Protocol for the TRANSLATE prospective, multicentre, randomised clinical trial of prostate biopsy technique.

OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.

Quality of life in the FOXFIRE, SIRFLOX and FOXFIRE-global randomised trials of selective internal radiotherapy for metastatic colorectal cancer.

Selective internal radiotherapy (SIRT) is a liver-directed treatment involving the injection of yttrium-90 microspheres into the blood supply of liver tumours. There are very few studies assessing health-related quality of life (HRQOL) in patients treated with SIRT. Patients with liver metastases from colorectal cancer (CRC) were randomised in the FOXFIRE (FFr; ISRCTN83867919), SIRFLOX (SF; NCT00724503) and FOXFIRE-Global (FFrG; NCT01721954) trials of first-line oxaliplatin-fluorouracil (FOLFOX) chemotherapy combined with SIRT versus FOLFOX alone. HRQOL was assessed using the three-level EQ-5D, European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and EORTC Colorectal Liver Metastases cancer module (EORTC QLQ-LMC21) at baseline, ≤3 months, 6 months, 12 months and annually thereafter from randomisation, and at disease progression. Analyses were conducted on an intention-to-treat basis. In total, 554 patients were randomised to SIRT + FOLFOX and 549 patients to FOLFOX alone. HRQOL was statistically significant lower in SIRT + FOLFOX patients ≤3 months after SIRT administration in all three instruments, particularly global health, physical and role functioning and symptoms of fatigue, nausea/vomiting and appetite loss. By accepted thresholds, these differences were deemed not clinically important. Differences between SIRT + FOLFOX and FOLFOX alone over the 2-year follow up and at disease progression were also not clinically important. Although there is some decrease in HRQOL for up to 3 months following SIRT, the addition of SIRT to FOLFOX chemotherapy does not change HRQOL to a clinically important degree in metastatic CRC patients.

The effectiveness of home versus community-based weight control programmes initiated soon after breast cancer diagnosis: a randomised controlled trial.

BACKGROUND: Breast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women. METHODS: Overweight or obese (n = 243) and normal weight (n = 166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes. RESULTS: Forty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight -2.3 (-3.5, -1.0) kg, body fat -1.6 (-2.6, -0.7) kg, community vs. control; weight -2.4 (-3.6, -1.1) kg, body fat -1.4 (-2.4, -0.5) kg (all p < 0.001). The community group increased physical activity, reduced insulin, cardiovascular disease risk markers, increased QOL and was cost-effective. CONCLUSIONS: The programmes were equally effective for weight control, but the community programme had additional benefits. CLINICAL TRIAL REGISTRATION: ISRCTN68576140.

PRIMEtime CE: a multistate life table model for estimating the cost-effectiveness of interventions affecting diet and physical activity.

BACKGROUND: Non-communicable diseases are the leading cause of death in England, and poor diet and physical inactivity are two of the principle behavioural risk factors. In the context of increasingly constrained financial resources, decision makers in England need to be able to compare the potential costs and health outcomes of different public health policies aimed at improving these risk factors in order to know where to invest so that they can maximise population health. This paper describes PRIMEtime CE, a multistate life table cost-effectiveness model that can directly compare interventions affecting multiple disease outcomes. METHODS: The multistate life table model, PRIMEtime Cost Effectiveness (PRIMEtime CE), is developed from the Preventable Risk Integrated ModEl (PRIME) and the PRIMEtime model. PRIMEtime CE uses routinely available data to estimate how changing diet and physical activity in England affects morbidity and mortality from heart disease, stroke, diabetes, liver disease, and cancers either directly or via raised blood pressure, cholesterol, and body weight. RESULTS: Model outcomes are change in quality adjusted life years, and change in English National Health Service and social care costs. CONCLUSION: This paper describes PRIMEtime CE and highlights its main strengths and limitations. The model can be used to compare any number of public policies affecting diet and physical activity, allowing decision makers to understand how they can maximise population health with limited financial resources.

Estimating the cost-effectiveness of salt reformulation and increasing access to leisure centres in England, with PRIMEtime CE model validation using the AdViSHE tool.

