The cost of implementing the COVID-19 shielding policy in Wales.

BACKGROUND: The EVITE Immunity study investigated the effects of shielding Clinically Extremely Vulnerable (CEV) people during the COVID-19 pandemic on health outcomes and healthcare costs in Wales, United Kingdom, to help prepare for future pandemics. Shielding was intended to protect those at highest risk of serious harm from COVID-19. We report the cost of implementing shielding in Wales. METHODS: The number of people shielding was extracted from the Secure Anonymised Information Linkage Databank. Resources supporting shielding between March and June 2020 were mapped using published reports, web pages, freedom of information requests to Welsh Government and personal communications (e.g. with the office of the Chief Medical Officer for Wales). RESULTS: At the beginning of shielding, 117,415 people were on the shielding list. The total additional cost to support those advised to stay home during the initial 14 weeks of the pandemic was £13,307,654 (£113 per person shielded). This included the new resources required to compile the shielding list, inform CEV people of the shielding intervention and provide medicine and food deliveries. The list was adjusted weekly over the 3-month period (130,000 people identified by June 2020). Therefore the cost per person shielded lies between £102 and £113 per person. CONCLUSION: This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true costs of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies.

Rationale for the shielding policy for clinically vulnerable people in the UK during the COVID-19 pandemic: a qualitative study.

INTRODUCTION: Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the first year of the pandemic from March 2020. As the first stage in the EVITE Immunity evaluation (Effects of shielding for vulnerable people during COVID-19 pandemic on health outcomes, costs and immunity, including those with cancer:quasi-experimental evaluation), we generated a logic model to describe the programme theory underlying the shielding intervention. DESIGN AND PARTICIPANTS: We reviewed published documentation on shielding to develop an initial draft of the logic model. We then discussed this draft during interviews with 13 key stakeholders involved in putting shielding into effect in Wales and England. Interviews were recorded, transcribed and analysed thematically to inform a final draft of the logic model. RESULTS: The shielding intervention was a complex one, introduced at pace by multiple agencies working together. We identified three core components: agreement on clinical criteria; development of the list of people appropriate for shielding; and communication of shielding advice. In addition, there was a support programme, available as required to shielding people, including food parcels, financial support and social support. The predicted mechanism of change was that people would isolate themselves and so avoid infection, with the primary intended outcome being reduction in mortality in the shielding group. Unintended impacts included negative impact on mental and physical health and well-being. Details of the intervention varied slightly across the home nations of the UK and were subject to minor revisions during the time the intervention was in place. CONCLUSIONS: Shielding was a largely untested strategy, aiming to mitigate risk by placing a responsibility on individuals to protect themselves. The model of its rationale, components and outcomes (intended and unintended) will inform evaluation of the impact of shielding and help us to understand its effect and limitations.

The Economic Potential of Smoking Cessation Interventions at the Point of Diagnosis of Non-Small Cell Lung Cancer.

OBJECTIVES: Stopping smoking has proven benefits in nearly all illnesses but the impact and health economic benefits of stopping smoking after a diagnosis of lung cancer are less well defined. We assessed the cost-effectiveness of smoking cessation (SC) services for patients with newly diagnosed lung cancer against current usual care, where patients are unlikely to receive SC service referral. METHODS: A health economic model was constructed in Excel. The modelled population comprised of patients with a new diagnosis of non-small cell lung cancer (NSCLC). Data from the LungCast data set (Clinical Trials Identifier NCT01192256) were used to estimate model inputs. A structured search of published literature identified inputs not represented in LungCast, including healthcare resource use and costs. Costs were estimated from a 2020/2021 UK National Health Service and Personal Social Services perspective. The model estimated the incremental quality-adjusted life-year (QALY) gained in patients with newly diagnosed NSCLC receiving targeted SC intervention than those receiving no intervention. Extensive one-way sensitivity analyses explored input and data set uncertainty. RESULTS: In the 5-year base case, the model estimated an incremental cost of £14 904 per QALY gained through SC intervention. Sensitivity analysis estimated an outcome range of between £9935 and £32 246 per QALY gained. The model was most sensitive to the estimates of relative quit rates and expected healthcare resource use. CONCLUSION: This exploratory analysis indicates that SC intervention for smokers with patients with newly diagnosed NSCLC should be a cost-effective use of UK National Health Service resources. Additional research with focused costing is needed to confirm this positioning.

