UK Perspective Research Articles

Carbon emission reduction associated with dapagliflozin compared to standard of care in the UK: translating the DAPA-HF and DELIVER trial findings to an environmental context

Abstract Background Healthcare systems account for 4–5% of UK national greenhouse gas emissions with delivery of care a major component.1 Preventing events that use healthcare resources should contribute to a reduction in emissions, in addition to the primary humanitarian aim of improving patient outcomes. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) and the Dapagliflozin Evaluation to Improve the Lives of Patient with Preserved Ejection Fraction Heart Failure (DELIVER) trials demonstrated that dapagliflozin reduced the frequency of hospitalizations for heart failure (hHF), urgent heart failure visits (UHFV) and cardiovascular (CV) death for patients with heart failure (HF).2,3 Purpose The study objective was to translate predicted differences in clinical events associated with dapagliflozin use in HF to a predicted carbon emission reduction from a UK perspective. Methods A previously published model4 based on pooled DAPA-HF and DELIVER event rates was used to predict hHF, UHFV and CV deaths in a cohort of 1,000 HF patients over a 3-year time horizon. Composite greenhouse gas (GHG) emissions (as kg CO2 equivalent) were calculated from components sourced from the Sustainable Healthcare Coalition’s Care Pathway Calculator according to assumed clinical pathways and were applied to predicted incidence of hHF, UHFV and CV death events. Average length of stay was sourced from the National Heart Failure Audit.5 CV deaths occurring outside hospital were assumed to incur no additional carbon emission except that associated with cremation. Proportion of funerals by cremation and associated GHG emissions were sourced from literature.6,7 Future emissions were not discounted, representing the NHS’s aim to approach ‘net zero’. Results Over a 3-year time horizon, treatment with dapagliflozin was projected to prevent 74 hHF events, 9 UHFV events and 20 CV deaths per 1,000 patients treated versus placebo. Total estimated GHG emissions associated with hHF (233.2 kg CO2e), UHFV (177.4 kg CO2e), and CV death (251.4 kg CO2e) were 85,660 kg CO2e per 1,000 patients treated with dapagliflozin versus 109,618 kg CO2e per 1,000 patients treated with placebo. The projected total reduction associated with dapagliflozin treatment was 23,958 kg CO2e over 3 years, a 22% reduction versus placebo. Per population (~690,000 HF patients), total emissions prevented by dapagliflozin over 3 years were projected to be equivalent to driving 42 million miles in an average gasoline-powered passenger vehicle. Conclusion While the main aim of any therapeutic intervention is to save lives and improve patient outcomes, to capture the full spectrum of benefit to stakeholders the environmental consequences of new therapies should be considered in addition to their clinical and economic effects. Our analysis suggests treating patients with dapagliflozin may contribute to reducing the environmental burden of HF in addition to improving patient outcomes.

Rock Mass Classification of Chalk, a UK Perspective

AbstractInvestigating the geomechanical engineering behaviour of Chalk is challenging since it is a generally soft rock formation and presents in cases a different behaviour from other competent rocks. Additionally, Chalk is widespread throughout the United Kingdom and other parts of the world. Thus, an in-depth understanding of Chalk is paramount when considered in engineering projects. In this research work, the geomechanical behaviour of Northern Province Chalk is examined. This study mainly involves characterising two significant units of Northern Province Chalk, namely Flamborough and Burnham Chalk, through intensive fieldwork and laboratory testing. Multiple scanline surveys are conducted along the cliffs of Flamborough to characterise the jointed nature of the Chalk. The samples collected are assessed in the lab to determine the physical properties of the intact Chalk. Moreover, the Chalk mass properties are compared to those estimated from empirical classification systems. Finally, the limitations of applying rock mass classification systems to Chalk have also been highlighted.

