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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.’
13th February 2025
Multiparametric magnetic resonance imaging (mpMRI) for the initial staging of muscle-invasive bladder cancer (MIBC) is both feasible and beneficial in reducing treatment delays, a new study shows.
New bladder cancers are initially staged using transurethral resection of bladder tumour (TURBT), however, in the case of MIBC, this may delay the primary treatment. The study therefore investigated whether using flexible cystoscopic biopsy and mpMRI for initial staging would be more effective.
The researchers conducted a prospective open-label, randomised study within 17 UK hospitals between May 2018 and December 2021. Over 600 patients with suspected new bladder cancer were screened. A total of 143 patients were randomly assigned to one of two groups: 72 patients received the standard staging care with TURBT and 71 patients received mpMRI-staged care. The primary outcomes assessed were feasibility and the time to correct treatment (TTCT) for MIBC.
Feasibility was tested on 36 out of 39 participants who had suspected MIBC and were in the mpMRI group. The median TTCT for patients with MIBC was 53 days for the mpMRI group (with a confidence interval of 20-89 days) and was significantly shorter with mpMRI compared to 98 days for the TURBT group (confidence interval of 72-125 days).
For patients without MIBC, the TTCT was similar whether they underwent initial mpMRI or TURBT, and there were no significant differences in primary outcomes between the two groups. The median TTCT was 17 days for the mpMRI group and 14 days for the TURBT group. The researchers reported no serious adverse events in either group.
Secondary outcomes included TTCT for all recruited participants and for those confirmed to have non-MIBC. The correct treatment for non-MIBC was TURBT, while for MIBC it was either chemotherapy, radiotherapy, cystectomy or palliative care.
The findings showed that using mpMRI in the MIBC pathway reduced TTCT by 45 days compared to standard investigation. The researchers concluded that introducing mpMRI ahead of TURBT into the standard pathway was beneficial for all patients with suspected MIBC as it could improve clinical decision making and accelerate the time to treatment.
Reference
Bryan, R et al. Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial. JCO 0 2025, Jan. 14: DOI:10.1200/JCO.23.02398.
Hospital Healthcare Europe is delighted to announce the launch of its new sustainability content zone and accompanying newsletter.
With pressure on the NHS to reduce its carbon footprint and progress towards net zero targets, sustainable healthcare is becoming an increasingly important consideration for clinicians and their teams in terms of greener prescribing, reusing and recycling medical devices, reducing waste and more.
Aligning with these aims, the new sustainability zone has been launched as part of the brand‘s commitment to support best practice and patient outcomes in secondary care.
Via the new sustainability zone, Hospital Healthcare Europe will curate innovative case studies highlighting pioneering initiatives at UK hospitals; overviews of novel research into sustainable practices of the future; and analyses of newly published guidelines, toolkits and reports to encourage clinicians and their teams to embrace positive change and support them in achieving individual, organisational and national goals.
All content is underpinned by first-hand insights from a dedicated and ever-expanding group of expert clinical contributors who have their finger on the pulse of the latest trends and innovations.
Recent examples include an exemplar case study on sustainable infection prevention and control at Great Western Hospital in Swindon, an overview of a new study addressing the environmental impact of inhalers, and the latest views on remanufacturing single-use medical devices, with insights from hospitals in England and France.
Alongside the zone, a new quarterly sustainability newsletter will be launched, delivering all the latest sustainability content into subscribers‘ inboxes in a convenient round-up to keep them abreast of the latest developments that can support and inspire their practice.
The inaugural sustainability newsletter will be circulated on Thursday, 20 February 2025, so sign up now to receive this as well as future newsletter bulletins and clinical round-ups.
As the healthcare sustainability agenda is intertwined with the evolution and adoption of technology within the healthcare landscape, and Hospital Healthcare Europe has also launched a health technology content zone.
This zone showcases examples of how technological advances can offer solutions to the challenges faced in day-to-day practice, allowing clinicians and their teams to improve efficiencies, respond to unmet patient need and optimise patient care and outcomes in their own hospitals and beyond.
12th February 2025
Machine learning tools can improve the personalised prognostication of aggressive skin cancers, such as Merkel cell carcinoma (MCC), according to a new study.
MCC is the most aggressive form of skin cancer, often presenting in advanced stages. Currently, no personalised prognostication tools exist, and survival rates are poor. As such, artificial intelligence (AI), including machine learning, is being utilised to address and improve the clinical management of skin cancers such as MCC.
In this study, researchers employed a two-step approach, using advanced machine learning techniques, to develop a diagnostic tool called DeepMerkel. The data came from two sources: the SEER database – a large cancer database maintained by the US National Cancer Institute (NCI), and a UK dataset. Together, they involved over 10,000 patients, all of whom had histologically confirmed MCC during the study period.