Effectiveness and cost-effectiveness of a personalised self-management intervention for living with long COVID: protocol for the LISTEN randomised controlled trial.

BACKGROUND: Individuals living with long COVID experience multiple, interacting and fluctuating symptoms which can have a dramatic impact on daily living. The aim of the Long Covid Personalised Self-managemenT support EvaluatioN (LISTEN) trial is to evaluate effects of the LISTEN co-designed self-management support intervention for non-hospitalised people living with long COVID on participation in routine activities, social participation, emotional well-being, quality of life, fatigue, and self-efficacy. Cost-effectiveness will also be evaluated, and a detailed process evaluation carried out to understand how LISTEN is implemented. METHODS: The study is a pragmatic randomised effectiveness and cost-effectiveness trial in which a total of 558 non-hospitalised people with long COVID will be randomised to either the LISTEN intervention or usual care. Recruitment strategies have been developed with input from the LISTEN Patient and Public Involvement and Engagement (PPIE) advisory group and a social enterprise, Diversity and Ability, to ensure inclusivity. Eligible participants can self-refer into the trial via a website or be referred by long COVID services. All participants complete a range of self-reported outcome measures, online, at baseline, 6 weeks, and 3 months post randomisation (the trial primary end point). Those randomised to the LISTEN intervention are offered up to six one-to-one sessions with LISTEN-trained intervention practitioners and given a co-designed digital resource and paper-based book. A detailed process evaluation will be conducted alongside the trial to inform implementation approaches should the LISTEN intervention be found effective and cost-effective. DISCUSSION: The LISTEN trial is evaluating a co-designed, personalised self-management support intervention (the LISTEN intervention) for non-hospitalised people living with long COVID. The design has incorporated extensive strategies to minimise participant burden and maximise access. Whilst the duration of follow-up is limited, all participants are approached to consent for long-term follow-up (subject to additional funding being secured). TRIAL REGISTRATION: LISTEN ISRCTN36407216. Registered on 27/01/2022.

Protocol for a feasibility study of a cancer symptom awareness campaign to support the rapid diagnostic centre referral pathway in a socioeconomically deprived area: Targeted Intensive Community-based campaign To Optimise Cancer awareness (TIC-TOC).

INTRODUCTION: Rapid diagnostic centres (RDCs) are being implemented across the UK to accelerate the assessment of vague suspected cancer symptoms. Targeted behavioural interventions are needed to augment RDCs that serve socioeconomically deprived populations who are disproportionately affected by cancer, have lower cancer symptom awareness and are less likely to seek help for cancer symptoms. The aim of this study is to assess the feasibility and acceptability of delivering and evaluating a community-based vague cancer symptom awareness intervention in an area of high socioeconomic deprivation. METHODS AND ANALYSIS: Intervention materials and messages were coproduced with local stakeholders in Cwm Taf Morgannwg, Wales. Cancer champions will be trained to deliver intervention messages and distribute intervention materials using broadcast media (eg, local radio), printed media (eg, branded pharmacy bags, posters, leaflets), social media (eg, Facebook) and attending local community events. A cross-sectional questionnaire will include self-reported patient interval (time between noticing symptoms to contacting the general practitioner), cancer symptom recognition, cancer beliefs and barriers to presentation, awareness of campaign messages, healthcare resource use, generic quality of life and individual and area-level deprivation indicators. Consent rates and proportion of missing data for patient questionnaires (n=189) attending RDCs will be measured. Qualitative interviews and focus groups will assess intervention acceptability and barriers/facilitators to delivery. ETHICS AND DISSEMINATION: Ethical approval for this study was given by the London-West London & GTAC Research Ethics (21/LO/0402). This project will inform a potential future controlled study to assess intervention effectiveness in reducing the patient interval for vague cancer symptoms. The results will be critical to informing national policy and practice regarding behavioural interventions to support RDCs in highly deprived populations.

Hughes abdominal closure versus standard mass closure to reduce incisional hernias following surgery for colorectal cancer: the HART RCT.

