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Take a look at a selection of our recent media coverage:
27th February 2025
Left ventricular outflow tract (LVOT) obstruction is the most prevalent structural heart defect leading to neonatal collapse presenting to an emergency department, but a significant proportion of cases are initially misdiagnosed, UK research finds.
Cardiac abnormality was one of the most common causes of neonatal collapse, the research team wrote in the journal BMJ Paediatrics Open, with early recognition crucial for timely interventions and referral.
There were different types of cardiac pathology that could cause collapse, requiring different management, but there was minimal literature on the proportions of these presenting to emergency departments and how they were managed prior to being transferred to critical care, they said.
To fill this knowledge gap, the researchers designed a retrospective cohort analysis of cardiac-related neonatal collapses referred to the South Thames Retrieval Service (STRS) of the Evelina London Children’s Hospital – a regional paediatric intensive care retrieval team based in London.
Over the course of the nine-year study (2013-2021), the researchers found LVOT obstruction was the most prevalent cause of cardiac-related neonatal collapse referred to the retrieval service.
In addition, a significant proportion of cardiac-related neonatal collapses were misdiagnosed as non-cardiac pathology at referral, particularly those with LVOT obstruction and cardiomyopathy/myocarditis.
There were 71 neonates identified who met the study inclusion criteria of whom 49 (69%) had a structural heart defect, 12 (17%) had arrhythmia and 10 (14%) had cardiomyopathy/myocarditis.
Among those who had structural defects, the majority were related to decreased systemic flow due to LVOT obstruction (71%), followed by abnormal and mixing of circulation (22%).
At referral, the referring team identified a potential cardiac cause in 49 neonates, which accounted for 69% of cases.
In the remaining 22 neonates, the documented provisional diagnoses included sepsis in 12 cases, bronchiolitis in four cases, ‘neonatal collapse’ in four cases, metabolic cause in one case and shock in one case.
Patients with cardiomyopathy/myocarditis (30%) and LVOT obstruction (63%) were under-recognised compared with patients with abnormal mixing of circulation who were all recognised.
The researchers noted that the group with cardiomyopathy/myocarditis remained challenging to diagnose at all time points.
They also found that less than half of neonates with duct-dependent lesions received prostaglandin at referral, however, this improved to 97% during retrieval.
The number of patients requiring intubation and inotropic support also increased at various time points throughout the patient journey.
Among patients with structural defects, 48 (98%) required cardiac interventions at a median of one day after admission, the study found.
The median age at the time of referral was 11 days and the median weight at referral was 3.5kg, which ranged from 1.8kg to 5kg.
Senior author Dr Jon Lillie, consultant in paediatric care at Evelina London Children’s Hospital, and co-authors concluded that the study had identified a gap in diagnostic accuracy among cardiac-related neonatal collapses.
They noted that nearly all patients in the study cohort needed early cardiac interventions, adding that these conditions were likely to deteriorate without timely and appropriate surgical or cardiac catheter invention.
‘Therefore, it is imperative to optimise respiratory and cardiovascular support at presentation and minimise delay in transfer to the cardiac centre to improve survival and clinical outcomes,’ they wrote.
High clinical vigilance should be promoted among healthcare professionals who might encounter neonatal collapse, the authors added. There was also a need for comprehensive assessment, including femoral pulse evaluation, measurement of pre-ductal and post-ductal blood pressures and oxygen saturation levels.
The study authors also recommended a lower threshold for initiating prostaglandin therapy and timely referral for cardiac assessment.
‘Training sessions and clinical guidelines on indications and preparation of prostaglandin infusions may facilitate early administration of the medication,’ they concluded.
Last year, a simple cheek swab test showed promise in giving clinicians an understanding of a child’s risk of arrhythmogenic cardiomyopathy so sudden cardiac deaths can be prevented.
25th February 2025
A new study has found a major drop in respiratory syncytial virus (RSV) related hospitalisations following vaccination among eligible age groups in Scotland.
The study, from Public Health Scotland and the University of Strathclyde, showed a 62% reduction in RSV-related hospitalisations among those who received the vaccine and concluded that the vaccine is effective in reducing such hospitalisations in older adults.
Described as one of the first real-world investigations from the UK and Europe into the impact of the RSV vaccine on older people, the study focused on a period of high seasonal RSV circulation.
Dr Sam Ghebrehewet, head of immunisation and vaccination at Public Health Scotland, said the results showed the importance of RSV vaccine uptake in protecting older groups.
‘Vaccinations have played a major role in protecting the health of people across the globe over the last 50 years and the success of the RSV programme marks another significant step in protecting the population of Scotland against preventable diseases,’ he said.
Estimates from the UK in 2022 pointed to a disproportionate clinical effect of RSV infection in older people, with an annual average of 71 respiratory hospital admissions per 100,000 adults during the winter months.
Hospitals across the UK have faced unprecedented levels of respiratory viruses in recent months, with NHS England tackling a ‘quad-demic’ of RSV, flu, norovirus and Covid-19 over winter.
Scotland launched an RSV vaccination programme in August 2024, with local adults aged between 75 and 79 invited to come forward for their free RSV vaccination before winter.
By the end of November 2024, there was a 68% uptake of the vaccine in this older adult population.
A separate programme was also run for pregnant women in their third trimester of pregnancy to protect infants from the virus.
The national RSV vaccination rollout in England, Wales and Northern Ireland for eligible groups began on 1 September 2024.
The study is the first to demonstrate the positive impact of the RSV vaccination programme in reducing hospital admissions in Scotland and shows the importance of older adults coming forward for their vaccine, the authors said.
Commenting on the results, Neil Gray, Scottish cabinet secretary for health and social care, said: ‘I’d urge all those eligible to come forward for their vaccine when called. It is incredibly important for older adults and pregnant women to protect their new born babies from RSV.’
A version of this article was originally published by our sister publication Nursing in Practice.
24th February 2025
As the UK’s first clinical professor of AI in radiotherapy, Professor Raj Jena talks to Helen Quinn about the impact of artificial intelligence and deep learning tools on radiotherapy and patient care, the opportunities and challenges he’s hoping to tackle in his new role, and the broader potential of AI in healthcare.
