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AI to improve treatments for people with multiple long-term conditions

Written by Louise Stanley on . Posted in Health inequalities, Inflammation and chronic disease.

The NIHR has awarded £2.5 million for new artificial intelligence (AI) research led by the University of Birmingham. The study will use AI to produce computer programmes and tools to help doctors improve the choice of drugs for patients with clusters of multiple long-term conditions.

Called the OPTIMAL study (OPTIMising therapies, discovering therapeutic targets and AI assisted clinical management for patients Living with complex multimorbidity), the research aims to understand how different combinations of long-term conditions – and the medicines taken for these diseases – interact over time to worsen or improve a patient’s health.

The study will be led by Dr Thomas Jackson and Professor Krish Nirantharakumar at the University of Birmingham and carried out in collaboration with the University of Manchester, University Hospitals Birmingham NHS Foundation Trust, NHS Greater Glasgow & Clyde, University of St Andrews,and the Medicines and Healthcare Products Regulatory Agency. Both the University of Birmingham and University Hospitals Birmingham are founding members of BHP.

An estimated 14 million people in England are living with two or more long-term conditions, with two-thirds of adults aged over 65 expected to be living with multiple long-term conditions by 2035.

Dr Thomas Jackson, Associate Professor in Geriatric Medicine at the University of Birmingham, said: “Currently, when people have multiple long-term conditions, we treat each disease separately. This means we prescribe a different drug for each condition, which may not help people with complex multimorbidity, which is a term we use when patients have four or more long-term health problems.

“A drug for one disease can make another disease worse or better, however, presently we do not have information on the effect of one drug on a second disease. This means doctors do not have enough information to know which drug to prescribe to people with complex multimorbidity.”

Krish Nirantharakumar, Professor in Health Data Science and Public Health at the University of Birmingham, added: “Through our research, we can group such people based on their mixes of disease. Then we can study the effects of a drug on each disease mix. This should help doctors prescribe better and reduce the number of drugs patients need. This will lead to changes in healthcare policy which would benefit most people with complex multimorbidity.”

The research is one of a number of studies being funded by the NIHR’s Artificial Intelligence for Multiple Long-Term Conditions (AIM) call, which is aligned to the aims of the NHSX AI Lab, that combine data science and AI methods with health, care and social science expertise to identify new clusters of disease and understand how multiple long-term conditions develop over the life course.

The call will fund up to £23 million of research in two waves, supporting a pipeline of research and capacity building in multiple long-term conditions research. The first wave has invested nearly £12 million into three Research Collaborations, nine Development Awards and a Research Support Facility, including the University of Birmingham-led study.

Improving the lives of people with multiple long-term conditions and their carers through research is an area of strategic focus for the NIHR, with its ambitions set out in its NIHR Strategic Framework for Multiple Long-Term Conditions Research.

Professor Lucy Chappell, NIHR Chief Executive and chair of the AIM funding committee, said: “This large-scale investment in research will improve our understanding of clusters of multiple long-term conditions, including how they develop over a person’s lifetime.

“Over time, findings from this new research will point to solutions that might prevent or slow down the development of further conditions over time. We will also look at how we shape treatment and care to meet the needs of people with multiple long-term conditions and carers.”

To date NIHR has invested £11million into research on multiple long-term conditions through two calls in partnership with the Medical Research Council, offering both pump-priming funds and funding to tackle multimorbidity at scale.

illustration of the heart and EKG trace

AI identifies patients with heart failure that respond to beta-blocker treatment

Written by Louise Stanley on . Posted in Early diagnosis and detection, Health inequalities, Inflammation and chronic disease.

Researchers at BHP founder-member the University of Birmingham have developed a new way to identify which patients with heart failure will benefit from treatment with beta-blockers.

Heart failure is one of the most common heart conditions, with substantial impact on patient quality of life, and a major driver of hospital admissions and healthcare cost.

The study involved 15,669 patients with heart failure and reduced left ventricular ejection fraction (low function of the heart’s main pumping chamber), 12,823 of which were in normal heart rhythm and 2,837 of which had atrial fibrillation (AF) – a heart rhythm condition commonly associated with heart failure that leads to worse outcomes.

Published in The Lancet, the study used a series of artificial intelligence (AI) techniques to deeply interrogate data from clinical trials.