BACKGROUND: Incisional hernias can cause chronic pain and complications and affect quality of life. Surgical repair requires health-care resources and has a significant associated failure rate. A prospective, multicentre, single-blinded randomised controlled trial was conducted to investigate the clinical effectiveness and cost-effectiveness of the Hughes abdominal closure method compared with standard mass closure following surgery for colorectal cancer. The study randomised, in a 1 : 1 ratio, 802 adult patients (aged ≥ 18 years) undergoing surgical resection for colorectal cancer from 28 surgical departments in UK centres. INTERVENTION: Hughes abdominal closure or standard mass closure. MAIN OUTCOME MEASURES: The primary outcome was the incidence of incisional hernias at 1 year, as assessed by clinical examination. Within-trial cost-effectiveness and cost-utility analyses over 1 year were conducted from an NHS and a social care perspective. A key secondary outcome was quality of life, and other outcomes included the incidence of incisional hernias as detected by computed tomography scanning. RESULTS: The incidence of incisional hernia at 1-year clinical examination was 50 (14.8%) in the Hughes abdominal closure arm compared with 57 (17.1%) in the standard mass closure arm (odds ratio 0.84, 95% confidence interval 0.55 to 1.27; p = 0.4). In year 2, the incidence of incisional hernia was 78 (28.7%) in the Hughes abdominal closure arm compared with 84 (31.8%) in the standard mass closure arm (odds ratio 0.86, 95% confidence interval 0.59 to 1.25; p = 0.43). Computed tomography scanning identified a total of 301 incisional hernias across both arms, compared with 100 identified by clinical examination at the 1-year follow-up. Computed tomography scanning missed 16 incisional hernias that were picked up by clinical examination. Hughes abdominal closure was found to be less cost-effective than standard mass closure. The mean incremental cost for patients undergoing Hughes abdominal closure was £616.45 (95% confidence interval -£699.56 to £1932.47; p = 0.3580). Quality of life did not differ significantly between the study arms at any time point. LIMITATIONS: As this was a pragmatic trial, the control arm allowed surgeon discretion in the approach to standard mass closure, introducing variability in the techniques and equipment used. Intraoperative randomisation may result in a loss of equipoise for some surgeons. Follow-up was limited to 2 years, which may not have been enough time to see a difference in the primary outcome. CONCLUSIONS: Hughes abdominal closure did not significantly reduce the incidence of incisional hernias detected by clinical examination and was less cost-effective at 1 year than standard mass closure in colorectal cancer patients. Computed tomography scanning may be more effective at identifying incisional hernias than clinical examination, but the clinical benefit of this needs further research. FUTURE WORK: An extended follow-up using routinely collected NHS data sets aims to report on incisional hernia rates at 2-5 years post surgery to investigate any potential mortality benefit of the closure methods. Furthermore, the proportion of incisional hernias identified by a computed tomography scan (at 1 and 2 years post surgery), but not during clinical examination (occult hernias), proceeding to surgical repair within 3-5 years after the initial operation will be explored. TRIAL REGISTRATION: This trial is registered as ISRCTN25616490. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 34. See the NIHR Journals Library website for further project information.

Bowel cancer treatment involves surgery for the majority of patients. A complication of this surgery is the formation of a hernia at the site of the incision in the abdominal wall, known as an incisional hernia. The lining of the abdomen, fat or the intestine can squeeze through the gap and form a lump under the skin. An incisional hernia can form any time after surgery and can cause serious complications and pain, and can also affect the patient's quality of life. Surgery to correct incisional hernias is not always successful, so finding a way of preventing them is important. This research compares the traditional way of sewing up the abdomen, where the two sides are brought together in one layer with a continuous thread, with an alternative method called the Hughes abdominal closure method/Hughes repair. In the Hughes repair, a series of horizontal and vertical stitches are arranged to spread the load and ease the tension across the wound. A total of 802 patients from 28 sites in the UK were recruited to the trial. Half of the patients were randomly allocated to have traditional abdominal closure and half were randomised to have Hughes abdominal closure. All were followed up for 1 year after surgery to assess whether or not an incisional hernia had occurred. We also assessed quality of life during follow-up, and we compared the costs and benefits of each procedure to see which option was the better value for money. By comparing the results from the two methods, it was hoped that the best method of abdominal closure to reduce the risk of an incisional hernia occurring would be found. The analysis of the data suggested that the risk of an incisional hernia was no different with either closure method. Furthermore, Hughes abdominal closure was more expensive and provided less value for money than standard abdominal closure.

Healthcare resource utilisation and cost analysis associated with opioid analgesic use for non-cancer pain: A case-control, retrospective study between 2005 and 2015.

