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Funding boost to research multimorbidity in hospital patients

Scientists have been given almost £4m to improve understanding of multimorbidity in hospital patients.

Research led by Newcastle University will focus on multiple long-term conditions in hospitalised patients and is funded by the Medical Research Council (MRC) and National Institute for Health Research (NIHR).

The four-year ADMISSION study aims to transform understanding of how different long-term conditions cluster or group together, why people are affected more often by some groups of conditions than others, and how hospital systems look after them.

NHS pressures

The number of people who have more than one long-term health condition, known as multimorbidity, is growing. This is increasing pressure on healthcare providers, such as the NHS, as these patients have complex needs – often staying in hospital for longer and taking more time to recover.

However, hospital systems are designed to treat single health conditions. Patients with multimorbidity often find their care is inefficient and unsatisfactory. For providers, this inefficiency translates into more costly care and potentially worse outcomes.

To find new ways to deliver hospital care, experts want to understand how long-term health conditions develop, and why particular conditions occur in groups.

Despite the recognised importance of multimorbidity in hospital patients, there has been little research in this area to date.

Professor Miles Witham, Deputy Lead for NIHR Newcastle BRC’s Ageing Syndromes theme, is co-investigator of the ADMISSION study.

He said: “We are delighted to have received this substantial award from the MRC and NIHR to fund our research.

“The results of ADMISSION will provide a springboard for developing, testing and delivering novel approaches to transform care for people with multiple long-term conditions before, during and after admission to hospital.”

ADMISSION will use cutting-edge data science, computing and statistical approaches to analyse ‘big data’ from routinely-collected healthcare records, along with information from the UK Biobank and the Scottish Health Research Register (SHARE).

Its focus will be on clusters of conditions: to describe how they occur across the population, to understand the mechanisms that explain them, and to examine their impact on patient pathways through healthcare.

Future care

This knowledge will inform the design of future care and treatments, with potential both to reduce costs, and to improve health outcomes for the millions of patients with multimorbidity admitted to hospital each year.

Newcastle University is leading the study, collaborating with Newcastle Hospitals NHS Foundation Trust, University of Birmingham, Manchester Metropolitan University, University College London and the University of Dundee.

Professor Liz Sapey, Professor of Acute and Respiratory Medicine at BHP founder-member the University of Birmingham, said: “As a doctor working in acute medicine, I see many people admitted with multiple long-term conditions.

“Currently, we do not understand how and why some illnesses cluster together, and so do not know the best ways to care for these patients.

“Our expertise in using ‘big data’ from patient records through our PIONEER Health Data Hub here in Birmingham forms an important part of the ADMISSION programme.

“Describing how these illnesses cluster together, as part of the ADMISSION collaborative, is a crucial first step to improving care for patients with multiple long-term conditions.”

For more information, visit: www.admissioncollab.org

Clinical trial confirms digoxin is effective for treatment of atrial fibrillation

A clinical trial has shown that digoxin has the same effect on physical wellbeing as beta-blockers when used to treat patients with permanent atrial fibrillation and symptoms of heart failure.

Beta-blockers have long been the drug of choice for controlling rapid heart rates in patients with atrial fibrillation (AF), but a clinical trial led by Professor Dipak Kotecha of Birmingham Health Partners has shown that digoxin is just as effective, but with less adverse effects.

The ‘Rate Control Therapy Evaluation in Permanent Atrial Fibrillation’ (RATE-AF) trial was the first of its kind to compare the effectiveness of digoxin and beta-blockers to treat AF. Beta-blockers, such as bisoprolol, are one of the most common groups of drugs used in clinical practice to reduce heart rate and improve pump function. Digoxin primarily works to slowly improve the contraction of the heart but also has other broad range effects which at low-dose can potentially be helpful to counter the body’s response to AF and heart strain, and is usually only used when other treatments are unsuccessful.