Medication Prescribing by Therapeutic Radiographers: A UK Perspective

Medication Prescribing by Therapeutic Radiographers: A UK Perspective

US global leadership beyond 2024: A UK and European perspective

US global leadership beyond 2024: A UK and European perspective

The journey to LDL-C goal in the era of combination lipid lowering therapy and why it matters for ASCVD patients: a UK perspective

Objective We aim to explore the concept of distance and journey to goal, and consideration of these 2 elements a priori when choosing LLT. Methods Modelling of expected % LDL-C reductions was carried out on a range of hypothetical patients’ baseline LDL-C values prior to any LLT being commenced. Therapies were then added in a stepwise manner based on the pathway demonstrated in current national guidance and compared with goal achievement on a novel LLT optimization pathway implemented in Morecambe Bay NHS Trust. Results Modelling of a stepwise lipid management pathway shows that high-intensity statin monotherapy is not sufficient in most modelled baseline LDL-C scenarios to achieve guideline-recommended goals. Furthermore, ezetimibe second line may preclude 3rd line injectable prescribing and lead to “ezetimibe limbo” where the patient is now below the reimbursement threshold for injectable prescribing but still not achieving their LDL-C target. Overall goal achievement is poor across the spectrum of modelled LDL-C levels. In contrast, by following the Morecambe Bay pathway all patients on statin for the range of hypothetical baseline LDL-C levels can reach an LDL-C target of < 1.8 mmol/L. Conclusions This study identifies a therapeutic gap when following a stepwise approach highlighted by recent national guidance. Our proposal of a novel pathway highlights that the order in which drugs are added is important in the context of national reimbursement thresholds and allows LDL-C goal to be reached in a timely manner, regardless of the starting baseline LDL-C level.

Single and Multiple Supplies – The UK Perspective

In this article, the author addresses the complex issue of single and multiple supplies from a UK perspective. She looks at HMRC’s approach and the developments in both UK and EU case law that influence this approach.

A structured process for the validation of a decision-analytic model: application to a cost-effectiveness model for risk-stratified national breast screening.

Decision-makers require knowledge of the strengths and weaknesses of decision-analytic models used to evaluate healthcare interventions to be able to confidently use the results of such models to inform policy. A number of aspects of model validity have previously been described, but no systematic approach to assessing the validity of a model has been proposed. This study aimed to consolidate the different aspects of model validity into a step-by-step approach to assessing the strengths and weaknesses of a decision-analytic model. A pre-defined set of steps were used to conduct the validation process of an exemplar early decision-analytic-model-based cost-effectiveness analysis of a risk-stratified national breast cancer screening programme [UK healthcare perspective; lifetime horizon; costs (£; 2021)]. Internal validation was assessed in terms of descriptive validity, technical validity and face validity. External validation was assessed in terms of operational validation, convergent validity (or corroboration) and predictive validity. The results outline the findings of each step of internal and external validation of the early decision-analytic-model and present the validated model (called 'MANC-RISK-SCREEN'). The positive aspects in terms of meeting internal validation requirements are shown together with the remaining limitations of MANC-RISK-SCREEN. Following a transparent and structured validation process, MANC-RISK-SCREEN has been shown to have satisfactory internal and external validity for use in informing resource allocation decision-making. We suggest that MANC-RISK-SCREEN can be used to assess the cost-effectiveness of exemplars of risk-stratified national breast cancer screening programmes (NBSP) from the UK perspective. A step-by-step process for conducting the validation of a decision-analytic model was developed for future use by health economists. Using this approach may help researchers to fully demonstrate the strengths and limitations of their model to decision-makers.

Recovery from Addiction on a University Campus – a UK Perspective

ABSTRACT Between 30 and 40% of 18-year olds in England, Wales and Northern Ireland enter tertiary education (university) each year. Young adulthood (ages 15 to 25) is the usual period in which problems with alcohol, drugs or other behaviors begin to emerge, and yet these issues have received limited study in the UK. Government policy dictates that a full continuum of treatment and recovery services should be available in each area of the country, but uptake of these services by university students appears to be limited. In this discussion paper we describe the background to, and components of, the Collegiate Recovery Program (CRP), an initiative that has grown rapidly in the USA in the past decade. We then describe how the first UK University-led CRP was set up, before outlining what has been learnt so far and the potential challenges facing this approach.