Objective: To examine differences in healthcare utilisation and costs associated with opioid prescriptions for non-cancer pain issued in primary care. Method: A longitudinal, case-control study retrospectively examined Welsh healthcare data for the period 1 January 2005-31 December 2015. Data were extracted from the Secure Anonymised Information Linkage (SAIL) databank. Subjects, aged 18 years and over, were included if their primary care record contained at least one of six overarching pain diagnoses during the study period. Subjects were excluded if their record also contained a cancer diagnosis in that time or the year prior to the study period. Case subjects also received at least one prescription for an opioid analgesic. Controls were matched by gender, age, pain-diagnosis and socioeconomic deprivation. Healthcare use included primary care visits, emergency department (ED) and outpatient (OPD) attendances, inpatient (IP) admissions and length of stay. Cost analysis for healthcare utilisation used nationally derived unit costs for 2015. Differences between case and control subjects for resource use and costs were analysed and further stratified by gender, prescribing persistence (PP) and deprivation. Results: Data from 3,286,215 individuals were examined with 657,243 receiving opioids. Case subjects averaged 5 times more primary care visits, 2.8 times more OPD attendances, 3 times more ED visits and twice as many IN admissions as controls. Prescription persistence over 6 months and greater deprivation were associated with significantly greater utilisation of healthcare resources. Opioid prescribing was associated with 69% greater average healthcare costs than in control subjects. National Health Service (NHS) healthcare service costs for people with common, pain-associated diagnoses, receiving opioid analgesics were estimated to be £0.9billion per year between 2005 and 2015. Conclusion: Receipt of opioid prescriptions was associated with significantly greater healthcare utilisation and accompanying costs in all sectors. Extended prescribing durations are particularly important to address and should be considered at the point of initiation.

STRategies to manage Emergency ambulance Telephone Callers with sustained High needs: an Evaluation using linked Data (STRETCHED) - a study protocol.

INTRODUCTION: UK ambulance services have identified a concern with high users of the 999 service and have set up 'frequent callers' services, ranging from within-service management to cross-sectoral multidisciplinary case management approaches. There is little evidence about how to address the needs of this patient group. AIM: To evaluate effectiveness, safety and efficiency of case management approaches to the care of people who frequently call the emergency ambulance service, and gain an understanding of barriers and facilitators to implementation. OBJECTIVES: (1) Develop an understanding of predicted mechanisms of change to underpin evaluation. (2) Describe epidemiology of sustained high users of 999 services. (3) Evaluate case management approaches to the care of people who call the 999 ambulance service frequently in terms of: (i) Further emergency contacts (999, emergency department, emergency admissions to hospital) (ii) Effects on other services (iii) Adverse events (deaths, injuries, serious medical emergencies and police arrests) (iv) Costs of intervention and care (v) Patient experience of care. (4) Identify challenges and opportunities associated with using case management models, including features associated with success, and develop theories about how case management works in this population. METHODS AND ANALYSIS: We will conduct a multisite mixed-methods evaluation of case management for people who use ambulance services frequently by using anonymised linked routine data outcomes in a 'natural experiment' cohort design, in four regional ambulance services. We will conduct interviews and focus groups with service users, commissioners and emergency and non-acute care providers. The planned start and end dates of the study are 1 April 2019 and 1 September 2022, respectively ETHICS AND DISSEMINATION: The study received approval from the UK Health Research Authority (Confidentiality Advisory Group reference number: 19/CAG/0195; research ethics committee reference number: 19/WA/0216).We will collate feedback from our Lived Experience Advisory Panel, the Frequent Caller National Network and Research Management Group for targeted dissemination activities.

Associations with Post-Consultation Health-Status in Primary Care Managed Acute Exacerbation of COPD.

