contacts preceding adverse events in order to identify individuals who might benefit most from an SMR. Discussion: By implementing and evaluating an AI-augmented visualisation of care records in an existing prescribing audit and feedback system we will create a learning system for medicines optimisation, co-designed throughout with end-users and patients.

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; multiple imputation supported the dominance of individualised screening. Incremental cost savings per person with individualised screening were £17.34 (95% CI 17.02, 17.67) from the National Health Service perspective and £23.11 (95% CI 22.73, 23.53) from the societal perspective, representing a 21% reduction in overall programme costs. Overall, 43.2% fewer screening appointments were required in the individualised arm. CONCLUSIONS/INTERPRETATION: Stakeholders involved in diabetes care can be reassured by this study, which is the largest ophthalmic RCT in diabetic retinopathy screening to date, that extended and individualised, variable-interval, risk-based screening is feasible and can be safely and cost-effectively introduced in established systematic programmes. Because of the 2 year time horizon of the trial and the long time frame of the disease, robust monitoring of attendance and retinopathy rates should be included in any future implementation. TRIAL REGISTRATION: ISRCTN 87561257 FUNDING: The study was funded by the UK National Institute for Health Research. Graphical abstract.

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.

Patient factors associated with duration of certified sickness absence and transition to long-term incapacity.

BACKGROUND: Despite a considerable increase in claims for long-term sickness benefits, and the impact of certifying sickness upon general practitioner (GP) workload, little is known about transition to long-term incapacity for work. AIM: To explore the relationship between patient factors and the transition from short-term to long-term work incapacity, in particular focusing on mild mental health and musculoskeletal problems. SETTING: Nine practices comprising the Mersey Primary Care R&D Consortium. DESIGN: Prospective data collection and audit of sickness certificate details. METHOD: GPs issued carbonised sickness certificates for a period of 12 months. The resulting baseline dataset included claimant diagnosis, age, sex, postcode-derived deprivation score, and sickness episode duration. Associations of patient factors with sickness duration outcomes were tested. RESULTS: Mild mental disorder accounted for nearly 40% of certified sickness. Relatively few claimants had their diagnosis changed during a sickness episode. Risk factors for longer-term incapacity included increasing age, social deprivation, mild and severe mental disorder, neoplasm, and congenital illness. For mild mental disorder claimants, age, addiction, and deprivation were risk factors for relatively longer incapacity. For musculoskeletal problems, the development of chronic incapacity was significantly related to the nature of the problem. Back pain claimants were likely to return to work sooner than those with other musculoskeletal problems. CONCLUSIONS: In addition to the presenting diagnosis, a range of factors is associated with the development of chronic incapacity for work, including age and social deprivation. GPs should consider these when negotiating sickness certification with patients.