Firstly, using explainability techniques, they were able to determine patterns in clinical data such as tumour size, age and immune status. This revealed which factors were most influential on survival in MCC patients.
The second step used combined deep learning feature selection, which meant the machine learnt to automatically select factors that were most important for predicting survival. It was combined with a modified XGBoost framework – an algorithm to structure the data – allowing time-dependent predictions to be made.
The machine learning tool was tested on an international clinical cohort and it made accurate, personalised, time-dependent survival predictions for MCC from readily available clinical information. Retaining accuracy across a wide range of patient groups highlights the broad-reach potential of the new tool.
It outperformed current population-based prognostic staging systems, such as the American Joint Committee on Cancer (AJCC) staging system. Considered the clinical gold standard, the AJCC predicts outcomes using general population data rather than personalised risk factors.
The new machine learning tool also accurately predicted disease-specific survival (DSS) at five years. Additionally, it was able to differentiate time-to-death, providing greater clinical insight and allowing clinicians to personalise treatments more effectively. They could also adjust patient care to improve outcomes, manage symptoms and, where appropriate, make decisions about end-of-life care.
The researchers described MCC and DeepMerkel as ‘the exemplar model’ of personalised machine learning prognostic tools in aggressive skin cancers, highlighting the potential for AI-driven approaches in other areas of oncology.
Reference
Andrew, T et al. A hybrid machine learning approach for the personalized prognostication of aggressive skin cancers. npj Digit. Med. 2025, Jan. 08: DOI: 10.1038/s41746-024-01329-9.
The long-awaited UK national joint guidelines for chronic asthma were launched at the 2024 Winter British Thoracic Society meeting. In this first of two articles, Ravijyot Saggu explores the key updates and implications of the new guidelines for practice, including diagnosis and monitoring, with a focus on chronic asthma in adults.
Previous iterations of asthma guidelines have been produced either by the National Institute for Health and Care Excellence (NICE) or the British Thoracic Society (BTS) in conjunction with the Scottish Intercollegiate Guidelines Network (SIGN), but these have sometimes conflicted, confusing their application in practice.
Earlier guidance has steered practitioners towards initial treatment of asthma or suspected asthma and infrequent wheeze, with short-acting beta-agonists (SABA) – usually salbutamol. These have traditionally been called ‘reliever’ inhalers, reinforcing the patient associating ‘relief’ with using SABA and inadvertently encouraging SABA reliance rather than inhaled corticosteroid (ICS) use as the mainstay of treatment.
For the first time, the NICE, BTS and SIGN have come together to produce one unified guideline and initiate a move away from SABA-only prescribing. This ensures consistent messaging and a change in treatment approach.1
The joint guideline is evidence-based and considers cost-utility analysis. It was developed with an expert committee and broad stakeholder consultation at the draft stage and is intended for use in patients with suspected or already diagnosed asthma.
The scope of the joint guideline was restricted to the diagnosis, monitoring and treatment of chronic asthma. Therefore, other areas, such as acute or severe asthma, have not been updated in this iteration.
Asthma care is still suboptimal in children and young people, leading to avoidable harm and mortality, with roughly one related death every four weeks. A recent national report on deaths of children and young people from asthma and anaphylaxis has highlighted key contributory themes and recommendations for action to prevent future asthma-related harm.2
Similarly, the National Review of Asthma Deaths (NRAD) 2014 report highlighted failures of basic asthma care.3 Sadly, many of the deaths reviewed were deemed to have been preventable.3
NRAD identified SABA overuse as one of the contributory factors to these preventable deaths. Some 39% were prescribed more than 12 SABA inhalers in the year before they died, while 4% had been prescribed more than 50 reliever inhalers. Those prescribed more than 12 reliever inhalers were likely to have had poorly controlled asthma.
There was also evidence of under-prescribing of preventer medication and inappropriate prescribing of long-acting beta-agonist (LABA) bronchodilator inhalers, including LABA monotherapy without ICS preventer treatment.3 LABA monotherapy is not recommended for the treatment of asthma.
Since NRAD, there has been more focus on SABA overprescribing as a flag for uncontrolled disease, with thresholds ranging from three to six SABA inhaler prescriptions per year as a marker of overprescribing, underutilisation of ICS and poorer asthma control.4,5
Despite the NRAD report findings, we still have poor asthma-related mortality and outcomes in the UK over 10 years later. An all-party parliamentary group (APPG) report in 2020 highlighted that asthma attacks in the UK had increased by a third in the decade prior.6
It is widely known that incidence and mortality of respiratory disease are generally higher in disadvantaged groups and areas of social deprivation. Asthma attacks kill three people in the UK each day – the highest level in Europe – and every 10 seconds someone has a potentially life-threatening asthma attack.7
Although some patients may perceive asthma as a cyclical condition, it is a chronic, inflammatory condition that can be well managed with the correct treatment and adherence. While SABA provide temporary bronchodilation, they do not target airway inflammation,6 which requires ICS.