BACKGROUND: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing. AIM: To investigate the factors associated with post-consultation COPD health status in patients presenting with AECOPD in this setting. DESIGN AND SETTING: A cohort study of patients enrolled in a randomised controlled trial. Patients aged 40+ years with a clinical diagnosis of COPD who presented in primary care across England and Wales with an AECOPD were included. METHODS: Participants were contacted for follow-up at one- and two-weeks by phone and attended the practice four weeks after the index consultation. The outcome of interest was the Clinical COPD Questionnaire (CCQ) score. Multivariable multilevel linear regression models fitted to examine the factors associated with COPD health status in the four-weeks following consultation for an AECOPD. RESULTS: A total of 649 patients were included, with 1947 CCQ total scores analysed. Post-consultation CCQ total scores were significantly higher (worse) in participants with diabetes (adjusted mean difference [AMD]=0.26; 95% confidence interval (CI) 0.08-0.45), obese patients compared to those with normal body mass index (AMD = 0.25, 95% CI 0.07-0.43), and those who were prescribed oral antibiotics in the prior 12 months (AMD = 0.26; 95% CI 0.11-0.41), but only the two latter associations remained after adjusting for other sociodemographic variables. CONCLUSION: COPD health status was worse in the four weeks following primary care consultation for AECOPD in patients with obesity and those prescribed oral antibiotics in the preceding year.

Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study.

INTRODUCTION: Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics. METHODS AND ANALYSIS: This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results; use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes; survey a stratified random sample of each group about activities and quality of life at 12 months; use routine and newly collected blood data to assess immunity; interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences; collect healthcare resource use data to calculate implementation costs and cost-consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study. ETHICS AND DISSEMINATION: The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks.

Randomised feasibility study of prehospital recognition and antibiotics for emergency patients with sepsis (PhRASe).

Severe sepsis is a time critical condition which is known to have a high mortality rate. Evidence suggests that early diagnosis and early administration of antibiotics can reduce morbidity and mortality from sepsis. The prehospital phase of emergency medical care may provide the earliest opportunity for identification of sepsis and delivery of life-saving treatment for patients. We aimed to assess the feasibility of (1) paramedics recognising and screening patients for severe sepsis, collecting blood cultures and administering intravenous antibiotics; and (2) trial methods in order to decide whether a fully-powered trial should be undertaken to determine safety and effectiveness of this intervention. Paramedics were trained in using a sepsis screening tool, aseptic blood culture collection and administration of intravenous antibiotics. If sepsis was suspected, paramedics randomly allocated patients to intervention or usual care using scratchcards. Patients were followed up at 90 days using linked anonymised data to capture length of hospital admission and mortality. We collected self-reported health-related quality of life at 90 days. We pre-specified criteria for deciding whether to progress to a fully-powered trial based on: recruitment of paramedics and patients; delivery of the intervention; retrieval of outcome data; safety; acceptability; and success of anonymised follow-up. Seventy-four of the 104 (71.2%) eligible paramedics agreed to take part and 54 completed their training (51.9%). Of 159 eligible patients, 146 (92%) were recognised as eligible by study paramedics, and 118 were randomised (74% of eligible patients, or 81% of those recognised as eligible). Four patients subsequently dissented to be included in the trial (3%), leaving 114 patients recruited to follow-up. All recruited patients were matched to routine data outcomes in the Secure Anonymised Information Linkage Databank. Ninety of the 114 (79%) recruited patients had sepsis or a likely bacterial infection recorded in ED. There was no evidence of any difference between groups in patient satisfaction, and no adverse reactions reported. There were no statistically significant differences between intervention and control groups in Serious Adverse Events (ICU admissions; deaths). This feasibility study met its pre-determined progression criteria; an application will therefore be prepared and submitted for funding for a fully-powered multi-centre randomised trial.Trial registration: ISRCTN36856873 sought 16th May 2017; https://doi.org/10.1186/ISRCTN36856873.

Randomised controlled trial and economic evaluation of a targeted cancer awareness intervention for adults living in deprived areas of the UK.

BACKGROUND: Cancer outcomes are poor in socioeconomically deprived communities, with low symptom awareness contributing to prolonged help-seeking and advanced disease. Targeted cancer awareness interventions require evaluation. METHODS: This is a randomised controlled trial involving adults aged 40+ years recruited in community and healthcare settings in deprived areas of South Yorkshire and South-East Wales. INTERVENTION: personalised behavioural advice facilitated by a trained lay advisor. CONTROL: usual care. Follow-up at two weeks and six months post-randomisation. PRIMARY OUTCOME: total cancer symptom recognition score two weeks post-randomisation. RESULTS: Two hundred and thirty-four participants were randomised. The difference in total symptom recognition at two weeks [adjusted mean difference (AMD) 0.6, 95% CI: -0.03, 1.17, p = 0.06] was not statistically significant. Intervention participants reported increased symptom recognition (AMD 0.8, 95% CI: 0.18, 1.37, p = 0.01) and earlier intended presentation (AMD -2.0, 95% CI: -3.02, -0.91, p < 0.001) at six months. "Lesser known" symptom recognition was higher in the intervention arm (2 weeks AMD 0.5, 95% CI: 0.03, 0.97 and six months AMD 0.7, 95% CI: 0.16, 1.17). Implementation cost per participant was £91.34, with no significant between-group differences in healthcare resource use post-intervention. CONCLUSIONS: Improved symptom recognition and earlier anticipated presentation occurred at longer-term follow-up. The ABACus Health Check is a viable low-cost intervention to increase cancer awareness in socioeconomically deprived communities. CLINICAL TRIAL REGISTRATION: ISRCTN16872545.

