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Press Releases

Take a look at a selection of our recent media coverage:

National patient safety initiatives in the Netherlands

28th April 2023

The Dutch Hospital Patient Safety Program started in 2008. It initially ran for five years, and its aim was to decrease adverse events by 50% in all Dutch hospitals.

A second National Safety Program launched in 2020. This focuses on reflection, interprofessional collaboration and explaining process variation in daily practice. It also looks to foster more patient involvement and shared decision making. The ultimate aim is to reach a significant reduction in preventable patient harm.

This webinar provides an overview of patient safety in the Netherlands and discusses these two initiatives and their implementation, outcomes and ongoing impact.

Development of a Regional Strategy for Patient Safety Improvement

Management of Belgium’s healthcare system is complex, with federal financing and regional regulation and strategy for areas such as patient safety improvement.

The development of a Regional Strategy for Patient Safety Improvement involved two surveys. The first looked at system-level, organisational and clinical-level interventions and resulted in a list of top priorities.

PAQS released a second survey at the end of 2018. It asked healthcare professionals to consider the current situation and how it could be improved.

This webinar discusses healthcare in Belgium and analyses the survey results and the development of the regional strategy.

Health in Bulgaria

The Covid-19 pandemic has temporarily reversed years of progress in life expectancy for people in Bulgaria, for whom life expectancy was already the lowest in the EU in 2019.

Despite health system improvements over the last decade, the impact of persistently high risk factors, high out-of-pocket payments and excessively hospital-centred care continue to hamper the system’s performance.

The Covid-19 pandemic highlighted the need for additional investment in the health sector, including better preparedness for future health system shocks. For Bulgaria, this challenge also includes investment to create a uniform health information system to speed up the use of e-health and to ensure appropriate working conditions for the health workforce.

Bulgaria’s health status

Overall life expectancy at birth in Bulgaria temporarily fell by 1.5 years in 2020 compared to 2019, largely due to the high number of deaths from the Covid-19 pandemic. Stroke, ischaemic heart disease and lung cancer are the leading causes of death and accounted for one third of all deaths in 2018.

Bulgaria life expectancy gains

Risk factors

Smoking, unhealthy diets, alcohol consumption and low physical activity are responsible for nearly half of all deaths in Bulgaria. The adult and adolescent smoking rates are the highest in the EU. Alcohol consumption among adolescents is also a concern. In contrast, obesity among adults is below the EU average.

Unhealthy habits

Bulgaria’s health system

Bulgaria’s health expenditure per capita has doubled overall since 2005. However, it remains much lower than that of the EU as a whole, both in absolute terms and as a share of GDP. Public financing of the health system accounted for 61% of health spending in 2019. Out-of-pocket spending (38%), driven mainly by costs for outpatient pharmaceuticals, was more than 2.5-times the EU average.

Per capita health expenditure

Effectiveness

Deaths from both preventable and treatable causes are well above the rates for the EU as a whole, reflecting weak primary prevention and health promotion activities, as well as the need to improve diagnosis and treatment protocols for leading causes of death. Survival rates for the most prevalent cancers are among the lowest in the EU.

Bulgaria age-standardised mortality rate

Accessibility

Prior to the Covid-19 pandemic, Bulgaria’s rate of self-reported unmet medical needs had declined to reach just below the EU’s average. However, during the first 12 months of the pandemic, nearly 25% of the population reported having to forgo care compared with 21% in the EU27. Out-of-pocket spending levels, insurance coverage gaps, referral quotas and uneven distribution of medical personnel and equipment across the country remain challenges to access.

Healthcare accessibility

Resilience

Bulgaria had enough intensive care unit and acute bed capacity to treat Covid-19 cases when the hospital system came under strain. The rollout of Bulgaria’s Covid-19 vaccination campaign has been slow and, as of the end of August 2021, only 17% of the population had received two doses (or equivalent).

Share of total population vaccinated against Covid-19

OECD/European Observatory on Health Systems and Policies (2021), Bulgaria: Country Health Profile 2021, State of Health in the EU, OECD Publishing, Paris/European Observatory on Health Systems and Policies, Brussels.

Critical incident reporting systems in Germany

20th April 2023

In Germany, hospital risk management is organised around cross-institutional critical incident reporting systems based on a legal framework to increase joint learning and improve patient safety.

This webinar outlines this legal framework, discusses the results of related projects and provides an example of such a system used for national, interprofessional and interdisciplinary learning: Krankenhaus-CIRS-Netz Deutschland 2.0.

Focus on heart failure: Dr Andrew Coats

17th April 2023

Dr Andrew Coats describes himself as a career cardiologist specialising in heart failure. He is CEO and scientific director of the Heart Research Institute in Sydney, Australia.

Andrew Coats

Spending around two-thirds of his time in Australia and the remainder in the UK, Dr Coats has had three separate careers. He left medicine to pursue several management and fund-raising roles, took up an academic position and finally moved into commercialisation – currently holding many patents and three start-up companies focusing on devices related to heart failure.

He spoke to Hospital Healthcare Europe about his career and work in cardiology.

Tell us about the work done by the Heart Research Institute

The Institute is dedicated to heart disease and is a basic science research institute looking at novel treatments. In addition to running the Institute, I still find time to see patients, where my focus is on heart failure. The centre is involved with the delivery of a wide range of cardiovascular treatments and interventions, including transplantations.

What do you think are the main challenges in setting up a clinical centre?

The challenge in healthcare is getting funding for ever more that you can do. Running a clinical service in the NHS, as I did in the early 2000s, brings its own challenges, especially managing performance, but having an MBA management qualification helps a lot. While most managers look for ways to increase staff performance, in the NHS setting I had to manage performance differently. Given a fixed annual budget for the services we could provide, my role was to prevent surgeons and cardiologists from undertaking too much work and spending the fixed annual budget too quickly. But managing a service is difficult with the overarching challenge being to make it all work under cost pressures, disease pressures, surviving the Covid-19 era, dealing with political diktats and doing it all affordably, despite the demand from an ageing population and expectations increasing.

Are there any professional achievements that particularly stand out for you?

While there are many clinical and scientific achievements within the organisation, the people are both our best weapon and our worst enemy. Consequently, it is fundamental to achieve a sense of team spirit, effective leadership and communication – you can do 10 times more if you align people and if they’re working together. You can have people who are working furiously for what they perceive as the important pressures and what they’re trying to achieve, but a lot of that effort is wasted if they’re not co-ordinated. The biggest challenges and the greatest successes are achieving a joined-up sense of working together.

It’s not so much the written strategy for an organisation that is ultimately important but the process of writing one because you get people to talk to each other and understand each other’s perspective. This creates a shared understanding of what they are trying to achieve together and not just their piece of the puzzle. This shared understanding is crucial to the success of a service, largely because it allows clinicians, whose primary focus is patient care, to appreciate the wider perspective of the service as a whole.

Does the Institute offer clinician training?

The Institute has formalised and written curricula, which are accredited, for young doctors wishing to specialise in cardiology. These doctors are allocated to hospitals with dedicated trainers and educators to allow them the necessary time to gain experience and become independent consultants a few years later. Over the last 10 to 15 years, there has been a greater and separate accreditation for their ability to perform certain complex or high-risk procedures. This requires the clinician to demonstrate capability, audit their practice and do a minimum number of procedures every year to maintain their accreditation.

Tell us about the clinical research you’re involved in for heart failure

Today, I’m a clinical researcher who evaluates patients rather than undertaking laboratory-based work. In other words, assessing patients’ responses to treatment or the impact of novel devices and involvement with clinical trials. I’ve been involved in many studies over the years and some have led to changes in clinical practice. For instance, I was the first to demonstrate the huge benefits of exercise among those with end-stage heart failure awaiting a transplant, dispelling the perceived wisdom at the time that such patients should not exercise. While not the only group, my team and I were able to show that beta-blockers – which were thought to worsen heart failure and should therefore be avoided – could in fact improve survival if started slowly. More recently, I’ve worked with others to discover that the SGLT-2 inhibitors designed for use in type 2 diabetes are effective in heart failure.

While there have been many benefits associated with medical treatments, devices are very much a growth area. This includes several device therapies that, for instance, can cause electrical stimulation and blockade of the reflex control system, as well as those pacing the heart in a more sophisticated way. Or even devices to control blood flow across the chambers of the heart. Such devices, together with stem cell and gene therapy and monoclonal antibodies, mean the developments in heart failure occur from a variety of different sources.

Looking forward, what do you feel are the key remaining challenges in heart failure and cardiovascular disease?