Quality of life case series review: wound bed preparation from a UK perspective.

Previous studies have reported that polyhexamethylene biguanide (PHMB) and betaine solution and gels remove biofilm, improve wound healing and reduce infection rates. Quality of life (QoL) outcomes are not commonly reported on when it comes to wound care. This review aims to summarise QoL data from a cohort of case studies previously published on chronic lower limb ulcers using PHMB products (Prontosan® Solution, Prontosan® Wound Gel X and Prontosan® Debridement Pad). Here, we report on and review a total of 38 case studies describing 56 wounds. From these 38 case studies, 36 reported that all the wounds involved had either healed or improved by the end of their respective study period. QoL themes explore malodour, slough, and exudate, pain, mobility, hair growth, antibiotic intake, return to work, social life and mood. This case series demonstrates that treatment with Prontosan® products improves many QoL outcomes for patients with non-healing wounds.

Designing regulations to combat online manipulation: a UK perspective

Designing regulations to combat online manipulation: a UK perspective

Physiologist-led management of heart failure patients using cardiac implantable electronic device diagnostics during COVID-19: a 2-year UK perspective

Abstract Background/ Introduction The COVID-19 pandemic prompted greater use of remote monitoring capabilities of cardiac implantable electronic devices (CIED). The HeartLogic Index incorporated within certain Boston Scientific CIEDs uses device-derived physiological parameters to generate a score which may be predictive of worsening heart failure (HF). We aimed to define the utility of a novel service, led by cardiac physiologists acting autonomously upon HeartLogic Index alerts, to guide HF patient care during the pandemic. Purpose To assess the utility of a physiologist-led HF service, using CIED diagnostics combined with clinical assessment, to improve HF management. Methods In a single-centre prospective study, 153 Boston Scientific CRT/ICD patients were reviewed over a 2-year period using the integrated HeartLogic algorithm. In response to a HeartLogic alert indicating worsening HF, the patient was contacted by a cardiac physiologist using a structured telephone triage to assess HF symptoms. In those deemed as being at risk of decompensated HF based on clinical assessment, an intervention was made e.g. face-to-face physiologist-led clinical assessment, consultant review, medication optimisation. Results During the 2-year audit, 748 alerts were received from 60 patients, the majority of which had a HF implant indication (n=42). Twenty-one patients within the study population required an intervention due to worsening HF. Following intervention, there were no further hospitalisations within this group. Five hospitalisations were documented during the audit, only 3 of which were HF related. Of these HF hospitalisations, one patient denied HF symptoms at the time of telephone contact, one had a HF decompensation due to deteriorating renal failure and the final patient had a disconnected remote monitor. During the 2-year audit, there were a total of 13 deaths, 3 of which were classified as caused by HF. Conclusion A physiologist-led service may be of clinical utility within this complex patient population, with the audit results demonstrating favourable outcomes with a low rate of mortality and HF hospitalisations. The addition of this service can act to streamline the time from patient presentation to HF review, and therefore improve patient care.

PAD: a UK Perspective - Contemplating Change is Challenging!