ICS are an effective, evidence-based and largely well-tolerated part of asthma management.
Asthma may be uncontrolled for various reasons, such as non-adherence, undertreatment or a specific type of inflammation that requires specialist review and investigation, and, in some cases, potentially treatment with biologics. To address poor control, the correctable factors should be modified and optimised, including consideration of additional diagnoses and optimal comorbidity management.
A useful pathway for recognising and optimising inadequately controlled asthma has been developed. It can be used in any setting to focus patient care promptly and ensure that the fundamentals are addressed early before appropriate referral to specialist care.
Uncontrolled asthma can lead to exacerbations and may result in hospital admission or emergency department attendance and an increased utilisation of health resources.
Some exacerbations may be severe or life-threatening, and it is essential to be able to recognise and assess signs of severe and life-threatening asthma, including exhaustion, cyanosis, inability to complete sentences in one breath, altered consciousness and reduced peak expiratory flow.
It is important that exacerbations are prevented and asthma control well managed. Management usually involves temporary increased SABA use, a short course of oral corticosteroids (OCS) and often accompanying antibiotics if a bacterial infection is suspected.
Additionally, it is prudent to limit the cumulative OCS and antimicrobial exposure that ensues with exacerbations to minimise side effects and antimicrobial resistance.
There is often a negative association of steroids being harmful, which may be a factor in patient non-adherence to therapy.7,8
ICS differ from OCS, but limiting the overall steroid burden, especially for OCS, and avoiding secondary adrenal insufficiency is important.
Many of the commonly known side effects associated with steroids, such as weight gain, osteoporosis and diabetes are related to OCS and their longer-term or repeated use, reiterating the importance of good disease control to prevent exacerbations.
Side effects with ICS are more local in comparison. They can be minimised by the correct inhaler technique and using an inhaler device best matched to the person’s inhalation ability, which includes using a spacer with a metered dose inhaler where appropriate.
It is important to be able to rule asthma in or out, using objective tests supported by a good clinical history and considering alternative and additional diagnoses. Key updates have been made to the diagnosis and monitoring of asthma in the new joint guideline and are discussed below.
There is no gold standard test to diagnose asthma. In adults aged 16 years and above, the new guidance recommends sequential use of the following tests to confirm a diagnosis of asthma:1
Additionally, the below considerations may support diagnosis or clinical review, especially where asthma may be uncontrolled; these are important to address before escalating therapy:
Please note that diagnosis is slightly different for children aged five to 16 years and this is outside the scope of this article, but see the algorithm for further information.
A key change in the new guidance is a move away from what is traditionally associated with monitoring asthma. Routine monitoring of PEF is now not recommended, although a small cohort of patients may still require this. A validated symptom questionnaire such as the Asthma Control Test can be considered at asthma-related reviews such as annual reviews.
Patient perceptions of disease severity, control and risk may not correlate with clinical state.3,9 It is important to explore the patient’s perceptions and the results of validated questionnaires, as they may contradict each other.7 Perceptions and illness beliefs also impact treatment adherence.
As FeNO is an indicator of airway inflammation, the joint guidelines suggest considering the measurement of FeNO at review, as well as before or after changing pharmacological therapy.
This may also be useful to support patient discussions on the level of disease control, in particular where their perception of it contrasts with the objective test, although various factors can impact FeNO levels.
As with diagnosis, a structured clinical history is vital to elicit the relevant information about symptoms, disease control and triggers. At patient review, ask about the following:
The new joint guidelines herald a radical change in diagnosis, treatment and monitoring and have been welcomed as a much-needed improvement in chronic asthma care. They represent a move to a more straightforward pathway and offer a new and pragmatic approach to implementation.
Part 2 of this series will focus on the joint guideline recommendations for the pharmacological management of adult chronic asthma.
Ravijyot Saggu
Respiratory pharmacist, London, UK, and chair of the UK Clinical Pharmacy Association Respiratory Committee and NICE Medicines and Prescribing Associate
11th February 2025
Speaking at Hospital Healthcare Europe’s recent Clinical Excellence in Respiratory Care event, Dr Zaheer Mangera shared insights into the evolution of the neoadjuvant lung cancer pathway, its benefits and challenges, and notable changes to the TNM standards used to classify malignant tumours.