Put simply, artificial Intelligence (AI) has the potential to transform healthcare. Effective use of emerging machine learning techniques can improve patient care, complement clinicians’ work and address a range of challenges. If used well and in the proper context, AI can enhance diagnostic processes, personalise treatment plans and efficiently manage healthcare data, all while freeing up clinicians’ time to focus on the direct human aspect of healthcare.
Within this rapidly evolving technology landscape, the University of Cambridge has appointed the UK’s first clinical professor of AI in radiotherapy, signalling a need for, and a commitment to, utilising AI in the fight against cancer. Taking up this novel role is Professor Raj Jena, who is also a research scientist and consultant oncologist at Cambridge University Hospitals NHS Foundation Trust.
Professor Jena specialises in using advanced imaging techniques to improve outcomes for patients with central nervous system tumours. Through his research, he has helped to develop an AI tool called Osairis, which can enhance and accelerate tumour analysis.
Machine learning for radiotherapy is now routinely used throughout Cambridge University Hospitals NHS Foundation Trust. It has reduced the waiting time for patients between referral and commencing curative radiotherapy treatment, which can, in turn, improve survival rates in some patients.
The new AI clinical professorship reflects the progress in balancing clinical practice and domain expertise in radiotherapy whilst maintaining and leading an academic group delivering high-quality research, says Professor Jena.
‘We’re trying to link the latest and greatest thinking in data science, machine learning and AI to what we do in the clinic,’ he explains. ‘Most people think an oncology consultant who’s active in research would either be working in a wet lab or work in the area of clinical trials. So, it’s quite nice to identify the fact that there is another way an academic oncologist can contribute to research.’
In fact, over the past 20 years, Professor Jena has concentrated on using mathematics and computation to analyse medical images – something he says has been recognised in the new clinical professor of AI in radiotherapy role. ‘I’ve been interested in computational approaches for years, but nowadays it’s reached the mainstream, and it’s called AI. It’s great because we can ride the wave of interest in AI,’ he says.
The use of AI in medical imaging involves applying a deep learning model to perform clinically valuable tasks. This is particularly applicable to analysing radiotherapy images, making it a highly effective technique in this field.
‘If you look at clinically useful applications of AI across the whole of medicine, the reality is that we’re still at the start of that story. But in radiation therapy, we happen to have a problem that lends itself to a solution in deep learning,’ Professor Jena explains. ‘We’ve gone quite quickly, from these approaches being just research to actually being plumbed into the clinic and helping patients get started on potentially life-saving radiotherapy more quickly.’
The development of the Osairis tool stemmed from a chance meeting between Professor Jena and Dr Antonio Criminisi PhD, a machine learning engineer and the head of Microsoft’s AI research programme in the UK.
Dr Criminisi taught computers to analyse the movement of the human body from the outside, recognising specific positions so a person’s body could be used effectively as a controller, for example, in sports-related video games. Professor Jena was curious whether this approach could be applied inside the body, too, and invited Dr Criminisi to his hospital department to observe radiation oncologists marking up scans of patients waiting to start radiotherapy treatment.
The outcome was the development of an open-source deep learning tool for automatic segmentation of radiotherapy images and the first AI technology to be developed and deployed within the NHS.
‘It was a very prescient point, we could then take the tooling and actually build our own machine learning models from our own patients’ data, test them out, and then for the first time, within the hospital, build a medical device,’ Professor Jena explains.
Cambridge University Hospitals Trust invested in cloud computing across its sites, allowing Professor Jena’s team to implement deep learning tools throughout the Trust. Now, when a patient with a head, neck or brain tumour comes for a scan, the scan data is anonymised, encrypted and sent off for analysis using the AI technology. It has been found to accelerate clinicians’ radiotherapy planning by approximately two and a half times.
‘What the algorithm does is to mark out every healthy structure we need to be aware of when planning radiotherapy treatment. And that means that the oncologist can be much faster in creating a safe radiotherapy plan,’ Professor Jena says. ‘Something that used to take maybe an hour and 40 minutes can be done in half an hour, so you can see patients faster and free up clinicians and patients get started on radiotherapy more quickly, too.’
Despite the myriad ways in which AI can support healthcare systems, challenges remain. Many machine learning models are built based on available data rather than in response to a particular patient need, and the data required to build specific models can be difficult to obtain.
Professor Jena says turning available data into necessary data requires considerable effort. He hopes his new professorship, which straddles both the research and clinical environments, will help him achieve this as he builds AI tooling to address specific patient needs and avoid bias in the system.
AI technology is also moving rapidly, and the journey has sometimes involved missteps, including breaches of data usage and sharing of data with industry. Professor Jena warns that robust governance needs to be in place to prevent further issues, particularly as AI models begin incorporating more sensitive data, such as genomic information.
‘I think we have to take those things and learn how to do it better. The biggest thing we can do is make examples where we do this right, that are highly shareable and highly applicable,’ Professor Jena says.
Radiotherapy is an exemplar of the successful use of AI in healthcare, but Professor Jena hopes there will be a cross-fertilisation of technology, enabling AI to evolve and excel at interpreting non-image data as well. He believes AI can ‘make real inroads’ in diagnostics for the early detection of cancer. Early works suggest it could be used in tests that can look for cancer in urine, blood or even exhaled breath, for example.
The tools could also play a role in personalising treatments for cancer patients since AI can look for patterns and simplify very high-dimensional data. In complicated cancers such as brain tumours, where several medications might be marginally effective, an AI model could examine that information, align it with changes in the patient’s tumour and suggest a personalised medication plan.
‘I think this is where we really want to push,’ says Professor Jena. ‘Personalised medicine is very interesting to us because we now get so much information when a cancer is diagnosed, including genomics, which can highlight mutations and indicate a patient may benefit from some kind of targeted drug. I think the paradigm changes around AI in medicine will come within the areas of precision medicine or drug discovery.’