AbstractPhysician assisted dying is not new, neither historically, nor globally. What has changed in the UK however, is the perspective of society. In the UK, the British Medical Association is both a union and a professional organisation representing doctors and liaising with governments departments in matters of healthcare. As with various specialties within medicine, there are those in favour of change and those against. There are matters on which there is common ground, and a consensus of experts has identified principles, which, if legislation is to change, would be sensible to follow. A profession has united around the idea that if change is coming, it is better to inform the debate proactively and ensure that the interest of patients and doctors are promoted. This session will look at how potential change in the UK has been approached and hopefully well managed.’Disclosure of InterestNone Declared

The experience of parenting a child with dyslexia – A UK perspective with single parents

Dyslexia is a specific learning difficulty that affects the development of literacy and language-related skills, unrelated to intellectual ability. While the impact of parenting an individual with dyslexia (IWD) for married parents has been widely studied, little is known about the impact on single parents. This study explored the lived experiences of single parents of an IWD. Six female participants completed semi-structured interviews discussing their experience of the diagnostic process, support received and general parenting perspectives. Interview transcripts were analysed using Interpretative Phenomenological Analysis. Three main themes were identified: Navigating the diagnosis; Various levels of support; Battling Misconceptions and Lack of Knowledge. Findings suggested that single parents had a mixed experience, both after receiving the diagnosis and in terms of the support they received from family and schools. Differences in the quality of statutory support were highlighted, implicating the need for improved dyslexia support in schools. Unique challenges of parenting an IWD as a single parent were also identified, highlighting important implications. Future research should explore differences in single fathers' experiences and the impact of dyslexia comorbidities on single parents.

Youth violence and knife crime in ethnic minorities in the UK: A review of the literature.

Youth violence and knife crime is increasing dramatically, so much so it has been described as a global epidemic. The social, economic and political forces fuelling this rise mean that minority groups are particularly affected. This paper reviews the literature primarily from a UK perspective, and illustrates the disparate factors that are influencing the rise in youth violence and knife crime and illustrates the complexities of integrating the perspectives of different disciplines into coherent intervention strategies. We conducted a systematic review of the literature that explores both the causes of increasing youth violence and knife crime as well as some of the interventions that have attempted to deal with the problem. A complex interplay of social, economic, mental health and political factors underpin the increase in youth violence and knife crime. An uneasy tension exists between a traditional criminal justice system-based approach based upon deterrence and punishment, and a more liberal preventative model focusing on adolescent mental health. None of the interventions thus far have been particularly effective. Youth violence and knife crime is a global social issue that causes untold suffering to individuals, families and communities as well as fear that reverberates through society. Interventions have often been devised through the lens of particular disciplines or ideologies. Integrating these perspectives into a coherent approach that is actually effective demands greater co-operation, dialogue and mutual understanding between disciplines and agencies, as well as a robust framework for the evidence-based assessment of outcomes.

Modelling the Effectiveness of Tepotinib in Comparison to Standard-of-Care Treatments in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Harbouring METex14 Skipping in the UK.

Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available. This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective. A partitioned-survival model assessed the survival and quality-adjusted life-year benefits of tepotinib versus immunotherapy ± chemotherapy and chemotherapy for untreated and previously treated patients, respectively, using evidence from the single-arm VISION trial (NCT02864992). Two approaches were used to inform an indirect treatment comparison: (1) published clinical trials in overall non-small cell lung cancer and (2) real-world evidence in the METex14 skipping population. Results are presented as median and total quality-adjusted life-year gain and survival for progression-free survival and overall survival. Survival curves were validated against the external literature and uncertainty assessed using a probabilistic sensitivity analysis. Using the indirect treatment comparison against the published literature, tepotinib is estimated to have a median progression-free survival gain versus pembrolizumab ± chemotherapy (11.0 and 9.2 months) in untreated patients, and docetaxel ± nintedanib (5.1 and 6.4 months) in previously treated patients. Across the populations, tepotinib is estimated to have a median survival gain of 15.4 and 9.2 months versus pembrolizumab ± chemotherapy in untreated patients and 12.8 and 5.1 months versus docetaxel ± nintedanib in previously treated patients. The total quality-adjusted life-year gain ranges between 0.56 and 1.17 across the untreated and previously treated populations. Results from the real-world evidence of indirect treatment comparisons are consistent with these findings. Despite the limitations of the evidence base, the numerous analyses conducted have consistently indicated positive outcomes for tepotinib versus the current standard of care.