Click here to read part one of Dr Mangera’s overview of lung cancer management and diagnosis, including insights into the latest guidance, diagnostic and treatment targets and a deep dive into lung cancer screening and incidental findings.
The neoadjuvant lung cancer pathway has triggered a paradigm shift in how we’re treating our patients. About 20-25% of patients with non-small cell lung cancer have resectable disease at the time of presentation, yet 30-55% of patients undergoing curative surgery have recurrence.
What can we do to try to improve the cure rates in these groups? Historically, there’s always been some modest success with both adjuvant and neoadjuvant approaches.
A big study, CheckMate 816, looked at patients with Stage 1B lung cancer, with a tumour size of over four centimetres without any nodal metastases, to anything up to Stage 3A.
The researchers looked at patients deemed to have resectable disease at the time of multidisciplinary team (MDT) input, with a very good performance status of zero or one. This would be the first instance of having cancer treated, and they shouldn’t have an anaplastic lymphoma kinase/epidermal growth factor receptor (EGFR) mutation.
They were offered nivolumab immunotherapy, regardless of their programmed death-ligand 1. Alongside, they had a platinum-based chemotherapy versus just chemotherapy alone. They then restaged patients then proceeded to surgery.
The primary endpoint was looking at event-free survival and pathological response to treatment. It found clear difference in the event-free survival curve between those who had nivolumab with chemotherapy versus those who had chemotherapy alone. A statistically meaningful difference was sustained well beyond the three-to-four-year period.
It’s now part of NICE guidance, albeit not part of the lung cancer guidance specifically, as it’s a separate NICE technological appraisal (TA876). It’s really made us think about how we can get these patients through a pathway and the challenges involved.
The first patient on this pathway at my hospital had excellent response to the neoadjuvant treatment, then went on to have an uncomplicated surgery and now is just on standard follow-up.
Trying to give chemotherapy before surgery makes an already complex pathway even more complex. It lengthens the pathway considerably, because those three cycles can take over two months to get through, plus the required follow-up scans.
So, although the first treatment would have been given, the time it takes for you to then close the loop at your MDT and say the whole treatment has been finished is definitely elongated.
For most patients, if you offer them surgery, they want a tumour out. Of course, there are lots of other tumour groups where you give neoadjuvant treatment and so having discussions about the process is not new to the oncologist, but it’s new to our surgeons.
There are risks of toxicities, although the trial data reports that the risk is not excessive, and patient tolerance is usually very high. It does mean we need to get an EGFR status as rapidly as possible. If you’re waiting a full four weeks for the EGFR status, before you can start treatment, it can mean considerable wait time to treatment in patients who have high-risk disease – those who are on the cusp of cure and not being cured.
We’re developing rapid EGFR pathways through our pathology labs where you can get the EGFR done more rapidly or even sometimes using the CtDNA blood tests.
And how do you standardise all these care plans and pathways across all cancer alliances and Trusts to ensure everyone is on board, everyone eligible for this treatment is getting it and to ensure we really accurately record it? It’s a real cornerstone of the National Lung Cancer Audit in how we collect our data now.
NICE guidance tells us that anyone with a PET-added lymph node, or a lymph node greater than 10 millimetres, should have an endobronchial ultrasound (EBUS). This sounds reasonable, but we know from different trials that there can be a discrepancy between PET and actual lymph node sampling itself, with false negatives and false positives.
This isn’t ideal if somebody is on the cusp between having radical surgery or needing combination therapy, for example, with neoadjuvant treatment. We know that even with PET/CT and EBUS, you can still miss some patients with nodal disease, and it only becomes evident at time of surgery when you’re removing the entire node.
Accurate staging is important. There are different ways of deciding which lymph nodes are higher risk. Sometimes it’s at ultrasonography when you recognise the risk. At the time of EBUS, you can accurately measure the size, which can be more accurate than CT, PET and PET/CT. And you may well see that the nodes are actually a conglomerate of nodes, for example.
The shape can be helpful: is it oval versus round? Are the margins clear? This is a really good one because very often when you can’t find the lymph node or you can’t really see the margins, it can sometimes be reassuring compared to where you see distinct margins.
Is it homogenous, does it echo-signal consistently throughout or have subtle changes between one area and the next? Is the central hilum structure present or is it absent? Is there any evidence of necrosis?
In future, we’re largely trying to transition to any lymph node over 10 millimetres on CT being biopsied, as well as any lymph node with fluorodeoxyglucose avidity and any lymph node with high-risk features. The only way you can do that is by doing an EBUS.