Ultimately, Professor Jena says that AI will complement and enhance much of what clinicians already do, freeing them from time-consuming, data-heavy tasks.
‘As you build these workflow acceleration tools, all staff will move towards a situation where they’re spending more time either listening to patients directly or making decisions. I think that will make a huge difference,’ he says. As well as awaiting the paradigm shift in AI, I’m a great believer in bringing together multiple AI tools where each one saves time or increases safety. Adding up all of these small increments can still make a huge impact on the delivery of human-centric care in the clinic.’
21st February 2025
Some hormonal contraceptives are associated with a small but significant increased risk of stroke and myocardial infarction, according to a large and detailed study from Denmark.
The analysis was based on national prescription records for more than two million Danish women between 1996 and 2021.
It showed that ‘contemporary’ oestrogen-progestin and progestin-only contraceptives were associated with an increased risk of arterial thrombotic events.
Reporting in the BMJ, the researchers said the highest risks were seen with oestrogen containing products, in particular the vaginal ring and skin patch.
But no increased risk was found for the levonorgestrel-releasing intrauterine device.
While an association between hormonal contraception and myocardial infarction and strokes has been reported before, these studies are outdated and have produced inconsistent results, they researchers noted.
There had also been a lack of detail on the different types of contraception, route of administration and duration of use, they added.
They stressed that the risk they found remains low but, given widespread use, clinicians need to be aware of the potential risks when prescribing, they added.
Women were excluded from the analysis if they had a history of blood clots, cancer, liver disease, kidney disease, polycystic ovary syndrome, endometriosis or infertility treatment; if they used psychiatric medication or hormone therapy; or had undergone a hysterectomy.
Researchers also took into account confounding factors such as age, education level and existing conditions such as hypertension and diabetes.
The combined pill – the most common type prescribed – was associated with double the risk of ischaemic stroke and myocardial infarction, which translates to one extra stroke for every 4,760 women using the combined pill for one year, and one extra myocardial infarction for every 10,000 women per year of use.
Progestin-only contraceptives, including pills and implants, carried a slightly elevated risk, though lower than the combined pills, they reported.
By contrast, the vaginal ring increased ischaemic stroke risk 2.4-fold and myocardial infarction risk 3.8-fold, while the patch increased ischaemic stroke risk 3.4-fold.
But they also found that duration of use of hormonal contraceptive did not seem to influence the risk.
‘Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing hormonal contraceptive method,’ they authors concluded.
A linked editorial noted that it was important women were able to make an informed choice but that clinicians needed up-to-date evidence and training.
Professor Angela Clerk, professor of biomedical science at the University of Reading, said the study appeared to be ‘comprehensive and rigorous’ but added there should be some caution in extrapolating to other populations with different ethnicities.
‘Genetic background and cultural variation could affect cardiovascular risk, and some ethnicities not fully covered by the Danish population could have greater vulnerability,’ she said.
‘This is clearly an important study but, while the focus is on the potential negative effects of contraception on cardiovascular risk, it is also clear that any increase in risk is actually very small.’
It highlighted the overall safety of the drugs, particularly when balanced against the negative effects of unwanted pregnancies resulting from a lack of contraception, she noted.
Dr Sonya Babu-Narayan, consultant cardiologist and clinical director at the British Heart Foundation, said: ‘The researchers made use of a wealth of long-term electronic healthcare information from over two million people in Denmark – this scale and breadth makes the findings more reliable and complete than previous studies and enables study of even rare complications like these.
‘However, the study is observational so it can’t prove cause and effect, and there may be other factors at play driving the links seen that aren’t sufficiently accounted for.
‘This latest study supports the current practice of recommending the option of a progestin intrauterine device – the hormonal coil – for those already living with high cardiovascular risk, as this wasn’t linked to more heart attacks and strokes.‘
Dr Channa Jayasena, consultant in reproductive endocrinology, Imperial College London, said it was well known that the pill increases blood clot risk.
‘The absolute risk of having a stroke or heart attack on the pill is still very low,’ he said. ‘Women should take away the importance of smoking cessation, healthy eating, and exercise to minimise the (small) increased risk of stroke or heart attack associated with being on the pill.
‘Women who have high risks of stroke or heart attack that cannot be reduced should strongly consider a hormonal coil, because of its lack of associated increased stroke or heart attack risk.’
A version of this article was originally published by our sister publication Pulse.
More than half of patients are unsure when their asthma inhaler is empty, with some continuing to use the device when it is empty with ‘serious implications’ for managing their condition, research has shown.
A study measured the amount of medicine left in more than 2,600 pressurised metered-dose inhalers that had been returned for recycling and found many were returned under or overused.
In an accompanying survey of 200 patients, 55% who were using inhalers without a dose counter said they could not confidently assess when their device was empty.
Of particular concern was the finding that a substantial proportion maintenance and reliever inhalers were returned overused, ‘with a remaining formulation mass amount more than 10% below zero’.
Writing in the journal BMJ Open Respiratory Research, the researchers said even with a dose counter, 20% of participants reported continuing to use their inhaler ‘past zero’.
The pattern was observed regardless of the presence of a dose counter, although the greatest extent of overuse (44.5%) was among maintenance inhalers without a dose counter, they said.
The findings suggest ‘significant gaps’ in the understanding and practice of inhaler use and disposing of them when they were finished, they concluded.
Almost 70% of patients surveyed also said they thrown unwanted inhalers away in household recycling or waste and more than half threw them away when done with them whether empty or not.
Ideally, all inhalers should be recycled or returned to a pharmacy for disposal, preferably when the inhaler has been used up to the number of labelled doses, the researchers added.
Study author Professor Anna Murphy, a consultant respiratory pharmacist at University Hospitals of Leicester NHS Trust, said: ‘This research shines a light on a concerning reality that patients lack the knowledge to know when to replace their inhaler device.
‘Patients may therefore be at risk of serious exacerbations and, potentially, hospitalisation due to overuse of their inhalers.
‘This is further concerning during the winter season when emergency services are already under significant strain. Tackling this challenge collectively, ensuring patients are educated, is crucial for improving outcomes.’