Perhaps one of the biggest challenges in cardiovascular disease is the need for a paradigm shift in the treatment approach. There are currently two diametrically opposed approaches: splitters and lumpers. The splitters’ philosophy is predicated on the belief that because every patient is unique, treatment should be personalised. In contrast, lumpers believe it is more productive to focus on a particular disease and perform trials to see what works. However, while the lumper approach identifies benefits for patients with a particular condition, these interventions are not always 100% effective.

In heart failure, for example, there are actually two types: a low and a high ejection fraction. Drug treatments mainly work in low ejection fraction. In fact, when drug therapy was used in those with a high ejection fraction, the treatment was ineffective simply because there are several possible causes of this type of heart failure. In trying to better understand which patients are likely to respond to a treatment intervention, cardiologists have borrowed the strategy of precision medicine used by oncologists.

It therefore becomes possible to define patients into much smaller subtypes of disease and then optimise the treatments for this subgroup. While patient identification may initially be more expensive, the overall cost to the health service is lower as there are a smaller number of patients within each subtype. In short, the challenge is therefore to move cardiology from lumpers to splitters and develop more precision medicine.

I’m also involved in multiple research projects developing a raft of innovations, and these will hopefully deliver improvements to the care of patients with heart failure in the coming years.

Dr Coats is an advisory board member for HHE Clinical Excellence in Cardiovascular Care. He will be chairing a panel discussion at the event on 10 May 2023. Find out more and register for free here.

Join us at HHE Clinical Excellence in Cardiovascular Care

6th April 2023

Hear the latest advances and innovations in cardiovascular care at a new event from Hospital Healthcare Europe in May 2023

In support of our mission to provide high-quality clinical education, Hospital Healthcare Europe is proud to announce a new series of events in 2023: the HHE Clinical Excellence programme.

Kicking off with cardiology and developed in conjunction with an expert advisory board of renowned key opinion and thought leaders from UK Centres of Excellence, our first one-day event on 10 May 2023 will allow you to explore the latest advances and innovations in cardiovascular care.

The event is free to attend and comprises individual presentations, panel discussions and sponsored sessions delivered virtually live and on-demand, all tailored to provide maximum convenience and work around your busy schedule.

Why should you attend?

  • Learn from Centres of Excellence across the UK about their pioneering approaches to optimising patient care
  • Explore clinical advances in areas ranging from preventative cardiology, heart failure and interventional cardiology
  • Understand how different hospitals and departments are utilising multidisciplinary teams to improve clinical outcomes
  • Select the sessions that are most relevant to your clinical practice
  • Recordings are available free for a minimum of three months, so catch up at your convenience, and
  • Gain CPD hours

What’s on the agenda?

  • Cardiology: evolution over the past 100 years
  • Advances in preventative cardiology in primary and secondary care
  • The demand for cardio-oncology services
  • Use and misuse of modern technologies
  • Advances in cardio-lipido-diabetology

How do you attend?

Tickets to attend the HHE Clinical Excellence events are free. Book them here. Tickets allow virtual access to all the talks throughout the day. And if you miss any of the sessions, catch up on-demand at a time to suit your schedule!

Save the date! And register to join us on 10 May 2023!

Automated dispensing systems for the safe management of controlled drugs

25th February 2023

The use of automated dispensing cabinets for controlled drugs on hospital wards has had proven benefits on patient care and medication safety. Can these benefits be replicated in a hospital pharmacy?

Controlled drug medicines must be stored securely and their use requires chronological detailed records in a controlled drug register.1,2 Challenges with management of controlled drugs in a hospital pharmacy include time-intensive mandatory record keeping processes and physical reconciliation of stock, often further compounded by inadequate storage facilities and capacity. 

UK hospital pharmacies have sought to increase the  use of robotics, and while there are limited published data on quantitative outcomes, the consensus is that they have provided benefits through a reduction in dispensing errors and improvements in dispensing efficiency.3,4 However, robotics systems have not been used for controlled drugs due to difficulties in complying with legislative storage and record keeping requirements, thus leaving controlled drugs to be managed through traditional lock and key cupboards and paper ledgers for documentation.

Automated dispensing cabinets

Automated dispensing cabinets (ADCs) utilise technology to increase efficiencies and effectiveness on hospital wards and reduce the rate and risk of adverse drug events.5,6 ADCs have been widely implemented in UK hospital wards but not in pharmacies. ADCs are computerised storage cabinets, which integrate with hospital systems, utilising biometric technology eliminating the requirements for keys. Configuration of the ADC allows separation of medicines that look alike and sound alike, thus minimising the risk of medication selection errors. 

There is extensive literature on medication errors, defined as any preventable event that may lead to an inappropriate medication use or patient harm.7 The use of automated systems has improved the processes for using medication safely. The Institute for Safe Medicines Practice has stated that the automation of medicines management processes is a high-powered risk minimisation strategy in enhancing medication safety.8 There are many reports on the benefits of ADCs in ward settings and their impact on reducing medicine administration errors, omission of medicines and medicine storage errors in addition to increasing resource management efficiency.7,9 

However, there is little information in the literature on using automated dispensing systems for the management of controlled drugs in a pharmacy setting.

Background

Belfast Health and Social Care Trust (BHSCT) is the largest health and social care trust in the UK. It provides the majority of regional specialist services and its hospitals are the major teaching and training hospitals for Northern Ireland. Within the Royal Victoria Hospital pharmacy department, controlled drug medicines were stored in a small controlled drug strong room on open shelving in alphabetical order. Over 80 paper controlled drug registers were in use at any time. There had been a 20% increase in controlled drug dispensing activity in the five-year period from 2013 to 2018. Additionally, the Carter Report recommended that hospital pharmacies should have a 15-day stock holding of medicines.10 This placed an enormous pressure on storage capacity and adversely affected working conditions within the strong room. The high volume of work processed led to an increase in errors including medicine mis-selection, documentation and stock control all of which contributed to heightened staff anxieties when assigned to controlled drug tasks.

The project sought to establish if an ADC in the pharmacy could improve medicines safety, release efficiencies and improve the experience of staff delivering the service. This was the first time an ADC had been installed in a pharmacy in Northern Ireland.

Method

A number of baseline measurements of controlled drug activities were completed to define the aims of the project. Observation of workflow patterns revealed that in addition to core dispensing and supply activities, a significant amount of time each day was required by staff to verify and correct controlled drug registers. These observations led to the development of a driver diagram (Figure 1).


Figure 1: Driver diagram (adapted from NHS Improvments11) – click image to enlarge

The project hypothesis was that the installation of an ADC would see a reduction in controlled drug errors along with a decrease in dispensing times, which would be achieved by reconfiguring process steps. The dispensary manager and controlled drug technicians took part in a focus group workshop to scope and design new workflows using an ADC. The workshop was crucial to the success of the project and ensured that the core dispensary team were engaged with the improvement process. An intensive training plan was developed; key personnel were nominated as super-users and received additional specific training commensurate with that role. The project team were mindful that change management was critical to obtaining a successful outcome and that challenges with a project such as this may be behavioural rather than technical.12 In total, 131 staff had received training on the ADC by the time of project Go-Live. 

A seven-cell Omnicell automated dispensing cabinet was installed in the pharmacy department in November 2019. 

Results and discussion

In the pre-ADC period, dispensing data were collated at various times over a two-week period; the data included controlled drug items dispensed to replenish ward stock, and controlled drug items required for patients’ discharge prescriptions. The sample size of 66 items was equivalent to approximately 20% of the weekly controlled drug dispensing workload. Analysis of the dispensing process revealed there were five core steps in the preparation of a controlled drug item:

  • Labelling
  • Assembly 
  • Product release 
  • CD register entry 
  • CD stock check verification.

The average time to dispense a controlled drug medicine was 6 minutes and 18 seconds. 

There are two distinct dispensing processes for controlled drugs within the pharmacy: items required for ward stock replenishment (typical supply is an original pack); and supply for discharge prescriptions, which must be the exact quantity for seven days as per regional policy.

The average length of time to dispense an original pack of a controlled drug for ward stock was 5 minutes and 47 seconds. The average length of time to dispense a 7-day supply of a controlled drug was 8 minutes and 12 seconds due the additional steps of packing down into individually labelled containers.

Analysis of the individual dispensing steps found that 43% of the total time was required to complete the controlled drug register entry and verify stock balance.

Three weeks after implementation of the ADC, dispensing data were collated for 76 items over a two-week period, equivalent to approximately 25% of the weekly workload. To replicate the pre-ADC data collection, a similar proportion of ward stock and prescription items dispensed was observed.

The number of discrete steps in the dispensing process had reduced from five to four. That is:

  • Labelling 
  • ADC input (formerly CD register and stock check verification)
  • Assembly 
  • Product release.