The TNM 8th edition is what we’re using at the moment and the TNM 9th edition, which is due to go live imminently. The changes are reasonably subtle and there’s no significant ground shift in how we stage lung cancers.
First of all, N2 lymph nodes are going to be split into N2a and N2b. Currently it’s just N1, N2, N3 and we’re now going to have a sub-category for lymph node station N2, with N2a being single station involvement and N2b being multiple station involvement.
It doesn’t really comment too much on size here, so it still does need a little bit of working out in MDT with what you’re going to do with different lymph node groups and how it may or may not change your management and approach to the patient.
Then you’ve got your M stages. M1a and M1b are largely unchanged but M1c is split into M1c1 and M1c2.
M1c1 is multiple extrathoracic metastases in a single organ system, so multiple liver or brain metastases, rather than single metastases, and M1c2 is extrathoracic metastases in multiple organ systems.
This will subtly change the staging and may make a difference to what your approach might be. Having metastases doesn’t mean you don’t have radically treatable disease, and our oncology teams have specific MDTs for patients with metastatic disease and stereotactic ablative radiotherapy MDTs.
More and more of these metastatic diseases can be treated and that’s why it’s important to differentiate between M1b, M1c1 and M1c2 because some of these patients, particularly with M1b may well still have radically treatable disease if it’s just a single metastasis in a single organ.
Dr Zaheer Mangera is a respiratory consultant and the lung cancer lead at North Middlesex University Hospital, now part of the Royal Free London NHS Foundation Trust in London, UK.
10th February 2025
Rising drug costs are putting increasing pressure on healthcare systems, highlighting the need for rational and responsible medicines use, according to a new study looking at cost-effective and sustainable drug use in hospitals.
Conducted at Erasmus University Medical Centre in Rotterdam, Netherlands, this research developed a systematic framework known as the 8-Step Efficiency Model to identify and implement medicines cost-saving strategies while maintaining high standards of patient care.
The Model was developed through collaboration between clinical pharmacists, physicians and business analysts.
Some 39 high-cost drugs, which accounted for 57% of national drug expenditure in 2021, were assessed using the Model, with strategies explored for implementing cost-effectiveness. Evidence-based practices guided the development of this framework, with input from a broad range of stakeholders.
From the initial analysis, cost-saving initiatives focused on 27 agents. For instance, switching anti-tumour necrosis factor therapies to biosimilars resulted in savings of 7–7.5% per patient annually, totalling €320,000. A further €10,000 was saved by dose-rounding to the nearest full vial of infliximab.
Additionally, the authors developed a strategy for intravenous immunoglobulin (IVIg) weight-based dosing. This database analysis comparing IVIg plasma concentrations across various body mass index groups will potentially reduce costs by €670,000 annually.
‘The model presented in this study can guide clinicians in identifying, developing, and implementing novel strategies for cost-effective drug use at the hospital level,’ the researchers said.
They also highlighted how the Model could help reduce the environmental footprint by promoting more sustainable drug use practices.
Hospital pharmacists can apply the 8-Step Efficiency Model at their own institutions to identify cost-optimisation opportunities, reduce drug waste and ultimately enhance sustainability in clinical practice.
A three-stage implementation framework, developed in parallel to the Model, was crucial for helping hospital pharmacists and other stakeholders integrate the Model effectively.
The authors recommended that future research should focus on interventional pharmacoeconomic trials which evaluate the impact of initiatives like this Model. They also call for increased collaboration between healthcare providers, insurers and pharmaceutical companies to accelerate the adoption of cost-effective drug use strategies across healthcare systems.
Reference
Zietse M, et al. Cost-Effective and Sustainable Drug Use in Hospitals: A Systematic and Practice-Based Approach. Appl Health Econ Health Policy. 2024 Dec 19. doi: 10.1007/s40258-024-00937-6.
With Great Western Hospitals NHS Foundation Trust recently receiving recognition from NHS England as an exemplar site for sustainability in infection prevention and control, Katherine Price finds out what initiatives they implemented, how clinical staff got involved and how other hospitals and Trusts can take inspiration to achieve their own sustainability goals.
From floods in Spain to wildfires in Los Angeles, healthcare professionals globally are continuing to see the devastating impacts of climate change first hand, and the UK is no exception.
While many individuals are identifying ways to reduce the environmental impact of their clinical practice and driving change, the NHS in England recognised the need for formal, integrated processes to meet its net zero by 2045 target.
Following discussions with NHS England, Great Western Hospitals (GWH) NHS Foundation Trust in Swindon became the pilot site for an exemplar sustainability project. It received around £2,000 towards a four-month programme of initiatives and to create a replicable model, including governance and reporting structures, for sustainability quality improvement.