The researchers said in patients using inhalers without dose counters, advice on making a note of when the inhaler was started and how long it should last could be useful as well as more careful tracking of its use.
Dr Andy Whittamore, a GP and clinical lead at the charity Asthma + Lung UK, said: ‘Many people do not know when their inhaler is empty.
‘This puts people at risk of harm if you are continuing to use your inhaler once it’s finished and you are not getting the medication you need. An empty preventer means you may develop a build up of inflammation and develop symptoms or exacerbations.
‘An empty reliever means you cannot treat life-threatening breathlessness. Some inhalers do have dose counters, with some being more accurate than others.’
The recent joint guidelines on chronic asthma highlighted the need to educate patients around correct inhaler technique, environmental sustainability and the correct disposal of inhalers through the pharmacy.
A study published last year concluded that poorly controlled asthma was contributing to more than 300,000 tons of greenhouse gas emissions.
The NHS has set a target of cutting its direct carbon footprint by 80% by 2032 and reaching net zero by 2040. Medicines account for a quarter of NHS emissions and asthma inhalers accounting for 3%.
A version of this article was originally published by our sister publication Pulse.
20th February 2025
Dosing anticancer drugs by body surface area was first introduced in the 1950s, based on preclinical animal models. The rationale was that this metric would better correlate with drug pharmacokinetics and organ function than weight-based dosing. But is it still appropriate in oncology practice today? Professor Alain Astier explains.
Body surface area (BSA), calculated using height and weight and expressed in square metres (m²), was thought to provide a universal dosing metric applicable across diverse patient populations. The approach was adopted widely, particularly for cytotoxic chemotherapy agents, with the aim of standardising drug exposure and minimising toxicity.
Despite its simplicity and widespread use, the scientific foundation of BSA-based dosing remains questionable. Studies have shown that BSA is only one of many factors influencing drug metabolism, and interpatient variability often remains high despite dose adjustments.1
The origins can be traced back to the work of Du Bois and Du Bois in 1916.2 Their formula was developed by assessing the weight and height of just nine patients: eight males and one female.
By today’s standards, the accuracy of the original BSA estimation seems poor. It has significant limitations, considering the sample size and the height and weight of people over a century ago are not comparable to the better-nourished population of today. However, this formula continues to be used to estimate BSA.
Their work was later adapted for drug dosing in oncology, as researchers observed that BSA correlated with metabolic rate and drug clearance in preclinical animal models.3 Early studies demonstrated that BSA was a better predictor of drug toxicity than body weight alone, particularly for agents such as fluorouracil and methotrexate.4
Adopting BSA-based dosing in humans was influenced by its success in standardising dosages in animal models, where interspecies differences in drug metabolism could be normalised using BSA scaling.5,6
Freireich et al’s work further validated this approach, showing that BSA correlated with drug efficacy and toxicity across several chemotherapy agents.5 However, subsequent evaluations revealed that while BSA provided a helpful starting point, its application lacked the precision required for individualised dosing.7
The primary limitation of BSA-based dosing is its inability to account for interpatient variability in pharmacokinetics. While BSA was intended to standardise drug exposure, studies have demonstrated significant variability in drug clearance among patients with similar BSA. Age, renal function, hepatic function and genetic polymorphisms often impact drug metabolism more than BSA.
For example, renal clearance of cisplatin is more closely linked to creatinine clearance than to BSA, rendering BSA-based dosing suboptimal for cisplatin chemotherapy. Similarly, hepatic enzyme activity, influenced by genetic factors like CYP2D6 polymorphisms, is critical in metabolising drugs such as tamoxifen, which cannot be accurately predicted using BSA alone.8
There are also challenges associated with BSA-based dosing in specific patient populations.9 For example, in obese patients, BSA calculations may lead to overdosing due to excessive weight, while in cachectic patients, the same calculations can result in underdosing. These discrepancies highlight the simplistic assumptions underlying the BSA model and its failure to address individual patient needs.9
Retrospective analyses of chemotherapy trials have further revealed that variability in toxicity remains high even after dose adjustments based on BSA. These findings suggest that other factors, such as organ function and genetic makeup, are more relevant in determining drug response and toxicity.10
In response to its limitations, alternatives to BSA-based dosing have emerged. These approaches focus on achieving greater precision and individualisation in drug delivery. Each strategy is tailored to address specific challenges posed by the variability in patient-specific factors. Some examples are given below.
Fixed dosing has gained significant traction due to its simplicity and demonstrated efficacy across various patient populations. Studies have shown that flat-fixed carboplatin dosing provided consistent therapeutic outcomes in advanced non-small cell lung cancer compared with traditional BSA-based dosing.6
This was particularly evident in its ability to reduce variability in drug exposure among patients. Fixed dosing offers a pragmatic solution to the challenges associated with BSA-based dosing. It eliminates interpatient variability stemming from calculation errors or incorrect BSA estimations.
Shimizu et al introduced dosing strategies that combined pharmacokinetics and patient-specific variables in treating chronic myeloid leukaemia. These strategies improved therapeutic precision and reduced toxicity.11
These approaches represent a significant step forward in addressing interpatient variability by integrating multiple dimensions of patient-specific data. By incorporating plasma drug monitoring, certain therapies (such as methotrexate) benefit from reduced variability and enhanced safety.
The role of pharmacogenomics in modern oncology cannot be understated. Henningsson et al demonstrated the critical impact of CYP2D6 genotypes on tamoxifen metabolism and breast cancer treatment outcomes.8
This finding highlights the importance of genetic profiling in optimising therapeutic regimens, particularly for agents with significant interindividual variability in metabolic processing. It also supports integrating gene profiling into dosing strategies to enhance efficacy and minimise adverse effects.
Weight-based dosing continues to provide reliable outcomes for biologics such as trastuzumab. Evidence corroborates its effectiveness in addressing patient-specific metabolic variations, particularly in diverse populations where BSA may fail to predict pharmacokinetics accurately.10
Hybrid dosing strategies integrating multiple metrics, including BSA, weight, pharmacokinetics and genetic data, are being explored.