BACKGROUND: PRIMEtime CE is a multistate life table model that can directly compare the cost effectiveness of public health interventions affecting diet and physical activity levels, helping to inform decisions about how to spend finite resources. This paper estimates the costs and health outcomes in England of two scenarios: reformulating salt and expanding subsidised access to leisure centres. The results are used to help validate PRIMEtime CE, following the steps outlined in the Assessment of the Validation Status of Health-Economic decision models (AdViSHE) tool. METHODS: The PRIMEtime CE model estimates the difference in quality adjusted life years (QALYs) and difference in NHS and social care costs of modelled interventions compared with doing nothing. The salt reformulation scenario models how salt consumption would change if food producers met the 2017 UK Food Standards Agency salt reformulation targets. The leisure centre scenario models change in physical activity levels if the Birmingham Be Active scheme (where swimming pools and gym access is free to residents during defined periods) was rolled out across England. The AdViSHE tool was developed by health economic modellers and divides model validation into five parts: validation of the conceptual model, input data validation, validation of computerised model, operational validation, and other validation techniques. PRIMEtime CE is discussed in relation to each part. RESULTS: Salt reformulation was dominant compared with doing nothing, and had a 10-year return on investment of £1.44 (£0.50 to £2.94) for every £1 spent. By contrast, over 10 years the Be Active expansion would cost £727,000 (£514,000 to £1,064,000) per QALY. PRIMEtime CE has good face validity of its conceptual model and has robust input data. Cross-validation produces mixed results and shows the impact of model scope, input parameters, and model structure on cost-per-QALY estimates. CONCLUSIONS: This paper illustrates how PRIMEtime CE can be used to compare the cost-effectiveness of two different public health measures affecting diet and physical activity levels. The AdViSHE tool helps to validate PRIMEtime CE, identifies some of the key drivers of model estimates, and highlights the challenges of externally validating public health economic models against independent data.

Preference-based measures to obtain health state utility values for use in economic evaluations with child-based populations: a review and UK-based focus group assessment of patient and parent choices.

BACKGROUND: No current guidance is available in the UK on the choice of preference-based measure (PBM) that should be used in obtaining health-related quality of life from children. The aim of this study is to review the current usage of PBMs for obtaining health state utility values in child and adolescent populations, and to obtain information on patient and parent-proxy respondent preferences in completing PBMs in the UK. METHODS: A literature review was conducted to determine which instrument is most frequently used for child-based economic evaluations and whether child or proxy responses are used. Instruments were compared on dimensions, severity levels, elicitation and valuation methods, availability of value sets and validation studies, and the range of utility values generated. Additionally, a series of focus groups of parents and young people (11-20 years) were convened to determine patient and proxy preferences. RESULTS: Five PBMs suitable for child populations were identified, although only the Health Utilities Index 2 (HUI2) and Child Heath Utility 9D (CHU-9D) have UK value sets. 45 papers used PBMs in this population, but many used non-child-specific PBMs. Most respondents were parent proxies, even in adolescent populations. Reported missing data ranged from 0.5 to 49.3%. The focus groups reported their experiences with the EQ-5D-Y and CHU-9D. Both the young persons' group and parent/proxy groups felt that the CHU-9D was more comprehensive but may be harder for a proxy to complete. Some younger children had difficulty understanding the CHU-9D questions, but the young persons' group nonetheless preferred responding directly. CONCLUSION: The use of PBMs in child populations is increasing, but many studies use PBMs that do not have appropriate value sets. Parent proxies are the most common respondents, but the focus group responses suggest it would be preferred, and may be more informative, for older children to self-report or for child-parent dyads to respond.

Estimating the variation in need for community-based social care by body mass index in England and associated cost: population-based cross-sectional study.

BACKGROUND: Adult obesity is linked to a greater need for social care because of its association with the development of long term conditions and because obese adults can have physical and social difficulties which inhibit daily living. Obesity thus has considerable social care cost implications but the magnitude of these costs is currently unknown. This paper outlines an approach to estimating obesity-related social care costs in adults aged over 65 in England. METHODS: We used univariable and multivariable logistic regression models to investigate the relation between the self-reported need for social care and potential determinants, including body mass index (BMI), using data from Health Survey for England. We combined these modelled estimates of need for social care with the mean hours of help received, conditional on receiving any help, to calculate the expected hours of social care received per adult by BMI. RESULTS: BMI is positively associated with self-reported need for social care. A one unit (ie 1 kg/m2) increase in BMI is on average associated with a 5% increase in the odds of need for help with social care (odds ratio 1.05, 95% CI 1.04 to 1.07) in an unadjusted model. Adjusting for long term illness and sociodemographic characteristics we estimate the annual cost of local authority funded care for those who receive it is £599 at a BMI of 23 but £1086 at a BMI of 40. CONCLUSION: BMI is positively associated with self-reported need for social care after adjustment for sociodemographic factors and limiting long term illness. The increase in need for care with BMI gives rise to additional costs in social care provision which should be borne in mind when calculating the cost-effectiveness of interventions aimed at reducing obesity.

Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults: A Randomized Clinical Trial.

Importance: Acute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment. Objective: To assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics. Design, Setting, and Participants: Double-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy. Interventions: Single oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283). Main Outcomes and Measures: Primary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events. Results: Among 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, -1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no significant differences in any other secondary outcomes. Conclusions and Relevance: Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours. Trial Registration: isrctn.org Identifier: ISRCTN17435450.

Symptoms, unmet needs, psychological well-being and health status in survivors of prostate cancer: implications for redesigning follow-up.

OBJECTIVE: To explore ongoing symptoms, unmet needs, psychological wellbeing, self-efficacy and overall health status in survivors of prostate cancer. PATIENTS AND METHODS: An invitation to participate in a postal questionnaire survey was sent to 546 men, diagnosed with prostate cancer 9-24 months previously at two UK cancer centres. The study group comprised men who had been subject to a range of treatments: surgery, radiotherapy, hormone therapy and active surveillance. The questionnaire included measures of prostate-related quality of life (Expanded Prostate cancer Index Composite 26-item version, EPIC-26); unmet needs (Supportive Care Needs Survey 34-item version, SCNS-SF34); anxiety and depression (Hospital Anxiety and Depression Scale, HADS), self-efficacy (modified Self-efficacy Scale), health status (EuroQol 5D, EQ-5D) and satisfaction with care (questions developed for this study). A single reminder was sent to non-responders after 3 weeks. Data were analysed by age, co-morbidities, and treatment group. RESULTS: In all, 316 men completed questionnaires (64.1% response rate). Overall satisfaction with follow-up care was high, but was lower for psychosocial than physical aspects of care. Urinary, bowel, and sexual functioning was reported as a moderate/big problem in the last month for 15.2% (n = 48), 5.1% (n = 16), and 36.5% (n = 105) men, respectively. The most commonly reported moderate/high unmet needs related to changes in sexual feelings/relationships, managing fear of recurrence/uncertainty, and concerns about the worries of significant others. It was found that 17% of men (51/307) reported potentially moderate-to-severe levels of anxiety and 10.2% (32/308) reported moderate-to-severe levels of depression. The presence of problematic side-effects was associated with higher psychological morbidity, poorer self-efficacy, greater unmet needs, and poorer overall health status. CONCLUSION: While some men report relatively few problems after prostate cancer treatment, this study highlights important physical and psycho-social issues for a significant minority of survivors of prostate cancer. Strategies for identifying those men with on-going problems, alongside new interventions and models of care, tailored to individual needs, are needed to improve quality of life.

Choosing an epidemiological model structure for the economic evaluation of non-communicable disease public health interventions.

Non-communicable diseases are the leading global causes of mortality and morbidity. Growing pressures on health services and on social care have led to increasing calls for a greater emphasis to be placed on prevention. In order for decisionmakers to make informed judgements about how to best spend finite public health resources, they must be able to quantify the anticipated costs, benefits, and opportunity costs of each prevention option available. This review presents a taxonomy of epidemiological model structures and applies it to the economic evaluation of public health interventions for non-communicable diseases. Through a novel discussion of the pros and cons of model structures and examples of their application to public health interventions, it suggests that individual-level models may be better than population-level models for estimating the effects of population heterogeneity. Furthermore, model structures allowing for interactions between populations, their environment, and time are often better suited to complex multifaceted interventions. Other influences on the choice of model structure include time and available resources, and the availability and relevance of previously developed models. This review will help guide modelers in the emerging field of public health economic modeling of non-communicable diseases.

Economic evaluations in bipolar disorder: a systematic review and critical appraisal.