The research showed that the AI approach could take account of different underlying health conditions for each patient, as well as the interactions of these conditions to isolate response to beta-blocker therapy. This worked in patients with normal heart rhythm, where doctors would normally expect beta-blockers to reduce the risk of death, as well as in patients with AF where previous work has found a lack of effectiveness. In normal heart rhythm, a cluster of patients was identified with reduced benefit from beta-blockers (combination of older age, less severe symptoms and lower heart rate than average). Conversely in patients with AF, the research found a cluster of patients who had a substantial reduction in death with beta-blockers (from 15% to 9% in younger patients with lower rates of prior heart attack but similar heart function to the average AF patient).

The research was led by the cardAIc group, a multi-disciplinary team of clinical and data scientists at the University of Birmingham and fellow BHP founder-member University Hospitals Birmingham, aiming to integrate AI techniques to improve the care of cardiovascular patients. The study uses data collated and harmonized by the Beta-blockers in Heart Failure Collaborative Group, a global consortium dedicated to enhancing treatment for patients with heart failure.

First Author Dr Andreas Karwath, Rutherford Research Fellow at the University of Birmingham and member of the cardAIc group, added: “We hope these important research findings will be used to shape healthcare policy and improve treatment and outcomes for patients with heart failure.”

Corresponding author Georgios Gkoutos, Professor of Clinical Bioinformatics at the University of Birmingham, Associate Director of Health Data Research UK Midlands and co-lead for the cardAIc group, said: “Although tested in our research in trials of beta-blockers, these novel AI approaches have clear potential across the spectrum of therapies in heart failure, and across other cardiovascular and non-cardiovascular conditions.”

Corresponding author Dipak Kotecha, Professor & Consultant in Cardiology at the University of Birmingham, international lead for the Beta-blockers in Heart Failure Collaborative Group and co-lead for the cardAIc group, added: “Development of these new AI approaches is vital to improving the care we can give to our patients; in the future this could lead to personalised treatment for each individual patient, taking account of their particular health circumstances to improve their well-being.”

The research used individual patient data from nine landmark trials in heart failure that randomly assigned patients to either beta-blockers or a placebo. The average age of study participants was 65 years, and 24% were women. The AI-based approach combined neural network-based variational autoencoders and hierarchical clustering within an objective framework, and with detailed assessment of robustness and validation across all the trials.

The research was presented this week at the ESC Congress 2021, hosted by the European Society of Cardiology – a non-profit knowledge-based professional association that facilitates the improvement and harmonisation of standards of diagnosis and treatment of cardiovascular diseases.

nurse discusses bowel disease with a patient. plastic model of bowel in foreground.

New Birmingham-Roche collaboration targets new treatments for inflammatory bowel disease

Written by Louise Stanley on . Posted in Clinical trials, Inflammation and chronic disease.

A new £850k collaboration between Birmingham Health Partners (BHP) and global biotechnology leaders Roche is set to improve both diagnosis and care of patients with inflammatory bowel disease (IBD) by investigating promising biomarkers and inflammatory mechanisms in the search for new treatment targets.

IBD affects around 250,000 people in the UK in the form of ulcerative colitis and Crohn’s disease, and is characterised by an imbalance in gut bacteria which causes debilitating damage to the intestines.

Current treatments, which target the body’s immune response, are ineffective for the majority (around two-thirds) of patients, meaning many of them eventually have to undergo invasive surgery. These diseases affect mainly younger people of working age, and as the precise cause is not yet fully understood, there is a pressing need to identify non-surgical therapies which can improve quality of life.

As host to the largest IBD clinic in Europe, BHP founder-member University Hospitals Birmingham NHS Foundation Trust (UHB) will lead the new active translational research collaboration with Roche scientists, alongside BHP colleagues at the University of Birmingham’s Institute of Cardiovascular Sciences (ICVS) and Microbiome Treatment Centre. Newly-diagnosed IBD patients will be seen weekly at new clinics across sister UHB sites Queen Elizabeth Hospital Birmingham and Heartlands Hospital.

This unique patient cohort will provide invaluable biological samples taken before they begin treatment – allowing researchers to investigate biomarkers identified by Dr Asif Iqbal of ICVS. Dr Iqbal’s team will study disease pathology including the role of immune cells, the microbiome and metabolome in driving the various inflammatory mechanisms associated with IBD.

Professor Tariq Iqbal, Consultant Gastroenterologist at UHB and Director of the Microbiome Treatment Centre at the University of Birmingham explained: “IBD is an underfunded disease area and the potential benefits to patients which will arise as a result of this collaboration are likely to be lifechanging for many. Those participating in the trial will help build the first clinical resource of its kind from which we aim to promote earlier diagnosis and more effective treatments.

“Cross-discipline collaboration, facilitated by BHP, will be crucial in unlocking these advances as we tap in to expertise in specialties such as genomic sequencing as well as the University’s Microbiome Treatment Centre.”