P821 Multi-site analysis of upadacitinib effectiveness in Crohn's Disease patients: A UK perspective

Abstract Background Upadacitinib, a selective Janus Kinase inhibitor, is the newest advanced therapy in our armamentarium for the treatment of Crohn’s Disease (CD). It has been licensed for use in moderate-to-severely active CD. However, we have limited evidence of its effectiveness in a ‘real-world’ setting. Methods We undertook a retrospective cohort study on CD patients treated with upadacitinib in 24 UK hospitals. Clinical endpoints were reviewed at 12 weeks compared to baseline. Clinical remission was defined as Harvey-Bradshaw Index (HBI) &amp;lt;4 and response as HBI reduction ≥3 or sustained HBI &amp;lt;4. Biochemical remission using faecal calprotectin (FCal) and CRP was defined as FCal &amp;lt;200 µg/g and CRP ≤5, and response as FCal or CRP reduction of 50% and no increase in either parameter. Corticosteroid or exclusive enteral nutrition (EEN) use was documented. Results 170 patients (50% male) were included. The breakdown of disease location included 15% ileal, 21% colonic, 61% ileocolonic and 3% upper GI. Prior advanced therapy exposure was seen in 168 patients, with 117 having failed 3 or more agents. Clinically active disease as defined by HBI ≥4 was seen in 133 patients at baseline. Median HBI at baseline was 8 (5-10) and by week 12 this had fallen to 3 (2-6) (p&amp;lt;0.001). 51% received prednisolone and/ or EEN during induction. Of the 128 patients with paired clinical assessment at baseline and 12 weeks clinical remission was achieved in 41% (figure 1A), 96% of whom were in steroid free clinical remission. This also included 39% of those with 3 or more previous advanced therapy failures. A further 40% were noted to have clinical response at 12 weeks. The median faecal calprotectin reduced from 781 µg/g (354-1800) to 255 µg/g (79-655) (p&amp;lt;0.0001) (figure 1B). In a multivariate analysis (table 1), a higher number of previous resections (p=0.031) and use of steroids (p=0.006) increased clinical remission rate whilst disease location/ behaviour, number of prior advanced therapy failures and baseline HBI did not have an effect. There were three significant adverse events noted including: a reported malignancy, zoster reactivation (drug withdrawal required), and thrombosis. Mild lipid, liver function, and full blood count changes were noted in 29 (17%) of patients, not requiring drug withdrawal. Conclusion Upadacitinib was effective in inducing clinical response in our cohort of patients with previously refractory CD regardless of the number of previous advanced therapy failures. A higher number of prior resections may represent lower overall disease burden but further investigation into the relationship with remission is required, as well as to review real-world endoscopic response and maintenance of remission.

Environmental impacts of equine parasiticide treatment: The UK perspective

SummaryWhile there are limited data on the environmental impact of administering equine parasiticide drugs, evidence from other species indicates significant negative ecological effects. Anthelmintic drugs are excreted unchanged or metabolised to other active and/or toxic metabolites that enter the environment through direct excretion. These chemicals can have significant toxic effects on insects, such as dung beetles, earthworms and aquatic animals. Of the frequently used equine anthelmintics, ivermectin is the most ecotoxic; available evidence indicates that moxidectin is less toxic and fenbendazole appears to have little impact on dung‐colonising insects but may be toxic to aquatic organisms and fungi. There are little data regarding the ecotoxicity of pyrantel and praziquantel, although their ecotoxic effects are thought to be low. Pasture hygiene reduces pharmaceutical contamination and also helps to break the endoparasitic cycle of infectivity, thus reducing reliance on anthelmintics. Judicious and targeted use of endoparasiticides, along with pasture hygiene measures, will limit the ecotoxic effects of these drugs as well as reduce the selection pressure that drives anthelmintic resistance. Anthelmintics may also negatively impact the equine gastrointestinal microbiota. Ectoparasiticides (such as fipronil, permethrin and cypermethrin) may also have significant negative ecological effects, with a risk of contamination of both the immediate environment and water courses following topical use of these drugs. The half‐life of fipronil in the environment is variable, but it degrades into compounds which are more toxic; for example, it is highly toxic to bees and is reported to bioaccumulate in fish and can be toxic to birds. Of the synthetic pyrethroids, permethrin degrades at a faster rate than cypermethrin and may therefore have a lower ecotoxic effect. The ecotoxic effects of injectable doramectin are likely to be similar to oral ivermectin, although persistence in faeces may be significantly prolonged compared to the oral treatment route for ivermectin.

Cost-effectiveness of intravascular ultrasound-guided percutaneous intervention in patients with acute coronary syndromes: A UK perspective.

Use of intravascular ultrasound (IVUS) during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes over angiography alone. Despite this, the adoption of IVUS in clinical practice remains low. To examine the cost-effectiveness of IVUS-guided PCI compared to angiography alone in patients with acute coronary syndromes (ACS). A one-year decision tree and lifetime Markov model were constructed to compare the cost-effectiveness of IVUS-guided PCI to angiography alone for two hypothetical adult populations consisting of 1,000 individuals: ST-elevation myocardial infarction (STEMI) and unstable angina/ non-ST-elevation myocardial infarction (UA/NSTEMI) patients undergoing drug-eluting stent (DES) implantation. The UK healthcare system perspective was applied using 2019/20 costs. All-cause death, myocardial infarction (MI), repeat PCI, lifetime costs, life expectancy and quality-adjusted life-years (QALYs) were assessed. Over a lifetime horizon, IVUS-guided PCI was cost-effective compared to angiography alone in both populations, yielding an incremental cost-effectiveness ratio of £3,649 and £5,706 per-patient in STEMI and UA/NSTEMI patients, respectively. In the one-year time horizon, the model suggested that IVUS was associated with reductions in mortality, MI and repeat PCI by 51%, 33% and 52% in STEMI and by 50%, 29% and 57% in UA/NSTEMI patients, respectively. Sensitivity analyses demonstrated the robustness of the model with IVUS being 100% cost-effective at a willingness-to-pay (WTP) threshold of £20,000 per QALY-gained. From a UK healthcare perspective, an IVUS-guided PCI strategy was highly cost-effective over angiography alone amongst ACS patients undergoing DES implantation due to the medium- and long-term reduction in repeat PCI, death, and MI.

The economic burden of stomas in the UK: a retrospective observational study of health records and hospital encounters

Background: Stomas divert waste from the small intestine (ileostomy), large intestine (colostomy) or ureters (urostomy), and complications are common. Aims: This study evaluated healthcare resource utilisation (HCRU) and costs of stomas from a UK perspective. Methods: This was a retrospective observational study of adults with new stomas (New Stoma Group) or new/existing stomas and &gt;6 months of follow-up (Established Stoma Group) using health records linked with hospital encounters (January 2009–December 2018). Age- and sex-matched controls were identified for each stoma case (1:50) Findings: Both the New (n=8533) and Established (n=9397) stoma groups had significantly higher HCRU (all P&lt;0.0001) and associated costs (all P&lt;0.01), driven by inpatient admissions. New Stoma Group: colostomy versus controls, £3227 versus £99 per person; ileostomy, £2576 versus £78 per person; and urostomy, £2850 versus £110 per person (all P&lt;0.0001). Findings were similar in the Established Stoma Group. Conclusion: Stomas are associated with a substantial economic burden in the UK driven by hospital care. (Supplementary data tables can be obtained from the authors.)

Delivering disease modifying treatments in Alzheimer's disease-An old age psychiatry UK perspective.

Delivering disease modifying treatments in Alzheimer's disease-An old age psychiatry UK perspective.