The impact on dispensing process times was immediate, with the average time taken to dispense a controlled drug item of 2 minutes and 41 seconds (a reduction of 57%).

The average time required to dispense a controlled drug for ward stock was 2 minutes and 8 seconds, which is a 63% reduction in dispensing time. The time taken to dispense a discharge item was on average of 3 minutes and 35 seconds, a reduction of 56%.

The SPC I-chart for dispensing a ward stock item (Figure 2) shows a level of instability and variation in dispensing times in phase 1; however, no rules for special cause variation were observed. In phase 2, there was one data point above the upper control limit, which could have been operator-related, possibly attributed to using the new system. There were 15 consecutive data points close to the centre line suggesting that the improvement in the mean dispensing times was not by chance.

Figure 2: SPC I chart: Time taken to dispense a controlled drug requisition – click image to enlarge

Review of the SPC I-chart for prescription dispensing times (Figure 3) found that in phase 1, although dispensing times were longer there was less variability between data points. In phase 2, although the mean dispensing time had reduced, none of the rules for special cause variation could be applied, possibly due to the smaller sample size. 

Figure 3: SPC I chart: Time take to dispense a controlled drug prescription – click image to enlarge

A Mann–Whitney test was performed on the dispensing times and resulted in a p-value <0.00001, suggesting that the elimination of the paper controlled drug register is significant in terms of efficiency gains.

Further analysis of the dispensing steps using the ADC found on average 36 seconds per transaction was saved during the selection and assembly phase.This can be attributed to ADC technology, which uses a series of guiding lights to direct the dispenser to the required bin location. 

The primary objective of this project was medication safety and therefore patient safety; the layout of the ADC was enhanced to optimise risk minimisation strategies, this included configuring all controlled drug items to individual bins or zones. The RVH Pharmacy ADC system was the first in the UK to implement this design approach.

Errors and documentation

In the three-week period prior to installation of the ADC, an error-recording log was designed to record controlled drug-related errors including documentation, issuing or selection errors. An error rate of 24 errors per 1000 items dispensed was calculated; analysis of the errors recorded found that 82% were attributed to documentation, subtraction errors in running balance or omitted entries. It took 135 minutes to correct the documentation errors. 

In the three-week period immediately following implementation of the ADC, the electronic controlled drug register was reviewed and an error rate of 9 errors per 1000 items dispensed was calculated. The errors recorded were categorised as operational, for example, wrong quantity selected on pharmacy dispensing system or counting errors. These errors were communicated to the team and operating protocols were revised to ensure staff were clear on management of procedural issues. The interface between the pharmacy dispensing system and electronic controlled drug register eliminated previously noted documentation errors. 

The BHSCT extended hours seven-day pharmacy service is delivered by the RVH Pharmacy department with staff from four pharmacy departments contributing to the weekend and evening rotas. Prior to the implementation of the ADC staff reported that controlled drug tasks were difficult and stressful particularly at weekends. Contributing factors were a high volume workload, and range and complexity of controlled drug dispensing, which led to documentation and discrepancy errors. There was staff dissatisfaction with the manual dispensing process and recognition of the potential risk of picking the wrong injection, including incorrect ampoule size or strength. All of these factors influenced the department’s ability to achieve key performance targets for dispensing times. 

Following implementation of the ADC, staff reported liking the layout of the cabinet, noting it was easy to use and felt safer as every item had a specific location within the cabinet. There was huge satisfaction that paper registers were no longer required. Staff perceptions were that the ADC enables them to perform their duties more safely; this is reflected in similar studies among staff using an ADC at ward level.13 The implementation of the ADC and associated workflow helps staff to complete dispensing processes accurately and safely eliminate documentation errors. 

Return on investment

Implementation of a large-scale automation project such as this requires significant financial investment. Efficiencies achieved from streamlining the dispensing processes and utilising an electronic controlled drug register has a wider impact on patient care. The improved turnaround times for dispensing stock requisitions reduces the risk of omitted doses of critical medicines at ward level. Prescriptions are dispensed more efficiently ensuring the successful discharge of patients, which, in turn, helps the smooth admission of the next patient.

Approximately 1200 controlled drug items are dispensed each month in RVH Pharmacy; thus the ADC is contributing to dispensing time savings of 67.3 hours per month, an equivalent of 808 hours per year. Utilisation of this resource will allow the release of staff to other duties including patient facing roles. 

Conclusions

This project has demonstrated the safety and effectiveness of an ADC in managing controlled drugs in a hospital pharmacy. A training programme will be developed for junior staff who would not have previously undertaken controlled drug duties to build contingency and stability into the pharmacy workforce.

Future developments will focus on linking ward-based ADCs with the pharmacy ADC to further enhance the efficiency of controlled drug workflow between ward and pharmacy. BHSCT plans to install controlled drug ADCs in all its hospital pharmacies.

Authors

Aideen O’Kane MPharm MSc MPSNI
Warren Francis MAT (Member Association of Pharmacy Technicians)
Conor Duffy BSc
John Mullan BSc MSc MPSNI
Rhona Fair BSc MSc PGDip MPSNI
Lucy Smart MPharm MPSNI
Aoife Ramsey MPharm MPSNI
Pharmacy Department, Belfast Health and Social Care Trust, Belfast

Acknowledgements

We thank L McKee and T Cameron for participating in the focus group for controlled drugs workflow.

References

  1.  The Misuse of Drugs Regulations (Northern Ireland), 2002. www.legislation.gov.uk/nisr/2002/1/contents/made (accessed January 2021).
  2. The Misuse of Drugs and Misuse of Drugs (Safe Custody) (Amendment) Regulations (Northern Ireland), 2007. www.legislation.gov.uk/nisr/2007/348/contents/made (accessed January 2021).
  3. Cottney A. Improving the safety and efficiency of nurse medication rounds through the introduction of an automated dispensing cabinet. BMJ Qual Improv Rep 2014;3:1–4. 
  4. Goundrey-Smith S. Technologies that transform: digital solutions for optimising medicines use in the NHS. BMJ Health Care Inform 2019: doi 10.1136/bmjhci-2019-100016.
  5. Darwesh BM, Machudo SY, Shiney J. The experience of using an automated dispensing system to improve medication safety and management at King Abdul Aziz University Hospital. J Pharm Pract Community Med 2017;3:114–19.
  6. McCarthy Jnr BC, Ferker M, Implementation and optimization of automated dispensing cabinet technology. Am J Health Syst Pharm 2016;73:1531–6.
  7. Chapuis C et al. Automated drug dispensing system reduces medication errors in an intensive care setting. Crit Care Med 2010;8:2275–81.
  8. Grissinger M. Your high-alert medication list Is relatively useless without associated risk-reduction strategies. PT 2016;41:598–600.
  9. de-Carvalho D et al. Impact assessment of an automated drug-dispensing system in a tertiary hospital. Clinics 2017;72:629–36. 
  10. Department of Health, Operational productivity and performance in English NHS acute hospitals: unwanted variations. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/499229/Operational_productivity_A.pdf (accessed January 2021).
  11. NHS Improvement Driver Diagrams. NHS Improvement. https://improvement.nhs.uk/resources/driver-diagrams-tree-diagrams/ (accessed January 2021).
  12. Metsamuuronen R et al. Nurses’ perceptions of automated dispensing cabinets – an observational study and online survey. BMC 2020;19:27. 
  13. Zaidan M et al. Nurses’ perceptions of and satisfaction with the use of automated dispensing cabinets at the Heart and Cancer Centres in Qatar: a cross-sectional study. BMC Nurs  2016;15:4. 

First published by our sister publication Hospital Pharmacy Europe.