Dr Asif Iqbal commented: “This project will demonstrate the power of combining basic science with translational clinical research for patient benefit. Through identifying targets in immune cells which drive this chronic inflammatory disease, we hope to develop a range of novel therapeutics.”

The collaborative research award of £844,163 from Roche funds two combined IBD projects from March 2021 to January 2023. UHB is aiming to recruit 60 patients to the study.

illustration of inflammation in the joint of the hand

Rheumatology Research Group awarded five year EULAR Centre of Excellence Status

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

The Rheumatology Research Group (RRG) at BHP founder-member the University of Birmingham has been awarded five-year EULAR Centre of Excellence status for the second time in a row.

EULAR (European League Against Rheumatism) represents people with arthritis/rheumatism as well as health professionals in rheumatology and scientific societies across Europe.

The application reflects extensive collaboration across rheumatology departments at the University of Birmingham, Sandwell and West Birmingham NHS Trust and fellow BHP member University Hospitals Birmingham NHS Foundation Trust. The RRG was first awarded Centre of Excellence status in 2016.

Professor Karim Raza, RRG lead said, “The whole of the Birmingham Rheumatology Research Group is immensely proud that our EULAR Centre of Excellence has been renewed. This award is testament to the outstanding research carried out in Birmingham in the fields of rheumatoid arthritis, systemic lupus erythematosus and Sjögren’s syndrome with research programmes spanning the full spectrum from discovery science to experimental medicine to applied health research. Collaboration with other EULAR centres of excellence in the UK and across mainland Europe has been critical to our ability to deliver high quality Rheumatology research and we look forward to continuing and expanding those collaborations.”

The Centre of Excellence status will be valid until June 2026.

New study aims to improve healthcare for pregnant women with multiple health conditions

Written by Louise Stanley on . Posted in Health inequalities, Inflammation and chronic disease, Maternal health, Mental health.

BHP founder-member the University of Birmingham is leading a new three-year UK-wide study aimed at improving healthcare and outcomes for pregnant women who have two or more active long-term health conditions.

Currently, one in five pregnant women in the UK have two or more active long-term health conditions. These can be both physical conditions (like diabetes or raised blood pressure), and mental health conditions (such as depression or anxiety). Often women also have to take several medications to manage their different health needs.

The new study, called Multimorbidity and Pregnancy: Determinants, Clusters, Consequences and Trajectories (MuM-PreDiCT), aims to use data-driven research to characterise and understand what makes having two or more long-term conditions more likely for pregnant women and the consequences for mother and child; and to predict and prevent adverse outcomes.

MuM-PreDiCT will be divided into five research work packages:

      1. Examining how health conditions accumulate over time and identifying what makes a woman more at risk of developing two or more long-term health conditions before pregnancy.
      2. Exploring women’s experiences of care during pregnancy, birth and after birth, working together with families and health professionals to establish how care could be improved.
      3. Deeper delve into how having two or more long-term health conditions may affect pregnant women and their children by identifying outcomes that women, health professionals and researchers feel should be reported in research; examining how often women experience pregnancy complications; and exploring how frequently women and their children develop additional long-term ill health
      4. Investigating how taking combinations of medication may affect pregnant women with two or more long-term health conditions and their babies.
      5. Building a prediction model to help identify how likely a previously healthy pregnant woman will develop multiple long-term conditions after pregnancy.

Professor Krish Nirantharakumar, of the University of Birmingham’s Institute of Applied Health Research and Principal Investigator of MuM-PreDiCT, said: “Having two or more health conditions is becoming more common in pregnant women as women are increasingly older when they start having a family and as obesity and mental health conditions are on the rise in general.

“However, we don’t really understand what the consequences are of multiple health conditions or medications for mothers and babies.

“This can make pregnancy, healthcare and managing medications more complicated. Without deeper understanding of the problem, women with several long-term health conditions may not have the best and safest experience of care before, during and after pregnancy because services have not been designed with their health needs in mind.”

Dr Beck Taylor, Clinical Senior Lecturer at the University of Birmingham and Co-Investigator of MuM-PreDiCT, said: “Our research will provide valuable information to help women and clinicians make informed decisions and identify points for prevention and intervention. We will also explore the experiences of maternity care for women with two or more long-term conditions and work with families and health and social care professionals to produce recommendations on how to plan and design services that meet the needs of women and their families before, during and after pregnancy.”