Advances in computational modelling have enabled the development of algorithms that predict optimal doses based on a combination of patient-specific factors. For example, George et al discussed how baseline characteristics in randomised trials can influence precision dosing outcomes.12
Hybrid models have the potential to achieve the precision required in personalised oncology, bridging the gap between traditional and emerging dosing paradigms. For example, in recent clinical trials, combining renal function data with pharmacogenomic markers has improved dosing accuracy for drugs like cisplatin and fluorouracil.13
Advances in genomics, proteomics and imaging technologies are enabling more individualised treatment approaches.11
Biomarkers of drug exposure and response, such as therapeutic thresholds for tyrosine kinase inhibitors, are being integrated into clinical practice. For instance, imatinib plasma levels correlate with clinical outcomes in chronic myeloid leukaemia, supporting plasma concentration monitoring to optimise dosing.14
Research by Fichtner et al highlighted how early-passage xenotransplanted colon carcinomas displayed varying responses to anticancer drugs based on the expression of molecular markers.15
This research emphasised the significance of molecular markers in tailoring therapy to individual tumour profiles, thereby underscoring the limitations of generalised dosing strategies and the need for more precise alternatives.
The advent of next-generation sequencing (NGS) and proteomic profiling has further expanded the horizon for personalised dosing.
By decoding tumour-specific mutations and protein expression patterns, clinicians can refine treatment plans to target molecular aberrations unique to each patient. For example, personalised dosing strategies for poly (ADP-ribose) polymerase inhibitors have been proposed based on DNA damage repair pathway alterations observed through NGS.16
Machine learning and artificial intelligence (AI) are transforming the field by integrating complex datasets from diverse sources, such as electronic health records, genetic profiles and real-time pharmacokinetic monitoring. AI-driven algorithms can predict optimal doses and identify patients at risk of adverse events, enabling dynamic adjustments in therapy.17
Collaboration among pharmaceutical companies, regulatory bodies and healthcare providers is essential for developing standardised frameworks for precision dosing.
Rosenberg et al emphasised the importance of coordinated efforts in establishing principles for cancer immunotherapy dosing.18 Large-scale, multi-institutional studies are needed to validate emerging approaches and assess their scalability across healthcare systems worldwide.
Future research should focus on validating these approaches in clinical trials, ensuring their feasibility and efficacy in diverse patient populations.
Korn et al explored statistical controversies surrounding the validation of surrogate endpoints, which could inform future clinical trial designs for precision oncology.19
By combining technological advances with rigorous clinical validation, the oncology community can pave the way for a new era of precision dosing that minimises toxicity while maximising efficacy.
While BSA-based dosing has played a fundamental role in oncology practice, its limitations have become increasingly apparent in modern medicine. The shift toward fixed dosing, pharmacokinetics-guided strategies and precision medicine reflects a broader movement toward individualised treatment.
By leveraging technological advances and biomarker research, the oncology community can overcome the constraints of BSA-based dosing and offer patients more effective and less toxic treatments.
Alain Astier PharmD PhD
Honorary head of the Department of Pharmacy, Henri Mondor University Hospital, and French Academy of Pharmacy, Paris, France
This article was originally published by our sister publication Hospital Pharmacy Europe.
Research exploring eco-directed sustainable prescribing has found that while awareness is increasing among healthcare professionals and the public, further education is required on the drivers, potential effects and possible interventions – of which the results highlighted several for consideration.
Medications contribute substantially to pharmaceutical pollution, impacting both ecological health and public safety. Growing environmental concerns about this issue highlight the need for more sustainable prescribing practices that minimise environmental harm while ensuring effective patient care.
This study examined public and prescriber perceptions of pharmaceutical pollution in Scotland’s water environment, with a focus on eco-directed sustainable prescribing as a strategy to mitigate this pollution.
Semi-structured qualitative interviews were conducted with nine members of the public and 17 prescribing healthcare professionals to explore perceptions, barriers and opportunities for implementing eco-directed sustainable prescribing practices.
Public participants recognised the environmental issues related to pharmaceutical pollution but stressed the need for further education on the topic. They suggested that pharmacy-specific interventions should include targeted messaging and informative displays at the point of care, clearer labelling on medications to highlight their environmental impact and better access to pharmacy return schemes for unwanted medicines.
Additionally, a more person-centred approach, with an emphasis on regular medication reviews and deprescribing, was seen as useful.
While participants were open to environmentally friendly alternatives, they emphasised that any change to prescriptions should not compromise their effectiveness. They preferred to make informed decisions based on clear, accessible information and discussions with prescribers.
Prescribers also agreed that pharmaceutical pollution should be incorporated into their training. They noted that similar conversations already occurred around changes such as inhaler switches and that eco-directed sustainable prescribing could align with these efforts.
They also emphasised the need for effective multidisciplinary communication and for accessible tools, such as environmental sections in formularies and integrated decision-support in prescribing systems. Key strategies for advancing sustainable prescribing included regular prescription reviews and shorter courses of treatments where possible.
The authors noted the need for healthcare to ‘undergo fundamental changes’ to create more sustainable medicines use practices, although they did acknowledge the difficulties in translating recommendations from prescribers and the public into policy.
Nevertheless, they highlighted ‘the need for accessible and robust knowledge support tools to enable [eco-directed sustainable prescribing], which should be underpinned by policy guidance and embedded into existing systems.’
And they championed cross-sector and transdisciplinary collaborative approaches to overcome the challenges for achieving this.
Further research will be needed to evaluate the long-term effects of eco-directed sustainable prescribing on both environmental health and patient outcomes, they concluded.
Reference
Niemi L, et al. Do you think medicines can be prescribed in a more eco-directed, greener way? A qualitative study based on public and prescriber focus groups on the impact of pharmaceuticals in Scotland’s water environment. BMJ Open. 2025 Jan 20;15(1):e088066. doi: 10.1136/bmjopen-2024-088066.
This article was originally published by our sister publication Hospital Pharmacy Europe.
