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Author: Louise Stanley

Clinical trial confirms digoxin is effective for treatment of atrial fibrillation

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

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

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

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.

Birmingham secures National Training Centre for the Advanced Therapies Skills Training Network

Written by Louise Stanley on . Posted in Experimental medicine.

The National Horizons Centre, RoslinCT and the University of Birmingham have been selected to deliver high impact physical and digitally-delivered training courses as part of the growing ATSTN programme. The three centres bring with them complementing capabilities and a vast wealth of experience across GMP/GxP, manufacturing and bioprocessing, and their expertise within virtual reality training will prove instrumental for driving the successful development of cell and gene therapy as well as vaccine manufacturing staff across the UK, through the delivery of these industry-leading training courses.

The core aim of the Advanced Therapies Skills Training Network (ATSTN) is to develop National Training Centres to deliver specialist on-site courses, including innovative digital training utilising virtual reality, providing learners with the hands-on expertise and experience to succeed in the advanced therapies and vaccine manufacturing sector. The ATSTN programme also includes an Online Training Platform focused on upskilling existing staff within the industry and a Career Converter which measures an individual’s transferable skills from outside the sector and recommends applicable roles within advanced therapies and vaccine manufacturing.

Professor Phil Newsome at BHP founder-member the University of Birmingham and Professor Ivan Wall at Aston University said:
“We are excited that Birmingham will play a central role in delivering these much-needed skills for the UK’s advanced therapies sector. This will ensure the UK retains a world-leading position in the manufacture and delivery of advanced therapies. Moreover, it will further strengthen and leverage the rapidly-growing health and life science sector in Birmingham and the Midlands.”

Mayor of the West Midlands, Andy Street, commented: “Hosting an ATSTN National Training Centre in Birmingham is testament to the expertise we have developed in advanced therapies for the benefit of patients with complex conditions.  Developing  the skills to enable the therapies of the future, including new vaccines, to be delivered to patients is critical to our region and nation. And as well as leading on training, the University of Birmingham is proposing the development of new clean room facilities at Birmingham Health Innovation Campus, providing businesses with access to the critical infrastructure and expertise they need to develop, commercialise and manufacture at scale.

“To capitalise on this opportunity, extend Birmingham’s position as a leading player in advanced therapies, and deliver on the Government’s goal to be an international leader in the field, we will be seeking further support to help the delivery of innovation infrastructure in this Campus.”

Matthew Durdy, Chief Executive Officer at Cell and Gene Therapy Catapult commented: “The involvement of the National Horizons Centre, RoslinCT and the University of Birmingham is a major step in the effective development and rollout of impactful training courses which will enable the ATSTN to upskill and attract talent into the advanced therapies and vaccine manufacturing industry. It is also indicative on how the ATSTN is a truly collaborative initiative which continues to be developed in partnership with industry and academia, and the valued expertise from these three centres will provide users access to in-person training centres which complement each other and the wealth of online resources already provided on the ATSTN platform. I look forward to witnessing the great strides which will be made over the course of next year.”

Birmingham maternity experts call for urgent action on pregnancy ‘drug drought’

Written by Louise Stanley on . Posted in Clinical trials, Experimental medicine, Maternal health.

Leaders in maternal healthcare from Birmingham Health Partners (BHP) have called for lifesaving research into pharmaceuticals for use during pregnancy, in a new report which highlights the challenges of pregnancy-related complications, pre-term birth and pre-existing conditions.

Globally, 2.7 million women and children die each year from causes related to pregnancy and childbirth – including one death every six minutes due to pre-eclampsia. As well as pregnancy-related health conditions which develop during pregnancy, expectant mothers may be diagnosed with infections such as COVID-19 or serious diseases including cancer, and many women enter pregnancy with pre-existing conditions like asthma, diabetes or depression. Despite this, only one new drug has been developed specifically for use in pregnancy in more than 30 years, and 73% of drugs used in pregnancy come with no safety information relating to their use by pregnant women.

Experts from BHP’s founding members the University of Birmingham and Birmingham Women’s and Children’s NHS Foundation Trust are today urging politicians, clinicians, academia, industry, patients and research funders to end this ‘drug drought’ through developing and testing new and existing medicines in pregnancy, and help achieve the UK Government’s aim to halve maternal and infant deaths by 2025. The report, ‘Safe and Effective Medicines for Use in Pregnancy: A Call to Action’ sets out how this crucial research can be managed to de-risk research, mitigate safety concerns and give confidence to women and their clinicians.

BHP’s Katie Morris, Professor of Obstetrics and Maternal Fetal Medicine, explained: “The COVID-19 pandemic and confusion surrounding the vaccine has brought into sharp focus the absence of pregnant women in most pharmaceutical trials. The lack of understanding of which drugs can be safely used in pregnancy combined with reluctance to develop new medicines for mothers-to-be adds up to a major global public health issue, but it’s one which could be reversed. With collaborative effort, we can stop excluding pregnant women and breastfeeding mothers from clinical research and give them access to the medicines they deserve.”