Palliative radiotherapy combined with stent insertion to reduce recurrent dysphagia in oesophageal cancer patients: the ROCS RCT.

BACKGROUND: Most patients with oesophageal cancer present with incurable disease. For those with advanced disease, the mean survival is 3-5 months. Treatment emphasis is therefore on effective palliation, with the majority of patients requiring intervention for dysphagia. Insertion of a self-expanding metal stent provides rapid relief but dysphagia may recur within 3 months owing to tumour progression. Evidence reviews have called for trials of interventions combined with stenting to better maintain the ability to swallow. OBJECTIVES: The Radiotherapy after Oesophageal Cancer Stenting (ROCS) study examined the effectiveness of palliative radiotherapy, combined with insertion of a stent, in maintaining the ability to swallow. The trial also examined the impact that the ability to swallow had on quality of life, bleeding events, survival and cost-effectiveness. DESIGN: A pragmatic, multicentre, randomised controlled trial with follow-up every 4 weeks for 12 months. An embedded qualitative study examined trial experiences in a participant subgroup. SETTING: Participants were recruited in secondary care, with all planned follow-up at home. PARTICIPANTS: Patients who were referred for stent insertion as the primary management of dysphagia related to incurable oesophageal cancer. INTERVENTIONS: Following stent insertion, the external beam radiotherapy arm received palliative oesophageal radiotherapy at a dose of 20 Gy in five fractions or 30 Gy in 10 fractions. MAIN OUTCOME MEASURES: The primary outcome was the difference in the proportion of participants with recurrent dysphagia, or death, at 12 weeks. Recurrent dysphagia was defined as deterioration of ≥ 11 points on the dysphagia scale of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire oesophago-gastric module questionnaire. Secondary outcomes included quality of life, bleeding risk and survival. RESULTS: The study recruited 220 patients: 112 were randomised to the usual-care arm and 108 were randomised to the external beam radiotherapy arm. There was no evidence that radiotherapy reduced recurrence of dysphagia at 12 weeks (48.6% in the usual-care arm compared with 45.3% in the external beam radiotherapy arm; adjusted odds ratio 0.82, 95% confidence interval 0.40 to 1.68; p = 0.587) and it was less cost-effective than stent insertion alone. There was no difference in median survival or key quality-of-life outcomes. There were fewer bleeding events in the external beam radiotherapy arm. Exploration of patient experience prompted changes to trial processes. Participants in both trial arms experienced difficulty in managing the physical and psychosocial aspects of eating restriction and uncertainties of living with advanced oesophageal cancer. LIMITATIONS: Change in timing of the primary outcome to 12 weeks may affect the ability to detect a true intervention effect. However, consistency of results across sensitivity analyses is robust, including secondary analysis of dysphagia deterioration-free survival. CONCLUSIONS: Widely accessible palliative external beam radiotherapy in combination with stent insertion does not reduce the risk of dysphagia recurrence at 12 weeks, does not have an impact on survival and is less cost-effective than inserting a stent alone. Reductions in bleeding events should be considered in the context of patient-described trade-offs of fatigue and burdens of attending hospital. Trial design elements including at-home data capture, regular multicentre nurse meetings and qualitative enquiry improved recruitment/data capture, and should be considered for future studies. FUTURE WORK: Further studies are required to identify interventions that improve stent efficacy and to address the multidimensional challenges of eating and nutrition in this patient population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12376468 and Clinicaltrials.gov NCT01915693. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 31. See the NIHR Journals Library website for further project information.