Adherence to NICE criteria for biologic treatment in atopic dermatitis

A retrospective study undertaken in a UK hospital to investigate adherence to National Institute for Health and Care Excellence (NICE) criteria and guidance in treatment of atopic dermatitis with a biologic therapy is detailed

Atopic dermatitis (AD) is a chronic, recurrently flaring, generalised skin condition that can be life-limiting, debilitating and isolating. It can affect all aspects of life (physical, psychological, social and financial). Severe disease is associated with intolerable itch that disrupts sleep, and there is a higher risk of depression and suicide.1 It affects 2%–10% of adults worldwide and can be associated with other systemic disorders such as asthma.2 

The severity of atopic dermatitis and its effect on quality of life is assessed by a variety of scoring systems that include both subjective and objective measurements.3 A typical treatment pathway involves emollients and topical corticosteroids (first line), topical calcineurin inhibitors (i.e., tacrolimus, pimecrolimus) as second line, phototherapy (third line) and systemic immunosuppressant therapies (fourth line) including oral corticosteroids, ciclosporin (the only licensed drug), methotrexate, azathioprine and mycophenolate mofetil. Long term use of systemic agents is not recommended due to the risk of adverse side effects.4

Dupilumab was the first therapy to be approved for moderate-to-severe AD that does not respond to topical therapies based on large, randomised, double-blind placebo-controlled clinical trials.5–7 Dupilumab (Dupixent, Sanofi Genzyme) is a human monoclonal antibody that targets the signalling mechanisms of cytokines interleukin (IL)-4 and IL-13. It is indicated for the ‘treatment of moderate to severe atopic dermatitis in adults who are candidates for systemic therapy’. It is given by subcutaneous injection and the recommended dose is 300mg every two weeks after an initial loading dose of 600 mg (two 300mg injections at different sites). Various national guidelines position dupilumab either after other systemic therapies6 or as another systemic therapy option in the pathway for uncontrolled atopic dermatitis.7–9

Across England and Wales, guidance from the National Institute for Health and Care Excellence (NICE) assesses the clinical and cost effectiveness of health technologies, including pharmaceuticals. The National Health Service (NHS) is legally obliged to fund and resource medicines and treatments recommended by NICE’s technology appraisals (TA). Furthermore, the NHS Constitution, which sets out rights to which patients, public and staff are entitled, and pledges which the NHS is committed to achieve, states that patients have the right to drugs and treatments that have been recommended by NICE for use in the NHS, if their doctor believes they are clinically appropriate.8 

Within the NICE TA, dupilumab is recommended as an option for treating moderate to severe AD in adults, only if: the disease has not responded to at least one other systemic therapy, such as ciclosporin, methotrexate, azathioprine and mycophenolate mofetil, or these are contraindicated or not tolerated; and the company provides dupilumab according to the commercial arrangement. Dupilumab should be stopped at 16 weeks if the AD has not responded adequately. An adequate response is: at least a 50% reduction in the Eczema Area and Severity Index (EASI) score from when treatment started; and at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) from when treatment started.1

EASI assesses both lesional intensity and extent. Four signs – erythema, papulation/oedema, excoriation, and lichenification – are assessed using a scale of 0 to 3. EASI assesses the average lesional intensity within four body regions: 

  • head and neck
  • arms
  • trunk
  • legs. 

Lesional extent is evaluated by estimating the surface area involved of those four body regions (1%–9%, 10%–29%, 30%–49%, 50%–69%, 70%–89%, and 90%–100%). Lesional intensity is multiplied by the surface area involved in that region and summed across regions, yielding a total score ranging from
0 to 72.9 DLQI consists of 10 queries that assess the patient’s perception of the effects of the specific skin condition on their health-related quality of life over the past week. Summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.10

The NHS price for dupilumab excluding VAT is £1,264.89 for 2x300mg, although a patient access scheme is in place as part of the NICE TA. A patient access scheme or commercial arrangement associated with the NICE guidance is a way for pharmaceutical companies to lower the acquisition cost to the NHS to improve its cost-effectiveness, so enabling patients to gain access to high-cost medicine treatments. High-cost medicines are so named as they are expensive prescribed items, representing a disproportionate cost relative to the total NHS cost of the relevant hospital episode in terms of volume and cost. 

The hospital

Royal Cornwall Hospitals NHS Trust is a 750-bed acute teaching district general hospital in the south-west of England. The hospital, in conjunction with the local clinical commissioning group (CCG, now integrated care board), utilises the Blueteq high-cost drug management system. CCGs were statutory regional NHS bodies responsible for the planning and commissioning of healthcare services for their local area. Many CCGs in England use this Blueteq web-based system which allows clinicians to complete an online proforma for patients prescribed a high-cost medicine and receive automatic approval for funding if the patient meets all the relevant criteria which normally reflect the NICE TA guidance. This ensure that clinicians receive the approval to treat immediately. The Blueteq system retains, as an audit trail, the request history, including patient name, drug, indication, criteria for use, date of request, requesting clinician, and whether the request was granted or not. This enables commissioners to monitor the use of expensive treatment, so that only treatments prescribed in line with NICE guidelines are reimbursed to the hospital. 

Aim

We aimed to identify whether dupilumab had been used according to the criteria based on the NICE TA.

Methods

This was a retrospective, single site study in an acute teaching district general hospital. An extract was downloaded from the Blueteq system for adult patients granted approval to commence dupilumab treatment for moderate to severe atopic dermatitis, and who were then potentially eligible to receive such treatment for more than 16 weeks. Relevant data (patient demographics and treatment details) were imported into Excel by a member of the pharmacy team. Dermatology correspondence (as part of the medical record) were examined as far back as 2012 if necessary for relevant information about patients’ treatment.

Health Research Authority criteria about research and service evaluation were considered. This was a retrospective assessment involving no changes to the service delivered to patients, and we used the NHS Health research authority tool (www.hra-decisiontools.org.uk/research/index.html) which helped confirm that no ethical approval was required for this project. Patient data were used in accordance with local NHS hospital policy.

Results

At the time of the Blueteq extract, there were 88 patients on the Blueteq system, and the records of 30 patients were reviewed. Most entries were from when the NICE TA first approved dupilumab, though a few entries were chosen from late 2021/early 2022

There were 18 males and 12 females who had commenced on dupilumab and been reviewed approximately 16 weeks later; mean age was 44 years (range 18–73).

Twenty-six (87%) patients had tried phototherapy and 26 (87%) had evidence in their dermatology records of having been prescribed a course of prednisolone at some point. As regards the named prior systemic therapy (ciclosporin, methotrexate, azathioprine, and mycophenolate) in the NICE TA, all but one patient had been on at least one of these medicines. Four patients had tried all four therapies. 

One patient, who began dupilumab at a tertiary centre, did not have a starting EASI score in our hospital records. Of the 29 patients with a baseline score, 28 (97%) experienced the required 50% or more reduction in EASI score at the review meeting, whilst 28 (93%) of all 30 patients achieved the at least 4-point reduction in DLQI. One patient did not meet both NICE criteria showing only a reduction in EASI score from 33.6 to 27.9 (and not the required 50% reduction) and DLQI from 30 to 28 (and not the 4-point reduction) , and one patient had the required reduction in EASI score from 48 to 2 but did not have the required DLQI reduction (only a decrease from 13 to 10 and not the 4-point reduction ). Both had their treatment ceased. Table 1 shows overall results at baseline and at review.

Discussion

This small-scale study found that 28 of 30 patients met all the NICE starting requirements for dupilumab treatment. The two instances of non-compliance were one patient who did not have recorded locally an EASI score, and one patient who did not try any prior systemic therapy. This latter patient, whilst waiting for an appointment to commence ciclosporin, was admitted acutely to hospital with severe atopic dermatitis and started on dupilumab as this was deemed to be quicker acting with no need to wait for the necessary blood tests associated with immunosuppressive therapy.

Two patients who did not meet the reduction in EASI or in DLQI at review both had their treatment ceased. The drug cost impact of continuing inappropriate treatment in these two patients would be about £33,000 per year at NHS price and excluding VAT as these are provided via homecare. The actual cost impact is less than this due to the commercial arrangement in place. 

A similar UK based study reported on 30 patients who received dupilumab after one or more immunosuppressive drugs.11 Their patients had average scores of 30 on EASI and 15 on the DLQI at baseline (compared to our study values of 29.7 and 18.9, respectively). All their 30 patients showed adequate response at 16 weeks and therefore continued to receive dupilumab. They report a mean 70% reduction in EASI after 16 weeks, and a 4-point or more reduction in DLQI for all the 30 patients. Of our 29 patients with a baseline EASI score, we saw at least a 70% reduction in 26 patients, with a further 2 patients achieving the NICE requirement of at least a 50% reduction and the one patient who did not achieve this reduction had therapy stopped. Two of our 30 patients did not meet the required DLQI score reduction. The patient who did not achieve the DLQI reduction had severe side effects from dupilumab and this would have adversely influenced the DLQI score. This patient with a poor DLQI response moved onto baricitinib as another option approved by NICE.12

The reported results from our small study are not directly comparable with the major controlled trials for dupilumab which enrolled different groups of patients. SOLO1 and SOLO2 enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment.5 LIBERTY AD CHRONOS included patients with moderate-to-severe atopic dermatitis and an inadequate response to topical corticosteroids. These patients were treated with topical corticosteroids as well as dupilumab or placebo.6 LIBERTY AD CAFÉ included patients with a history of inadequate response or intolerance to ciclosporin, or for whom ciclosporin treatment was medically inadvisable.7 For these trials, the Dupixent Summary of Product Characteristics reports on mean EASI score reductions at week 16 of approximately 72%, 67%, 80% and 80%, respectively.13 Overall, we saw a 90% reduction in EASI score for the 29 patients with both a baseline and review score.