19th February 2025
In her second article on the new UK joint guidelines for chronic asthma, Ravijyot Saggu discusses the principles of pharmacological management it outlines, how new maintenance and combination treatments will contribute to improved outcomes and opportunities to work in partnership with patients to improve asthma care, and top tips for implementation.
The National Institute for Health and Care Excellence (NICE), the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN), have recently come together to produce a single national guideline on the diagnosis, monitoring and management of chronic asthma.
Read more about the context around the joint guideline and its recommendations for the diagnosis and monitoring of chronic asthma in part one of this series.
When it comes to the pharmacological management of chronic asthma, notably, the guidance initiates a move away from prescribing short-acting beta-agonist (SABA) as a monotherapy.
It is known that overprescribing of SABA is not without risks.1 SABA do not treat the inflammation seen in asthma and inhaled corticosteroids (ICS) are therefore a necessary, evidence-based part of treatment.
The pharmacological management of people aged 12 and over is summarised in a joint guideline algorithm and it is explicit that there should be no SABA prescribing without concomitant ICS prescription.2
Reminding patients and healthcare professionals of this update is important so they move away from legacy prescribing.
A fundamental recommended change is combination therapy with ICS and a long-acting beta-agonist (LABA) – specifically formoterol – in a single-inhaler device. Formoterol has a quick onset of action compared with SABA and has a longer-lasting effect,3 making a formoterol-containing regime ideal for ‘as needed’ doses.
Two new treatment approaches are recommended: anti-inflammatory reliever (AIR) and maintenance and reliever therapy (MART), both of which use ICS+LABA.
The advantages of this combination include:
1 The fast-onset action of formoterol, so no requirement for concurrent SABA prescribing
2 Expected overall reduction of SABA use and its associated side effects for patients
3 A single inhaler device to carry and be trained to use
4 Allows flexibility for patients, potentially with a greater sense of ownership and control
5 Most ICS+formoterol products available are dry powder inhalers (DPI) with a lower carbon footprint and less environmental impact.
AIRis intended for patients who have mild asthma with occasional symptoms, but patients’ perception of their disease should be assessed to ensure this regime is the most clinically appropriate option.
MART has been available for many years but is not widely used. It is a sliding-scale approach using a fixed dose of ICS+LABA twice a day plus supplementary doses to a designated maximum amount, if needed. This allows the patient to step up treatment as necessary.
It should be noted that supplementary dosing is not intended as a long-term option; instead, it is a short-term intervention if necessary. Continued use of supplemental doses suggests inadequate asthma control – and potentially harbinger of exacerbation – and should be reviewed to adjust therapy accordingly.
Beyond AIR, the guidance suggests starting on low-dose MART – usually up to 400 mcg beclomethasone diproprionate (BDP) equivalent daily – and increasing to a moderate dose of up to 800 mcg BDP equivalent, should this be warranted clinically.
The regimens do not promote high-dose ICS and, if this occurs, it warrants clinical review and onward specialist referral if appropriate. High-dose ICS is when daily doses of >1000mcg BDP equivalent are reached.4
While it is encouraging that no high-dose ICS use is recommended in the joint guideline, it is acknowledged that patients inadequately controlled on moderate-dose MART might inadvertently receive higher-dose ICS by using many supplementary doses.
In this case, fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) tests are needed to guide further action. If either is raised, and all modifiable factors optimised, the patient should be referred for review by an asthma specialist.2
While MART is a pragmatic treatment approach for most patients, it may not suit all. For example, some patients might be sensitive to beta-agonists or have cardiac issues, so it is important to prescribe the treatment best suited to the individual.
Achieving good asthma control requires a holistic approach following medicines optimisation principles.5
Person-centred care should consider individual preferences, treatment beliefs and history, using shared decision-making to agree on treatment in partnership. Tools such as the BRAN model (Benefits, Risks, Alternatives, Nothing) are helpful in structuring conversations in shared decisions about treatment.6
Non-adherence to medicines may be intentional or unintentional, and this should be reviewed and addressed with the patient. Non-adherence can be monitored by reviewing prescription records, looking at numbers of ICS-containing inhalers, SABA and oral corticosteroid (OCS) dispensing, as well as calculating the medicines possession ratio and reconciling these with FeNO levels, which might be raised for a number of reasons including non-adherence and poor asthma control.
The BTS asthma attack bundle sets out four high-impact actions likely to improve outcomes if implemented following an asthma attack.7 These can be applied in any healthcare setting for adults and adolescents over 16 years transitioning to adult services.
The actions are a medication review, personalised asthma action plan (PAAP), tobacco dependence advice and support for current smokers, and clinical review within four weeks.
PAAPs and other information to support patients and healthcare professionals can be accessed from the website of the charity Asthma + Lung UK.
The evidence on treatment sequencing beyond moderate-dose MART is less clear. Where there is inadequate asthma control, both FeNO and BEC should be checked, and other factors such as adherence, inhaler technique and comorbidities should be optimised. If, despite this, FeNO and BEC tests are elevated, referral to an asthma specialist is warranted.
If there is inadequate control but BEC and FeNO are not raised, a leukotriene receptor antagonist (LTRA) or long-acting antimuscarinic agent (LAMA) can be added as a trial. There is no convincing evidence of the superiority of one agent over the other; hence, choice, benefits and risks should be discussed with the patient.
The benefits of an LTRA are that it is a more economical option in England, it is available orally and is easier than adding a new inhaler and being trained on correct use. However, the recent MHRA alert on the LTRA montelukast reiterated the risk of neuropsychiatric reactions with use,8 so this should form part of patient shared decision-making discussions.
If the patient is controlled with the additional agent, treatment should continue. However, if control is improved but not adequate after addition, the other agent can be added, for example, if an LTRA was initially added, progress to include a LAMA.
Response to treatment should be reviewed eight to 12 weeks afterwards.
Refer to the joint guideline for further detailed information on transferring patients from existing therapies to newer guideline approaches.
Moving away from SABA use is a positive step. Apart from not targeting airway inflammation, we know certain salbutamol brands, such as Ventolin MDI, have a very high carbon footprint, as does SABA overuse and poor disease control.