Most people are diagnosed with oesophageal (gullet) cancer when it is already at an advanced stage. Losing the ability to swallow food and even fluids is very common when patients are approaching the last months of life. Placing a flexible metal tube, or stent, in the gullet opens it up and improves the ability to swallow quickly. Unfortunately this can fail after around 3 months because the cancer grows and presses on the stent. We designed this trial to see if giving a small dose of radiotherapy alongside insertion of the stent would allow more people to remain swallowing well after 3 months. This could then improve their quality of life and reduce hospitalisation towards the end of life. It may also reduce bleeding from the gullet, as well as other symptoms. We recruited 220 people across the UK, randomly assigning them to have the stent as usual or the stent and a low dose of radiotherapy. We collected a lot of information from the participants at home on how the cancer, the stent and the radiotherapy affected their ability to swallow and their quality of life. Overall, the study showed that the radiotherapy did not improve the ability to swallow 3 months following stent insertion and was less cost-effective than stent insertion alone. It seemed to reduce the risk of bleeding from the tumour itself, but patients found that radiotherapy made them tired and attending extra hospital visits could be troublesome. We also learned that, even after a stent was inserted, patients still struggled with food and needed more support with managing daily life with the stent. The trial results are important. They show that, to answer questions such as these, studies should use different ways of assessing what works, particularly focusing on patients' and families' viewpoints. The results will guide doctors to not routinely give radiotherapy in this situation. The results also suggest that, after the insertion of a stent, patients need extra help in managing their diet, their worries about the stent and their worries about the future.

Associations with antibiotic prescribing for acute exacerbation of COPD in primary care: secondary analysis of a randomised controlled trial.

BACKGROUND: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible. AIM: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care. DESIGN AND SETTING: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial). METHOD: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l). RESULTS: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85). CONCLUSION: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions.

Protocol for an open label: phase I trial within a cohort of foetal cell transplants in people with Huntington's disease.

Huntington's disease is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington's disease is characterized by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell-replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration is a phase I Trial Within a Cohort designed to assess safety and feasibility of transplanting human foetal striatal cells into the striatum of people with Huntington's disease. A minimum of 18 participants will be enrolled in the study cohort, and up to five eligible participants will be randomly selected to undergo transplantation of 12-22 million foetal cells in a dose escalation paradigm. Independent reviewers will assess safety outcomes (lack of significant infection, bleeding or new neurological deficit) 4 weeks after surgery, and ongoing safety will be established before conducting each subsequent surgery. All participants will undergo detailed clinical and functional assessment at baseline (6 and 12 months). Surgery will be performed 1 month after baseline, and transplant participants will undergo regular clinical follow-up for at least 12 months. Evaluation of trial processes will also be undertaken. Transplant participants and their carers will be interviewed ∼1 month before and after surgery. Interviews will also be conducted with non-transplanted participants and healthcare staff delivering the intervention and involved in the clinical care of participants. Evaluation of clinical and functional efficacy outcomes and intervention costs will be carried out to explore plausible trial designs for subsequent randomized controlled trials aimed at evaluating efficacy and cost-effectiveness of cell-replacement therapy. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration will enable the assessment of the safety, feasibility, acceptability and cost of foetal cell transplants in people with Huntington's disease. The data collected will inform trial designs for complex intra-cranial interventions in a range of neurodegenerative conditions and facilitate the development of stable surgical pipelines for delivery of future stem cell trials. Trial Registration: ISRCTN52651778.

Palliative radiotherapy after oesophageal cancer stenting (ROCS): a multicentre, open-label, phase 3 randomised controlled trial.

BACKGROUND: Patients with advanced oesophageal cancer have a median survival of 3-6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion. METHODS: This was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I-III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (>11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed. FINDINGS: 220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40-1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4-27·7) with usual care and 18·9 weeks (14·7-25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78-1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3-not reached) with usual care versus 65·9 weeks (52·7-not reached) with EBRT (adjusted subhazard ratio 0·52 [95% CI 0·28-0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3-4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care. INTERPRETATION: Patients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Examining opioid prescribing trends for non-cancer pain using an estimated oral morphine equivalence measure: a retrospective cohort study between 2005 and 2015.