MuM-PreDiCT is being funded via the £20M UK Research and Innovation’s (UKRI) Strategic Priorities Fund (SPF) initiative ‘Tackling multi-morbidity at scale: Understanding disease clusters, determinants & biological pathways’. SPF is delivered by the Medical Research Council and National Institute for Health Research in partnership with the Economic and Social Research Council, and in collaboration with the Engineering and Physical Sciences Research Council. It is jointly funded by UKRI and the Department of Health and Social Care, through the NIHR.

MuM-PreDiCT is being led by the University of Birmingham in collaboration with the University of Aberdeen, University of St Andrews, Swansea University, Queen’s University of Belfast, University of Ulster, The University of Manchester, Keele University, University Hospitals Bristol & Weston NHS Foundation Trust, Bradford Teaching Hospitals NHS Foundation Trust, and Guy’s & St Thomas’ NHS Foundation Trust.

Siang Ing Lee, Academic Clinical Fellow at the University of Birmingham and MuM-PreDiCT, added: “We would like to extend our heartfelt gratitude to our amazing patient and public involvement (PPI) advisory group and PPI co-investigators who will play an integral part in MuM-PreDiCT.”

a mother and daughter select healthy foods from a selection of fruits and grains

Increased risk of chronic kidney disease in people with ‘healthy’ obesity

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

People with ‘healthy’ obesity have a 66% increased risk of chronic kidney disease compared to metabolically healthy individuals with normal weight, finds a new study led by the University of Birmingham.

Those that are metabolically healthy (do not suffer with metabolic conditions such as hypertension, diabetes, high cholesterol or cardiovascular disease) and are overweight but do not have obesity are at a 30% risk of chronic kidney disease compared to healthy people with normal weight, the study found.

The research also found that the increased risk was greater in those aged under 65, while also the more the number of the metabolic complications a person has the higher risk of chronic kidney disease even in the normal weight range.

The research, published in the American Journal of Kidney Disease, was carried out in collaboration with University Hospitals Birmingham NHS Foundation Trust and the University of Warwick.

The retrospective population-based cohort study examined the GP records of around 4.5 million individuals from the UK and tracked their health over an average of almost five-and-a-half-years. Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) were metabolically healthy overweight and metabolically healthy obese, respectively.

Chronic kidney disease has a major impact on global health and cost the UK National Health Service £1.45 billion in 2009-2010. In 2017, 697.5 million people in the world had the disease, and it accounted for 1.2 million deaths. The prevalence of chronic kidney disease increased by almost 30% between 1990 and 2017, while the number of deaths caused by the condition rose by 41.5% in the same period. Similarly, the prevalence of obesity is also on the rise, tripling between 1975 and 2016.

First author Dr Jingya Wang, Research Fellow at the University of Birmingham, said: “Our results demonstrate that individuals with metabolically healthy obesity might have a higher risk of developing chronic kidney disease compared with normal weight individuals, especially those younger than 65 years.

“Looking to the future, a clinical trial of a weight loss intervention could be considered in these individuals to help us establish whether this can reduce their high risk of chronic kidney disease.”

Dr Abd Tahrani, Senior Lecturer in Metabolic Endocrinology and Obesity Medicine at the University of Birmingham, says: “It is likely that weight loss in people with metabolically healthy obesity is likely to reduce their risk of chronic kidney disease as it will also reduce their risk of future type 2 diabetes, and hypertension, both of which can worsen kidney function and result in chronic kidney disease, however this needs to be examined in future trials.

“In addition, we know from previous trials that weight loss in individuals with normal weight can reverse non-alcoholic fatty liver disease for example, hence weight loss could offer an important strategy to prevent obesity complications in this population.”

Dr Krish Nirantharakumar, also of the University of Birmingham, said: “Furthermore, our results suggest that individuals with normal weight who have metabolic abnormalities are also at a higher risk of chronic kidney disease and as such might benefit from meticulous metabolic control to reduce the risk of developing the condition.

“Ultimately, chronic kidney disease is largely preventable, and therefore, it is important to identify and treat the underlying modifiable causes and risk factors.”

This new study follows previous research led by the University of Birmingham and published in 2017 in the Journal of the American College of Cardiology which showed that individuals living with obesity who are metabolically healthy have an increased risk of cardiovascular disease events compared to those who are normal weight without metabolic abnormalities.

Neil Thomas, Professor in Epidemiology and Research Methods at the University of Birmingham, adds: “This new study and our previously published study together demonstrate that individuals who are metabolically healthy can develop organ damage over time.

“Therefore, metabolically healthy obesity should not be considered ‘benign’ or harmless and addressing obesity in metabolically health people might reduce organ damage including chronic kidney disease.”