A clinical sustainability group – chaired by Graham Pike, associate director of nursing and infection prevention and control and clinical sustainability lead – was established in January 2024 to oversee progress. The group included representatives from infection prevention and control (IPC), sustainability, quality improvement, facilities management, pharmacy and procurement.
Following the successful pilot, GWH became the first organisation recognised by NHS England as an exemplar site for sustainability in IPC practices.
As IPC touches all areas of practice, it is ‘crucial to optimise sustainable practice’ in this area, says Rachel McLean, sustainable quality improvement programme lead at the Centre for Sustainable Healthcare.
Many practices in hospitals are driven by fear or risk of infection, and Graham says this includes ‘the products we use, the procedures we do, the way we do them and how we dispose of things’. And while sometimes those risks are real, if the rationale and evidence are lacking, there may be opportunities to identify and adopt more sustainable practices without compromising patient care.
As part of its efforts in the pilot project, GWH implemented a series of 11 initiatives that other hospitals around the UK and beyond can take inspiration from to make strides towards their own sustainability goals, of which three had a particularly big impact.
Many UK hospitals change patient bedsheets daily. Although regular linen changes are important for IPC, evidence supporting the daily changing of unsoiled sheets is lacking. ‘This is a really good example of “we do it this way because we’ve always done it this way”, and how we need to review everything we do – can we do it less, can we do it differently?’ says Graham.
A proposal to move to twice-weekly linen changes – excepting specified circumstances – was approved by the Trust’s infection control group, received positive feedback from the public and now is being trialled.
Reducing glove use was a priority, which saw GWH adopt the Intensive Care Society’s Gloves Off in Critical Care campaign.
‘There’s plenty of evidence out there that the unnecessary use of gloves, as well as being a waste and costing money, increases the risk of infection,’ says Graham. Posters showing when and when not to wear gloves were displayed by patient bedspaces and emails, articles and a webinar on glove use were shared among to team members.
Subsequently, the percentage of staff observed performing a procedure where inappropriate use of gloves risked cross-contamination fell from 63% to 20%. Hand washing observed before glove application improved from 15% to 70% of cases, and hand washing after glove removal increased from 20% to 90%.
Procurement data showed a 22% reduction in glove use over three months that, if sustained, would lead to a £1,382 annual saving for the hospital and prevent 1.6 tonnes of CO2e emissions.
GWH’s emergency department (ED) also set about working towards the Royal College of Emergency Medicine’s GreenED sustainability accreditation. ‘There were challenges on that – how do you release the staff to do the project and how do you fund [it]?’ says Graham. Pilot funding helped pay for the registration fee and staff time – and GWH became one of the first five GreenED accredited sites in the UK, and one of just two to achieve silver.
This scheme specifically encourages reduced cannulation and, after developing and displaying clear cannulation criteria, GWH saw a 29% reduction over three months. Since the pilot, this has continued to a 40% reduction – approximately the same amount of CO2e as nine flights between London and New York.
There can be a perceived conflict between IPC and sustainability, and Graham says existing case studies were a valuable resource to allay anxiety, for example when shifting to use reusable theatre caps.
‘Data demonstrating the potential or actual impact of improvement is important,’ explains Rachel. ‘If you don’t fully understand the problem beforehand and have baseline data, you won’t be able to show you have improved care later. Utilising existing case studies which demonstrate tangible benefits – for example, carbon and cost savings – can build trust that similar initiatives will be successful in another setting.’
She also suggests tailored messaging highlighting the range of benefits, including time savings, and, of course, improvement in patient outcomes.
Generally, it was straightforward to achieve buy-in for the project from colleagues across all departments and seniority, Graham recalls, partly because there is increasing concern about the effects of climate change.
‘There are a lot of staff out there who are worried,’ he says. ‘They see the waste that’s generated by healthcare every day and people are increasingly aware of climate change.’
Graham recommends working with managers to identify team members keen to drive sustainability projects within their departments. Two intensive care nurses at GWH led the Gloves Off project, for example. Already frustrated by glove waste in their unit, the project empowered them to implement and drive change, and Graham says they ‘did a cracking job of engaging the rest of the team’.
Rachel adds that collaboration ensures staff ‘feel ownership over an improvement and that changes are made in a way that best embeds them into the existing workflow and everyday systems’.
Following completion of the pilot at GWH, trials continue, initiatives are being rolled out, more sustainability groups have been established across the hospital. Sights are also set on GreenED gold accreditation.
Every project created a ripple of discussion and action, says Graham, and funding staff time to focus on sustainability identified significant cost savings as well as opportunities to reduce environmental impact, highlighting an important return on investment.