BACKGROUND: Over the past 20 years prescription of opioid medicines has markedly increased in the UK, despite a lack of supporting evidence for use in commonly occurring, painful conditions. Prescribing is often monitored by counting numbers of prescriptions dispensed, but this may not provide an accurate picture of clinical practice. AIM: To use an estimated oral morphine equivalent (OMEQe) dose to describe trends in opioid prescribing in non-cancer pain, and explore if opioid burden differed by deprivation status. DESIGN & SETTING: A retrospective cohort study using cross-sectional and longitudinal trend analyses of opioid prescribing data from Welsh Primary Care General Practices (PCGP) took place. Data were used from the Secure Anonymised Information Linkage (SAIL) databank. METHOD: An OMEQe measure was developed and used to describe trends in opioid burden over the study period. OMEQe burden was stratified by eight drug groups, which was based on usage and deprivation. RESULTS: An estimated 643 436 843 milligrams (mg) OMEQe was issued during the study. Annual number of prescriptions increased 44% between 2005 and 2015, while total daily OMEQe per 1000 population increased by 95%. The most deprived areas of Wales had 100 711 696 mg more OMEQe prescribed than the least deprived over the study period. CONCLUSION: Over the study period, OMEQe burden nearly doubled, with disproportionate OMEQe prescribed in the most deprived communities. Using OMEQe provides an alternative measure of prescribing and allows easier comparison of the contribution different drugs make to the overall opioid burden.

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. OBJECTIVE: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. DESIGN: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. SETTING: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. PARTICIPANTS: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours' and 21 days' duration. INTERVENTION: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. MAIN OUTCOME MEASURES: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. RESULTS: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI -0.33 to -0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI -£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. CONCLUSIONS: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. FUTURE WORK: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24346473. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information.

People with chronic obstructive pulmonary disease (COPD) often experience flare-ups known as acute exacerbations of chronic obstructive pulmonary disease. Antibiotics are prescribed for most flare-ups, but they do not always benefit patients and may cause harm, such as side effects or subsequent infections that are resistant. Rapid point-of-care tests (POCTs) can be used to help determine when antibiotics are more likely to be needed. C-reactive protein (CRP) is a marker of inflammation that can be measured with a POCT. Patients with flare-ups and a low CRP value are less likely to benefit from antibiotics. The PACE trial asked whether or not measuring CRP with a POCT could lead to fewer antibiotics being consumed for flare-ups, without having negative effects for patients. We aimed to recruit 650 patients with a COPD flare-up from primary care. Patients were randomly assigned to either (1) usual care with the addition of a CRP POCT, or (2) usual care without the addition of the test. Antibiotic use over the first 4 weeks and patients' self-assessment of their health 2 weeks after enrolment were measured in both groups. Patients in the CRP test group used fewer antibiotics than those managed as usual, and had improved patient-reported outcomes. Costs were a little higher in the CRP POCT group. Interviews with patients and clinicians found that they appreciated the CRP test being included in the decision-making process.

Rapid cancer diagnosis for patients with vague symptoms: a cost-effectiveness study.

BACKGROUND: A pilot rapid diagnosis centre (RDC) allows GPs within targeted clusters to refer adults with vague and/or non-specific symptoms suspicious of cancer, who do not meet criteria for referral under an urgent suspected cancer (USC) pathway, to a multidisciplinary RDC clinic where they are seen within 1 week. AIM: To explore the cost-effectiveness of the RDC compared with standard clinical practice. DESIGN AND SETTING: Cost-effectiveness modelling using routine data from Neath Port Talbot Hospital, Wales. METHOD: Discrete-event simulation modelled a cohort of 1000 patients from referral to radiological diagnosis based on routine RDC and hospital data. Control patients were those referred to a USC pathway but then downgraded. Published sources provided estimates of patient quality of life (QoL) and pre-diagnosis anxiety. The model calculates time to diagnosis, costs, and quality-adjusted life years (QALYs), and estimates the probability of the RDC being a cost-effective strategy. RESULTS: The RDC reduces mean time to diagnosis from 84.2 days in usual care to 5.9 days if a diagnosis is made at clinic, or 40.8 days if further investigations are booked during RDC. RDC provision is the superior strategy (that is, less costly and more effective) compared with standard clinical practice when run near or at full capacity. However, it is not cost-effective if capacity utilisation drops below 80%. CONCLUSION: An RDC for patients presenting with vague or non-specific symptoms suspicious of cancer in primary care reduces time to diagnosis and provides excellent value for money if run at ≥80% capacity.