Other real-world evidence has looked at efficacy and safety at 52 weeks.14,15 These reports may have investigated different cohorts of patients and different efficacy measures, making direct comparisons difficult. Recognising that long-term ongoing treatment in patients with persistently controlled atopic dermatitis might lead to overtreatment and an increase in adverse events (e.g., injection site reactions, conjunctivitis), there is some limited research into how tapering of dupilumab dosing should be undertaken.16 

As regards use of the EASI score: because this has moderate inter-observer reliability, it was suggested that the same investigator should perform the EASI in a patient at baseline and follow-up.17 This does not always occur in our centre; however, use of a tool such as EASI score.com18 (which has picture guidance) helps to reduce the subjectiveness of the scoring process.

We recognise the limitations of a single centre, very small-scale retrospective study that sampled approximately 34% of the patients recorded on Blueteq as having commenced dupilumab. We do not report prolonged follow up of patients in relation to any improvement in their atopic dermatitis other than what we observed documented in dermatology letters at commencement and review of treatment. These results therefore cannot be generalised to other hospitals.

Conclusion

In this very small study, 28 of 30 patients were compliant with NICE criteria for commencing dupilumab in atopic dermatitis. Two patients who did not achieve the required improvement at the 16-week review and had their treatment ceased.

Authors

Michael Wilcock BSc (Hons) MPhil

Leanne Roberson MAPharmT

Alison McInnes DIP(HE)Nursing/NIP

Pharmacy and Dermatology Departments, Royal Cornwall Hospitals NHS Trust, Truro, UK

Declaration of interests: The authors have no interests to declare

Key points

  • Dupilumab is indicated for the treatment of moderate to severe atopic dermatitis in adults who are candidates for systemic therapy.
  • National Institute for Health and Care Excellence (NICE) technology appraisal guidance describes starting and stopping criteria in adults.
  • In this retrospective study of dermatology correspondence, we found 28 of 30 patients were compliant with NICE criteria for commencing dupilumab in atopic dermatitis. 
  • Two patients who did not achieve the required improvement at the 16-week review and had their treatment ceased.
  • Seeking assurance that this payment-by-results-excluded drug is used according to NICE guidance is important for the commissioners as well as internally for the hospital and the department.

References 

  1. National Institute for Health and Care Excellence. Dupilumab for treating moderate to severe atopic dermatitis. TA534, August 2018. www.nice.org.uk/guidance/ta534 (accessed November 2022).
  2. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a United States population-based study. J Allergy Clin Immunol 2013;132:1132–8.
  3. Ud Din AT et al. Dupilumab for atopic dermatitis: the silver bullet we have been searching for? Cureus. 2020;12(4):e7565.
  4. Sidbury R et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol 2014;71:327–49.
  5. Simpson EL et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med 2016;375:2335–48.
  6. Kulthanan K et al. Clinical practice guidelines for the diagnosis and management of atopic dermatitis. Asian Pac J Allergy Immunol 2021;39:145-–55.
  7. Wollenberg A et al. ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children. J Eur Acad Dermatol Venereol 2020;34:2717–44.
  8. National Institute for Health and Care Excellence. NICE technology appraisal guidance. www.nice.org.uk/About/What-we-do/Our-Programmes/NICE-guidance/NICE-technology-appraisal-guidance (accessed November 2022).
  9. Chopra R, Silverberg JI. Assessing the severity of atopic dermatitis in clinical trials and practice. Clin Dermatol 2018;36:606–15.
  10. Dermatology Life Quality Index. www.cardiff.ac.uk/medicine/resources/quality-of-life-questionnaires/dermatology-life-quality-index (accessed November 2022).
  11. Deif E, Bali S, Rajeev A. Dupilumab in the treatment of moderate-to-severe atopic dermatitis: A focused review. J Skin Sex Transm Dis 2021;3:151–5.
  12. National Institute for Health and Care Excellence. Baricitinib for treating moderate to severe atopic dermatitis. TA681, March 2021. www.nice.org.uk/guidance/ta681 (accessed November 2022).
  13. Dupixent 300mg solution for injection in prefilled pen. www.medicines.org.uk/emc/product/11321/smpc#gref (accessed November 2022).
  14. Jo CE et al. Evaluation of long-term efficacy, safety, and reasons for discontinuation of dupilumab for moderate to severe atopic dermatitis in clinical practice: A retrospective cohort study. J Am Acad Dermatol 2020;82:1530–2.
  15. Napolitano M et al. Efficacy and safety of dupilumab in clinical practice: one year of experience on 165 adult patients from a tertiary referral centre. Dermatol Ther (Heidelb) 2021;11:355–61.
  16. Spekhorst LS et al. Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis. Allergy 2022; Jul 15: doi: 10.1111/all.15439 (online ahead of print).
  17. Schmitt J et al. The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials. J Allergy Clin Immunol 2014;134:800–7.
  18. www.EasiScore.com/ (accessed November 2022).

First published on our sister publication Hospital Pharmacy Europe

Tracking the anticholinergic burden score during hospital admission in acute care

23rd February 2023

Here we report on a retrospective study undertaken in a UK hospital that found that the overall anticholinergic drug burden did not change significantly during an inpatient stay on five wards typically caring for older people

Anticholinergic medications (ACM) are prescribed for the management of conditions such as depression, psychosis, Parkinson’s disease, overactive bladder, and chronic obstructive pulmonary disease. These are among the most prescribed medications in patients with polypharmacy. One systematic review looking at adverse effects found that certain individual ACM or increased overall exposure to ACM may increase the risks of cognitive impairment, falls and all-cause mortality in older adults,1 though others argue that the evidence for harmful outcomes in certain groups of older patients remains uncertain or deficient.2,3

What is the anticholinergic burden?

Anticholinergic burden (ACB) is defined as the “accumulation of higher levels of exposure due to one or more ACM and the attendant increased risk of medication-related adverse effects”.4 A number of anticholinergic quantification scales have been reported in the literature, providing a list of ACM and a rank of low- to high-risk based on anticholinergic activity. However, most scales are constructed using expert opinion panels, in vitro data and literature reviews. These scales each include different drugs and have variations in the rating of the included drugs, meaning variability and inconsistency among the scales exist.5,6 As an example, it is suggested that the relationship between ACB and fracture risk might differ depending on the ACB scale used.7

Inappropriate prescription of ACM to older patients in primary care has been reported extensively.8.9 In England, the NHS Business Services Authority anticholinergic burden prescribing comparator can be used to identify the number of patients at risk of anticholinergic side effects at Clinical Commissioning Group, Primary Care Network and GP Practice level, and to prioritise work in this area.10 However, ACM use in a hospital setting has been less extensively studied and with varying results. ACM prescription was found in 10% of hospitalised, older patients using a database from a French general hospital covering 14,090 hospital stays by patients aged 75 and over.11 A Danish study, utilising the Anticholinergic Risk Scale, examined the association between ACM at hospital admission and mortality in older patients and found that such use is associated with short- and long-term mortality in geriatric patients, even when adjusting for other important variables such as comorbidity and activities of daily living.12 In this Danish study, nearly two-thirds of a total of 74,589 patients received ACM. Few patients received medications with an ACB score of two or three while a score of one accounted for 88.1% of the overall anticholinergic intake. 

Previously in our Trust, a RADAR (RCHT Analysis, Data and Reporting) report had been developed that pulls daily prescribing data for ACM from the hospital’s e-prescribing system (CareFlow Medicines Management) for patients on five selected wards. These wards covered elder care, trauma (mainly older patients), stroke, and neurology. For each patient, the report generates the total ACB score, together with the names of any drugs that fall into the categories of an ACB score of 1, 2, or 3. This report was developed using the Ageing Brain Care scoring system.13 Patient characteristics (age and gender) are also displayed. The intention was that this report would be used by clinical staff to identify those patients with a high ACB who might be suitable for a medication review. However, a previous unpublished internal study has found that this electronically available report was not used by clinicians, mainly because of a lack of compatibility with workflow.

Our overall aim was to identify if the ACB score altered between admission and the last day on the ward for patients on those specific wards that are the subject of this RADAR report. The objectives were to report on changes to ACB score over the hospital stay and to ascertain if, in general, any particular ACM was stopped to reduce the ACB score.