BACKGROUND: Bipolar disorder (BD) is a chronic illness and is one of the worldwide leading causes of disability. It is often a lifelong illness and incurs a substantial economic burden on the health care system, the patients, and society as a whole. However, there are few studies evaluating the economic impact of alternative strategies in the management of BD. OBJECTIVES: We reviewed and critically appraised the available published economic evidence on BD management. In addition, we explored advantages and disadvantages of different methods used in the economic evaluation of the management of BD. METHODS: A systematic literature search was undertaken using seven electronic databases to identify all English language articles published between January 1980 and March 2012 that provided data on complete economic evaluations for any treatment strategy for BD. The quality of included studies was appraised according to recommendations from the Cochrane Collaboration. RESULTS: A total of 7,284 citations were obtained. After initial screening, 20 eligible studies were identified, five of which were trial-based, and 15 of which were model-based economic evaluations. Given the variability in methods and the quality of the identified studies, no conclusive recommendation for the most cost-effective therapy for BD could be provided. CONCLUSIONS: The cost-effectiveness of different treatment strategies varied between settings, and transferability of these results across settings remains questionable. Although additional research using a longer time horizon is required to validate the findings for trial-based economic evaluations, discrete event simulation appears to be the most natural and plausible technique for modeling the cost-effectiveness of alternative BD treatment strategies.

Estimating age and ethnic variation in the histological prevalence of prostate cancer to inform the impact of screening policies.

OBJECTIVES: To estimate histological prevalence of prostate cancer by age and ethnic group. METHODS: A literature review identified autopsy studies of men without clinical diagnosis of prostate cancer during their lifetime. A total of 25 studies fulfilled the inclusion criteria, and a Bayesian logistic meta-regression was carried out to examine the association between histological prevalence, age by decade and ethnic group (white, African American and Chinese/Japanese). RESULTS: Histological cancer was estimated to increase with age from 2% (95% confidence interval 1-3%) between 20-29 years-of-age to 69% (95% confidence interval 51-83%) by 90-99 years-of-age in the white ethnic group. The African American group was associated with the highest prevalence of cancer, albeit non-significantly (odds ratio 1.2, 95% confidence interval 0.9-1.5), whereas the Chinese/Japanese group was significantly associated with the lowest prevalence relative to the white group (odds ratio 0.6, 95% confidence interval 0.4-0.9). CONCLUSIONS: The present study provides an updated and improved analysis of the histological prevalence of prostate cancer. The results confirm ethnicity as a potential predictor of prevalence, but highlight the need for further research in the area. The findings are valuable for understanding the epidemiology and natural history of prostate cancer across ethnicities, and increasing the body of evidence aimed at estimating benefits and risks associated with prostate cancer screening programs.

Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial.

Chronic kidney disease (CKD) is associated with a substantial risk of progression to end-stage renal disease and vascular events. The nonsteroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardiorenal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomized, open, blinded endpoint trial, we assessed the effectiveness of 25 mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age = 74.8 years and s.d. = 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomization until the first occurrence of death, hospitalization for heart disease, stroke, heart failure, transient ischemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across 3 years of follow-up, the primary endpoint occurred in 113 of 677 participants randomized to spironolactone (16.7%) and 111 of 695 participants randomized to usual care (16.0%) with no significant difference between groups (hazard ratio = 1.05, 95% confidence interval: 0.81-1.37). Two-thirds of participants randomized to spironolactone stopped treatment within 6 months, predominantly because they met prespecified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met prespecified stop criteria (n = 239, 35.4%), followed by participants being withdrawn due to treatment side effects (n = 128, 18.9%) and hyperkalemia (n = 54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369 .

NHS reference costs: a history and cautionary note.

Historically, the NHS did not routinely collect cost data, unlike many countries with private insurance markets. In 1998, for the first time the government mandated NHS trusts to submit estimates of their costs of service, known as reference costs. These have informed a wide range of health economic evaluations and important functions in the health service, such as setting prices.Reference costs are collected by progressively disaggregating budgets top-down into disease and treatment groups. Despite ongoing improvements to methods and guidance, these submissions continued to suffer a lack of accuracy and comparability, fundamentally undermining their credibility for critical functions.To overcome these issues, there was a long-held ambition to collect "patient-level" cost data. Patient-level costs are estimated with a combination of disaggregating budgets but also capturing the patient-level "causality of costs" bottom-up in the allocation of resources to patient episodes. These not only aim to capture more of the drivers of costs, but also improve consistency of reporting between providers.The change in methods may confer improvements to data quality, though judgement is still required and achieving consistency between trusts will take further work. Estimated costs may also change in important ways that may take many years to fully understand. We end on a cautionary note that patient-level cost methods may unlock potential, they alone contribute little to our understanding of the complexities involved with service quality or need, while that potential will require substantial investment to realise. Many healthcare resources cannot be attributed to individual patients so the very notion of "patient-level" costs may be misplaced. High hopes have been put in these new data, though much more work is now necessary to understand their quality, what they show and how their use will impact the system.

TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.

Estimating BMI distributions by age and sex for local authorities in England: a small area estimation study.

OBJECTIVES: Rates of overweight and obesity vary across England, but local rates have not been estimated for over 10 years. We aimed to produce new small area estimates of body mass index (BMI) by age and sex for each lower tier and unitary local authority in England, to provide up-to-date and more detailed estimates for the use of policy-makers and academics working in non-communicable disease risk and health inequalities. DESIGN: We used generalised linear modelling to estimate the relationship between BMI with social/demographic markers in a cross-sectional survey, then used this model to impute a BMI for each adult in locally-representative populations. These groups were then disaggregated by 5-year age group, sex and local authority group. SETTING: The Health Survey for England 2018 (cross-sectional BMI data for England) and Census microdata 2011 (locally representative). PARTICIPANTS: A total of 6174 complete cases aged 16 and over were included. OUTCOME MEASURES: Modelled group-level BMI as mean and SD of log-BMI. Extensive internal validation was performed, against the original data and external validation against the National Diet and Nutrition Survey and Active Lives Survey and previous small area estimates. RESULTS: In 94% of age-sex are groups, mean BMI was in the overweight or obese ranges. Older and more deprived areas had the highest overweight and obesity rates, which were particularly in coastal areas, the West Midlands, Yorkshire and the Humber. Validation showed close concordance with previous estimates by local area and demographic groups. CONCLUSION: This work updated previous estimates of the distribution of BMI in England and contributes considerable additional detail to our understanding of the local epidemiology of overweight and obesity. Raised BMI now affects the vast majority of demographic groups by age, sex and area in England, regardless of geography or deprivation.

Quality of life, healthcare use and costs in 'at-risk' children after early antibiotic treatment versus placebo for influenza-like illness: within-trial descriptive economic analyses of the ARCHIE randomised controlled trial.

OBJECTIVES: To characterise the quality of life, healthcare use and costs associated with early antibiotic treatment of influenza-like illness (ILI) in 'at-risk' children. DESIGN: Economic analysis of a two-arm double-blind parallel group pragmatic randomised controlled trial. SETTING: Children were recruited from community-based healthcare settings, including general practices, walk-in centres and hospital ambulatory care. PARTICIPANTS: Children with risk factors for influenza-related complications, including respiratory, cardiac and neurological conditions, who presented within the first 5 days of an ILI. INTERVENTIONS: Co-amoxiclav 400/57 suspension or placebo. OUTCOME MEASURES: This economic analysis focused on quality of life measured by the EQ-5D-Y, symptoms assessed by the Canadian Acute Respiratory Infection and Flu Scale (CARIFS), healthcare use and costs including medication, hospital visits and admissions, general practitioner and nurse contacts. Outcomes were assessed for up to 28 days post randomisation. RESULTS: Information on resource use, EQ-5D-Y (day 28) and CARIFS (day 7) was available for 265 (98%), 72 (27%) and 123 (45%) out of 271 participants, respectively. Average costs in the co-amoxiclav group were £25 lower (95% CI -£113 to £65), but this difference was not statistically significant (p=0.566). The difference in EQ-5D-Y scores between groups was also not statistically significant (-0.014 (95% CI -0.124 to 0.096), p=0.798). However, day 7 CARIFS scores were 3.5 points lower in the co-amoxiclav arm (95% CI -6.9 to -0.1, p=0.044). CONCLUSIONS: Our findings did not show evidence that early co-amoxiclav treatment improves quality of life or reduces healthcare use and costs in 'at-risk' children with ILI, but may reduce symptom severity though confirmation from further research would be important. Reliable data collection from children's parents/carers was challenging, and resulted in high levels of missing data, which is common in pragmatic trials involving children with acute respiratory tract infections. TRIAL REGISTRATION NUMBER: ISRCTN70714783; EudraCT 2013-002822-21.

Quality of life in older adults with chronic kidney disease and transient changes in renal function: Findings from the Oxford Renal cohort.