The RATE-AF trial showed there was no difference in physical wellbeing between digoxin and beta-blockers and there was no difference in the effect on long-term heart rate between the two drugs. Importantly, digoxin at low dose was found to cause substantially and significantly less adverse effects than beta-blockers, lessened the impact of AF on the daily lives of patients by improving symptoms, and reduced a marker of heart strain, natriuretic peptide.

AF is caused by disorganised electrical impulses firing from different places in the top chambers of the heart and patients usually require medication to control an irregular heartbeat. Patients can also have a reduced quality of life, be admitted to hospital more frequently and have a higher chance of strokes and heart failure.  This trial, embedded in the NHS, involved 160 patients aged 60 or older. It has addressed a major evidence gap in the management of patients with permanent atrial fibrillation. The research team will plan a larger trial to see if digoxin can reduce hospital admissions in this patient group.

Chief Investigator Professor Kotecha said: “I hope that the results of this trial show the importance of randomised clinical trials to see how treatments actually work. On behalf of the research team and all the patients who designed and took part in the RATE-AF trial, we are delighted to show that digoxin is a drug that can be used to improve the lives of patients with AF.”

The trial was publicly funded by the National Institute for Health Research (NIHR). RATE-AF was coordinated by the Institute of Cardiovascular Sciences at BHP founder member the University of Birmingham, a Patient & Public Involvement Team and the Birmingham Clinical Trials Unit. Patients and staff involved in the trial were from BHP founder member University Hospitals Birmingham NHS Foundation Trust as well as Sandwell and West Birmingham Hospitals NHS Trust and local General Practitioners.

‘Weak’ and ‘strong’ cells bonding boosts body’s diabetes fight

Scientists have broadened our understanding of how ‘weak’ cells bond with their more mature cellular counterparts to boost the body’s production of insulin – improving our knowledge of the processes leading to type 2 diabetes.

Type 2 diabetes mellitus occurs when β-cells cannot release enough insulin – a tightly controlled process requiring hundreds of such cells clustered together to co-ordinate their response to signals from food, such as sugar, fat and gut hormones.

An international research team – led by scientists at BHP founder-member the University of Birmingham – have discovered that immature β-cells (PDX1LOW/MAFALOW) are able to overcome their relative deficiencies by partnering with ‘stronger’ counterparts to drive insulin release.

Publishing their findings in Nature Communications, the researchers reveal that subtle differences in the levels of PDX1 and MAFA proteins (found only in β-cells) , and more broadly, differences in β-cell maturity, contribute to how clusters of insulin-producing cells, known as islets, function.

The corresponding author David Hodson, Professor of Cellular Metabolism, at the University of Birmingham, commented: “Our research shows that differences in β-cell maturity, defined using PDX1 and MAFA levels, are needed across the islet for proper insulin release. Unexpectedly, increases in the proportion of mature β-cells, is associated with islet failure. It seems that, rather like society, the islet needs cells with all ages to be properly functional.

“Redressing the balance between immature and mature β-cells restores islet function under conditions of metabolic stress – an excess of sugar and fat in the diet – providing evidence that both ’weak’ and ‘strong’ β-cells could contribute to proper islet function and insulin release.”

“This is the first glimpse that immature cells might contribute to the regulation of insulin release across the islet. Our study indicates a promising line of investigation that could be leveraged to make islets more resilient during type 2 diabetes or when generating new islets in a ‘dish’ for the purpose of transplantation.”

Normally, mature and immature β-cells co-exist within the adult islet and can be grouped into subpopulations according to differences in their levels of specific genes and proteins. Immature β-cells are generally considered to be poorly functional when viewed alone, as single cells.

Researchers found that islets containing proportionally more PDX1HIGH and MAFAHIGH β-cells showed defects in cell function (metabolism, ionic fluxes and insulin secretion). The team believes maintaining a mix of ‘strong’ and ‘weak’ β-cells is important for effective insulin production.