Peter Brocklehurst, Professor of Women’s Health at BHP, commented: “Pregnancy complications, including pre-term birth and pre-eclampsia have a huge impact on families and society as a whole. The consequences of preterm birth alone cost the UK economy almost £3bn annually and, while we have the ability to tackle these issues for mothers at home and abroad, we have barely begun. Many of the women and babies who die during pregnancy and birth could be saved, and 15 million babies could be spared the disability and mortality risks linked with being born too early, if we act now.”

Dr Sheuli Porkess, Medical Director at the Association of the British Pharmaceutical Industry, commented: “We completely agree on the need for action to address the needs of pregnant women and the lack of licensed medicines and treatments researched for use in pregnancy and breastfeeding.

“We have already started work, including on better representation of pregnant women in the design of and recruitment for clinical trials. We are pleased to have Maternal Health reflected in our Memorandum of Understanding with Birmingham Health Partners and to be working with our members, BHP, the MHRA, HRA and others on this important area.”

The report concludes that, through collaboration, research into medicines for pregnancy could be progressed at pace. By creating financial incentives for investment, building public-private partnerships, addressing regulatory gaps and hurdles and harnessing new technologies, the UK can directly impact the health, safety and wellbeing of pregnant women worldwide.

‘Safe and Effective Medicines for Use in Pregnancy: A Call to Action’ can be downloaded from https://www.birminghamhealthpartners.co.uk/wp-content/uploads/2021/01/21560-Policy-Commission-Maternal-Health-Report-AW-accessible.pdf. Its signatories – BHP Professors Katie Morris, Peter Brocklehurst, Arri Coomarasamy and Shakila Thangaratinam – will next establish a major policy commission to review evidence, opportunities and options for policy which will be integral to the formation of clear, multi-stakeholder recommendations to the UK Government.

The BHP Starter Fellowship – Anna’s story

Written by Louise Stanley on . Posted in Uncategorized.

Anna Price

Dr Anna Price, ST3 in Renal Medicine at the Queen Elizabeth Hospital Birmingham, undertook a Birmingham Health Partners Starter Fellowship in 2015-2016 and is currently undertaking a PhD at University of Birmingham. We spoke to Anna about her thoughts on her fellowship experience.

What attracted you to the BHP Starter Fellowship?

During my undergraduate intercalation I became involved in cardio renal research. I thoroughly enjoyed it and knew from that point on I wanted to do a PhD. After completing an Academic Foundation Programme I was unsuccessful obtaining an Academic Clinical Fellowship. In Core Medical Training the clinical workload was naturally busy and the MRCP and medical curriculum became all consuming. Research projects became squeezed into early mornings and late nights. I was fortunate enough to meet my current supervisor in my cardiology rotation and we made an application to the British Heart Foundation but unfortunately this was unsuccessful.

I applied for speciality training in Renal Medicine but felt like the opportunities to do research were dwindling away. I became resigned to a career without research when the BHP fellowship flyer was emailed to me. The fellowship was a unique opportunity to gain independent funding to complete a PhD on a topic of my choosing. It gave me the break I had been waiting for.

What were the benefits of the Fellowship?

The BHP fellowship gave me dedicated time to make several funding applications and successfully fund my study consumables and time out of programme for three years. Within my BHP fellowship year I was awarded three grants including a personal British Heart Foundation Clinical Training Fellowship totalling £249,000. I have had the time to set up my study protocol, gain ethical approval, buy equipment and learn the skills required to hit the ground running.

Were there any challenges during the fellowship?

This was my golden opportunity to achieve ongoing funding so there was some pressure, this was the biggest hurdle. Most of my colleagues already had funding and were well on their way with a project. It can be frustrating at times waiting for news on grant applications!

How much clinical work did you do while undertaking the fellowship?

During the fellowship I took up half a slot on the on call Renal registrar rota at the Queen Elizabeth Hospital Birmingham. All of my on call commitments are outside of normal working hours i.e. lates, nights and weekends so they don’t interfere with patient recruitment. It does allow me to keep up my clinical skills and in the long run I know it will be much less daunting when I return to training.

Did the fellowship help with your clinical practice?

The fellowship has taught me perseverance and persistence. My confidence has grown and I have more self-belief that I can work through challenges and find my own solutions. I approach research papers in a completely different way now. I am more critical of the methodology used and I don’t take findings at face value.

Do you feel the fellowship has helped with your career development and aspirations?

It has reaffirmed my desire to have a career in Academic Medicine. Completing a PhD is the first step in achieving that goal. Being involved in an established research group has given me experience in clinical trials and multi-centre studies. I have been lucky enough to work with some of the best academics in their field. I have really enjoyed aspects of research that I didn’t think I would such as statistics. I have also been able to explore sub specialities such as hypertension which I hadn’t considered before.

What advice would you give to a prospective applicant?

  1. Identify a supervisor who shares your academic interests and will support you during your research. Someone you can develop a good rapport with is important as you will be working with them closely for a number of years.
  2. Review potential funders early and be aware of grant deadlines (there may only be one application cycle per year).
  3. Develop your project proposal as much as you can. Use existing funding application forms to guide you.