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Author: Louise Stanley

Drugs to delay preterm birth are safe for global reduction in neonatal death

Women around the world should be able to access the best drug treatments that help to delay preterm births and improve outcomes for newborns, suggests new research.

Researchers from BHP founder-member the University of Birmingham worked with colleagues from the World Health Organization to review 122 randomised trials – published between 1966 and 2021, involving 13,697 women and conducted in 39 countries including high, middle and low-income states. The study, published in Cochrane Reviews, has allowed researchers to create a league table of drugs that delay birth, called tocolytics, based on their effectiveness and side effects.

Women benefitted from all preterm delay treatments included in the meta-analysis of studies, although the research team noted that the effectiveness of different drugs was less clear in some of the studies. The team also looked at the side effects of different drugs and combinations, including the likelihood of having to stop treatment.

The team have bought together the evidence on the benefits as well as the harms of these treatments (compared to no treatment or placebo), to arm clinicians and policy makers around with world with the information to decide upon the best treatment for the women in their care in their specific setting.

Dr Amie Wilson, Research Fellow Global Maternal Health at the University of Birmingham said: “The findings show that the benefits of these drugs outweigh any risks associated with unwanted side effects. These treatments are leading to a significant reduction in the number of deadly preterm births, and we now need to further understand the effectiveness of tocolytics for specific groups depending on pregnancy length.

“Our previous research has led to the improvement of guidelines for use of tocolysis drug use to delay preterm birth in the UK. Knowing that this paper helped to inform the forthcoming recommendations of the World Health Organization on the use of tocolytics, we hope that many more women around the globe will have access to these drugs, and have healthier births.”

Dr Victoria Hodgetts Morton, NIHR Clinical Lecturer in Obstetrics at the University of Birmingham and co-author of the paper said: “Preterm birth is the most common reason why a newborn baby may die, and the leading cause of death in children under five years of age.

“Tocolytics aim to delay preterm birth and allow time for the women to receive medicines that can help with baby’s breathing and feeding if born preterm, and medicines that lower the chance of cerebral palsy of the infant. Crucially, a short delay in preterm birth can enable women to reach specialist care.”

    Professor Peter Brocklehurst responds to the Women’s Health Strategy

    The Chair of the Birmingham Health Partners Commission which led the Healthy Mum, Healthy Baby, Healthy Future report has welcomed the first ever Women’s Health Strategy for England to tackle the gender health gap.

    The commission set out a raft of recommendations for the UK to lead the development of safe, effective and accessible medicines for use in pregnancy. The key ambitions in the Women’s Health Strategy which are aligned to the recommendations from the Healthy Mum, Healthy Baby, Healthy Future report include:

        • Boosting participation of pregnant women in clinical research, particularly clinical trials, key components to improving maternal health outcomes for women and their babies
        • A greater use of routine health data to improve outcomes for pregnant women
        • Improving the safety of medicines in pregnancy to ensure women have access to high quality and updated information about medicines that they may need to take during pregnancy

    Commenting on the Women’s Health Strategy, Professor Peter Brocklehurst, Professor of Women’s Health and Director of Research and Development for the Birmingham Clinical Trials Unit (BCTU), said:

    “I am really pleased to see that women’s health is being given the prominence it needs and I find the plans outlined in the Women’s Health Strategy encouraging. It is vital that women are treated as equal partners in the delivery of their care and that they have the option to be included in research and clinical trials that affect them. Over 50% of respondents to the initial call for evidence felt that pregnancy should be included in the strategy, providing a clear message that healthy pregnancies are a health priority for women, their families and society.

    “The focus on the importance of research to continue to improve health is also very encouraging, however, there is little mention of the research needed to ensure that new therapies, particularly safe and effective medicines, are developed for many of the women’s health problems highlighted in the report. Investment in discovery science and the need for close collaboration with other groups, particularly the pharmaceutical industry, is essential if we are to continue to improve health outcomes for women.  I look forward to building on these plans with colleagues in Government and across sectors to reduce the gender health gap, place women’s voices at the heart of research, increase participation in research and ultimately improve maternal health outcomes for women and future generations.”

    Baroness Thornton – the Shadow Women and Equalities Minister, recently spoke about the Healthy Mum, Healthy Baby, Healthy Future report during her statement to the House of Lords on the Women’s Health Strategy. The full debate can be watched here. (Baroness Thornton’s speech starts at 16:07:05 and is answered by Baroness Penn at 16:23:45, she ends her point on the report at 16:25:15).

    The BHP Starter Fellowship – Pip’s story

    Pip Nicholson is a clinical lecturer in haematology at BHP founder-member the University of Birmingham, and completed his BHP Starter Fellowship between 2015 and 2016. His research is currently focused on translating tyrosine kinase inhibitors to be used as anti-platelet drugs, and investigating the mechanisms of vaccine-induced thrombocytopaenia with thrombosis. He holds research grants from the British Heart Foundation, Wellcome Trust Translational Discovery Fund, the NIHR and a number of pharmaceutical companies, and is also chair of the HaemSTAR Network. He spoke to BHP about how his experience of the fellowship had led him to this point in his research career.