An assessment of the carbon footprint of the NHS in England estimated a carbon footprint of 125 kg CO2e per bed-day and 76 kg CO2e per outpatient appointment for acute care, 66 kg CO2e per general practice visit, and 75 kg CO2e per ambulance emergency response.9 Good disease control has a lower environmental impact and lower CO2 emissions are expected as a result of this and lower SABA use.
Inhalers for MART are mainly available as DPI devices, which have a comparably lower carbon footprint than MDIs.
There is often a mismatch between the patient’s ability and their prescribed inhaler, usually an MDI first line, and incorrect inhaler technique is used. For example, MDIs require a deep but slow inhalation, whereas DPIs require deep and fast inspiration. DPIs are a better option and especially suited where patient inspiration is fast, thereby benefitting both patient and population health.
Patients should also be reminded to return unused, expired or old inhalers to their pharmacy for disposal or recycling rather than using domestic waste, which can adversely impact the environment.
The recommendations made in the joint guideline are pragmatic, with the view to simplify and improve asthma care, which is very welcomed. As the name suggests, guidelines offer a ‘guide’, however, they have to be applied whilst tailoring them to individual patient circumstances. Healthcare professionals play a key role in the optimisation and maintenance of good asthma control and can do this by understanding and applying key principles of the guidance:
Healthcare professionals must become familiar with the guideline and their local inhaler formulary. The guideline presents opportunities for enhancing patient care and outcomes through greater shared decision-making conversations and improving asthma awareness while addressing concerns and illness beliefs – but this may extend consultation time.
Key points to note regarding implementation are:
These are some top tips on how to optimise practice in accordance with the guideline recommendations:
Whilst the new guidance is not explicitly SABA-free, it signals a welcome move in that direction. Overall, the update has simplified the approach to diagnosis and management and presents many opportunities for healthcare professionals to work in partnership with patients to improve chronic asthma care.
The new treatment approaches are cost-effective for the NHS and will reduce the number of exacerbations requiring treatment and the number of hospital admissions.
To reduce health inequalities and for uptake of guideline recommendations, concerted implementation programmes factoring behavioural insights, implementation science, theory of change, local population intelligence and educational updates for health staff and patients are useful.
Patients should be signposted to reputable sources of information and their local health providers for further advice and support.
Ravijyot Saggu
Respiratory pharmacist, London, UK, chair of the UK Clinical Pharmacy Association Respiratory Committee and NICE Medicines and Prescribing Associate
17th February 2025
The reasons for alterations in the gut microbiome and gastrointestinal function in coeliac disease and how gluten-free dietary restrictions may further impact the gut are not well understood. Here, Carolyn Costigan, Frederick Warren and Luca Marciani, co-investigators of a recent study assessing gut function and the metagenome in coeliac disease, discuss how the results could provide a first step towards finding new targeted ways of treating the condition.
Coeliac disease is an autoimmune condition in which ingesting gluten – a protein found in wheat, rye and barley – triggers an immune response that damages the small intestine. The only current treatment for coeliac disease is adherence to a lifelong gluten-free diet, which aims to heal the intestinal mucosa, reverse enteropathy and relieve symptoms.
Despite avoiding gluten altogether, many people with coeliac disease have ongoing gastrointestinal problems, suggesting that the diet might not fully restore gut function or the microbiome.
Our observational cohort study (MARCO – MAgnetic Resonance Imaging in COeliac disease) sought to explore the effects of coeliac disease and a gluten-free diet on gut function and the microbiome.
Using novel magnetic resonance imaging (MRI) methods, we investigated small bowel water content and whole gut transit time. Using state-of-the-art shotgun metagenomics techniques, microbiome composition was investigated before and after one year of following a gluten-free diet.
The study recruited 36 newly diagnosed individuals with coeliac disease and 36 healthy volunteers as controls. Patients were matched for age, sex and body mass index. All underwent MRI scans to assess gut function and provided stool samples for microbiome analysis.
The patients with coeliac disease were studied at diagnosis and again after 12 months of following a strict gluten-free diet. The controls did not alter their diet.
People with coeliac disease had higher small bowel water content at the start of the study, suggesting impaired absorption and motility in the gut. While this increased water content improved slightly after one year of the diet, it did not return to normal levels.
Initially, transit time for food through the gut was longer in people with coeliac disease compared with healthy controls. Transit times improved after a year of being gluten-free but remained slower than in the control group.
Gastrointestinal symptoms such as bloating and abdominal pain, as well as overall wellbeing, in people with coeliac disease improved after a year of avoiding gluten, but they did not return to the levels seen in healthy individuals.
Before starting the gluten-free diet, the patients’ microbiomes differed distinctly from those of the healthy control group. For example, patients had higher levels of Escherichia coli (E. coli) and Enterobacter and lower levels of certain beneficial bacteria. These differences may be linked to the inflammation and malabsorption in coeliac disease.
After one year on the gluten-free diet, there were significant shifts in the microbiome of the patients, although they still did not revert to the microbiome seen in healthy controls. Notably:
Our study also found that gut transit time and colonic volume were linked to microbiome composition. For instance, slower gut transit was associated with certain bacteria such as Akkermansia muciniphila.
Faster transit correlated with different bacterial species including Faecalibacterium prausnitzii, Gemmiger formicilis and several Agathobacter species.
These associations highlight the complex relationship between gut function and microbial communities.
Limitations included a relatively short follow-up period of one year, which might not be long enough to see a full recovery of the intestinal lining. Histological recovery of the gut mucosa was not assessed, as only serological tests were used to confirm adherence to the diet. The stool microbiome analysis may also not fully reflect changes in the small intestine, which could be more directly impacted by gluten-related inflammation.
Nevertheless, the findings suggest that while the gluten-free diet alleviates some symptoms and improves gut function, it does not completely restore gut health or the microbiome in people with coeliac disease.
The reduction in beneficial gut bacteria, such as Bifidobacterium, and the increase in bacteria associated with inflammation, such as E. coli, indicate that the diet might have unintended negative effects on gut health. This opens the door for potential future therapies, such as targeted prebiotics or probiotics, that could help restore the gut microbiome and improve overall health in coeliac disease.