Formalising the relationship between IPC and sustainability also ensured projects progressed more quickly and consistently, resulting in an exemplar site project report that can be adapted to service, resource and patient need.
7th February 2025
New research highlights the potential of a novel diagnostic tool to determine the innate immune profiles of patients with stage 2 melanoma and help predict who is most likely to respond to immunotherapy treatment.
Using immune time-resolved Förster resonance energy transfer (iFRET), researchers measured functional biomarkers and provided real-time information to profile immune responses in melanoma patients. For patients with stage 2 melanoma, iFRET was able to predict the value and effectiveness of neoadjuvant oncolytic virus therapy.
The UK and US researchers used tissue from a pilot phase II study of neoadjuvant talimogene laherparepvec (TVEC) – this is a modified oncolytic virus injected directly into melanoma to stimulate an immune response and destroy cancer cells before standard surgery.
They used iFRET to determine how the therapy affected immune checkpoint activity, specifically examining the interactions of the proteins programmed death-ligand 1 (PD-L1) on tumour cells or immune cells and programmed cell death protein 1 (PD-1) on immune cells in the tumour immune microenvironment before and after therapy.
The tumours responsive to immunotherapy showed a significant increase in iFRET efficiency, reflecting a more active immune response and the likelihood of a better response. Unresponsive tumours either showed decreased checkpoint engagement with fewer PD-L1:PD-1 interactions or failed to demonstrate an immune response to therapy.
The researchers also found that traditional biomarkers did not reliably predict a tumour’s response to immunotherapy, as the level of checkpoint engagement did not link to changes in PD-L1 expression.
However, macrophage behaviour did correlate with patients who responded to the treatment and those who did not, suggesting that tumour-associated macrophage phenotypes play a key role in the effectiveness of TVEC therapy.
Clinicians could potentially reprogramme the tumour’s immune environment by targeting macrophages in non-responding patients, the researchers concluded.
In addition, strong PD-L1:PD-1 interactions in the tumour beds correlated with a better response to the treatment.
The findings highlight the importance of examining the whole immune response environment to predict which patients would be better served by either surgery or immune checkpoint blockade via immunotherapy.
In future work, the team will attempt to characterise all cells contributing to the immune checkpoint interaction, further improving patient stratification and personalised medicine.
Reference
Kirane, A et al. Toward Functional Biomarkers of Response to Neoadjuvant Oncolytic Virus in Stage II Melanoma: Immune-Förster Resonance Energy Transfer and the Dynamic Tumor Immune Microenvironment. JCO Oncology Advances 2025; Jan 02: DOI: 10.1200/OA-24-00049.
6th February 2025
Phage therapy presents a promising solution in the fight against antimicrobial resistance, particularly for infections caused by multidrug-resistant bacteria. As the need for, and interest in, phage therapy grows, hospital pharmacists and clinicians must understand guidance on patient selection, treatment administration and regulatory compliance. Here, Gerry Hughes explores the current landscape of phage therapy, including the role of healthcare professionals and optimising patient outcomes, with insights into two established phage services.
The phages discussed in this article refer to naturally occurring phages and phage cocktails and do not refer to genetically modified phages.
Bacteriophages, or phages, are naturally occurring viruses that specifically target and kill bacteria. Discovered in the early 20th century, phages were initially used as an alternative to antibiotics for treating bacterial infections. However, the widespread use of antibiotics led to a decline in their use in Western medicine.
In recent years, phages have regained attention due to the growing problem of antimicrobial resistance (AMR). This issue arises when bacteria develop resistance to multiple antibiotics, rendering traditional treatments less effective, especially for infections caused by multidrug-resistant (MDR) organisms such as Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.
Phage therapy has shown promise as a targeted, adaptive solution for these infections. As global demand for effective AMR treatments grows, phage therapy provides an alternative to combatting MDR infections.
Phage therapy is especially beneficial for treating infections caused by MDR bacteria when conventional antibiotics fail. A recent multicentre, retrospective study involving 100 patients treated with personalised phage therapy reported promising results. The study, conducted from 2008 to 2022, involved 35 hospitals across 12 countries and demonstrated clinical improvement in 77.2% of infections, with 61.3% of bacterial infections eradicated by the targeted bacteriophages.
The most commonly treated pathogens were Pseudomonas aeruginosa and Staphylococcus aureus, with phage preparations tailored to the specific bacterial strains isolated from each patient. When phage therapy was combined with antibiotics, bacterial eradication was more likely, highlighting the synergy between the two.
The process of guiding hospital pharmacists and clinicians on the safe and effective delivery of phage therapy is collaborative and involves multiple stages.