    What attracted you to apply for the fellowship?

    The fellowship was announced at a really opportune time for me. I’d just had a discussion with my now supervisor about the idea for the research and we’d been puzzling over how we could fund my salary to allow me to be released from my clinical duties. One of the limitations with other fellowships is that they require such detailed background and large amount of preliminary data. This means that doctors without a research background are effectively excluded from getting their foot on the first rung of the research ladder. While competitive, the BHP fellowship (or ITM fellowship as it was known then), didn’t require such extensive background information and the preliminary data required was a reasonable amount that could be generated by someone without any dedicated research time.

    What were the benefits of fellowship?

    The fellowship didn’t come with any significant strings attached such as teaching requirements. This meant that I could get on with the job of learning techniques and quickly generating further data to submit for larger, prestigious fellowship applications to support a full PhD.

    Were there any challenges during the fellowship?

    The main challenge was getting a full research fellowship application written and submitted in time for the various deadlines. To a clinician, a year to learn new skills and develop preliminary data seems like a huge chunk of time (my experience is that clinicians in training are happy if they get an hour to work on our own projects!). But the research environment is very different and long periods of time are required to learn skills, iron out issues with laboratory assays, and gain ethical approvals for the work.

    While a year is sufficient time to generate data if you are focussed about things, the deadlines for the full research fellowships didn’t fall nicely near the end of the BHP fellowship and meant I had to put in applications before they were really ready. Towards the end of the fellowship I was still left wondering whether I had any ongoing research funding and this led to quite a lot of anxiety. I was fortunate to be placed in a well-funded lab where the brief shortfall in funding between finishing my BHP fellowship and subsequent funding from a British Heart Foundation Clinical Research Training Fellowship could be picked up.

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

    I very much wanted to keep my ‘hand in’ clinically, and so I did continue doing some clinical work. I was worried that if I didn’t, I wouldn’t be safe to look after patients when I returned on a more regular basis. So, I undertook in one outpatient clinic a week at the Queen Elizabeth Hospital, and I also did daytime on-calls at weekends at about a 1 in 5 frequency. In hindsight I think this probably slightly hindered my progress in the lab and actually my clinical skills probably wouldn’t have suffered significantly if I’d just stopped doing any clinical work for that year of the BHP fellowship.

    Did the fellowship help with your clinical practice?

    It definitely helped me identify the area of subspecialist clinical practice I wanted to do long term (i.e. thrombosis and haemostasis). It also gave me time to delve more into the clinical literature of this sub specialist area in order to better understand the pathophysiology and existing treatments and where the current limitations are in our knowledge.  I also gained experience in dealing with ethics applications and working with NHS Trust Research and Development departments which have been a useful skill.

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

    Without a doubt, if it wasn’t for the BHP fellowship I can’t see how I would have got my foot in the door of the clinical academic world. I’m now a clinical lecturer, chair a national research network and am in the process of applying for intermediate clinical research fellowships to support me in a consultant role and as a senior clinical lecturer. I wouldn’t be in this position without that initial year of funding that the BHP fellowship provided.

    What would your advice be to anyone thinking of applying for a BHP fellowship?

    Talk to people who have successfully been award the fellowship and have completed it and moved on to higher research degrees and other fellowships. Ask them to look at their successful applications to use as a template. Talk to them about their experience of the fellowship itself. Identify a supportive research environment and speak to various members of that research group (e.g. PhD students and post-doctoral researchers). They are the ones who will be able to tell you what the research training in that group is really like. Don’t just rely on your impression of the supervisor!

    BHP launches Seed Fund to invest in innovation

    Today (20 June) Birmingham Health Partners officially launches its BHP Seed Fund – a new initiative which will kick-start innovation by providing researchers with up to £100,000 initial investment.

    Designed to support our culture of research-embedded healthcare practice while simultaneously addressing common challenges across our member organisations, the Seed Fund will bring together healthcare professionals, academics, students and entrepreneurs, to deliver the initial steps towards implementable solutions. The aim of the fund is to provide early-stage support and proof-of-concept for projects which will have swift impact on patients outcomes and experiences, but can also be further developed or rolled out more widely.

    Working with NHS partners, BHP has identified a number of broad themes which are both of key importance to the region, and are also primed for innovation and investment. We will therefore strongly support applications for projects which directly relate to these priority areas for our region:

        • Health data and AI
        • Engineering into health settings
        • Sustainability
        • Health inequalities
        • Health systems and evaluation

    BHP Chair, Ed Smith, commented: “Birmingham Health Partners is delighted to offer this opportunity for innovation, funded with seed money to stimulate support and growth for health-based solutions for the West Midlands and beyond. We hope and expect this funding will be exciting for applicants and deliver meaningful contributions.”

    Colleagues from all healthcare professional backgrounds working across all BHP’s partner organisations are welcome to apply.