Method

This was a retrospective study utilising the electronically available RADAR ACB score report that was run for November 2021 for those patients admitted to the five target wards. Data were extracted such that the report displayed any ACM that contributed to the patient’s ACB score both at admission and the final day on the ward. This extraction did not include medication listed on any discharge prescription. Patients on the same medication, for example, morphine prescribed as a standard-release oral formulation and an injectable formulation ‘as required’ accrued a score of only one. Likewise, the presence of both cyclizine lactate and cyclizine hydrochloride on the same patient’s electronic prescribing chart accrued a score of only one. Data were entered into Excel for analysis. Data for two wards that were more typical of care of the elderly patients were also analysed separately.

Ethics

Health Research Authority criteria for research and service evaluation were considered. This was a retrospective assessment involving no changes to the service delivered to patients, and we used the NHS Health research authority tool (www.hra-decisiontools.org.uk/research/index.html) which helped confirm that no ethical approval was required for this project.

Results

Over an approximate three-week period in November 2021, there were 262 episodes of patients admitted to the five wards. Sixty-two of these episodes were on the two wards grouped together for further analysis as they were considered to be more representative of care of the elderly patients. Excluding those whose admission was apparently less than one day, this left a total of 212 patient episodes (mean age 70 years, range 21–99, 100 male), of which 59 (mean age 74 years, range 23–97 years, 27 male) were on the two subset wards. Overall, the duration of stay ranged from one day (29%) to 5 days and longer (27%). 

Overall, there was an increase in the total ACB score between admission and final day on the ward for the 212 patient spells from 322 (mean 1.52 per spell) to 456 (mean 2.15 per spell), and also across the subgroup of 59 spells from 105 (mean 1.78 per spell) to 120 (mean 2.03 per spell). This overall increase in ACB score was also seen when considering only those patient spells that were for 5 days or longer. The number of patients with an ACB score of 2 or ≥3 was greater on the final day on the ward than at admission when considering all 212 spells (Table 1). For the subgroup of 59 patient spells, it was only the number of patients with an ACB score of ≥3 that increased during the acute stay.

However, 9% (20/212) and 15% (9/59) of patient spells did show a decrease in their ACB score (Table 2). Across all patient spells, the most frequent medicines that were ceased were fentanyl, morphine, furosemide and co-dydramol.

Discussion

We examined the ACB of medication for patients admitted to a select group of wards caring for, in the main, older people. This analysis has shown an overall increase in ACB score during the acute inpatient stay for 212 patient spells from a mean of 1.52 per spell to 2.15 per spell. There were some instances where a reduction did occur – 9% of 212 patient spells and 15% of the subgroup of 59 spells. 

Several studies with varying results have tracked changes to ACB during the hospital stay of older people. A study, utilising the Anticholinergic Risk Scale (ARS),14 described the burden of prescribed ACM in all older adults admitted as an emergency to any specialty in a large hospital in the UK. These authors looked at how ARS scores changed from admission to discharge and evaluated associations between both admission ARS and change in ARS score and hospital outcomes, primarily inpatient and post-discharge mortality.15 They found that from 33,360 patients included, just under one-third were prescribed an anticholinergic on admission, with 3266 (9.8%), 2479 (7.4%) and 4438 (13.3%) patients scoring 1, 2 or >3 respectively on the ARS. In our much smaller study, we found 46/212 (22%), 34/212 (16%) and 51/212 (24%) patients scoring 1, 2 or >3 respectively on the scale we used. These UK authors15 did find a statistically significant reduction in mean ARS from admission to discharge in all specialties. Interestingly, the largest absolute and relative reductions in mean ARS scores were seen in patients discharged by Geriatric Medicine and Trauma and Orthopaedics, although they report that patients experiencing either an increase or a decrease in ARS score from admission to discharge were more likely to have a prolonged (>10 days) hospital stay. Our five wards would be similarly classified as Geriatrics and Trauma and Orthopaedics, although we found an overall increase in mean ACB score. However, we only had ten patients with a prolonged stay and two of these had a decrease in ACB score

A similar study in New Zealand measured the ACB using the total Anticholinergic Drug Scale (ADS) score for 224 patients on presentation to and at discharge from a geriatric unit.17 Despite medication changes occurring during the hospital stay, there was no significant change in ADS score between admission and discharge. Compared with admission, 35% patients had a reduced ACB; 28% patients had an increased ACB, whereas 37% had no change on discharge. 

A study based in the UK and Europe,18 described changes in the ACB in 549 patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment, or falls. They utilised an adapted 2012 revision of the original ACB scale.13 Key findings were that 21.1% of patients had their ACB score reduced, 19.7% had their ACB increased, 22.8% of ACM-naïve patients were discharged on ACM, and there was no change in the ACB scores in 59.2% of patients. The European study also observed that the same medications, while stopped in some patients, were started in others, and that more than one in five patients who were not taking anticholinergics when admitted were prescribed them by discharge.18 Compared with this European-based study18 and the New Zealand study,17 we found 9% had a reduced ACB, 37% had an increased ACB, and 53% had no change by the final day on the ward. 

A specialist multidisciplinary team based in a UK Emergency Department was able to perform targeted medication reviews and significantly reduced anticholinergic drug exposure in frail older patients as measured by the ACB scale.19 Interestingly, only 2.3% (n=3/129) of ACB-naive patients were started on an anticholinergic drug (that is, ACB score 0 pre- to 1 post-review) and there were no other examples of patients experiencing an increase in ACB score during admission.

The importance of this topic of ACB is highlighted in the national Getting It Right First Time report, which recommends that older patients should have an initial review of medicines management when they are admitted to hospital. This report notes that the admission might be triggered by adverse drug reactions and the risks and benefits of drugs need to be reviewed. This can be done using a structured approach such as the STOPP-START tool, or the anticholinergic burden score to assess the risk of drugs that contribute to falls and delirium.20

It is recognised that the provision of guidelines and education alone do not seem to be sufficient to ensure the best medicines review and optimisation in older people. Whereas evidence shows an improvement in the quality of prescribing and deprescribing via the use of multidisciplinary teams, geriatric case conferences, medication review by pharmacists and the use of information technology to support medication decisions.21 In the context of reviewing and possibly reducing ACB score, we have in place in our Trust an electronic tool that identifies possible opportunities for review. However, we know this RADAR report is not utilised.

A strength of our study was the use of an e-prescribing system, which facilitated the accurate extraction of prescribed medication. We recognise the limitations of this retrospective study of patients admitted to a single acute trust during a relatively short follow-up period. During the pandemic, these five wards may have held outlier patients not under the care of the elderly team and so any review of ACM may not have been a priority. It is important to note that what was prescribed on the e-prescribing system at admission may be different to medicines identified at the reconciliation (clerking in) process, that is, some ACM might have been ceased/withheld at admission to the ward and we did not record this. Also, we looked only at prescribed medication, and we recognise that, especially for ‘as required’ medication, these might not have actually been administered to patients. In particular, those patients on Trauma would have had analgesic requirements (weak or strong opioids) accruing an ACB score typically of one per different opioid prescribed and this continued throughout the hospital stay with little opportunity to reduce the score, although these opioids might not then have continued into discharge medication. Finally, we did not record patient comorbidities.

Conclusion

In this study, the overall ACB did not change significantly during an inpatient stay on five wards typically caring for older people. It might be appropriate to raise prescribers’ and pharmacy team awareness of these practices such that there is more of a focus on ACB and the potential for corresponding iatrogenic effects.

Learning points

  • Anticholinergic medication is associated with adverse clinical outcomes, including delirium and cognitive decline. 
  • Various anticholinergic burden (ACB) or risk scales have been devised to aid medication reviews. 
  • Anticholinergic medication use in a hospital setting has been less extensively reported than in primary care, although some studies have tracked changes in ACB during hospital admission.
  • In this retrospective study, there was an increase in the total ACB score between admission and the final day on the ward for the 212 patient spells from 322 (mean 1.52 per spell) to 456 (mean 2.15 per spell).
  • It might be appropriate to raise prescribers’ awareness of these practices such that there is more of a focus on ACB, and the potential for corresponding iatrogenic effects. 