BACKGROUND: Quality of life (QoL) is an important measure of disease burden and general health perception. The relationship between early chronic kidney disease (CKD) and QoL remains poorly understood. The Oxford Renal Study (OxRen) cohort comprises 1063 adults aged ≥60 years from UK primary care practices screened for early CKD, grouped according to existing or screen-detected CKD diagnoses, or biochemistry results indicative of reduced renal function (referred to as transient estimated glomerular filtration rate (eGFR) reduction). OBJECTIVES: This study aimed to compare QoL in participants known to have CKD at recruitment to those identified as having CKD through a screening programme. METHODS: Health profile data and multi-attribute utility scores were reported for two generic questionnaires: 5-level EuroQol-5 Dimension (EQ-5D-5L) and ICEpop CAPability measure for Adults (ICECAP-A). QoL was compared between patients with existing and screen-detected CKD; those with transient eGFR reduction served as the reference group in univariable and multivariable linear regression. RESULTS: Mean and standard deviation utility scores were not significantly different between the subgroups for EQ-5D-5L (screen-detected:0.785±0.156, n = 480, transient:0.779±0.157, n = 261, existing CKD:0.763±0.171, n = 322, p = 0.216) or ICECAP-A (screen-detected:0.909±0.094, transient:0.904±0.110, existing CKD:0.894±0.115, p = 0.200). Age, smoking status, and number of comorbidities were identified as independent predictors of QoL in this cohort. CONCLUSION: QoL of participants with existing CKD diagnoses was not significantly different from those with screen-detected CKD or transient eGFR reduction and was similar to UK mean scores for the same age, suggesting that patient burden of early CKD is minor. Moreover, CKD-related comorbidities contribute more significantly to disease burden in earlier stages of CKD than renal function per se. Larger prospective studies are required to define the relationship between QoL and CKD progression more precisely. These data also confirm the essentially asymptomatic nature of CKD, implying that routine screening or case finding are required to diagnose it.

The costs of bipolar disorder in the United Kingdom.

OBJECTIVES: To estimate the individual cost and population-level economic burden of Bipolar Disorder (BD), and explore the impact of clinical and sociodemographic factors on costs in the United Kingdom. METHODS: Annual UK health care, social care and societal cost data were collected from a prospective cohort of 91 BD patients using digital monitoring of symptoms. Costs (in £) were calculated for the year of resource use collection (2010-2011) and main results inflated to year 2018-2019. A Generalized Estimating Equation framework was used to investigate individual factors influencing costs. An economic burden estimate was derived by multiplying the mean annual cost per patient with literature-based population prevalence. RESULTS: The average annual cost of BD per patient was £12,617 (SE = ±£1085) or £14,938 (SE = ±£1281) at 2018-2019 prices with 68% of the total costs attributed to lost productivity and informal care, 31% to health care costs, 1% to private out-of-pocket expenses, and 0.5% to social care costs. A unit increase in average levels of depressive or manic symptoms were associated with 7% and 11% higher societal costs, respectively. The estimated annual prevalence of BD in the United Kingdom was 0.8% resulting in a population-level economic burden estimate of £5.1 billion for 2010-2011 or £6.43 billion for 2018-2019. CONCLUSIONS: BD is a disease of substantial costs in the United Kingdom with the majority of the economic burden falling outside the health care system in the form of productivity losses and informal care. These costs highly correlate with patient outcomes highlighting further needs for improved treatment efforts into functionality.

Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial.

BACKGROUND: Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on clinical outcomes after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. OBJECTIVE: To evaluate the long-term quality-adjusted life years (QALYs) gained of endovascular coiling compare to neurosurgical clipping in the UK cohort of ISAT. METHODS: Between September 12, 1994 and May 1, 2002, patients with ruptured intracranial aneurysms who were assumed treatment equipoise were randomly allocated to either neurosurgical clipping or endovascular coiling. We followed-up 1644 patients in 22 UK neurosurgical centers for a minimum of 10 yr. Health-related quality of life (HRQoL) was collected through yearly questionnaires, measured by utilities calculated from the EQ-5D-3L. We compared HRQoL between the 2 treatment groups over a period of 10 yr. In all, 1-yr, 5-yr, and 10-yr QALYs were estimated by combining utility and survival information. RESULTS: Higher average utility values were found in the endovascular group throughout the follow-up period, with mean differences between groups statistically significant in most years. The 10-yr QALYs were estimated to be 6.68 (95% CI: 6.45-6.90) in the coiling group and 6.32 (95% CI: 6.10-6.55) in the clipping group, respectively, a significant mean difference of 0.36 (95% CI: 0.04-0.66). A third of this mean QALYs gain was estimated to derive solely from HRQoL differences. CONCLUSION: HRQoL after treatment of a ruptured intracranial aneurysm was better after endovascular coiling compared to neurosurgical clipping, which contributed significantly to the QALYs gained over a 10-yr period.