The findings point to the need for further research on cutting-edge interventions to complement the diet and further improve gut health and quality of life in people with coeliac disease.
Carolyn Costigan PhD
Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, UK
Frederick Warren PhD
Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
Luca Marciani PhD
Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, UK
14th February 2025
A new Green Paper published by the European Society of Intensive Care Medicine highlights the importance of addressing environmental sustainability in intensive care. Katherine Price speaks to Professor Jan De Waele, who led the work, to find out the context, conclusions and key takeaways of the Green Paper and how frontline intensivists can help to drive the sustainability agenda forwards while maintaining high quality patient care.
Intensive care units (ICUs) are among the most resource-intensive hospital departments, with high levels of energy consumption, waste, reliance on single-use devices, medicines and resource-intensive therapies.
One study found the greenhouse gas emissions per ICU bed per day were more than double that of an acute care bed. This creates a vicious cycle in which ICU emissions are contributing to climate change, which itself is producing more patients, increasingly complex conditions and even new diseases.
Against this backdrop, the European Society of Intensive Care Medicine (ESICM) sought to produce a white paper demonstrating how it is possible to maintain and even enhance patient care at a high standard while limiting the environmental impact of ICU activities.
Objectives included evaluating the impact of climate change on ICUs, the environmental impact of ICU activities, identifying key opportunities to reduce this impact, and developing a framework for initiatives including actionable strategies. The resulting Green Paper entitled ‘Environmental sustainability in intensive care: the path forward‘ was published in October 2024.
The ESICM Executive Committee appointed a task force of experts and committee representatives to develop the Green Paper. They worked to identify key areas and actions informed by personal experience, relevant literature and member feedback.
Lead author and task force chair, Professor Jan De Waele, is an intensivist in the surgical ICU at Ghent University Hospital in Belgium. President of the ESICM since October 2024, he was drawn to intensive care medicine by the dynamics of acute disease and multifaceted, fast-changing environment.
‘Intensive care medicine is becoming a speciality in its own right,’ he says. ‘It has become much more complex over the last 20-30 years compared to when I started my training.’
Interested in environmental sustainability, he noticed that while many intensive care professionals were taking steps to be more sustainable in their private lives, this wasn’t necessarily being applied to their practice in the hospital.
‘This Green Paper is not only a practical guide, it’s also a call to action. The fact that we prioritised this hopefully helps people understand that this is an important thing for them, and that it’s not just something that you can switch off when you enter the hospital,’ he explains.
‘It’s an overview of the little information we have right now and trying to give some direction and guidance for our members.’
While he says the intensive care community mirrors society at large in that there is a growing awareness of the importance of environmental sustainability, equally, there are those who turn a blind eye to the problem or resist change, presenting a challenge to the task force and the aims of the Green Paper.
‘There is, of course, always some resistance. Climate change is still something that is contested around the world and, based on recent trends in international politics, one may expect that we still have some work to do,’ Professor De Waele says.
As well as highlighting four main areas for strategies and solutions – clinical care; research and innovation; awareness and education; and ESICM leadership – the Green Paper categorises actions into three tiers.
Tier 1 actions require minimal resources and can quickly contribute to environmental sustainability, such as energy-saving measures, training and promoting reusables. Tier 2 actions require more investment and coordination but can result in significant benefits, for example digitising communications and recordkeeping, or investing in more energy-efficient equipment. Tier 3 includes highly impactful actions that may require considerable investment, long-term planning, like sourcing renewable energy and retrofitting buildings, and cultural change within an organisation.
Intensivists and other intensive care professionals are encouraged to contribute to a multidisciplinary ‘green team’ and evaluate systems and processes to identify low-value clinical practices that could be changed or removed to reduce costs and environmental burden but also improve patient care. Professor De Waele explains that this includes ‘unnecessary lab tests, examinations, having patients in the hospital for too long’, among others.
The paper also lists recommendations for the ESICM itself, such as developing sustainability educational pathways, embedding the topic into courses and organising an annual sustainability conference.
Professor De Waele hopes the main takeaway for intensivists is ‘that what we do in the ICU does significantly impact the environment’ and that to mitigate this goes beyond switching the lights off.
‘Part of the resistance to environmental sustainability is often rooted in the fact that people think, “people are taking things away from me”. But it’s more than that, it’s added value,’ he explains, noting that there’s much more to do. For example, integrating sustainability into research, such as including the environmental impact of a new drug or intervention in the outcome measures.
The Green Paper also stresses the ‘critical’ need to develop flexible sustainability strategies that can be adapted to local needs, resources and conditions. Initiatives that have been seen across Europe include the UK Intensive Care Society’s Gloves Off in Critical Care campaign or efforts in the Netherlands to reduce the amount of paracetamol delivered intravenously in ICUs.
‘There is no uniform solution for every unit and country. You need to look at the low-hanging fruit, and the best to see that are those working at the bedside – the nurses and clinicians,’ explains Professor De Waele.
Green teams, he says, need to be multidisciplinary to ensure initiatives are rooted in clinical practice, are context specific and work for all members of the team – and the best place for teams to start is by focusing on actions that reduce environmental impact but also save time, money and maintain quality of care.
Priorities for the ESICM for 2025 include updating the Surviving Sepsis Campaign guidelines, which are expected to be published within the next 12 months, as well as addressing the Green Paper’s recommendations – towards which the environmental sustainability task force will evolve into a formal multidisciplinary environmental sustainability committee.
The ESICM plans to provide research grants and set up infrastructure to support knowledge exchange on sustainable ICU practice, such as hosting an annual online sustainability conference. There is also work to be done on making ESICM operations more sustainable and engaging with patient and community groups to ensure people understand why changes are being made and that they will not compromise patient care.
‘Now we need to bring this to the bedside, to our members,’ says Professor De Waele. ‘We’ve laid out a number of ideas and solutions, but now it’s up to us – and all of us, not only the ESICM – to solve it and take it seriously and take action.’
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