References

  1. Ruxton K, Woodman RJ, Mangoni AA. Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: A systematic review and meta-analysis. Br J Clin Pharmacol 2015;80:209–20. 
  2. Wang K et al. Anticholinergics and clinical outcomes amongst people with pre-existing dementia: A systematic review. Maturitas 2021;151:1–14. 
  3. Mehdizadeh D et al. Associations between anticholinergic medication exposure and adverse health outcomes in older people with frailty: A systematic review and meta‑analysis. Drugs Real World Outcomes 2021;8:431–58. 
  4. Boustani M et al. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health 2008;4(3):311–20. 
  5. Naples JG et al. Concordance between anticholinergic burden scales. J Am Geriatr Soc 2015;63:2120–4. 
  6. Al Rihani SB et al Quantifying anticholinergic burden and sedative load in older adults with polypharmacy: A systematic review of risk scales and models. Drugs Aging 2021;38:977–94. 
  7. Ogawa Y, Hirai T, Mihara K. A meta-analysis of observational studies on anticholinergic burden and fracture risk: evaluation of conventional burden scales. J Pharm Health Care Sci 2021;7:30. 
  8. Myint PK et al. Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle-aged and older men and women of EPIC-Norfolk prospective population Study. Age Ageing 2015;44:219–25. 
  9. Hanlon P et al. Assessing risks of polypharmacy involving medications with anticholinergic properties. Ann Fam Med 2020;18:148–55. 
  10. NHS Business Services Authority. The AHSN Network. July 2017. Medicines Optimisation Polypharmacy Prescribing Comparators. www.nhsbsa.nhs.uk/sites/default/files/2018-02/PolyPharmacy%20Specification%20v1%200%20July%202017_0.pdf (accessed June 2022)
  11. Ferret L et al. Inappropriate anticholinergic drugs prescriptions in older patients: analysing a hospital database. Int J Clin Pharm 2018;40:94–100. 
  12. Sørensen SR et al. Use of drugs with anticholinergic properties at hospital admission associated with mortality in older patients: A Danish nationwide register‑based cohort study. Drugs Real World Outcomes 2022;9:129–140. 
  13. Aging Brain Care. Anticholinergic Cognitive Burden Scale. www.idhca.org/wp-content/uploads/2018/02/DESAI_ACB_scale_-_Legal_size_paper.pdf (accessed June 2022). 
  14. Rudolph JL et al. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008;168:508–13. 
  15. Herrero-Zazo M et al. Anticholinergic burden in older adult inpatients: patterns from admission to discharge and associations with hospital outcomes. Ther Adv Drug Saf 2021;12:20420986211012592. 
  16. Carnahan RM et al. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol 2006;46:
    1481–6. 
  17. Lee MSS, Hanger HC. Audit of anticholinergic medication changes in older hospitalised patients using the Anticholinergic Drug Scale. Intern Med J 2017;47:689–94. 
  18. Weichert I et al. Anticholinergic medications in patients admitted with cognitive impairment or falls (AMiCI). The impact of hospital admission on anticholinergic cognitive medication burden. Results of a multicentre observational study. J Clin Pharm Ther 2018;43:682–4. 
  19. Neilson V, Palmer S. The effectiveness of a multidisciplinary frailty team in reducing anticholinergic burden in frail older patients: A quantitative service evaluation. Geriatr Nurs 2021;42(4):
    943–7. 
  20. Hopper A. Geriatric Medicine. GIRFT Programme National Specialty Report. Getting It Right First Time. 2021. 
  21. Topinková E et al. Evidence-based strategies for the optimization of pharmacotherapy in older people. Drugs Aging. 2012;29:477–94.

First published in our sister publication Hospital Pharmacy Europe

Fetal alcohol spectrum disorders: An overview

22nd February 2023

FASD is a common disorder that often is unrecognised and might present with one of a number of comorbid presentations. Recognition and management are the key to changing the trajectory of people’s lives

Fetal alcohol spectrum disorders (FASD) represent a range of body and brain conditions that are caused by consuming alcohol during pregnancy. First labelled and recognised in the English scientific journals by Smith and Jones as fetal alcohol syndrome (FAS), it later became understood and established that this condition had existed for a long time but had simply not been properly identified or labelled.1

Initial reports focused on some specific groups and very much on the physical presentation more than the neurological. For example, Smith and Jones reported on a case series from a first Nations population based around Seattle, Washington, USA. Earlier reports, in other journals, included a large case series from France identifying children who had physical and cognitive difficulties.1

It was only later that the spectrum of presentation began to be better understood and the physical stigma took less prominence. it became understood that the cognitive features have the greatest impact on behaviour and cause the lifelong difficulties.2

Diagnostic criteria

Early work identified four components that were crucial to a diagnosis. These included facial features, growth retardation, cognitive deficits and alcohol exposure. 

The facial features include short palpebral fissures, an elongated and thinner philtrum and a thin upper lip vermilion as core (Figure 1). Additionally, a small head size and flat midface were noted as discriminatory but the former being part of neurological domain and the latter not quantifiable at the time. Other features, such as micrognathia, upturned nasal flares and characteristic hand and ear presentations, were also noted but presented more inconsistently.

Whist the prevalence of FASD is relatively common, all these features seen together is rare. Most recent UK prevalence estimates suggest that FASD presents in 1.8–3.8% of the population3 but full FAS criteria might only be seen in around 2% of this group.4 Therefore, FAS represents not the most severe, but the most recognisable part of the spectrum. 

It became evident that there were timing effects of alcohol exposure that led to the physical manifestations.5 Also, in the late 1970s and early 1980s, when much of this work was being undertaken, technology did not exist to allow accurate measurement of many of these features. More recent work and understanding has led, through computer technology and 3D camera analyses, to a better quantification of dysmorphology. Because these techniques use thousands of landmarks for accurate measurements, linked to mathematical computer algorithms and calculations, better recognition of the features is possible. Therefore, early established features such as a flat midface can now be measured and quantified whereas before it was only assessed subjectively.6 

The recognition that there were a range of presentations related to different levels of alcohol exposure led to different criteria being established. In 1996, the Institute of Medicine developed a consensus statement to begin to consider this broader-spectrum presentation.7 The terms fetal alcohol syndrome with or without confirmed alcohol exposure, partial fetal alcohol syndrome, through to alcohol-related neurodevelopmental disorder or alcohol-related birth defect were created. These did not define severity, only how clear-cut or obvious the diagnostic presentation might be. The lack of consensus around thresholds for the cognitive domain has continued to cause differences and discussion within the FASD community, which is unresolved even now.

Different criteria such as the four-digit schedule from the University of Washington,8 the IOM criteria,9 DSM V,10 the Canadian FASD network,11 Australian guidance,12 and, most recently, the Scottish Intercollegiate Guidance Network (SIGN) review in 201913 have all established sets of criteria. 

These differences have led some to question the diagnosis. However, it is important to note that there is broad agreement between all groups as to the core components of the presentation. It is the sensitivity and specificity of the cut-offs that continues to be debated. The threshold at which a disorder is labelled remains the core of ongoing debate. Since the Scottish government sponsored review and the SIGN 156 guidance document were created, the National Institute for Health and Care Excellence in England has adopted these recommendations as a whole and therefore going forward,14 SIGN guidance will be the approach taken. Therefore, diagnostic criteria in the UK are FASD with or without sentinel features.

If clinicians are focused primarily on the dysmorphic features, it is unlikely that most cases will be identified. The wider prevalence of those who have prenatal alcohol and significant cognitive demands, that is, FASD without dysmorphic symptoms, is relatively common.

Primary features and disabilities

The most recognisable features, as highlighted, are those that are physical. It is the invisible, however, that cause the greatest impact for the individual. It is the underlying damage to the neurological pathways that have the greatest impact on the individual’s ability to live a relatively normal life. Due to alcohol having numerous mechanistic and pathological effects, there is great variability between individuals, yet a characteristic profile can be seen.2

Neurologically, alcohol is known to cause damage to central brain structures which particularly have white matter involvement. For example, the corpus callosum, the white matter tract that connects the two hemispheres, is known to show deficits and impacts on left and right brain connectivity. Other central structures such as the hippocampus, amygdala, orbitofrontal cortex, cerebellum and interconnected structures are also known to be affected. This means that deficits in executive function, emotional regulation, social communication, memory and neural processing speed can be present.15

Furthermore, evidence would suggest that damage can be seen at a cellular level. One such example is that neural migration can be affected to the point that cells appear in the wrong position within the brain. This can lead to inefficient processing and greater effort to complete a task compared with non-affected individuals.15

Research evidence would suggest that due to the relative preservation of some areas of function, the impact of the prenatal alcohol and FASD can go unnoticed until challenges are presented. For example, there is a difference between emotional regulated situations and how the individual functions. This can be defined as hot and cold executive function problems. In essence, this means in a clinic setting where the individual has no emotional or external distractions, function can appear to be better than in scenarios where these wider effects are impinged upon, leading to a lower ability to complete tasks.16 It is important therefore that these are considered during clinical testing. Real-world function is as important as observation in order to understand the impact on the individual as well as their ongoing support needs.