‘Once a request comes in, we get in touch with the treating doctor,’ explains Dr Maya Merabishvili, senior scientist at Queen Astrid Military Hospital (QAMH) in Belgium – a leading centre for phage therapy. ‘We then receive the medical file, assess whether the case is eligible for phage therapy, and if we have phages available for the pathogen.
‘The bacterial strain is sent to our lab, where we test our phage collection for compatibility. If no phages work, we inform the hospital that we have no solution. If several phages are effective, we test their compatibility to determine the best combination.’
The information on phage-antibiotic synergy is then provided to the clinicians involved in the patient’s care. ‘We prepare a phagogram detailing which phages showed activity,’ Dr Merabishvili continues. ‘We also check which antibiotics can be used with the phages and send the phages along with this information to the hospital pharmacy.’
In the UK, the National Clinical Phage Service, which was established in 2022, provides similar support. Dr Josh Jones, virologist and director of this service, explains that the service ‘operates a “bench to bedside” service for clinicians using phage therapy’, which begins with the clinician filling out a request form.
‘We’ll screen our phage library against the bacterial isolate we receive, and if we get a match, we’ll contact the manufacturer to get the phage produced, often within the EU, and then import it,’ he explains. ‘If we don’t get a match from our diagnostic panel, we go to international groups to source phages from there.’
Hospital pharmacists are essential brokers in sourcing safe, evidence-based phage therapy for patients with infections.
Phage therapy is particularly suitable for patients with chronic infections or those infected with MDR pathogens, and hospital pharmacists involved in antimicrobial stewardship or infectious disease management may assist in selecting appropriate candidates.
Once phage therapy is deemed suitable, hospital pharmacists with expertise in medicines management or aseptic compounding are typically involved in the safe procurement, storage, and administration of phages.
Dr Jones and a group of consultants from the UK have recently published guidance on assessing the suitability of patients for phage therapy, including considerations for special populations such as pregnant or breastfeeding patients, which can be used alongside support from the National Clinical Phage Service.
‘We offer clinical and scientific support to multidisciplinary teams and help with unlicensed medicines applications,’ Dr Jones says. ‘For pharmacists, we provide support in handling and storing phages safely. It’s about capacity building, education and awareness for NHS pharmacy departments so they can confidently handle phages in their own Trusts.’
Hospital pharmacists must ensure that phage preparations meet stringent safety standards and there are a range of quality assurance measures that should be taken into account, including dosing, stability and, as Dr Merabishvili explains, sterility.
‘The phages we send are sterile preparations, and we make sure the environment guarantees the sterility of the final product that will go to the patient. We work within biosafety cabinets to ensure the final product is sterile,’ she says.
In some cases, hospital pharmacists may need to perform further compounding of phage products and guidance on dilution of phages is also provided within Dr Merabishvili’s process.
‘Sometimes, the phage preparations we send are concentrated, and they need to be diluted by 100 or 1,000 times,’ she says. ‘This can be challenging for pharmacists [so] we provide a schema outlining the proper dilution steps.’
In contrast, phage therapy supplied by the UK’s National Clinical Phage Service comes in a ready-to-use format with no further manipulation required.
As phage therapy is still considered an unlicensed treatment, including in the EU and UK, hospital pharmacists must ensure that it is administered in compliance with regional regulations, and that informed consent is obtained from patients.
‘Phage therapy should be used in accordance with unlicensed medicines guidance, which pharmacists should be familiar with. Each local NHS Trust will also have its own unlicensed medicines policy,’ says Dr Jones.
How is phage therapy perceived by clinicians and patients? A recent survey of clinicians showed significant interest in phage therapy, especially given the rising threat of AMR. A majority of clinicians (71%) expressed willingness to consider phage therapy in appropriate cases, though just over half (59%) had previously heard of it.
Patient perceptions are similarly positive. In a study of diabetic foot infection patients, most were initially unfamiliar with phage therapy. However, when provided with clear information, over 89% said they would consider phage therapy if antibiotics failed. Patients viewed phage therapy as a hopeful alternative to invasive treatments like amputation.
Many patients also expressed interest in participating in clinical trials for phage therapy, indicating a strong desire for additional treatment options in the face of AMR.
Phage therapy holds significant potential in the fight against AMR, offering a promising solution for difficult-to-treat infections. The establishment of the UK’s National Clinical Phage Service marked a major step forward, and this, along with the work being done elsewhere in Europe, suggests there is considerable hope for the future.
As phage therapy develops, its integration into healthcare systems could revolutionise the treatment of infections, providing a sustainable, antibiotic-sparing approach. This innovation is poised to become a critical tool in addressing the global AMR crisis.