    Visit our BHP Seed Fund page for full details

    ‘Cellular brake’ offers clue to autoimmune response during immunotherapy

    A ‘cellular brake’ which could prevent lung cancer patients from developing a dangerous autoimmune response during treatment has been identified by scientists.

    The finding, published in Nature Communications, is the first clue to the cause of autoimmune toxicity, in which patients develop dangerous additional conditions during immunotherapy treatment.

    Immunotherapy works by enabling the body’s immune cells (T cells) to engage with and kill tumour cells. They do this by suppressing proteins called immune checkpoints. These exist to prevent an immune response from being so strong that it destroys healthy cells in the body.

    Autoimmune toxicity, which includes conditions such as pneumonitis, or inflammation of the lungs, can affect lung cancer patients undergoing immunotherapy treatment. Pneumonitis is responsible for around 35 per cent of treatment-related deaths in lung cancer patients.

    Given the increasing use of immunotherapy treatment against cancer, the management of these reactions has become a significant healthcare challenge. Most commonly, clinicians will recommend discontinuing the treatment and exploring other options.

    Led by Professor Gary Middleton, the team, in the University’s Institute of Immunology and Immunotherapy pinpointed a specific biological response among patients who develop autoimmune toxicity. They found a ‘cellular brake’ – a protein which would normally limit the activity of the T cells – is missing or not functioning properly.

    By identifying patients who lack this cellular brake, it may be possible to recognise patients at high risk of developing severe autoimmune complications.

    Lead author Dr Akshay Patel said: “Immunotherapy is an extremely important weapon in cancer treatment and so identifying people who are at particular risk of developing these potentially life-threatening autoimmune conditions is key to weighing the risks and benefits of different treatments. It would enable clinicians to closely monitor high-risk patients, develop preventative strategies, or pursue alternative treatments altogether.”

    The research was funded by Cancer Research UK and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre.

    The BHP Starter Fellowship – Shaun’s story

    Shaun Thein is a Clinical Research Fellow in Respiratory Medicine at the University of Birmingham, and undertook his BHP Starter Fellowship between November 2020 and November 2021. He’s currently in the second year of an internally-funded PhD, investigating neutrophil dysfunction in COVID-19 patients, as well as undertaking a PGDip in Medical Education. He took some time out to share his experience of participating in a research fellowship during the pandemic.

    What attracted you to apply for the fellowship?

    I applied for the BHP Starter Fellowship as I had developed a project during my academic clinical fellowship (ACF), but due to the time restrictions and COVID-19 redeployment, I hadn’t accumulated enough pilot data for a strong fellowship application. The BHP fellowship allowed me to collect more data to present a stronger case.

    What were the benefits of fellowship?

    The main benefits of the fellowship have been the long stretch of dedicated academic time and funding. This has allowed me to recruit patients in a block and have more time to become involved with other projects. I was able to defer finishing the modules I completed as part of my ACF, giving me the option to submit for an MRes if I was unsuccessful in my clinical research training fellowship application.

    In addition, I was able to access the support of the College of Medical and Dental Sciences, attending a Scriptoria workshop, statistics courses and weekly seminars.

    Were there any challenges during the fellowship?

    Due to a further COVID-19 restriction, patient recruitment to the clinical trial my project was linked to was suspended.  As a result, I shifted focus to use my skillset in another project, investigating COVID neutrophil dysfunction.

    Unfortunately, I was unable to secure funding after interview, so it was challenging to find a way for me to continue my research and PhD.  I was fortunate that my supervisor was able to internally fund another year of research for me to complete experiments and patient recruitment.

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

    I did extra out-of-hours shifts at a local NHS Trust to supplement my salary, as there was a significant drop when not doing on-call shifts. I continued this throughout my fellowship as it also helped me to feel more confident in maintaining clinical competencies – especially procedural skills.

    Did the fellowship help with your clinical practice?

    There was significant patient recruitment as part of my project, involving screening, reviewing imaging and consenting patients for research. I have also been involved in helping with clinical trial research as part of my group. Together this has helped me gain confidence in this aspect of clinical work, and I will be more proactive in recruiting patients and advertising clinical trials in the future.  However, being away from day-to-day ward and clinical work will always generate a degree of anxiety when returning.

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

    Yes! It has given me the opportunity to complete a PhD, which I would have not been able to do otherwise, and has enabled me to be involved with clinical research trials and work with leaders in these fields. Being released from an on-call rota has also allowed me to pursue other personal developmental opportunities. For instance, I completed a PGCert in Medical Education and I am continuing with the PGDip this year.  I have also been appointed as the Chair of the British Thoracic Society Specialist Trainees Advisory Group.

    What would your advice be to anyone thinking of applying for a BHP fellowship?

    There is no reason not to!

    However, it is important to apply with a project plan, supervisor and supportive group, and to think about alternative plans and contingency plans if funding applications are not successful.

    While a year seems much longer than the 3 month blocks in the ACF, it goes by very quickly – the more that you can hit the ground running, the more you will be able to get out of the year.