Associated with these presentations are wider neurodevelopmental comorbidities. Because essentially this is a neurological condition affecting pathways that are affected in other diagnoses, such as autism and ADHD, these are conditions that are common comorbidities. The nature and degree of the neurological damage will define whether these conditions are also seen. In a general population study, the rates are variable. Yet, increasing evidence points towards those with the most severe presentations, also having the most affected neurological function and the greatest long-term issues.17 This also impacts on an understanding of the therapeutic interventions that can be directed to support these individuals

Importance of multidisciplinary assessment

Because the neurological deficits seen with FASD are extensive, they cover broad areas. These include cognition, sensory processing, neurological deficits, communication and language, education, and adaptive behaviour. These therefore can be evaluated most easily if the assessment is completed by a multidisciplinary team (MDT).13 When considering the need to take account of the physical as well as the psychological features, teams can comprise a physician familiar with FASD and other associated conditions alongside psychologists, speech and language therapists and occupational therapists.13 Unfortunately, these professionals are not always available in many clinical practices. 

Different availabilities of service provision and differing pathways offer different challenges. While an MDT may be gold standard, in the NHS at least, gold standard is not always possible. In some cases, approaches might need to be taken whereby one individual can collate a multidisciplinary assessment undertaken by differing professionals. 

There are various ways of doing this. Genetic testing, for example, is an important exclusion factor in diagnosing FASD. Genetic conditions make up the most common presentation for neurodevelopmental problems and must therefore be ruled out.18 A geneticist can also identify dysmorphology and other possible physical manifestations.

There are questionnaires to assess communication, executive function, memory, adaptive behaviour as well as sensory and motor functioning. These can be used by individual clinicians to give indications of levels of deficit, without the need for multi-professional involvement, in less complex cases at least. 

Evidence would suggest that these tests do not consider the same things as direct assessment19 but can be used to adequately provide insights into underlying function to support diagnostic processes.

Therefore, while all the criteria suggest an MDT is preferable, it is feasible for a single individual to pull together information from multidisciplinary sources. This is akin to general physicians using haematology, radiology and other pathological samples to come to a diagnostic conclusion alongside their own history and examination. This would allow more straightforward cases to be held locally by single practitioner, leaving the more complex cases for the more expensive and less available MDT. Here, where direct observation by a trained specialist, alongside these psychological measures become vital, the MDT is most needed, but resource is then used efficiently.

Importance of early recognition

Numerous secondary disabilities have been linked to FASD. Due to FASD presenting with one of its many recognised comorbidities, it can often be a hidden presentation.20 When unrecognised, these secondary issues can have significant lifelong effects. 

The classic study was completed in the early 2000s and carried out over 30 years.17 This identified that in people who were not identified early, then presented late to clinical services, poor secondary outcomes were common. These included 90% having mental health problems, over 50% experiencing some form of confinement during their life and over 50% having a disrupted school experience; 30% of the same group went on to have their own addictions.17

By identifying the individual early, a different trajectory can be created, thereby leading to better lives for these individuals. Interventions continue to develop. Interventions in the past were more generic, but as research continues, these interventions are directed more specifically at those with FASD.

Another factor that is increasingly being recognised is the importance of early recognition and intervention for an individual’s vulnerability associated with FASD to reduce the impact of abuse and neglect. Complex trauma models are increasingly being investigated; with this comes the understanding that psychological challenges overlay neurological functioning, which  cancan further impact on an individual’s behaviour and presentation. Even if the neurological deficits remain, understanding the person’s needs and not perpetuating extra trauma leads to a better quality of life overall.21,22

Interventions

What remains vital is not just the diagnosis, but also an understanding of an individual’s function and then subsequently what interventions can be offered to change an individual trajectory. This can be led by the diagnosis, pointing towards the specific needs. These interventions can also be multidisciplinary. Pharmacological interventions alongside social and psychological interventions offer the best overall approach to improving an individual’s presentation. 

For example, several studies have suggested that by understanding the individual with FASD can help modify medical treatment pathways. One such was a consensus pathway for comorbid ADHD; this identified that routine approaches for ADHD might not always be appropriate. Based on the wider profile and comorbidity linked to the FASD, treatments would need to be changed to meet the individual’s needs.23

The same can be said for psychological interventions, where it is understood that due to underlying problems with emotional recognition and the underlying cognitive deficits, some emotion-focused approaches do not work as well as educational approaches designed to build on strengths and support teaching around the deficits.24 Several interventions have been created and continue to be developed. Parenting involvement is an area where there is great scope for immediate intervention that could have significant benefits. These are examples of specific interventions for FASD that are currently going through testing and clinical trials. 

Conclusions

FASD is a common condition that presents often as an invisible disability. Because superficially, individuals can appear to function reasonably well and test reasonably well in clinical settings, this can belie an individual’s actual level of function when wider factors are borne in mind. Complex cognitive processing is often missed, leading to attributions of difficulty and blame which may be inappropriate. It is only by early recognition and bespoke individual intervention that change can be made.

References

  1. Price A. Overview of FASD: How our understanding has progressed. In: Mukherjee R, Aiton N (eds) Prevention, Recognition and Management of FASD. Cham: Springer; 2021.
  2. Riley EP, McGee CL. FASD: an overview and emphasis on changes in brain and behaviour. Exp Biol Med 2005;230(6):357–65.
  3. McCarthy R et al. Prevalence of fetal alcohol spectrum disorder in Greater Manchester, UK: An active case ascertainment study. Alcohol Clin Exp Res 2021;45(11):2271–81.
  4. McQuire C et al. Screening prevalence of fetal alcohol spectrum disorders in a region of the United Kingdom: A population-based birth-cohort study. Prev Med 2019;118:344–51.
  5. Sulik KK. Genesis of alcohol induces cranial dysmorphism. Exp Biol Med 2005;230:366–75.
  6. Suttie M et al. Facial Curvature Detects and Explicates Ethnic Differences in Effects of Prenatal Alcohol Exposure. Alcohol Clin Exp Res 2017;41(8):1471–83.
  7. Stratton K, Howe C, Battaglia F. Foetal alcohol syndrome: diagnosis epidemiology, prevention and treatment. Washington: National Academy Press; 1996.
  8. Astley SJ. Comparison of the 4-Digit code and the Hoyme diagnostic guidelines for Fetal Alcohol Spectrum disorders. Paediatrics 2006(118):1532–45.
  9. Hoyme HE et al. A practical clinical approach to diagnosis of fetal alcohol spectrum disorders; clarification of the 1996 Institute of Medicine Criteria. Pediatrics 2005;115(1):39–47.
  10. American Psychiatric Association. DSM V. Washington: American Psychiatric Association; 2013.
  11. Cook JL et al. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. CMAJ 2016;188(3):191–7.
  12. Bower C et al. Australian guide to the diagnosis of foetal alcohol spectrum disorder: A summary. J Paediatr Child Health 2017;53(10):1021–3.
  13. SIGN. Children and young people exposed to prenatal alcohol. Edinburgh: Health Improvement Scotland; 2019.
  14. NICE. FASD Quality Standards Consultation 2021. www.nice.org.uk/guidance/indevelopment/gid-qs10139/documents (accessed January 2022).
  15. Sadrian B, Wilson DA, Saito M. Long lasting neural circuit dysfunction following developmental alcohol exposure. Brain Sci 2013;3:704–27.
  16. Carlisle ACS, Livesey AC. The role of formal psychometric assessment in FASD. In: Mukherjee R, Aiton N, editors. Prevention, Recognition and Management of FASD. Cham: Springer; 2021.
  17. Streissguth AP et al. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr 2004;25(4):228–38.
  18. Douzgou S et al. Diagnosing Fetal Alcohol Syndrome: new insights from newer genetic technologies. Arch Dis Child 2012:1–6.
  19. Mohamed Z et al. Comparisons of the BRIEF parental report and neuropsychological clinical tests of executive function in Fetal Alcohol Spectrum Disorders: data from the UK national specialist clinic. Child Neuropsychol 2019;25(5):648–63.
  20. Popova S et al. Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. Lancet 2016;387(10022):978–87.
  21. Mukherjee RAS et al. Neurodevelopmental outcomes in individuals with fetal alcohol spectrum disorder (FASD) with and without exposure to neglect: Clinical cohort data from a national FASD diagnostic clinic. Alcohol 2019;76:23–8.
  22. Price A et al. Prenatal alcohol exposure and traumatic childhood experiences: A systematic review. Neurosci Biobehav Rev 2017;80:89–98.
  23. Young S et al. Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus. BMC Psychiatry 2016;16(1):324.
  24. Taylor NM. What psychological therapies might be helpful. In: Mukherjee R, Aiton N (eds) Prevention, recognition and management of FASD. Cham: Springer; 2021.

First published on our sister publication Hospital Pharmacy Europe

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