More than half of people over 65 live with multiple long-term health conditions. Studying multiple conditions is complex. Many trials focus on single health conditions, and people with multiple conditions are often excluded. This means that clinical guidance focuses on single conditions with little guidance for people with multiple long-term conditions.
This project investigates possible links between long-term conditions to try to understand causes and health impacts. We hope this will help to understand why conditions occur in the same person and why some people have worse outcomes than others. It might also help to find new potential treatments.
We have organised patient and public involvement and engagement workshops. These workshops will focus on prioritizing pairs of conditions that are often experienced together. We will look at these pairs of conditions to explore shared risk factors, genetics, and how having both conditions affect a person's health. We will also examine what puts individuals at risk of developing the second condition if they already have one. The insights gained from these workshops will help us determine important outcomes for each pair of conditions.
The results of our work will help healthcare providers better understand the risks associated with developing multiple long-term conditions. This would also prompt future clinical trials for medicines already in use for one condition that might help to improve patient outcomes for different conditions.
GEMINI (Genetic Evaluation of Multimorbidity towards INdividualisation of Interventions) is a large, multicentre international research project funded by the Medical Research Council (MR/W014548/1) to study people living with multiple long-term conditions (MLTC). GEMINI focuses on elucidating shared mechanisms of disease progression to improve patient outcomes. We aim to combine genetic and epidemiological approaches with large-scale data to understand the risks and health outcomes of developing specific pairs of long-term conditions (LTC). We hypothesise that unrecognised combinations of conditions arise due to shared biological pathways and that these can be discovered and characterised using combined epidemiological and genetic approaches.
The CPRD analysis aims to investigate shared risk factors associated with commonly co-occurring conditions with shared genetic heritability and the impact of specific co-existing LTCs on mortality, hospitalisation, and disability. Other health outcomes will be informed by our workshops with patients with lived experience of the conditions as well as by clinicians.
In CPRD AURUM, we will investigate the most prevalent co-existing conditions using logistic regression for a cross-sectional analysis of LTC pairs in those over 65. We will investigate the progression of groups of individuals with pairs of LTCs from pre-diagnosis to death, analysing risk factors for onset and clinical prognosis. We will investigate longitudinal health outcomes, co-developed in PPIE and clinician workshops, in individuals over 40 for the most prevalent LTC pairs. We will use binomial conditional logistic regression to define risk factors common to both conditions and Fine and Gray survival analysis to investigate the effect of having both conditions on outcomes, including mortality and hospitalisation.
Overall, GEMINI will expand knowledge on common combinations of causally related LTCs, defining shared targets and mechanisms for improved therapeutic management. Knowledge of causally related conditions will point to new pathways and paradigms of care, potentially reducing polypharmacy and informing personalised treatment approaches.
Common Disease Pairs; All Cause Hospitalisation; All-Cause Mortality; Falls; Fractures; Frailty; Charlson Comorbidity Score; Disability dichotomised from Activities of Daily Living assessment; Pneumonia; Sepsis; UTI; Care home admission; Pain medications; potentially Inappropriate prescribing; Exacerbation within Common disease pairs.
Timothy Frayling - Chief Investigator - University of Exeter
Joao Delgado - Corresponding Applicant - University of Exeter
Chris Fox - Collaborator - University of East Anglia
David Melzer - Collaborator - University of Exeter
Jane Masoli - Collaborator - University of Exeter
Luke Pilling - Collaborator - University of Exeter
Olivia Murrin - Collaborator - University of Exeter
Sara Khalid - Collaborator - University of Oxford
Sarah Lamb - Collaborator - University of Exeter
Seyed Alireza Hasheminasab - Collaborator - University of Oxford
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation