UK Setting Research Articles

Extensive Study of Breast Milk and Infant Growth: Protocol of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF)

Growth and nutrition during early life have been strongly linked to future health and metabolic risks. The Cambridge Baby Growth Study (CBGS), a longitudinal birth cohort of 2229 mother–infant pairs, was set up in 2001 to investigate early life determinant factors of infant growth and body composition in the UK setting. To carry out extensive profiling of breastmilk intakes and composition in relation to infancy growth, the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) was established upon the original CBGS. The strict inclusion criteria were applied, focusing on a normal birth weight vaginally delivered infant cohort born of healthy and non-obese mothers. Crucially, only infants who were exclusively breastfed for the first 6 weeks of life were retained in the analysed study sample. At each visit from birth, 2 weeks, 6 weeks, and then at 3, 6, 12, 24, and 36 months, longitudinal anthropometric measurements and blood spot collections were conducted. Infant body composition was assessed using air displacement plethysmography (ADP) at 6 weeks and 3 months of age. Breast milk was collected for macronutrients and human milk oligosaccharides (HMO) measurements. Breast milk intake volume was also estimated, as well as sterile breastmilk and infant stool collection for microbiome study.

Transnational Education in the Anglophone University: A Viewpoint Article

This viewpoint article provides a critical reflection on the gatekeeping and academic language practices of Anglophone universities, evaluating these in light of the promotional claims universities make about internationalization and global reach. I then consider the arguments put forward in each of the main articles in this special issue from this critical perspective, connecting the authors’ accounts of EMI practices in transnational higher education contexts with the language requirements and practices of the Anglophone university. I argue that there is considerable overlap between the concerns of stakeholders in EMI settings and those of international students and academics in Anglophone universities in a UK setting. I find that the English language requirements for admissions as well as orientations to academic language in higher education curricula can in EMI settings and ‘international’ Anglophone universities alike be underpinned by language ideological positions that do not reflect an especially global outlook, and that remain in many senses tethered to ‘native’ language and ‘native’ academic discourse norms.

A registry study of relapsed or refractory multiple myeloma pre-exposed to three or more prior therapies including a proteasome inhibitor, an immunomodulatory agent and CD38-targeted monoclonal antibody therapy in England.

Some patients with multiple myeloma are receiving treatment in clinical practice in England after prior exposure to a proteasome inhibitor, an immunomodulatory agent, and an anti‐CD38 monoclonal antibody. We investigated the characteristics of these patients, their outcomes, and the salvage therapies they received using the national cancer registry for England and linked healthcare data. After a median follow‐up time of 6.4 months from T 0, median overall survival and time to next treatment were 8.2 and 5.3 months, respectively. This real‐world data provide useful clinical insight into a little‐studied patient population and highlight the poor outcomes in the UK setting.

Left atrial appendage occlusion in the UK: prospective registry and data linkage to Hospital Episode Statistics.

AimsNon-valvular atrial fibrillation (AF) greatly increases the risk of ischaemic stroke. For people with contraindications to oral anticoagulation, left atrial appendage occlusion (LAAO) provides a non-pharmacological management alternative. The aim of this study was to measure the procedural safety and longer-term effectiveness of LAAO for AF in a UK setting.Methods and resultsThis was a prospective, single-armed registry of patients with AF for whom anticoagulation was unsuitable. Registry data were collected between October 2014 and April 2018 and linked to routine data sources for follow-up. Data from 583 LAAO procedures were entered into the registry, of which 537 (from 525 patients) were eligible for inclusion (median CHA2DS2-VASc score 4). A closure device was successfully implanted in 93.4% of cases, with a procedural success rate (device implanted without major complication) of 88.9%. Five patients (1.0%) died in hospital. During follow-up [median 729 (Q1:Q3, 523:913) days] 45 patients experienced neurological events; 33 of which were ischaemic. The ischaemic neurological event rate was 3.3 (1.6–5.0)% at 1 year (n = 387) and 7.0 (4.3–9.6)% at 2 years (n = 196). There were significant improvements in overall patient health (via Visual Analogue Scale) measured at 6 weeks and 6 months, but no significant improvements observed in patient utility over time.ConclusionThe findings of our study suggest that LAAO is not without procedural risk, but that this risk may be justified in high-risk patients with AF who cannot take an anticoagulant. Moreover, the data do not provide support for more widespread use of LAAO as the complication rate was relatively high and would be difficult to justify in many patients with AF who tolerate anticoagulation.

PND33 A Cost-Effectiveness Analysis of Fenfluramine for the Treatment of Seizures for Patients with Dravet Syndrome (DS) in the UK Setting

DS is a rare, genetic epileptic encephalopathy presenting in early childhood, characterised by frequent, severe and pharmaco-resistant seizures; associated with developmental and cognitive impairment, premature death and poor patient and carer quality of life (QoL). As DS is highly heterogeneous, a novel patient-level simulation model was developed to evaluate the cost-effectiveness of fenfluramine - a newly licensed ‘add-on therapy’ for the treatment of DS, in the UK setting. Patient-level data from the placebo arm of fenfluramine registration studies were used to model the number of convulsive seizures and convulsive seizure-free days per 28-day cycle in a DS population generalisable to the UK. Utility values were mapped from patient and carer QoL data from the trials. Carer utility values were included in line with the NICE reference case. Natural and DS-specific mortality rates were derived from literature and UK healthcare resource use data from a DS-specific pathway study. The primary base case analysis compared standard of care (SoC) with either add-on fenfluramine or NICE-recommended cannabidiol (with clobazam), over a lifetime horizon. A robust indirect treatment comparison provided relative treatment effects for SoC, fenfluramine and cannabidiol. The estimated ICER of fenfluramine at the proposed NHS price compared with cannabidiol (list price) is £31,773/QALY. Deterministic and probabilistic sensitivity analyses demonstrated the base case analysis results are robust to parameter uncertainty. Scenario analyses indicate the most influential assumptions are the inclusion of utility values for carers, and doses assumed for cannabidiol. At plausible maximum doses of cannabidiol, fenfluramine dominates cannabidiol. In fully incremental analyses, fenfluramine had a lower ICER vs SoC than did cannabidiol, i.e. fenfluramine extendedly dominated cannabidiol. This novel patient-level simulation model, which appropriately characterises the population heterogeneity in DS, demonstrates fenfluramine provides a clinically and cost-effective alternative to existing ‘add-on therapy’ options for this rare, life-threatening syndrome.

Evaluation of the Cost-Effectiveness of Iron Formulations for the Treatment of Iron Deficiency Anaemia in Patients with Inflammatory Bowel Disease in the UK.

IntroductionIn patients with inflammatory bowel disease (IBD), iron deficiency anaemia (IDA) can impair quality of life and increase healthcare costs. Treatment options for IDA-associated IBD include oral iron and intravenous iron formulations (such as ferric carboxymaltose [FCM], ferric derisomaltose [FD, previously known as iron isomaltoside 1000], and iron sucrose [IS]). The present analysis compared the cost-effectiveness of FCM versus FD, IS, and oral iron sulfate in terms of additional cost per additional responder in the UK setting.MethodsCost-effectiveness was calculated for FCM versus FD, IS, and oral iron individually in terms of the additional cost per additional responder, defined as haemoglobin normalisation or an increase of ≥2 g/dL in haemoglobin levels, in a model developed in Microsoft Excel. Relative efficacy inputs were taken from a previously published network meta-analysis, since there is currently no single head-to-head trial evidence comparing all therapy options. Costs were calculated in 2020 pounds sterling (GBP) capturing the costs of iron preparations, healthcare professional time, and consumables.ResultsThe analysis suggested that FCM may be the most effective intervention, with 81% of patients achieving a response. Response rates with FD, IS, and oral iron were 74%, 75%, and 69%, respectively. Total costs with FCM, FD, IS, and oral iron were GBP 296, GBP 312, GBP 503, and GBP 56, respectively. FCM was found to be more effective and less costly than both FD and IS, and therefore was considered dominant. Compared with oral iron, FCM was associated with an incremental cost-effectiveness ratio of GBP 2045 per additional responder.ConclusionsFCM is likely to be the least costly and most effective IV iron therapy in the UK setting. Compared with oral iron, healthcare payers must decide whether the superior treatment efficacy of FCM is worth the additional cost.

Modelling palliative and end-of-life resource requirements during COVID-19: implications for quality care

ObjectivesThe WHO estimates that the COVID-19 pandemic has led to more than 1.3 million deaths (1 377 395) globally (as of November 2020). This surge in death necessitates identification of...

Home phototherapy for neonatal jaundice in the UK: a single-centre retrospective service evaluation and parental survey

BackgroundIn the UK setting, where neonatal jaundice treatment is required, it is largely carried out in hospitals. However, it is possible to safely administer home phototherapy (HPT).ObjectiveTo report on our...

Reflections on leadership in advanced and consultant radiographic practice within the UK

IntroductionThis Educational Perspective provides an overview of how leadership fits into advanced and consultant radiographic roles within the UK setting. It draws on research in the area as well as reviewing some of the wider healthcare literature beyond the medical radiation sciences. The reflections outlined suggest how leadership at these levels may look and differ in practice. DiscussionLeadership should be seen as fundamental to practice and not necessarily a discreet element to either role, but one that supports all other areas. The proportion of the role that leadership takes up, along with the degree of influence, increases from advanced to consultant practice. Consideration over conflict with management and leadership within roles is also important. Ultimately leadership is about relationships with people, for which interpersonal skills are required, along with establishing networks, supported by training and development to maximise effectiveness. ConclusionA clearer understanding of leadership is needed to help conceptualise and measure its impact at advanced and consultant levels of practice. The content is intended to provide an opportunity for reflection and discussion around the topic, serving as a development tool in practice.

Developing information literacy through independent learning projects in a UK setting

Two information literacy skills pilot projects are being undertaken at Malvern St James School (MSJ) with Year 6 and Year 9 pupils during 2009-10. The projects encourage the development of independent learning skills, with pupils planning, managing and executing both the research and practical elements of their project. Each pupil sets their own aims and objectives and it is the process skills as well as the project that is assessed. The projects examine pupil motivation levels, if pupils can use research to inform their practical project and how pupils respond to opportunities to undertake self-directed learning.

Hong Kong Protests—A Commentary on Stott et al.

It is important to clarify from the outset that my observations are not a commentary on either the aims or actions of the Hong Kong protesters, or indeed the legitimacy of the policing response, but rather they are focussed on the research methodology and findings, particularly their applicability in a UK setting. Policing protest is a challenge because it is unpredictable: the bigger the protest group the greater the challenge, because by definition there are more individuals involved, each of whom has an independent mind and can be capable of instigating an action that can alter the course of events. Contentious protest is a dance between protesters and police, the action of one party will prompt a reaction from the other, which can escalate or calm a situation. As such, the assumptions underpinning the model advanced in the paper have long been recognized in public order policing. Evaluating the key...

External validation of the Dutch prediction model for prehospital triage of trauma patients in South West region of England, United Kingdom.

This paper investigates the use of a major trauma prediction model in the UK setting. We demonstrate that application of this model could reduce the number of patients with major trauma being incorrectly sent to non-specialist hospitals. However, more research is needed to reduce over-triage and unnecessary transfer to Major Trauma Centres. To externally validate the Dutch prediction model for identifying major trauma in a large unselected prehospital population of injured patients in England. External validation using a retrospective cohort of injured patients who ambulance crews transported to hospitals. South West region of England. All patients ≥16 years with a suspected injury and transported by ambulance in the year from February 1, 2017. 1) Patients aged ≤15 years; 2) Non-ambulance attendance at hospital with injuries; 3) Death at the scene and; 4) Patients conveyed by helicopter. This study had a census sample of cases available to us over a one year period. Tested the accuracy of the prediction model in terms of discrimination, calibration, clinical usefulness, sensitivity and specificity and under- and over triage rates compared to usual triage practices in the South West region. Major trauma defined as an Injury Severity Score>15. A total of 68799 adult patients were included in the external validation cohort. The median age of patients was 72 (i.q.r. 46-84); 55.5% were female; and 524 (0.8%) had an Injury Severity Score>15. The model achieved good discrimination with a C-Statistic 0.75 (95% CI, 0.73 - 0.78). The maximal specificity of 50% and sensitivity of 83% suggests the model could improve undertriage rates at the expense of increased overtriage rates compared with routine trauma triage methods used in the South West, England. The Dutch prediction model for identifying major trauma could lower the undertriage rate to 17%, however it would increase the overtriage rate to 50% in this United Kingdom cohort. Further prospective research is needed to determine whether the model can be practically implemented by paramedics and is cost-effective.

The cost-effectiveness of dapagliflozin in treating high-risk patients with type 2 diabetes mellitus: An economic evaluation using data from the DECLARE-TIMI 58 trial.

AimTo undertake a cost‐effectiveness analysis of dapagliflozin in treating high‐risk patients with type 2 diabetes mellitus (T2DM), using both directly observed events in the DECLARE‐TIMI 58 trial and surrogate risk factors to predict endpoints not captured within the trial.MethodsAn established T2DM model was adapted to integrate survival curves derived from the DECLARE‐TIMI 58 trial, and extrapolated over a lifetime for all‐cause mortality, hospitalization for heart failure, stroke, myocardial infarction, hospitalization for unstable angina, and end‐stage kidney disease. The economic analysis considered the overall DECLARE trial population, as well as reported patient subgroups. Total and incremental costs, life‐years and quality‐adjusted life‐years associated with dapagliflozin versus placebo were estimated from the perspective of the UK healthcare payer.ResultsIn the UK setting, treatment with dapagliflozin compared to placebo was estimated to be dominant, with an expected increase in quality‐adjusted life‐years from 10.43 to 10.48 (+0.06) and a reduction in lifetime total costs from £39 451 to £36 899 (−£2552). Across all patient subgroups, dapagliflozin was estimated to be dominant, with the greatest absolute benefit in the prior heart failure subgroup (incremental lifetime costs −£4150 and quality‐adjusted life‐years +0.11).ConclusionsThe results of this study demonstrate that dapagliflozin compared to placebo appears to be cost‐effective, when considering evidence reported from the DECLARE‐TIMI 58 trial, at established UK willingness‐to‐pay thresholds. The findings highlight the potential of dapagliflozin to have a meaningful impact in reducing the economic burden of T2DM and its associated complications across a broad T2DM population.

Evaluating the Cost-Effectiveness of Once-Weekly Semaglutide 1mg Versus Empagliflozin 25mg for Treatment of Patients with Type2 Diabetes in the UK Setting.

IntroductionType 2 diabetes represents a continuing healthcare challenge, and choosing cost-effective treatments is crucial to ensure that healthcare resources are used efficiently. The present analysis assessed the cost-effectiveness of once-weekly semaglutide 1 mg versus empagliflozin 25 mg for the treatment of patients with type 2 diabetes mellitus with inadequate glycaemic control on metformin monotherapy from a healthcare payer perspective in the UK.MethodsOutcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects of initiation of once-weekly semaglutide 1 mg and empagliflozin 25 mg were based on an indirect comparison conducted using patient-level data, as there is currently no head-to-head clinical trial comparing these therapies. Modelled patients received treatments until glycated haemoglobin exceeded 7.5% (58 mmol/mol), at which point patients initiated basal insulin. The analysis captured pharmacy costs and costs of diabetes-related complications, expressed in 2019 pounds sterling (GBP). Projected outcomes were discounted at 3.5% annually. Scenario analyses were prepared to assess uncertainty around projected outcomes.ResultsOnce-weekly semaglutide 1 mg was associated with increases in life expectancy and quality-adjusted life expectancy of 0.12 years and 0.23 quality-adjusted life years (QALYs), respectively, compared with empagliflozin 25 mg. Projected improvements in quality and duration of life resulted from a reduced cumulative incidence and a delayed time to onset of diabetes-related complications. Once-weekly semaglutide was associated with increased pharmacy costs, but this was partially offset by avoided costs of treating complications. Once-weekly semaglutide was associated with an increase in costs of GBP 1017 per patient, leading to an incremental cost-effectiveness ratio of GBP 4439 per QALY gained.ConclusionOnce-weekly semaglutide 1 mg was projected to be a cost-effective treatment option from a healthcare payer perspective compared with empagliflozin 25 mg for the treatment of patients with type 2 diabetes in the UK setting.

Protocol for a qualitative study to identify strategies to optimise hospital ePrescribing systems

IntroductionElectronic prescribing (ePrescribing) is a key area of development and investment in the UK and across the developed world. ePrescribing is widely understood as a vehicle for tackling medication-related safety...

A cost-utility analysis of SIR-Spheres Y-90 resin microspheres versus best supportive care in the treatment of unresectable metastatic colorectal cancer refractory to chemotherapy in the UK

Background Limited treatment options are available in chemotherapy-refractory or -intolerant metastatic colorectal cancer (mCRC). The objective of the present analysis was to evaluate the cost-utility of SIR-Spheres Y-90 resin microspheres relative to best supportive care (BSC) in the treatment of chemotherapy refractory mCRC from the perspective of the UK national healthcare payer. Methods A cost-utility model was developed in Microsoft Excel to simulate transitions from progression-free survival to post-progression survival and death in patients with mCRC. Unit costs were captured in 2019 pounds sterling (GBP) based on the literature, formulary listings, and National Health Service (NHS) England reference costs. Future costs and effects were discounted at 3.5% per annum. A series of one-way sensitivity analyses, and probabilistic sensitivity analysis (PSA) were conducted. Results The base case analysis showed that SIR-Spheres Y-90 resin microspheres would result in an increase in discounted quality-adjusted life years gained from 0.69 quality-adjusted life years (QALYs) to 1.50 QALYs, with an associated increase in cost from GBP 15,268 to GBP 34,168 yielding an incremental cost-utility ratio of GBP 23,435 per QALY. PSA showed that there would be a 56% likelihood that SIR-Spheres Y-90 resin microspheres would be cost-effective relative to BSC at a willingness-to-pay threshold of GBP 30,000 per QALY gained. Conclusions This cost-utility analysis showed that, relative to BSC, SIR-Spheres Y-90 resin microspheres would be a cost-effective treatment option for patients with mCRC in the UK setting from the national healthcare payer perspective.

Lung cancer screening by low-dose computed tomography: a cost-effectiveness analysis of alternative programmes in the UK using a newly developed natural history-based economic model

BackgroundA systematic review of economic evaluations for lung cancer identified no economic models of the UK setting based on disease natural history. We first sought to develop a new model of natural history for population screening, then sought to explore the cost-effectiveness of multiple alternative potential programmes.MethodsAn individual patient model (ENaBL) was constructed in MS Excel® and calibrated against data from the US National Lung Screening Trial. Costs were taken from the UK Lung Cancer Screening Trial and took the perspective of the NHS and PSS. Simulants were current or former smokers aged between 55 and 80 years and so at a higher risk of lung cancer relative to the general population. Subgroups were defined by further restricting age and risk of lung cancer as predicted by patient self-questionnaire. Programme designs were single, triple, annual and biennial arrangements of LDCT screens, thereby examining number and interval length. Forty-eight distinct screening strategies were compared to the current practice of no screening. The primary outcome was incremental cost-effectiveness of strategies (additional cost per QALY gained).ResultsLDCT screening is predicted to bring forward the stage distribution at diagnosis and reduce lung cancer mortality, with decreases versus no screening ranging from 4.2 to 7.7% depending on screen frequency. Overall healthcare costs are predicted to increase; treatment cost savings from earlier detection are outweighed by the costs of over-diagnosis. Single-screen programmes for people 55–75 or 60–75 years with ≥ 3% predicted lung cancer risk may be cost-effective at the £30,000 per QALY threshold (respective ICERs of £28,784 and £28,169 per QALY gained). Annual and biennial screening programmes were not predicted to be cost-effective at any cost-effectiveness threshold.LimitationsLDCT performance was unaffected by lung cancer type, stage or location and the impact of a national screening programme of smoking behaviour was not included.ConclusionLung cancer screening may not be cost-effective at the threshold of £20,000 per QALY commonly used in the UK but may be cost-effective at the higher threshold of £30,000 per QALY.

The status of hydrogen technologies in the UK: A multi-disciplinary review

Hydrogen has the potential to offer deep decarbonisation across a range of global heavy-emitting sectors. To have an impact on the global energy system, hydrogen technologies must be deployed with greater urgency. This review article facilitates the much needed, multi-disciplinary discussion around hydrogen. In doing so, the paper outlines recent advancements, prevailing challenges and areas of future research concerning hydrogen technologies, policy, regulation and social considerations in a UK setting. Findings suggest that hydrogen will play a significant role in decarbonising several UK sectors whilst simultaneously addressing challenges faced by alternative low-carbon technologies. Optimal production, delivery and storage systems must be developed to accommodate perceived future demand. Whilst this will be largely dictated by scale, efficiency, cost and technological maturity, significant improvements in existing policies and regulation will also be critical. The future role of hydrogen in the UK’s decarbonisation strategy is not clearly defined. In comparison to alternative low-carbon technologies, policy and regulatory support for hydrogen has been minimal. Whilst there is growing evidence concerning the public perception of hydrogen in UK homes, additional research is required given its many potential applications. The findings detailed in this article support the urgency for further multi-disciplinary collaborative research.

Repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK: a cost-effectiveness analysis

ObjectivesTo assess the cost-effectiveness of universal repeat screening for syphilis in late pregnancy, compared with the current strategy of single screening in early pregnancy with repeat screening offered only to...

Unscheduled return to the operating theatre after head and neck surgery with free flap repair

The purpose of this study was to benchmark the unscheduled postoperative return to theatre rate (URTT) of patients undergoing head and neck surgery with free tissue transfer in a UK setting, and identify opportunities for quality improvement. Between August 2009 and June 2019, data on 1000 patients undergoing surgery in a single institution were prospectively assembled, and the electronic healthcare records of all patients scrutinised to obtain data on putative predictive factors. Categorical factors were analysed with the chi squared test, and continuous variables with the t test or Mann-Whitney U test, as appropriate. Multivariate logistic regression was used to identify independent predictive variables and to determine the predictive value of the final model. Of the 1000 patients 26.5% had one or more URTT, and 4.6% experienced flap failure with a 1% perioperative mortality. Failure of primary healing at the flap to mucosal interface with leakage of whole saliva into the neck wound was the single most prevalent problem (15.4%) followed by flap salvage procedures (7.4%). Independent predictive variables of URTT were perioperative transfusion, duration of procedure, requirement for tracheostomy, and previous radiotherapy to the head and neck. The C-index was weak (0.61) for this model. URTT substantially increased the duration of hospital stay. It is a poor experience for patients, and is associated with increased healthcare costs. It potentially disrupts the flow of care to other patients, and may be associated with a delay to required adjuvant therapy. Quality improvement initiatives should focus on optimising the probability of primary healing at the flap to mucosal interface, and reducing the number of flap salvage procedures.